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Proclivity ID
18813001
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Specialty Focus
Psoriatic Arthritis
Spondyloarthropathies
Rheumatoid Arthritis
Osteoarthritis
Negative Keywords
gaming
gambling
compulsive behaviors
ammunition
assault rifle
black jack
Boko Haram
bondage
child abuse
cocaine
Daech
drug paraphernalia
explosion
gun
human trafficking
ISIL
ISIS
Islamic caliphate
Islamic state
mixed martial arts
MMA
molestation
national rifle association
NRA
nsfw
pedophile
pedophilia
poker
porn
pornography
psychedelic drug
recreational drug
sex slave rings
slot machine
terrorism
terrorist
Texas hold 'em
UFC
substance abuse
abuseed
abuseer
abusees
abuseing
abusely
abuses
aeolus
aeolused
aeoluser
aeoluses
aeolusing
aeolusly
aeoluss
ahole
aholeed
aholeer
aholees
aholeing
aholely
aholes
alcohol
alcoholed
alcoholer
alcoholes
alcoholing
alcoholly
alcohols
allman
allmaned
allmaner
allmanes
allmaning
allmanly
allmans
alted
altes
alting
altly
alts
analed
analer
anales
analing
anally
analprobe
analprobeed
analprobeer
analprobees
analprobeing
analprobely
analprobes
anals
anilingus
anilingused
anilinguser
anilinguses
anilingusing
anilingusly
anilinguss
anus
anused
anuser
anuses
anusing
anusly
anuss
areola
areolaed
areolaer
areolaes
areolaing
areolaly
areolas
areole
areoleed
areoleer
areolees
areoleing
areolely
areoles
arian
arianed
arianer
arianes
arianing
arianly
arians
aryan
aryaned
aryaner
aryanes
aryaning
aryanly
aryans
asiaed
asiaer
asiaes
asiaing
asialy
asias
ass
ass hole
ass lick
ass licked
ass licker
ass lickes
ass licking
ass lickly
ass licks
assbang
assbanged
assbangeded
assbangeder
assbangedes
assbangeding
assbangedly
assbangeds
assbanger
assbanges
assbanging
assbangly
assbangs
assbangsed
assbangser
assbangses
assbangsing
assbangsly
assbangss
assed
asser
asses
assesed
asseser
asseses
assesing
assesly
assess
assfuck
assfucked
assfucker
assfuckered
assfuckerer
assfuckeres
assfuckering
assfuckerly
assfuckers
assfuckes
assfucking
assfuckly
assfucks
asshat
asshated
asshater
asshates
asshating
asshatly
asshats
assholeed
assholeer
assholees
assholeing
assholely
assholes
assholesed
assholeser
assholeses
assholesing
assholesly
assholess
assing
assly
assmaster
assmastered
assmasterer
assmasteres
assmastering
assmasterly
assmasters
assmunch
assmunched
assmuncher
assmunches
assmunching
assmunchly
assmunchs
asss
asswipe
asswipeed
asswipeer
asswipees
asswipeing
asswipely
asswipes
asswipesed
asswipeser
asswipeses
asswipesing
asswipesly
asswipess
azz
azzed
azzer
azzes
azzing
azzly
azzs
babeed
babeer
babees
babeing
babely
babes
babesed
babeser
babeses
babesing
babesly
babess
ballsac
ballsaced
ballsacer
ballsaces
ballsacing
ballsack
ballsacked
ballsacker
ballsackes
ballsacking
ballsackly
ballsacks
ballsacly
ballsacs
ballsed
ballser
ballses
ballsing
ballsly
ballss
barf
barfed
barfer
barfes
barfing
barfly
barfs
bastard
bastarded
bastarder
bastardes
bastarding
bastardly
bastards
bastardsed
bastardser
bastardses
bastardsing
bastardsly
bastardss
bawdy
bawdyed
bawdyer
bawdyes
bawdying
bawdyly
bawdys
beaner
beanered
beanerer
beaneres
beanering
beanerly
beaners
beardedclam
beardedclamed
beardedclamer
beardedclames
beardedclaming
beardedclamly
beardedclams
beastiality
beastialityed
beastialityer
beastialityes
beastialitying
beastialityly
beastialitys
beatch
beatched
beatcher
beatches
beatching
beatchly
beatchs
beater
beatered
beaterer
beateres
beatering
beaterly
beaters
beered
beerer
beeres
beering
beerly
beeyotch
beeyotched
beeyotcher
beeyotches
beeyotching
beeyotchly
beeyotchs
beotch
beotched
beotcher
beotches
beotching
beotchly
beotchs
biatch
biatched
biatcher
biatches
biatching
biatchly
biatchs
big tits
big titsed
big titser
big titses
big titsing
big titsly
big titss
bigtits
bigtitsed
bigtitser
bigtitses
bigtitsing
bigtitsly
bigtitss
bimbo
bimboed
bimboer
bimboes
bimboing
bimboly
bimbos
bisexualed
bisexualer
bisexuales
bisexualing
bisexually
bisexuals
bitch
bitched
bitcheded
bitcheder
bitchedes
bitcheding
bitchedly
bitcheds
bitcher
bitches
bitchesed
bitcheser
bitcheses
bitchesing
bitchesly
bitchess
bitching
bitchly
bitchs
bitchy
bitchyed
bitchyer
bitchyes
bitchying
bitchyly
bitchys
bleached
bleacher
bleaches
bleaching
bleachly
bleachs
blow job
blow jobed
blow jober
blow jobes
blow jobing
blow jobly
blow jobs
blowed
blower
blowes
blowing
blowjob
blowjobed
blowjober
blowjobes
blowjobing
blowjobly
blowjobs
blowjobsed
blowjobser
blowjobses
blowjobsing
blowjobsly
blowjobss
blowly
blows
boink
boinked
boinker
boinkes
boinking
boinkly
boinks
bollock
bollocked
bollocker
bollockes
bollocking
bollockly
bollocks
bollocksed
bollockser
bollockses
bollocksing
bollocksly
bollockss
bollok
bolloked
bolloker
bollokes
bolloking
bollokly
bolloks
boner
bonered
bonerer
boneres
bonering
bonerly
boners
bonersed
bonerser
bonerses
bonersing
bonersly
bonerss
bong
bonged
bonger
bonges
bonging
bongly
bongs
boob
boobed
boober
boobes
boobies
boobiesed
boobieser
boobieses
boobiesing
boobiesly
boobiess
boobing
boobly
boobs
boobsed
boobser
boobses
boobsing
boobsly
boobss
booby
boobyed
boobyer
boobyes
boobying
boobyly
boobys
booger
boogered
boogerer
boogeres
boogering
boogerly
boogers
bookie
bookieed
bookieer
bookiees
bookieing
bookiely
bookies
bootee
booteeed
booteeer
booteees
booteeing
booteely
bootees
bootie
bootieed
bootieer
bootiees
bootieing
bootiely
booties
booty
bootyed
bootyer
bootyes
bootying
bootyly
bootys
boozeed
boozeer
boozees
boozeing
boozely
boozer
boozered
boozerer
boozeres
boozering
boozerly
boozers
boozes
boozy
boozyed
boozyer
boozyes
boozying
boozyly
boozys
bosomed
bosomer
bosomes
bosoming
bosomly
bosoms
bosomy
bosomyed
bosomyer
bosomyes
bosomying
bosomyly
bosomys
bugger
buggered
buggerer
buggeres
buggering
buggerly
buggers
bukkake
bukkakeed
bukkakeer
bukkakees
bukkakeing
bukkakely
bukkakes
bull shit
bull shited
bull shiter
bull shites
bull shiting
bull shitly
bull shits
bullshit
bullshited
bullshiter
bullshites
bullshiting
bullshitly
bullshits
bullshitsed
bullshitser
bullshitses
bullshitsing
bullshitsly
bullshitss
bullshitted
bullshitteded
bullshitteder
bullshittedes
bullshitteding
bullshittedly
bullshitteds
bullturds
bullturdsed
bullturdser
bullturdses
bullturdsing
bullturdsly
bullturdss
bung
bunged
bunger
bunges
bunging
bungly
bungs
busty
bustyed
bustyer
bustyes
bustying
bustyly
bustys
butt
butt fuck
butt fucked
butt fucker
butt fuckes
butt fucking
butt fuckly
butt fucks
butted
buttes
buttfuck
buttfucked
buttfucker
buttfuckered
buttfuckerer
buttfuckeres
buttfuckering
buttfuckerly
buttfuckers
buttfuckes
buttfucking
buttfuckly
buttfucks
butting
buttly
buttplug
buttpluged
buttpluger
buttpluges
buttpluging
buttplugly
buttplugs
butts
caca
cacaed
cacaer
cacaes
cacaing
cacaly
cacas
cahone
cahoneed
cahoneer
cahonees
cahoneing
cahonely
cahones
cameltoe
cameltoeed
cameltoeer
cameltoees
cameltoeing
cameltoely
cameltoes
carpetmuncher
carpetmunchered
carpetmuncherer
carpetmuncheres
carpetmunchering
carpetmuncherly
carpetmunchers
cawk
cawked
cawker
cawkes
cawking
cawkly
cawks
chinc
chinced
chincer
chinces
chincing
chincly
chincs
chincsed
chincser
chincses
chincsing
chincsly
chincss
chink
chinked
chinker
chinkes
chinking
chinkly
chinks
chode
chodeed
chodeer
chodees
chodeing
chodely
chodes
chodesed
chodeser
chodeses
chodesing
chodesly
chodess
clit
clited
cliter
clites
cliting
clitly
clitoris
clitorised
clitoriser
clitorises
clitorising
clitorisly
clitoriss
clitorus
clitorused
clitoruser
clitoruses
clitorusing
clitorusly
clitoruss
clits
clitsed
clitser
clitses
clitsing
clitsly
clitss
clitty
clittyed
clittyer
clittyes
clittying
clittyly
clittys
cocain
cocaine
cocained
cocaineed
cocaineer
cocainees
cocaineing
cocainely
cocainer
cocaines
cocaining
cocainly
cocains
cock
cock sucker
cock suckered
cock suckerer
cock suckeres
cock suckering
cock suckerly
cock suckers
cockblock
cockblocked
cockblocker
cockblockes
cockblocking
cockblockly
cockblocks
cocked
cocker
cockes
cockholster
cockholstered
cockholsterer
cockholsteres
cockholstering
cockholsterly
cockholsters
cocking
cockknocker
cockknockered
cockknockerer
cockknockeres
cockknockering
cockknockerly
cockknockers
cockly
cocks
cocksed
cockser
cockses
cocksing
cocksly
cocksmoker
cocksmokered
cocksmokerer
cocksmokeres
cocksmokering
cocksmokerly
cocksmokers
cockss
cocksucker
cocksuckered
cocksuckerer
cocksuckeres
cocksuckering
cocksuckerly
cocksuckers
coital
coitaled
coitaler
coitales
coitaling
coitally
coitals
commie
commieed
commieer
commiees
commieing
commiely
commies
condomed
condomer
condomes
condoming
condomly
condoms
coon
cooned
cooner
coones
cooning
coonly
coons
coonsed
coonser
coonses
coonsing
coonsly
coonss
corksucker
corksuckered
corksuckerer
corksuckeres
corksuckering
corksuckerly
corksuckers
cracked
crackwhore
crackwhoreed
crackwhoreer
crackwhorees
crackwhoreing
crackwhorely
crackwhores
crap
craped
craper
crapes
craping
craply
crappy
crappyed
crappyer
crappyes
crappying
crappyly
crappys
cum
cumed
cumer
cumes
cuming
cumly
cummin
cummined
cumminer
cummines
cumming
cumminged
cumminger
cumminges
cumminging
cummingly
cummings
cummining
cumminly
cummins
cums
cumshot
cumshoted
cumshoter
cumshotes
cumshoting
cumshotly
cumshots
cumshotsed
cumshotser
cumshotses
cumshotsing
cumshotsly
cumshotss
cumslut
cumsluted
cumsluter
cumslutes
cumsluting
cumslutly
cumsluts
cumstain
cumstained
cumstainer
cumstaines
cumstaining
cumstainly
cumstains
cunilingus
cunilingused
cunilinguser
cunilinguses
cunilingusing
cunilingusly
cunilinguss
cunnilingus
cunnilingused
cunnilinguser
cunnilinguses
cunnilingusing
cunnilingusly
cunnilinguss
cunny
cunnyed
cunnyer
cunnyes
cunnying
cunnyly
cunnys
cunt
cunted
cunter
cuntes
cuntface
cuntfaceed
cuntfaceer
cuntfacees
cuntfaceing
cuntfacely
cuntfaces
cunthunter
cunthuntered
cunthunterer
cunthunteres
cunthuntering
cunthunterly
cunthunters
cunting
cuntlick
cuntlicked
cuntlicker
cuntlickered
cuntlickerer
cuntlickeres
cuntlickering
cuntlickerly
cuntlickers
cuntlickes
cuntlicking
cuntlickly
cuntlicks
cuntly
cunts
cuntsed
cuntser
cuntses
cuntsing
cuntsly
cuntss
dago
dagoed
dagoer
dagoes
dagoing
dagoly
dagos
dagosed
dagoser
dagoses
dagosing
dagosly
dagoss
dammit
dammited
dammiter
dammites
dammiting
dammitly
dammits
damn
damned
damneded
damneder
damnedes
damneding
damnedly
damneds
damner
damnes
damning
damnit
damnited
damniter
damnites
damniting
damnitly
damnits
damnly
damns
dick
dickbag
dickbaged
dickbager
dickbages
dickbaging
dickbagly
dickbags
dickdipper
dickdippered
dickdipperer
dickdipperes
dickdippering
dickdipperly
dickdippers
dicked
dicker
dickes
dickface
dickfaceed
dickfaceer
dickfacees
dickfaceing
dickfacely
dickfaces
dickflipper
dickflippered
dickflipperer
dickflipperes
dickflippering
dickflipperly
dickflippers
dickhead
dickheaded
dickheader
dickheades
dickheading
dickheadly
dickheads
dickheadsed
dickheadser
dickheadses
dickheadsing
dickheadsly
dickheadss
dicking
dickish
dickished
dickisher
dickishes
dickishing
dickishly
dickishs
dickly
dickripper
dickrippered
dickripperer
dickripperes
dickrippering
dickripperly
dickrippers
dicks
dicksipper
dicksippered
dicksipperer
dicksipperes
dicksippering
dicksipperly
dicksippers
dickweed
dickweeded
dickweeder
dickweedes
dickweeding
dickweedly
dickweeds
dickwhipper
dickwhippered
dickwhipperer
dickwhipperes
dickwhippering
dickwhipperly
dickwhippers
dickzipper
dickzippered
dickzipperer
dickzipperes
dickzippering
dickzipperly
dickzippers
diddle
diddleed
diddleer
diddlees
diddleing
diddlely
diddles
dike
dikeed
dikeer
dikees
dikeing
dikely
dikes
dildo
dildoed
dildoer
dildoes
dildoing
dildoly
dildos
dildosed
dildoser
dildoses
dildosing
dildosly
dildoss
diligaf
diligafed
diligafer
diligafes
diligafing
diligafly
diligafs
dillweed
dillweeded
dillweeder
dillweedes
dillweeding
dillweedly
dillweeds
dimwit
dimwited
dimwiter
dimwites
dimwiting
dimwitly
dimwits
dingle
dingleed
dingleer
dinglees
dingleing
dinglely
dingles
dipship
dipshiped
dipshiper
dipshipes
dipshiping
dipshiply
dipships
dizzyed
dizzyer
dizzyes
dizzying
dizzyly
dizzys
doggiestyleed
doggiestyleer
doggiestylees
doggiestyleing
doggiestylely
doggiestyles
doggystyleed
doggystyleer
doggystylees
doggystyleing
doggystylely
doggystyles
dong
donged
donger
donges
donging
dongly
dongs
doofus
doofused
doofuser
doofuses
doofusing
doofusly
doofuss
doosh
dooshed
doosher
dooshes
dooshing
dooshly
dooshs
dopeyed
dopeyer
dopeyes
dopeying
dopeyly
dopeys
douchebag
douchebaged
douchebager
douchebages
douchebaging
douchebagly
douchebags
douchebagsed
douchebagser
douchebagses
douchebagsing
douchebagsly
douchebagss
doucheed
doucheer
douchees
doucheing
douchely
douches
douchey
doucheyed
doucheyer
doucheyes
doucheying
doucheyly
doucheys
drunk
drunked
drunker
drunkes
drunking
drunkly
drunks
dumass
dumassed
dumasser
dumasses
dumassing
dumassly
dumasss
dumbass
dumbassed
dumbasser
dumbasses
dumbassesed
dumbasseser
dumbasseses
dumbassesing
dumbassesly
dumbassess
dumbassing
dumbassly
dumbasss
dummy
dummyed
dummyer
dummyes
dummying
dummyly
dummys
dyke
dykeed
dykeer
dykees
dykeing
dykely
dykes
dykesed
dykeser
dykeses
dykesing
dykesly
dykess
erotic
eroticed
eroticer
erotices
eroticing
eroticly
erotics
extacy
extacyed
extacyer
extacyes
extacying
extacyly
extacys
extasy
extasyed
extasyer
extasyes
extasying
extasyly
extasys
fack
facked
facker
fackes
facking
fackly
facks
fag
faged
fager
fages
fagg
fagged
faggeded
faggeder
faggedes
faggeding
faggedly
faggeds
fagger
fagges
fagging
faggit
faggited
faggiter
faggites
faggiting
faggitly
faggits
faggly
faggot
faggoted
faggoter
faggotes
faggoting
faggotly
faggots
faggs
faging
fagly
fagot
fagoted
fagoter
fagotes
fagoting
fagotly
fagots
fags
fagsed
fagser
fagses
fagsing
fagsly
fagss
faig
faiged
faiger
faiges
faiging
faigly
faigs
faigt
faigted
faigter
faigtes
faigting
faigtly
faigts
fannybandit
fannybandited
fannybanditer
fannybandites
fannybanditing
fannybanditly
fannybandits
farted
farter
fartes
farting
fartknocker
fartknockered
fartknockerer
fartknockeres
fartknockering
fartknockerly
fartknockers
fartly
farts
felch
felched
felcher
felchered
felcherer
felcheres
felchering
felcherly
felchers
felches
felching
felchinged
felchinger
felchinges
felchinging
felchingly
felchings
felchly
felchs
fellate
fellateed
fellateer
fellatees
fellateing
fellately
fellates
fellatio
fellatioed
fellatioer
fellatioes
fellatioing
fellatioly
fellatios
feltch
feltched
feltcher
feltchered
feltcherer
feltcheres
feltchering
feltcherly
feltchers
feltches
feltching
feltchly
feltchs
feom
feomed
feomer
feomes
feoming
feomly
feoms
fisted
fisteded
fisteder
fistedes
fisteding
fistedly
fisteds
fisting
fistinged
fistinger
fistinges
fistinging
fistingly
fistings
fisty
fistyed
fistyer
fistyes
fistying
fistyly
fistys
floozy
floozyed
floozyer
floozyes
floozying
floozyly
floozys
foad
foaded
foader
foades
foading
foadly
foads
fondleed
fondleer
fondlees
fondleing
fondlely
fondles
foobar
foobared
foobarer
foobares
foobaring
foobarly
foobars
freex
freexed
freexer
freexes
freexing
freexly
freexs
frigg
frigga
friggaed
friggaer
friggaes
friggaing
friggaly
friggas
frigged
frigger
frigges
frigging
friggly
friggs
fubar
fubared
fubarer
fubares
fubaring
fubarly
fubars
fuck
fuckass
fuckassed
fuckasser
fuckasses
fuckassing
fuckassly
fuckasss
fucked
fuckeded
fuckeder
fuckedes
fuckeding
fuckedly
fuckeds
fucker
fuckered
fuckerer
fuckeres
fuckering
fuckerly
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Rheumatology News
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The leading independent newspaper covering rheumatology news and commentary.

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Nurse-Led Care for Gout Generates Best Uric Acid Control

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Mon, 06/24/2024 - 15:04

— To maintain gout in remission, nurses in a rheumatology service do better than doctors in implementing a straightforward treat-to-target (T2T) strategy, according to a randomized study that showed a consistent advantage across subgroups.

“Our study provides evidence that nurse-led therapy for gout leads to better uric acid control, which is an important consideration with the increasing incidence and the increasing costs of managing this condition,” said Jesper W. Larsen, a registered nurse affiliated with the Department of Rheumatology at North Denmark Regional Hospital, Hjørring, Denmark. He presented the study at the annual European Congress of Rheumatology.

The advantage of nurse-led care was seen across every subgroup evaluated. Moreover, more patients in the nurse-led group than in the usual care group remained on urate-lowering therapy at the end of the 2-year study.

The optimal management of gout is based on the treatment goal of lowering serum uric acid (sUA) to below the physiologic level of 0.36 mmol/L (6 mg/dL), a strategy called T2T that is endorsed by both EULAR and the American College of Rheumatology.

“This target can be reached in most patients with commonly used therapies, including allopurinol, which is relatively inexpensive,” Mr. Larsen said. Given that disease control and sustained remission are largely based on this target, he and his colleagues tested the hypothesis that nurses working in a rheumatology service could provide efficient and cost-effective care.

A total of 286 patients with gout defined by microscopy who were treated between 2015 and 2021 were enrolled in the study. Of these, 100 patients who had been enrolled before the introduction of nurse-led care received and were maintained on usual care, which generally included diagnosis by an orthopedist, an emergency room physician, or an internist, with subsequent treatment and follow-up with a general practitioner.

Of 186 patients treated after nurse-led care was implemented, 72 were transitioned to usual care, and the remaining 114 continued receiving nurse-led care over the next 2 years of follow-up. In the nurse-led care arm, nurses who specialized in rheumatology and were trained in gout management monitored a structured T2T strategy. They were available for consultation, provided patient education, and followed laboratory values, including sUA, which they used to adjust treatments.

Except in the case of complications, “there was no more contact with physicians” once care was transferred to the nurse, Mr. Larsen said. Most of the nurse management was based on sUA laboratory values and performed by telephone.

At 2 years, 112 patients in the nurse-led care group were compared with the 144 in the usual care group. Two of the 114 patients who entered the nurse-care cohort and 28 of the 172 in the usual care cohort died before the study ended.

At 2 years, the proportion of patients maintained at the target sUA was almost twice as great in the nurse-led arm (83% vs 44%). This was also true of patients aged 70 years or older (84% vs 45%), patients with tophi (60% vs 33%), and patients with sUA > 0.5 mmol/L at baseline (84% vs 44%). Nurse-led care also kept a greater proportion of patients at target who entered the study with an estimated glomerular filtration rate < 60 mL/min per 1.73 m2 (84% vs 52%) or were taking diuretics (89% vs 52%). All differences reached statistical significance (P < .05).

The reason for the lower mortality at 2 years in the nurse-led group (4% vs 23%; P < .001) is unclear, according to Mr. Larsen. In addition to considering a selection bias that might have channeled patients with more severe disease to usual care, he and his coinvestigators are also considering whether the lower rates of sUA control in the usual care group might have led to a higher rate of cardiovascular events.

Because of some baseline imbalances, a selection bias cannot be ruled out, but the imbalances did not uniformly favor nurse-led care. For example, the proportion of patients with diabetes (23% vs 13%) or a baseline cancer diagnosis (11% vs 5%) was higher in the nurse-led care group. The proportion of patients with atrial fibrillation (45% vs 35%) or on diuretics (47% vs 33%) at baseline was higher in the usual care group.

The median age of 69 years was the same in the two groups, although the nurse-led group included a higher proportion of men to women (86% vs 76%).

Within a T2T strategy, nurses focused on reaching the target might do a better job than physicians in consistently monitoring and adjusting therapies as needed, but Mr. Larsen also speculated that nurses might offer a more collaborative approach and provide greater support through patient education and regular telephone contact.
 

 

 

Potential Advantages of Nurse-Led Care

Clinicians concerned about nurses missing nuances in disease progression or being slow to recognize complications might be surprised to learn about the advantage of nurse-led care, but Mwidimi Ndosi, PhD, an associate professor in rheumatology nursing at the University of the West of England, Bristol, England, was not.

“There is quite a large literature to show that nursing care is often superior to physician-led patient management in the appropriate circumstances,” Mr. Ndosi said. In this specific instance of gout management, he said that the treatment target is clear, and nurses are often able to devote more time to a specific goal, like T2T, than clinicians balancing more priorities.

Dr. Mwidimi Ndosi


“In this trial, the care was administered by nurse specialists who presumably are skilled in this disease and know their limitations if a consultation with a physician is needed,” he said.

Mr. Ndosi, like Mr. Larsen, considers it likely that nurse-led programs for a T2T gout protocol will be implemented elsewhere. Mr. Ndosi pointed out that patients who are concerned about the quality of nurse-led care are generally convinced of its merits over time.

Because of factors such as nurses’ ability to spend more clinical time with patients and greater willingness to engage in resolving obstacles to self-care, compared with physicians, “there are many studies to show that patients are often more satisfied with care provided by nurses,” he said.

Mr. Larsen and Mr. Ndosi reported no potential conflicts of interest.

A version of this article first appeared on Medscape.com.

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— To maintain gout in remission, nurses in a rheumatology service do better than doctors in implementing a straightforward treat-to-target (T2T) strategy, according to a randomized study that showed a consistent advantage across subgroups.

“Our study provides evidence that nurse-led therapy for gout leads to better uric acid control, which is an important consideration with the increasing incidence and the increasing costs of managing this condition,” said Jesper W. Larsen, a registered nurse affiliated with the Department of Rheumatology at North Denmark Regional Hospital, Hjørring, Denmark. He presented the study at the annual European Congress of Rheumatology.

The advantage of nurse-led care was seen across every subgroup evaluated. Moreover, more patients in the nurse-led group than in the usual care group remained on urate-lowering therapy at the end of the 2-year study.

The optimal management of gout is based on the treatment goal of lowering serum uric acid (sUA) to below the physiologic level of 0.36 mmol/L (6 mg/dL), a strategy called T2T that is endorsed by both EULAR and the American College of Rheumatology.

“This target can be reached in most patients with commonly used therapies, including allopurinol, which is relatively inexpensive,” Mr. Larsen said. Given that disease control and sustained remission are largely based on this target, he and his colleagues tested the hypothesis that nurses working in a rheumatology service could provide efficient and cost-effective care.

A total of 286 patients with gout defined by microscopy who were treated between 2015 and 2021 were enrolled in the study. Of these, 100 patients who had been enrolled before the introduction of nurse-led care received and were maintained on usual care, which generally included diagnosis by an orthopedist, an emergency room physician, or an internist, with subsequent treatment and follow-up with a general practitioner.

Of 186 patients treated after nurse-led care was implemented, 72 were transitioned to usual care, and the remaining 114 continued receiving nurse-led care over the next 2 years of follow-up. In the nurse-led care arm, nurses who specialized in rheumatology and were trained in gout management monitored a structured T2T strategy. They were available for consultation, provided patient education, and followed laboratory values, including sUA, which they used to adjust treatments.

Except in the case of complications, “there was no more contact with physicians” once care was transferred to the nurse, Mr. Larsen said. Most of the nurse management was based on sUA laboratory values and performed by telephone.

At 2 years, 112 patients in the nurse-led care group were compared with the 144 in the usual care group. Two of the 114 patients who entered the nurse-care cohort and 28 of the 172 in the usual care cohort died before the study ended.

At 2 years, the proportion of patients maintained at the target sUA was almost twice as great in the nurse-led arm (83% vs 44%). This was also true of patients aged 70 years or older (84% vs 45%), patients with tophi (60% vs 33%), and patients with sUA > 0.5 mmol/L at baseline (84% vs 44%). Nurse-led care also kept a greater proportion of patients at target who entered the study with an estimated glomerular filtration rate < 60 mL/min per 1.73 m2 (84% vs 52%) or were taking diuretics (89% vs 52%). All differences reached statistical significance (P < .05).

The reason for the lower mortality at 2 years in the nurse-led group (4% vs 23%; P < .001) is unclear, according to Mr. Larsen. In addition to considering a selection bias that might have channeled patients with more severe disease to usual care, he and his coinvestigators are also considering whether the lower rates of sUA control in the usual care group might have led to a higher rate of cardiovascular events.

Because of some baseline imbalances, a selection bias cannot be ruled out, but the imbalances did not uniformly favor nurse-led care. For example, the proportion of patients with diabetes (23% vs 13%) or a baseline cancer diagnosis (11% vs 5%) was higher in the nurse-led care group. The proportion of patients with atrial fibrillation (45% vs 35%) or on diuretics (47% vs 33%) at baseline was higher in the usual care group.

The median age of 69 years was the same in the two groups, although the nurse-led group included a higher proportion of men to women (86% vs 76%).

Within a T2T strategy, nurses focused on reaching the target might do a better job than physicians in consistently monitoring and adjusting therapies as needed, but Mr. Larsen also speculated that nurses might offer a more collaborative approach and provide greater support through patient education and regular telephone contact.
 

 

 

Potential Advantages of Nurse-Led Care

Clinicians concerned about nurses missing nuances in disease progression or being slow to recognize complications might be surprised to learn about the advantage of nurse-led care, but Mwidimi Ndosi, PhD, an associate professor in rheumatology nursing at the University of the West of England, Bristol, England, was not.

“There is quite a large literature to show that nursing care is often superior to physician-led patient management in the appropriate circumstances,” Mr. Ndosi said. In this specific instance of gout management, he said that the treatment target is clear, and nurses are often able to devote more time to a specific goal, like T2T, than clinicians balancing more priorities.

Dr. Mwidimi Ndosi


“In this trial, the care was administered by nurse specialists who presumably are skilled in this disease and know their limitations if a consultation with a physician is needed,” he said.

Mr. Ndosi, like Mr. Larsen, considers it likely that nurse-led programs for a T2T gout protocol will be implemented elsewhere. Mr. Ndosi pointed out that patients who are concerned about the quality of nurse-led care are generally convinced of its merits over time.

Because of factors such as nurses’ ability to spend more clinical time with patients and greater willingness to engage in resolving obstacles to self-care, compared with physicians, “there are many studies to show that patients are often more satisfied with care provided by nurses,” he said.

Mr. Larsen and Mr. Ndosi reported no potential conflicts of interest.

A version of this article first appeared on Medscape.com.

— To maintain gout in remission, nurses in a rheumatology service do better than doctors in implementing a straightforward treat-to-target (T2T) strategy, according to a randomized study that showed a consistent advantage across subgroups.

“Our study provides evidence that nurse-led therapy for gout leads to better uric acid control, which is an important consideration with the increasing incidence and the increasing costs of managing this condition,” said Jesper W. Larsen, a registered nurse affiliated with the Department of Rheumatology at North Denmark Regional Hospital, Hjørring, Denmark. He presented the study at the annual European Congress of Rheumatology.

The advantage of nurse-led care was seen across every subgroup evaluated. Moreover, more patients in the nurse-led group than in the usual care group remained on urate-lowering therapy at the end of the 2-year study.

The optimal management of gout is based on the treatment goal of lowering serum uric acid (sUA) to below the physiologic level of 0.36 mmol/L (6 mg/dL), a strategy called T2T that is endorsed by both EULAR and the American College of Rheumatology.

“This target can be reached in most patients with commonly used therapies, including allopurinol, which is relatively inexpensive,” Mr. Larsen said. Given that disease control and sustained remission are largely based on this target, he and his colleagues tested the hypothesis that nurses working in a rheumatology service could provide efficient and cost-effective care.

A total of 286 patients with gout defined by microscopy who were treated between 2015 and 2021 were enrolled in the study. Of these, 100 patients who had been enrolled before the introduction of nurse-led care received and were maintained on usual care, which generally included diagnosis by an orthopedist, an emergency room physician, or an internist, with subsequent treatment and follow-up with a general practitioner.

Of 186 patients treated after nurse-led care was implemented, 72 were transitioned to usual care, and the remaining 114 continued receiving nurse-led care over the next 2 years of follow-up. In the nurse-led care arm, nurses who specialized in rheumatology and were trained in gout management monitored a structured T2T strategy. They were available for consultation, provided patient education, and followed laboratory values, including sUA, which they used to adjust treatments.

Except in the case of complications, “there was no more contact with physicians” once care was transferred to the nurse, Mr. Larsen said. Most of the nurse management was based on sUA laboratory values and performed by telephone.

At 2 years, 112 patients in the nurse-led care group were compared with the 144 in the usual care group. Two of the 114 patients who entered the nurse-care cohort and 28 of the 172 in the usual care cohort died before the study ended.

At 2 years, the proportion of patients maintained at the target sUA was almost twice as great in the nurse-led arm (83% vs 44%). This was also true of patients aged 70 years or older (84% vs 45%), patients with tophi (60% vs 33%), and patients with sUA > 0.5 mmol/L at baseline (84% vs 44%). Nurse-led care also kept a greater proportion of patients at target who entered the study with an estimated glomerular filtration rate < 60 mL/min per 1.73 m2 (84% vs 52%) or were taking diuretics (89% vs 52%). All differences reached statistical significance (P < .05).

The reason for the lower mortality at 2 years in the nurse-led group (4% vs 23%; P < .001) is unclear, according to Mr. Larsen. In addition to considering a selection bias that might have channeled patients with more severe disease to usual care, he and his coinvestigators are also considering whether the lower rates of sUA control in the usual care group might have led to a higher rate of cardiovascular events.

Because of some baseline imbalances, a selection bias cannot be ruled out, but the imbalances did not uniformly favor nurse-led care. For example, the proportion of patients with diabetes (23% vs 13%) or a baseline cancer diagnosis (11% vs 5%) was higher in the nurse-led care group. The proportion of patients with atrial fibrillation (45% vs 35%) or on diuretics (47% vs 33%) at baseline was higher in the usual care group.

The median age of 69 years was the same in the two groups, although the nurse-led group included a higher proportion of men to women (86% vs 76%).

Within a T2T strategy, nurses focused on reaching the target might do a better job than physicians in consistently monitoring and adjusting therapies as needed, but Mr. Larsen also speculated that nurses might offer a more collaborative approach and provide greater support through patient education and regular telephone contact.
 

 

 

Potential Advantages of Nurse-Led Care

Clinicians concerned about nurses missing nuances in disease progression or being slow to recognize complications might be surprised to learn about the advantage of nurse-led care, but Mwidimi Ndosi, PhD, an associate professor in rheumatology nursing at the University of the West of England, Bristol, England, was not.

“There is quite a large literature to show that nursing care is often superior to physician-led patient management in the appropriate circumstances,” Mr. Ndosi said. In this specific instance of gout management, he said that the treatment target is clear, and nurses are often able to devote more time to a specific goal, like T2T, than clinicians balancing more priorities.

Dr. Mwidimi Ndosi


“In this trial, the care was administered by nurse specialists who presumably are skilled in this disease and know their limitations if a consultation with a physician is needed,” he said.

Mr. Ndosi, like Mr. Larsen, considers it likely that nurse-led programs for a T2T gout protocol will be implemented elsewhere. Mr. Ndosi pointed out that patients who are concerned about the quality of nurse-led care are generally convinced of its merits over time.

Because of factors such as nurses’ ability to spend more clinical time with patients and greater willingness to engage in resolving obstacles to self-care, compared with physicians, “there are many studies to show that patients are often more satisfied with care provided by nurses,” he said.

Mr. Larsen and Mr. Ndosi reported no potential conflicts of interest.

A version of this article first appeared on Medscape.com.

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FROM EULAR 2024

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Low Hydroxychloroquine Levels in Early Pregnancy Tied to Greater Flares in SLE

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Mon, 06/24/2024 - 14:32

 

TOPLINE:

A study reveals that hydroxychloroquine levels during the first trimester in pregnant women with systemic lupus erythematosus (SLE) are linked to severe maternal flares but not to adverse pregnancy outcomes.

METHODOLOGY:

  • Researchers included pregnant women with SLE (median age, 32.1 years; median duration of disease, 8.3 years) who were enrolled in an ongoing French prospective observational study and were receiving hydroxychloroquine.
  • The study assessed hydroxychloroquine blood levels during the first trimester. It defined severe nonadherence as having levels < 200 ng/mL and classified levels < 500 ng/mL as subtherapeutic.
  • Primary outcomes were maternal flares during pregnancy and adverse pregnancy outcomes, including fetal/neonatal death and preterm delivery.

TAKEAWAY:

  • Overall, 32 women experienced at least one flare during the second and third trimester; four had severe flares.
  • The rates of severe maternal SLE flares were significantly associated with hydroxychloroquine levels in the first trimester that were classified as subtherapeutic (8.8% vs 0.7% with above subtherapeutic levels, P = .02) and severely nonadherent (13.3% vs 1.3% with above severely nonadherent levels, P = .04).
  • There was no significant difference in adverse pregnancy outcomes by hydroxychloroquine level, suggesting its specific effect on maternal health rather than fetal health.

IN PRACTICE:

According to the authors, “this study supports hydroxychloroquine blood level assessment in pregnant women with SLE, as a predictor of severe maternal disease activity in pregnancy.”

SOURCE:

The study was led by Gelsomina Alle, MD, Assistance Publique-Hôpitaux de Paris, Paris, France. It was published online in Rheumatology.

LIMITATIONS:

The study’s sample size limited the ability to perform multivariate analyses for severe flares. Patients had to have an ongoing pregnancy at 12 weeks to be included, potentially excluding those with early pregnancy loss. The study only observed first-trimester hydroxychloroquine levels, not accounting for adherence variations throughout pregnancy.

DISCLOSURES:

The study funding source was not disclosed. Several authors declared financial relationships with pharmaceutical companies, including research support and consulting fees.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

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TOPLINE:

A study reveals that hydroxychloroquine levels during the first trimester in pregnant women with systemic lupus erythematosus (SLE) are linked to severe maternal flares but not to adverse pregnancy outcomes.

METHODOLOGY:

  • Researchers included pregnant women with SLE (median age, 32.1 years; median duration of disease, 8.3 years) who were enrolled in an ongoing French prospective observational study and were receiving hydroxychloroquine.
  • The study assessed hydroxychloroquine blood levels during the first trimester. It defined severe nonadherence as having levels < 200 ng/mL and classified levels < 500 ng/mL as subtherapeutic.
  • Primary outcomes were maternal flares during pregnancy and adverse pregnancy outcomes, including fetal/neonatal death and preterm delivery.

TAKEAWAY:

  • Overall, 32 women experienced at least one flare during the second and third trimester; four had severe flares.
  • The rates of severe maternal SLE flares were significantly associated with hydroxychloroquine levels in the first trimester that were classified as subtherapeutic (8.8% vs 0.7% with above subtherapeutic levels, P = .02) and severely nonadherent (13.3% vs 1.3% with above severely nonadherent levels, P = .04).
  • There was no significant difference in adverse pregnancy outcomes by hydroxychloroquine level, suggesting its specific effect on maternal health rather than fetal health.

IN PRACTICE:

According to the authors, “this study supports hydroxychloroquine blood level assessment in pregnant women with SLE, as a predictor of severe maternal disease activity in pregnancy.”

SOURCE:

The study was led by Gelsomina Alle, MD, Assistance Publique-Hôpitaux de Paris, Paris, France. It was published online in Rheumatology.

LIMITATIONS:

The study’s sample size limited the ability to perform multivariate analyses for severe flares. Patients had to have an ongoing pregnancy at 12 weeks to be included, potentially excluding those with early pregnancy loss. The study only observed first-trimester hydroxychloroquine levels, not accounting for adherence variations throughout pregnancy.

DISCLOSURES:

The study funding source was not disclosed. Several authors declared financial relationships with pharmaceutical companies, including research support and consulting fees.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

 

TOPLINE:

A study reveals that hydroxychloroquine levels during the first trimester in pregnant women with systemic lupus erythematosus (SLE) are linked to severe maternal flares but not to adverse pregnancy outcomes.

METHODOLOGY:

  • Researchers included pregnant women with SLE (median age, 32.1 years; median duration of disease, 8.3 years) who were enrolled in an ongoing French prospective observational study and were receiving hydroxychloroquine.
  • The study assessed hydroxychloroquine blood levels during the first trimester. It defined severe nonadherence as having levels < 200 ng/mL and classified levels < 500 ng/mL as subtherapeutic.
  • Primary outcomes were maternal flares during pregnancy and adverse pregnancy outcomes, including fetal/neonatal death and preterm delivery.

TAKEAWAY:

  • Overall, 32 women experienced at least one flare during the second and third trimester; four had severe flares.
  • The rates of severe maternal SLE flares were significantly associated with hydroxychloroquine levels in the first trimester that were classified as subtherapeutic (8.8% vs 0.7% with above subtherapeutic levels, P = .02) and severely nonadherent (13.3% vs 1.3% with above severely nonadherent levels, P = .04).
  • There was no significant difference in adverse pregnancy outcomes by hydroxychloroquine level, suggesting its specific effect on maternal health rather than fetal health.

IN PRACTICE:

According to the authors, “this study supports hydroxychloroquine blood level assessment in pregnant women with SLE, as a predictor of severe maternal disease activity in pregnancy.”

SOURCE:

The study was led by Gelsomina Alle, MD, Assistance Publique-Hôpitaux de Paris, Paris, France. It was published online in Rheumatology.

LIMITATIONS:

The study’s sample size limited the ability to perform multivariate analyses for severe flares. Patients had to have an ongoing pregnancy at 12 weeks to be included, potentially excluding those with early pregnancy loss. The study only observed first-trimester hydroxychloroquine levels, not accounting for adherence variations throughout pregnancy.

DISCLOSURES:

The study funding source was not disclosed. Several authors declared financial relationships with pharmaceutical companies, including research support and consulting fees.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

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Sex-Related Differences Found in IgG4-Related Disease Epidemiology

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Changed
Mon, 06/24/2024 - 14:27

 

TOPLINE:

Men with immunoglobulin G4 (IgG4)-related disease exhibit significantly lower serum lipase levels and a greater likelihood of organ involvement than women, highlighting significant sex-dependent differences in disease manifestations.

METHODOLOGY:

  • Researchers conducted a retrospective study of 328 patients (69% men) diagnosed with IgG4-related disease at the Massachusetts General Hospital – Rheumatology Clinic, Boston, who met the American College of Rheumatology–European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria between January 2008 and May 2023.
  • Among the 328 patients, 69% were men and 31% were women, with a significant male-to-female ratio of 2.2:1.0. Men were typically older at diagnosis (median age, 63.7 vs 58.2 years).
  • Data on serum lipase levels, renal involvement, and other clinical and laboratory parameters were collected.

TAKEAWAY:

  • Men had higher baseline ACR-EULAR scores, indicating more severe disease (median score of 35.0 vs 29.5; P = .0010).
  • Male patients demonstrated a median baseline serum lipase concentration of 24.5 U/L, significantly lower than the 33.5 U/L observed in women.
  • Pancreatic (50% vs 26%) or renal (36% vs 18%) involvement was more common in men.
  • Men exhibited higher IgG4 levels (P = .0050) and active B-cell responses in the blood (P = .0095).

IN PRACTICE:

According to the authors, this work confirms “the impression of an important sex disparity among patients with IgG4-related disease, with most patients being male, and male patients demonstrating strong tendencies toward more severe disease than female patients.”

SOURCE:

The study was led by Isha Jha, MD, Massachusetts General Hospital, Boston. It was published online on May 30, 2024, in The Lancet Rheumatology

LIMITATIONS:

The study’s retrospective design may limit the ability to establish causality between sex differences and IgG4-related disease manifestations. A relatively small percentage of patients were assessed before receiving any immunosuppressive treatment, potentially influencing the observed clinical parameters.

DISCLOSURES:

This work was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors declared financial ties outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

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TOPLINE:

Men with immunoglobulin G4 (IgG4)-related disease exhibit significantly lower serum lipase levels and a greater likelihood of organ involvement than women, highlighting significant sex-dependent differences in disease manifestations.

METHODOLOGY:

  • Researchers conducted a retrospective study of 328 patients (69% men) diagnosed with IgG4-related disease at the Massachusetts General Hospital – Rheumatology Clinic, Boston, who met the American College of Rheumatology–European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria between January 2008 and May 2023.
  • Among the 328 patients, 69% were men and 31% were women, with a significant male-to-female ratio of 2.2:1.0. Men were typically older at diagnosis (median age, 63.7 vs 58.2 years).
  • Data on serum lipase levels, renal involvement, and other clinical and laboratory parameters were collected.

TAKEAWAY:

  • Men had higher baseline ACR-EULAR scores, indicating more severe disease (median score of 35.0 vs 29.5; P = .0010).
  • Male patients demonstrated a median baseline serum lipase concentration of 24.5 U/L, significantly lower than the 33.5 U/L observed in women.
  • Pancreatic (50% vs 26%) or renal (36% vs 18%) involvement was more common in men.
  • Men exhibited higher IgG4 levels (P = .0050) and active B-cell responses in the blood (P = .0095).

IN PRACTICE:

According to the authors, this work confirms “the impression of an important sex disparity among patients with IgG4-related disease, with most patients being male, and male patients demonstrating strong tendencies toward more severe disease than female patients.”

SOURCE:

The study was led by Isha Jha, MD, Massachusetts General Hospital, Boston. It was published online on May 30, 2024, in The Lancet Rheumatology

LIMITATIONS:

The study’s retrospective design may limit the ability to establish causality between sex differences and IgG4-related disease manifestations. A relatively small percentage of patients were assessed before receiving any immunosuppressive treatment, potentially influencing the observed clinical parameters.

DISCLOSURES:

This work was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors declared financial ties outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

 

TOPLINE:

Men with immunoglobulin G4 (IgG4)-related disease exhibit significantly lower serum lipase levels and a greater likelihood of organ involvement than women, highlighting significant sex-dependent differences in disease manifestations.

METHODOLOGY:

  • Researchers conducted a retrospective study of 328 patients (69% men) diagnosed with IgG4-related disease at the Massachusetts General Hospital – Rheumatology Clinic, Boston, who met the American College of Rheumatology–European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria between January 2008 and May 2023.
  • Among the 328 patients, 69% were men and 31% were women, with a significant male-to-female ratio of 2.2:1.0. Men were typically older at diagnosis (median age, 63.7 vs 58.2 years).
  • Data on serum lipase levels, renal involvement, and other clinical and laboratory parameters were collected.

TAKEAWAY:

  • Men had higher baseline ACR-EULAR scores, indicating more severe disease (median score of 35.0 vs 29.5; P = .0010).
  • Male patients demonstrated a median baseline serum lipase concentration of 24.5 U/L, significantly lower than the 33.5 U/L observed in women.
  • Pancreatic (50% vs 26%) or renal (36% vs 18%) involvement was more common in men.
  • Men exhibited higher IgG4 levels (P = .0050) and active B-cell responses in the blood (P = .0095).

IN PRACTICE:

According to the authors, this work confirms “the impression of an important sex disparity among patients with IgG4-related disease, with most patients being male, and male patients demonstrating strong tendencies toward more severe disease than female patients.”

SOURCE:

The study was led by Isha Jha, MD, Massachusetts General Hospital, Boston. It was published online on May 30, 2024, in The Lancet Rheumatology

LIMITATIONS:

The study’s retrospective design may limit the ability to establish causality between sex differences and IgG4-related disease manifestations. A relatively small percentage of patients were assessed before receiving any immunosuppressive treatment, potentially influencing the observed clinical parameters.

DISCLOSURES:

This work was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors declared financial ties outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

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Why Do Investigational OA Drugs Need Better Trial Endpoints? Lorecivivint Serves as an Example

Article Type
Changed
Mon, 06/24/2024 - 14:20

 

— The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

Ted Bosworth/Medscape Medical News
Dr. Francis Berenbaum


Of primary targets to modify the course of OA, cartilage is not one of them, according to Dr. Berenbaum, who spoke in a session on DMOADs and regenerative OA therapies at the annual European Congress of Rheumatology.
 

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

Dr. Philip G. Conaghan


In his talk, he listed some of the many disappointments, including those which have targeted cartilage thickness, before updating the numerous ongoing development programs. There are many targets that appear viable, but none are in final stages of testing.

In remarks to this news organization, he said he generally agreed with Dr. Berenbaum about the need for greater rigor for developing drugs to meet regulatory criteria for disease-modifying effects.

Of the drugs he reviewed, Dr. Conaghan identified lorecivivint, an intra-articular CLK/DYRK inhibitor that’s thought to modulate Wnt and inflammatory pathways, as the only drug with DMOAD potential to go to a multicenter phase 3 trial so far. The drug’s negative outcome in phase 3 was particularly disappointing after the substantial promise shown in a phase 2b study published in 2021.

In the phase 3 study, lorecivivint, relative to placebo, did not achieve a significant improvement in the primary endpoint of improved medial joint space width (JSW) in the target knee as assessed at the end of a 48-week, double-blind trial.
 

 

 

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

Ted Bosworth/Medscape Medical News
Dr. Yusuf Yazici


In a second open-label extension described by Dr. Yazici at EULAR 2024, a third injection was administered to the lorecivivint-start patients and a second injection to the placebo-start patients. After 52 more weeks of follow-up, there were now 3 years of follow-up in the lorecivivint-start group and 2 years of follow-up in the placebo-start group.

At the end of this second extension, lorecivivint-start patients had a median increase in JSW that was approaching the baseline level at study entry. Although the placebo-start group had experienced a decline in the medial JSW at the end of the first extension when they had received one injection, JSW had also improved in the direction of baseline after a second injection with 2 years of follow-up. The advantage of three injections of lorecivivint over 3 years had now reached statistical significance (P = .031) despite the improvement seen in the placebo-start group following two injections over 2 years.
 

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

A version of this article first appeared on Medscape.com.

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— The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

Ted Bosworth/Medscape Medical News
Dr. Francis Berenbaum


Of primary targets to modify the course of OA, cartilage is not one of them, according to Dr. Berenbaum, who spoke in a session on DMOADs and regenerative OA therapies at the annual European Congress of Rheumatology.
 

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

Dr. Philip G. Conaghan


In his talk, he listed some of the many disappointments, including those which have targeted cartilage thickness, before updating the numerous ongoing development programs. There are many targets that appear viable, but none are in final stages of testing.

In remarks to this news organization, he said he generally agreed with Dr. Berenbaum about the need for greater rigor for developing drugs to meet regulatory criteria for disease-modifying effects.

Of the drugs he reviewed, Dr. Conaghan identified lorecivivint, an intra-articular CLK/DYRK inhibitor that’s thought to modulate Wnt and inflammatory pathways, as the only drug with DMOAD potential to go to a multicenter phase 3 trial so far. The drug’s negative outcome in phase 3 was particularly disappointing after the substantial promise shown in a phase 2b study published in 2021.

In the phase 3 study, lorecivivint, relative to placebo, did not achieve a significant improvement in the primary endpoint of improved medial joint space width (JSW) in the target knee as assessed at the end of a 48-week, double-blind trial.
 

 

 

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

Ted Bosworth/Medscape Medical News
Dr. Yusuf Yazici


In a second open-label extension described by Dr. Yazici at EULAR 2024, a third injection was administered to the lorecivivint-start patients and a second injection to the placebo-start patients. After 52 more weeks of follow-up, there were now 3 years of follow-up in the lorecivivint-start group and 2 years of follow-up in the placebo-start group.

At the end of this second extension, lorecivivint-start patients had a median increase in JSW that was approaching the baseline level at study entry. Although the placebo-start group had experienced a decline in the medial JSW at the end of the first extension when they had received one injection, JSW had also improved in the direction of baseline after a second injection with 2 years of follow-up. The advantage of three injections of lorecivivint over 3 years had now reached statistical significance (P = .031) despite the improvement seen in the placebo-start group following two injections over 2 years.
 

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

A version of this article first appeared on Medscape.com.

 

— The hypothesis that pivotal clinical trials for osteoarthritis (OA)-modifying therapies are not using appropriate designs or endpoints appears to be consistent with the recent failure of the phase 3 trial of the investigational agent lorecivivint, according to experts tackling this issue.

For the elusive target of disease-modifying OA drugs (DMOADs), “there have been a lot of developments in the last few years but so far a lot of disappointments,” said Francis Berenbaum, MD, PhD, head of the department of rheumatology, Saint-Antoine Hospital, Paris, France.

Disagreement on the target most likely to favorably alter the natural history of disease might be the key issue. Dr. Berenbaum considers it essential to determine which changes in the joint signify a favorable drug effect and will lead to what regulatory agencies consider a clinically meaningful benefit. These include improved function and long-term preservation of the joint, as well as symptom control.

Ted Bosworth/Medscape Medical News
Dr. Francis Berenbaum


Of primary targets to modify the course of OA, cartilage is not one of them, according to Dr. Berenbaum, who spoke in a session on DMOADs and regenerative OA therapies at the annual European Congress of Rheumatology.
 

OA Is Not a Cartilage-Only Disease

“There is now a big consensus that osteoarthritis is not a cartilage-only disease,” he said. Rather, he addressed the inadequate appreciation of the “whole joint” pathology that underlies OA. He called for a fundamental “paradigm change” to work toward a disease-modifying effect that produces benefit on a hard endpoint.

There are multiple steps needed to work toward this goal after a consensus is reached on a meaningful surrogate endpoint, Dr. Berenbaum said. While symptom reduction is a good start, he called for evidence of disease attenuation or a regenerative effect on an important surrogate such as improved integrity of synovial tissue and improved bone health. Such surrogates are necessary to guide DMOAD development but not sufficient. The proof that a therapy is a DMOAD depends on a favorable effect on a hard endpoint. In the case of the knee, freedom from joint replacement is an example, Dr. Berenbaum said.

Philip G. Conaghan, MBBS, PhD, director of rheumatic and musculoskeletal medicine, University of Leeds, England, agreed with this general premise. Speaking just before Dr. Berenbaum in the same session, Dr. Conaghan traced this history of the effort to create DMOADs and updated those in clinical trials.

Dr. Philip G. Conaghan


In his talk, he listed some of the many disappointments, including those which have targeted cartilage thickness, before updating the numerous ongoing development programs. There are many targets that appear viable, but none are in final stages of testing.

In remarks to this news organization, he said he generally agreed with Dr. Berenbaum about the need for greater rigor for developing drugs to meet regulatory criteria for disease-modifying effects.

Of the drugs he reviewed, Dr. Conaghan identified lorecivivint, an intra-articular CLK/DYRK inhibitor that’s thought to modulate Wnt and inflammatory pathways, as the only drug with DMOAD potential to go to a multicenter phase 3 trial so far. The drug’s negative outcome in phase 3 was particularly disappointing after the substantial promise shown in a phase 2b study published in 2021.

In the phase 3 study, lorecivivint, relative to placebo, did not achieve a significant improvement in the primary endpoint of improved medial joint space width (JSW) in the target knee as assessed at the end of a 48-week, double-blind trial.
 

 

 

New Follow-Up Data Support DMOAD Activity

Yet, additional extension data from the phase 3 lorecivivint trial presented in the EULAR DMOAD session challenge the conclusion even if they do not change the results.

The new data presented at EULAR is the second of two sets of extension data. The first, reported earlier, involved an analysis at 96 weeks or 48 weeks after the double-blind trial. At the beginning of this extension, lorecivivint-start patients had received a second intraarticular injection of 0.07 mg, while placebo patients were crossed over to receive their first injection.

Over the course of this first extension, the gradual loss in medial JSW observed from baseline to the end of the initial 48 weeks had plateaued in those treated with lorecivivint, but the decline continued in the placebo group. As a result, the lorecivivint-start patients had a numerical but not a statistically significant advantage for medial JSW over the placebo-switch group, according to Yusuf Yazici, MD, chief medical officer of Biosplice Therapeutics, San Diego, which developed lorecivivint.

Ted Bosworth/Medscape Medical News
Dr. Yusuf Yazici


In a second open-label extension described by Dr. Yazici at EULAR 2024, a third injection was administered to the lorecivivint-start patients and a second injection to the placebo-start patients. After 52 more weeks of follow-up, there were now 3 years of follow-up in the lorecivivint-start group and 2 years of follow-up in the placebo-start group.

At the end of this second extension, lorecivivint-start patients had a median increase in JSW that was approaching the baseline level at study entry. Although the placebo-start group had experienced a decline in the medial JSW at the end of the first extension when they had received one injection, JSW had also improved in the direction of baseline after a second injection with 2 years of follow-up. The advantage of three injections of lorecivivint over 3 years had now reached statistical significance (P = .031) despite the improvement seen in the placebo-start group following two injections over 2 years.
 

At 3 Years, Benefit Is Finally Potentially Significant

If placebo-treated patients had not received a second shot of lorecivivint and progressed at the rate seen before their second shot, the hypothetical trajectory would have provided lorecivivint with a highly statistically significant advantage (P < .001), said Dr. Yazici, displaying a hypothetical graph.

Along with improvements in pain and function associated with lorecivivint relative to placebo at 6 months, 12 months, and 24 months, the structural improvements in 3 years now suggest that “long-term treatment with lorecivivint has the potential to be a DMOAD for knee OA,” Dr. Yazici said.

While Dr. Berenbaum did not comment on this speculation, he did note the potential need for long-term studies to prove a disease-modifying effect in OA. This is the rationale for identifying surrogates.

To illustrate this point, Dr. Berenbaum made an analogy between OA and cardiovascular disease. In cardiovascular disease, surrogates of disease-modifying therapies, such as control of hypertension or hyperlipidemia, are accepted by regulatory agencies on the basis of their proven association with hard endpoints, such as myocardial infarction, stroke, or cardiovascular death. Like joint failure, these events can take years or decades to arise.

“For trials in OA, we need to agree on these surrogates,” Dr. Berenbaum said, although he acknowledged that they would then have to be validated. Noting that the US Food and Drug Administration has now identified OA as a serious disease for which accelerated drug approvals will be considered to address an unmet need, Dr. Berenbaum suggested there is an even greater impetus for improving strategies for DMOAD development.

Dr. Berenbaum reported financial relationships with Grünenthal, GlaxoSmithKline, Eli Lilly, Novartis, Pfizer, and Servier. Dr. Conaghan reported financial relationships with AbbVie, AstraZeneca, Eli Lilly, Galapagos, GlaxoSmithKline, Grünenthal, Janssen, Levicept, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB. Dr. Yazici is an employee of Biosplice Therapeutics, which provided funding for the OAS-07 trial.
 

A version of this article first appeared on Medscape.com.

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Ixekizumab Met Phase 3 Trial Endpoint in Juvenile PsA, Enthesitis-Related Arthritis

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— Ixekizumab (Taltz), an interleukin-17A inhibitor that’s already approved for the treatment of psoriatic arthritis and axial spondyloarthritis in adults appears likely to be granted the same corresponding indications for children, based on initial results from an open-label, phase 3 trial that employed adalimumab as a reference.

With a safety profile comparable with that seen in adult patients, ixekizumab “met the prespecified criterion for success at 16 weeks,” reported Athimalaipet V. Ramanan, MD, PhD, of Bristol Royal Hospital for Children and Translational Health Sciences, Bristol, England.

In this multicenter, randomized, open-label trial called COSPIRIT-JIA, which is still ongoing, investigators enrolled 101 children with active juvenile PsA (JPsA) or enthesitis-related arthritis (ERA), which is akin to spondyloarthritis in adults.

The efficacy and safety data at 16 weeks were presented as a late-breaking abstract at the annual European Congress of Rheumatology. Dr. Ramanan said that the open-label extension to 104 weeks is underway and further follow-up out to 264 weeks is planned.
 

Nearly 90% Achieve ACR30

The trial had an adaptive design in which the first 40 patients without biologics experience were randomized to ixekizumab or adalimumab, stratified by JPsA or ERA diagnosis, and the following 61 patients with either no biologic experience or an inadequate response or intolerance to biologics all received ixekizumab. The drugs were dosed according to weight. Dr. Ramanan explained that a placebo-controlled trial was considered unethical because of the strong evidence of benefit from biologics for JPsA and ERA.

The trial easily met its predefined threshold for success, which required ≥ 80% probability, based on Bayesian analysis, that ≥ 50% of patients would have 30% improvement in American College of Rheumatology response criteria (ACR30) at week 16. ACR30 was achieved in 88.9% of those treated with ixekizumab overall vs 95.0% of those treated with adalimumab, but the trial was not designed as a head-to-head comparison. Rather, adalimumab served as a reference.

When compared for the distinct diseases, the ACR30 rates were also numerically lower for ixekizumab relative to adalimumab for both ERA (88.9% vs 93.8%) and JPsA (88.9% vs 100%), but all of the adalimumab patients were naive to biologics. In comparison, about 75% of patients receiving ixekizumab were biologic-therapy naive.

Response rates to ixekizumab overall were numerically higher for patients without previous biologic experience than for those with experience (90.0% vs 85.7%), and this was also the case for patients with ERA (92.5% vs 78.6%). However, in the JPsA group, biologic-experienced patients had higher numerical response rates to ixekizumab (100% vs 85.0%).

An ACR30 is not a clinical goal that satisfies most patients and clinicians, Dr. Ramanan conceded, but he noted that ACR50 was reached with ixekizumab by 81.5% with ERA and 74.1% with JPsA, and ACR70 was reached by 68.5% and 55.6%, respectively. The highest responses of ACR90 (27.8% and 33.3%) and ACR100 (14.8% and 25.9%) were lower but still substantial in the ERA and JPsA groups, respectively.

Through week 16, 58.0% of those treated with ixekizumab had an adverse event considered treatment-related. Nearly half were of mild severity, and the remainder were moderate. Only 3.7% were considered serious. No patient discontinued study treatment because of an adverse event.

In this study, the presence of at least three active peripheral joints was an inclusion criterion. The median age was about 13 years in the biologic-naive adalimumab and ixekizumab groups and 14 years in the ixekizumab biologic-experienced group. The youngest patient in the study was aged 5 years, and the oldest was aged 18 years. Although about 40% of patients were women in the two biologic-naive subgroups, it was 60% in the biologic-experienced group.

On average, patients in the biologic-naive group were entered about 1 year after diagnosis. In the experienced patients, the average duration of disease at entry was nearly 4 years. About 45% of patients remained on conventional synthetic disease-modifying antirheumatic drugs while receiving ixekizumab. The proportion was 35% in the adalimumab reference arm.
 

 

 

Ixekizumab Might Fulfill Need for More Options

There are several biologics that have received regulatory approval or are already widely used for the treatment of JPsA or ERA, but more options are needed, according to Dr. Ramanan and the chair of the abstract session in which these data were reported. According to Caroline Ospelt, MD, PhD, a researcher at the Center for Experimental Rheumatology, University Hospital Zurich, Switzerland, regulatory approval of ixekizumab will depend on sustained efficacy and safety in longer follow-up from the COSPIRIT-JIA trial, but this trial supports continued development.

Despite a novel mechanism of action, “the data so far suggest a level of efficacy similar to that of anti-TNF [anti-tumor necrosis factor] biologics,” said Dr. Ospelt, who, in addition to moderating the late-breaking session, served as Scientific Program Chair of EULAR 2024.

While Dr. Ospelt emphasized that she is a researcher involved in translational rheumatology studies and not a clinician, she said there was consensus within the program committee to select this abstract from other high-quality latebreaker submissions on the basis of its potential clinical significance.

Dr. Ramanan reported financial relationships with AbbVie, AstraZeneca, Novartis, Pfizer, Roche, SOBI, UCB, and Eli Lilly, which provided funding for this study. Dr. Ospelt reported no potential conflicts of interest.
 

A version of this article first appeared on Medscape.com.

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— Ixekizumab (Taltz), an interleukin-17A inhibitor that’s already approved for the treatment of psoriatic arthritis and axial spondyloarthritis in adults appears likely to be granted the same corresponding indications for children, based on initial results from an open-label, phase 3 trial that employed adalimumab as a reference.

With a safety profile comparable with that seen in adult patients, ixekizumab “met the prespecified criterion for success at 16 weeks,” reported Athimalaipet V. Ramanan, MD, PhD, of Bristol Royal Hospital for Children and Translational Health Sciences, Bristol, England.

In this multicenter, randomized, open-label trial called COSPIRIT-JIA, which is still ongoing, investigators enrolled 101 children with active juvenile PsA (JPsA) or enthesitis-related arthritis (ERA), which is akin to spondyloarthritis in adults.

The efficacy and safety data at 16 weeks were presented as a late-breaking abstract at the annual European Congress of Rheumatology. Dr. Ramanan said that the open-label extension to 104 weeks is underway and further follow-up out to 264 weeks is planned.
 

Nearly 90% Achieve ACR30

The trial had an adaptive design in which the first 40 patients without biologics experience were randomized to ixekizumab or adalimumab, stratified by JPsA or ERA diagnosis, and the following 61 patients with either no biologic experience or an inadequate response or intolerance to biologics all received ixekizumab. The drugs were dosed according to weight. Dr. Ramanan explained that a placebo-controlled trial was considered unethical because of the strong evidence of benefit from biologics for JPsA and ERA.

The trial easily met its predefined threshold for success, which required ≥ 80% probability, based on Bayesian analysis, that ≥ 50% of patients would have 30% improvement in American College of Rheumatology response criteria (ACR30) at week 16. ACR30 was achieved in 88.9% of those treated with ixekizumab overall vs 95.0% of those treated with adalimumab, but the trial was not designed as a head-to-head comparison. Rather, adalimumab served as a reference.

When compared for the distinct diseases, the ACR30 rates were also numerically lower for ixekizumab relative to adalimumab for both ERA (88.9% vs 93.8%) and JPsA (88.9% vs 100%), but all of the adalimumab patients were naive to biologics. In comparison, about 75% of patients receiving ixekizumab were biologic-therapy naive.

Response rates to ixekizumab overall were numerically higher for patients without previous biologic experience than for those with experience (90.0% vs 85.7%), and this was also the case for patients with ERA (92.5% vs 78.6%). However, in the JPsA group, biologic-experienced patients had higher numerical response rates to ixekizumab (100% vs 85.0%).

An ACR30 is not a clinical goal that satisfies most patients and clinicians, Dr. Ramanan conceded, but he noted that ACR50 was reached with ixekizumab by 81.5% with ERA and 74.1% with JPsA, and ACR70 was reached by 68.5% and 55.6%, respectively. The highest responses of ACR90 (27.8% and 33.3%) and ACR100 (14.8% and 25.9%) were lower but still substantial in the ERA and JPsA groups, respectively.

Through week 16, 58.0% of those treated with ixekizumab had an adverse event considered treatment-related. Nearly half were of mild severity, and the remainder were moderate. Only 3.7% were considered serious. No patient discontinued study treatment because of an adverse event.

In this study, the presence of at least three active peripheral joints was an inclusion criterion. The median age was about 13 years in the biologic-naive adalimumab and ixekizumab groups and 14 years in the ixekizumab biologic-experienced group. The youngest patient in the study was aged 5 years, and the oldest was aged 18 years. Although about 40% of patients were women in the two biologic-naive subgroups, it was 60% in the biologic-experienced group.

On average, patients in the biologic-naive group were entered about 1 year after diagnosis. In the experienced patients, the average duration of disease at entry was nearly 4 years. About 45% of patients remained on conventional synthetic disease-modifying antirheumatic drugs while receiving ixekizumab. The proportion was 35% in the adalimumab reference arm.
 

 

 

Ixekizumab Might Fulfill Need for More Options

There are several biologics that have received regulatory approval or are already widely used for the treatment of JPsA or ERA, but more options are needed, according to Dr. Ramanan and the chair of the abstract session in which these data were reported. According to Caroline Ospelt, MD, PhD, a researcher at the Center for Experimental Rheumatology, University Hospital Zurich, Switzerland, regulatory approval of ixekizumab will depend on sustained efficacy and safety in longer follow-up from the COSPIRIT-JIA trial, but this trial supports continued development.

Despite a novel mechanism of action, “the data so far suggest a level of efficacy similar to that of anti-TNF [anti-tumor necrosis factor] biologics,” said Dr. Ospelt, who, in addition to moderating the late-breaking session, served as Scientific Program Chair of EULAR 2024.

While Dr. Ospelt emphasized that she is a researcher involved in translational rheumatology studies and not a clinician, she said there was consensus within the program committee to select this abstract from other high-quality latebreaker submissions on the basis of its potential clinical significance.

Dr. Ramanan reported financial relationships with AbbVie, AstraZeneca, Novartis, Pfizer, Roche, SOBI, UCB, and Eli Lilly, which provided funding for this study. Dr. Ospelt reported no potential conflicts of interest.
 

A version of this article first appeared on Medscape.com.

— Ixekizumab (Taltz), an interleukin-17A inhibitor that’s already approved for the treatment of psoriatic arthritis and axial spondyloarthritis in adults appears likely to be granted the same corresponding indications for children, based on initial results from an open-label, phase 3 trial that employed adalimumab as a reference.

With a safety profile comparable with that seen in adult patients, ixekizumab “met the prespecified criterion for success at 16 weeks,” reported Athimalaipet V. Ramanan, MD, PhD, of Bristol Royal Hospital for Children and Translational Health Sciences, Bristol, England.

In this multicenter, randomized, open-label trial called COSPIRIT-JIA, which is still ongoing, investigators enrolled 101 children with active juvenile PsA (JPsA) or enthesitis-related arthritis (ERA), which is akin to spondyloarthritis in adults.

The efficacy and safety data at 16 weeks were presented as a late-breaking abstract at the annual European Congress of Rheumatology. Dr. Ramanan said that the open-label extension to 104 weeks is underway and further follow-up out to 264 weeks is planned.
 

Nearly 90% Achieve ACR30

The trial had an adaptive design in which the first 40 patients without biologics experience were randomized to ixekizumab or adalimumab, stratified by JPsA or ERA diagnosis, and the following 61 patients with either no biologic experience or an inadequate response or intolerance to biologics all received ixekizumab. The drugs were dosed according to weight. Dr. Ramanan explained that a placebo-controlled trial was considered unethical because of the strong evidence of benefit from biologics for JPsA and ERA.

The trial easily met its predefined threshold for success, which required ≥ 80% probability, based on Bayesian analysis, that ≥ 50% of patients would have 30% improvement in American College of Rheumatology response criteria (ACR30) at week 16. ACR30 was achieved in 88.9% of those treated with ixekizumab overall vs 95.0% of those treated with adalimumab, but the trial was not designed as a head-to-head comparison. Rather, adalimumab served as a reference.

When compared for the distinct diseases, the ACR30 rates were also numerically lower for ixekizumab relative to adalimumab for both ERA (88.9% vs 93.8%) and JPsA (88.9% vs 100%), but all of the adalimumab patients were naive to biologics. In comparison, about 75% of patients receiving ixekizumab were biologic-therapy naive.

Response rates to ixekizumab overall were numerically higher for patients without previous biologic experience than for those with experience (90.0% vs 85.7%), and this was also the case for patients with ERA (92.5% vs 78.6%). However, in the JPsA group, biologic-experienced patients had higher numerical response rates to ixekizumab (100% vs 85.0%).

An ACR30 is not a clinical goal that satisfies most patients and clinicians, Dr. Ramanan conceded, but he noted that ACR50 was reached with ixekizumab by 81.5% with ERA and 74.1% with JPsA, and ACR70 was reached by 68.5% and 55.6%, respectively. The highest responses of ACR90 (27.8% and 33.3%) and ACR100 (14.8% and 25.9%) were lower but still substantial in the ERA and JPsA groups, respectively.

Through week 16, 58.0% of those treated with ixekizumab had an adverse event considered treatment-related. Nearly half were of mild severity, and the remainder were moderate. Only 3.7% were considered serious. No patient discontinued study treatment because of an adverse event.

In this study, the presence of at least three active peripheral joints was an inclusion criterion. The median age was about 13 years in the biologic-naive adalimumab and ixekizumab groups and 14 years in the ixekizumab biologic-experienced group. The youngest patient in the study was aged 5 years, and the oldest was aged 18 years. Although about 40% of patients were women in the two biologic-naive subgroups, it was 60% in the biologic-experienced group.

On average, patients in the biologic-naive group were entered about 1 year after diagnosis. In the experienced patients, the average duration of disease at entry was nearly 4 years. About 45% of patients remained on conventional synthetic disease-modifying antirheumatic drugs while receiving ixekizumab. The proportion was 35% in the adalimumab reference arm.
 

 

 

Ixekizumab Might Fulfill Need for More Options

There are several biologics that have received regulatory approval or are already widely used for the treatment of JPsA or ERA, but more options are needed, according to Dr. Ramanan and the chair of the abstract session in which these data were reported. According to Caroline Ospelt, MD, PhD, a researcher at the Center for Experimental Rheumatology, University Hospital Zurich, Switzerland, regulatory approval of ixekizumab will depend on sustained efficacy and safety in longer follow-up from the COSPIRIT-JIA trial, but this trial supports continued development.

Despite a novel mechanism of action, “the data so far suggest a level of efficacy similar to that of anti-TNF [anti-tumor necrosis factor] biologics,” said Dr. Ospelt, who, in addition to moderating the late-breaking session, served as Scientific Program Chair of EULAR 2024.

While Dr. Ospelt emphasized that she is a researcher involved in translational rheumatology studies and not a clinician, she said there was consensus within the program committee to select this abstract from other high-quality latebreaker submissions on the basis of its potential clinical significance.

Dr. Ramanan reported financial relationships with AbbVie, AstraZeneca, Novartis, Pfizer, Roche, SOBI, UCB, and Eli Lilly, which provided funding for this study. Dr. Ospelt reported no potential conflicts of interest.
 

A version of this article first appeared on Medscape.com.

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See the Medical World Through Neurodivergent Doctors’ Eyes

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Some 15%-20% of the world’s population are neurodivergent, with conditions such as autism, dyslexia, Tourette syndrome, attention-deficit/hyperactivity disorder (ADHD), and others. With different strengths and challenges around learning, engaging socially, or completing certain tasks, neurodivergent people can face barriers in the workforce.

Meanwhile, studies suggest that neurodivergent people may be overrepresented in STEM fields such as medicine. The medical field may self-select for traits associated with neurodivergent conditions, researchers say, including a hyperfocus on intense interests, pattern recognition, increased curiosity and empathy, and thinking quickly under pressure.

But neurodivergent physicians report difficult, even damaging, experiences in the healthcare field. They struggle with stigma, a culture of nondisclosure, and lack of accommodations, which can lead to burnout and poor mental health.

“The medical system and the mental health system are some of the spaces that are holding on tightly to some of the outdated understandings of things like autism and ADHD,” says Megan Anna Neff, PsyD, a psychologist with autism and ADHD based in Portland, Oregon.

Situations can get dire: A 2023 survey of more than 200 autistic doctors from several countries found that 77% had considered suicide and 24% had attempted it.

But here’s the crux of it: Many neurodivergent doctors believe their unique ways of thinking and outside-the-box creativity are skills and strengths that can benefit the field. And they say making medicine more inclusive — and better understanding how a neurodivergent physician’s brain works — would allow them to thrive.
 

Blending In and Breaking Down

The exact number of neurodivergent physicians in the workforce remains unknown. Existing studies are small and focus mainly on autism. But researchers believe the percentage could be higher than we think, because neurodiversity can be underidentified.

Although autism can sometimes be diagnosed as early as 18 months, it’s not uncommon to receive a diagnosis well into adulthood. “Like many late-identified autistic adults, I got my autism diagnosis in the context of autistic burnout,” says Melissa Houser, MD, a primary care physician who received a diagnosis in 2021. Dr. Houser, who uses the pronouns she/they, explains that her experience is common, “a consequence of chronically having your life’s demands exceed your capacity.”

Dr. Houser, who also has ADHD and dyslexia, among other neurodivergent conditions, says that before her diagnosis, she worked in a traditional practice setting. Eventually, she began to notice intense dysregulation and fatigue. “I began to have a lot more difficulties with communication and my motor planning and sequencing,” Dr. Houser says. “I was sleep-deprived, and my needs were not being met. I was in a situation where I had a complete lack of autonomy over my practice.”

Deep in burnout, Dr. Houser says she lost her ability to “mask,” a term used to describe how some neurodivergent people work to “blend in” with societal expectations. This led to further communication breakdowns with her supervisor. Finally, Dr. Houser saw a psychiatrist.

Shortly after her diagnosis, Dr. Houser quit her job and founded All Brains Belong, a nonprofit that provides neurodiversity-affirming medical care, education, and advocacy. Research has found that people with autism are at increased risk for physical health conditions, including immune conditions, gastrointestinal disorders, metabolic conditions, and increased mortality in hospital settings. Understanding these connections can “mean the difference between life and death” for neurodivergent patients, Dr. Houser says.

Yet, in a 2015 study that assessed providers’ ability to recognize autism, a high proportion were not aware that they had patients with autism spectrum disorder, and most reported lacking both the skills and the tools to care for them.
 

 

 

Different as a Doctor and a Patient

Bernadette Grosjean, MD, a retired associate professor of psychiatry at David Geffen School of Medicine at UCLA and a distinguished Fellow of the American Psychiatric Association, also found insight into lifelong experiences as both a doctor and a patient with her autism diagnosis, which came when she was 61.

“Looking back, I was a smart kid but kind of clumsy and different in other ways,” Dr. Grosjean says. According to a 2021 survey by Cambridge University, autistic individuals are significantly more likely to identify as LGBTQ+, and Dr. Grosjean, who is gay, says that not being fully accepted by family or friends played a role in her struggles with mental health issues.

Throughout her mental health treatment, Dr. Grosjean felt as though her providers “were expecting from me things that I didn’t know how to do or fix. I didn’t know how to be a ‘good’ patient,” she recalls.

As a psychiatrist, Dr. Grosjean started to notice that many of the women she treated for borderline personality disorder, which is categorized by unstable relationships and emotions, were autistic. “I then started asking lots of questions about myself — the fact that I’ve always been very sensitive or that I’ve been accused of being both hypersensitive and not having emotions, and I understood a lot.”

When Dr. Grosjean came across Autistic Doctors International, a group of over 800 autistic doctors worldwide, she says, “I found my tribe.” She now serves as the US lead for psychiatry for the group, which is focused on support, advocacy, research, and education around neurodiversity.

Psychiatric comorbidities can accompany neurodivergent conditions. But a growing body of research, including a 2022 study published in the European Archives of Psychiatry and Clinical Neuroscience, indicates that autism and ADHD are frequently misdiagnosed as depression or anxiety.

Dr. Neff was unaware of her conditions until one of her children was diagnosed with autism in 2021. She started to research it. “As I was learning about autism and girls, I was like, ‘Oh, my gosh, this is me,’ ” Dr. Neff recalls. Within a few weeks, she had her own diagnosis.

In hindsight, Dr. Neff has more clarity regarding her struggles in the traditional medical space. She had found it difficult to fit patients into short appointment windows and keep their notes concise. Although she loved hospital work, the environment had been overwhelming and led to burnout.
 

‘A Deficit-Based Lens’

Dr. Houser believes that too often, autism is viewed through a “deficit-based lens.” Stressors like sensory overload, changes in routine, or unexpected events can exacerbate behavioral challenges for neurodivergent people in the workplace. The DSM-5 criteria for autism, she points out, are largely based on autistic “stress behaviors.”

The result, Dr. Houser says, is that neurodivergent doctors are judged by their response to stressors that put them at a disadvantage rather than their capabilities under more positive circumstances. “The more dysregulated someone is,” she says, “the more likely they are to manifest those observable behaviors.”

Dr. Neff notes that medicine is a very “sensory overwhelming work environment.” Working in ob.gyn. and primary care clinics, she remembers often coming home with a headache and a low-grade fever. “I had no idea why, but I now realize it’s because I was so sensory sick.”

Fearing for her job, Dr. Neff intentionally waited until she was in private practice to disclose her neurodiversity. “I don’t think it would have been received well if I was in a hospital system,” she says. “There’s a lot of invalidation that can come when someone chooses to self-disclose, and their colleagues don’t have a framework in mind to understand.” In one instance, after revealing her diagnosis, she remembers a well-known researcher telling her she wasn’t autistic.
Dr. Grosjean has also had former colleagues invalidate her diagnosis, something she says “keeps people quiet.”
 

 

 

Understanding the Neurodivergent Brain

The general lack of education on how neurodivergent brains work, physicians with these conditions say, means they are not often recognized for how they can function with certain accommodations and how they could contribute in unique ways if their workplace challenges were reduced.

“What we know about autistic brains is that we are systems-thinking pattern matchers,” says Dr. Houser, who formed an interdisciplinary task force to explore medical conditions that are more common in autistic people. Through that comprehensive approach, she has worked to find best practices to treat the constellation of conditions that can arise among these patients. “My autistic brain allowed me to do that,” Dr. Houser says.

Catriona McVey, a medical student in the United Kingdom and creator of the blog Attention Deficit Doctor, points out that “ADHD brains are interest-driven; they can be very focused when you’re doing something enjoyable or new due to increased dopaminergic stimulation.” Ms. McVey speaks from personal experience. “I’ve hyperfocused before on an essay that interested me for over 10 hours,” she recalls, “so I imagine if I was interested in surgery, I could easily hyperfocus on a long operation.” 

Empathy is another key part of medical practice. Contrary to stereotypes of neurodivergent people lacking empathy, current research suggests this isn’t true. A concept known as the “double empathy problem,” a term coined by British researcher Damian Milton in 2012, challenges the misconception that autistic people do not have empathy, explains Dr. Grosjean.

Mr. Milton theorized that there are two types of empathy: emotional, when you feel someone else’s pain, and cognitive, which involves critical thinking to understand someone’s emotions or thoughts. “Autistic people have, in general, a lot of emotional empathy,” Dr. Grosjean says, “but the cognitive empathy they don’t have as well.”

Dr. Neff has experienced this in her practice. “I will often feel what my clients are feeling as they’re feeling it,” she says, adding that she has always had an innate ability to analyze and connect with clients. She’s good at observing the interplay of health conditions, incorporating biology, psychology, and social conceptualizations of issues, with nuance. She feels that recognizing behavioral patterns or psychological triggers in her patients helps her see them holistically and provide better care. “That was a skill even before I realized I was autistic, but I always thought it was just intuitive to everyone,” she says. 
 

Support Can Lead to Success

The Americans with Disabilities Act requires employers to provide reasonable accommodations to neurodivergent employees. However, getting those accommodations involves disclosure, which many physicians have reasons to avoid.

It also means more work. Requesting and putting adjustments in place can take a lot of time and energy to organize. Ms. McVey says they can be “long-winded, multistep tasks” that are not very compatible with ADHD. “Some doctors report that service pressures and funding are used as excuses to refuse adjustments,” she adds. 

Ms. McVey lists several workplace accommodations that could be helpful, including flexible working hours, a quiet space to complete paperwork, dictation software, and extra time for medical students to complete written exams.

Neurodivergent physicians have also called for increased diversity of senior leadership and utilizing “cognitive apprenticeship models,” where employees explain their thought processes and receive timely feedback.

But far too often, there is little intervention until a doctor reaches a crisis point. “I look forward to the day when we don’t have to wait until people are profoundly depleted to discover how their brains work,” says Dr. Houser.

Beyond logistical and structural changes in the medical field, Dr. Grosjean speaks of the simple need to listen to colleagues with an open mind and believe them when they express their feelings and experiences. “Everyone has a role to play in challenging stigma, misconceptions, and stereotypes,” Ms. McVey agrees. Ask yourself the old question, she suggests: “If not me, then who? If not now, then when?”

A version of this article first appeared on Medscape.com.

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Some 15%-20% of the world’s population are neurodivergent, with conditions such as autism, dyslexia, Tourette syndrome, attention-deficit/hyperactivity disorder (ADHD), and others. With different strengths and challenges around learning, engaging socially, or completing certain tasks, neurodivergent people can face barriers in the workforce.

Meanwhile, studies suggest that neurodivergent people may be overrepresented in STEM fields such as medicine. The medical field may self-select for traits associated with neurodivergent conditions, researchers say, including a hyperfocus on intense interests, pattern recognition, increased curiosity and empathy, and thinking quickly under pressure.

But neurodivergent physicians report difficult, even damaging, experiences in the healthcare field. They struggle with stigma, a culture of nondisclosure, and lack of accommodations, which can lead to burnout and poor mental health.

“The medical system and the mental health system are some of the spaces that are holding on tightly to some of the outdated understandings of things like autism and ADHD,” says Megan Anna Neff, PsyD, a psychologist with autism and ADHD based in Portland, Oregon.

Situations can get dire: A 2023 survey of more than 200 autistic doctors from several countries found that 77% had considered suicide and 24% had attempted it.

But here’s the crux of it: Many neurodivergent doctors believe their unique ways of thinking and outside-the-box creativity are skills and strengths that can benefit the field. And they say making medicine more inclusive — and better understanding how a neurodivergent physician’s brain works — would allow them to thrive.
 

Blending In and Breaking Down

The exact number of neurodivergent physicians in the workforce remains unknown. Existing studies are small and focus mainly on autism. But researchers believe the percentage could be higher than we think, because neurodiversity can be underidentified.

Although autism can sometimes be diagnosed as early as 18 months, it’s not uncommon to receive a diagnosis well into adulthood. “Like many late-identified autistic adults, I got my autism diagnosis in the context of autistic burnout,” says Melissa Houser, MD, a primary care physician who received a diagnosis in 2021. Dr. Houser, who uses the pronouns she/they, explains that her experience is common, “a consequence of chronically having your life’s demands exceed your capacity.”

Dr. Houser, who also has ADHD and dyslexia, among other neurodivergent conditions, says that before her diagnosis, she worked in a traditional practice setting. Eventually, she began to notice intense dysregulation and fatigue. “I began to have a lot more difficulties with communication and my motor planning and sequencing,” Dr. Houser says. “I was sleep-deprived, and my needs were not being met. I was in a situation where I had a complete lack of autonomy over my practice.”

Deep in burnout, Dr. Houser says she lost her ability to “mask,” a term used to describe how some neurodivergent people work to “blend in” with societal expectations. This led to further communication breakdowns with her supervisor. Finally, Dr. Houser saw a psychiatrist.

Shortly after her diagnosis, Dr. Houser quit her job and founded All Brains Belong, a nonprofit that provides neurodiversity-affirming medical care, education, and advocacy. Research has found that people with autism are at increased risk for physical health conditions, including immune conditions, gastrointestinal disorders, metabolic conditions, and increased mortality in hospital settings. Understanding these connections can “mean the difference between life and death” for neurodivergent patients, Dr. Houser says.

Yet, in a 2015 study that assessed providers’ ability to recognize autism, a high proportion were not aware that they had patients with autism spectrum disorder, and most reported lacking both the skills and the tools to care for them.
 

 

 

Different as a Doctor and a Patient

Bernadette Grosjean, MD, a retired associate professor of psychiatry at David Geffen School of Medicine at UCLA and a distinguished Fellow of the American Psychiatric Association, also found insight into lifelong experiences as both a doctor and a patient with her autism diagnosis, which came when she was 61.

“Looking back, I was a smart kid but kind of clumsy and different in other ways,” Dr. Grosjean says. According to a 2021 survey by Cambridge University, autistic individuals are significantly more likely to identify as LGBTQ+, and Dr. Grosjean, who is gay, says that not being fully accepted by family or friends played a role in her struggles with mental health issues.

Throughout her mental health treatment, Dr. Grosjean felt as though her providers “were expecting from me things that I didn’t know how to do or fix. I didn’t know how to be a ‘good’ patient,” she recalls.

As a psychiatrist, Dr. Grosjean started to notice that many of the women she treated for borderline personality disorder, which is categorized by unstable relationships and emotions, were autistic. “I then started asking lots of questions about myself — the fact that I’ve always been very sensitive or that I’ve been accused of being both hypersensitive and not having emotions, and I understood a lot.”

When Dr. Grosjean came across Autistic Doctors International, a group of over 800 autistic doctors worldwide, she says, “I found my tribe.” She now serves as the US lead for psychiatry for the group, which is focused on support, advocacy, research, and education around neurodiversity.

Psychiatric comorbidities can accompany neurodivergent conditions. But a growing body of research, including a 2022 study published in the European Archives of Psychiatry and Clinical Neuroscience, indicates that autism and ADHD are frequently misdiagnosed as depression or anxiety.

Dr. Neff was unaware of her conditions until one of her children was diagnosed with autism in 2021. She started to research it. “As I was learning about autism and girls, I was like, ‘Oh, my gosh, this is me,’ ” Dr. Neff recalls. Within a few weeks, she had her own diagnosis.

In hindsight, Dr. Neff has more clarity regarding her struggles in the traditional medical space. She had found it difficult to fit patients into short appointment windows and keep their notes concise. Although she loved hospital work, the environment had been overwhelming and led to burnout.
 

‘A Deficit-Based Lens’

Dr. Houser believes that too often, autism is viewed through a “deficit-based lens.” Stressors like sensory overload, changes in routine, or unexpected events can exacerbate behavioral challenges for neurodivergent people in the workplace. The DSM-5 criteria for autism, she points out, are largely based on autistic “stress behaviors.”

The result, Dr. Houser says, is that neurodivergent doctors are judged by their response to stressors that put them at a disadvantage rather than their capabilities under more positive circumstances. “The more dysregulated someone is,” she says, “the more likely they are to manifest those observable behaviors.”

Dr. Neff notes that medicine is a very “sensory overwhelming work environment.” Working in ob.gyn. and primary care clinics, she remembers often coming home with a headache and a low-grade fever. “I had no idea why, but I now realize it’s because I was so sensory sick.”

Fearing for her job, Dr. Neff intentionally waited until she was in private practice to disclose her neurodiversity. “I don’t think it would have been received well if I was in a hospital system,” she says. “There’s a lot of invalidation that can come when someone chooses to self-disclose, and their colleagues don’t have a framework in mind to understand.” In one instance, after revealing her diagnosis, she remembers a well-known researcher telling her she wasn’t autistic.
Dr. Grosjean has also had former colleagues invalidate her diagnosis, something she says “keeps people quiet.”
 

 

 

Understanding the Neurodivergent Brain

The general lack of education on how neurodivergent brains work, physicians with these conditions say, means they are not often recognized for how they can function with certain accommodations and how they could contribute in unique ways if their workplace challenges were reduced.

“What we know about autistic brains is that we are systems-thinking pattern matchers,” says Dr. Houser, who formed an interdisciplinary task force to explore medical conditions that are more common in autistic people. Through that comprehensive approach, she has worked to find best practices to treat the constellation of conditions that can arise among these patients. “My autistic brain allowed me to do that,” Dr. Houser says.

Catriona McVey, a medical student in the United Kingdom and creator of the blog Attention Deficit Doctor, points out that “ADHD brains are interest-driven; they can be very focused when you’re doing something enjoyable or new due to increased dopaminergic stimulation.” Ms. McVey speaks from personal experience. “I’ve hyperfocused before on an essay that interested me for over 10 hours,” she recalls, “so I imagine if I was interested in surgery, I could easily hyperfocus on a long operation.” 

Empathy is another key part of medical practice. Contrary to stereotypes of neurodivergent people lacking empathy, current research suggests this isn’t true. A concept known as the “double empathy problem,” a term coined by British researcher Damian Milton in 2012, challenges the misconception that autistic people do not have empathy, explains Dr. Grosjean.

Mr. Milton theorized that there are two types of empathy: emotional, when you feel someone else’s pain, and cognitive, which involves critical thinking to understand someone’s emotions or thoughts. “Autistic people have, in general, a lot of emotional empathy,” Dr. Grosjean says, “but the cognitive empathy they don’t have as well.”

Dr. Neff has experienced this in her practice. “I will often feel what my clients are feeling as they’re feeling it,” she says, adding that she has always had an innate ability to analyze and connect with clients. She’s good at observing the interplay of health conditions, incorporating biology, psychology, and social conceptualizations of issues, with nuance. She feels that recognizing behavioral patterns or psychological triggers in her patients helps her see them holistically and provide better care. “That was a skill even before I realized I was autistic, but I always thought it was just intuitive to everyone,” she says. 
 

Support Can Lead to Success

The Americans with Disabilities Act requires employers to provide reasonable accommodations to neurodivergent employees. However, getting those accommodations involves disclosure, which many physicians have reasons to avoid.

It also means more work. Requesting and putting adjustments in place can take a lot of time and energy to organize. Ms. McVey says they can be “long-winded, multistep tasks” that are not very compatible with ADHD. “Some doctors report that service pressures and funding are used as excuses to refuse adjustments,” she adds. 

Ms. McVey lists several workplace accommodations that could be helpful, including flexible working hours, a quiet space to complete paperwork, dictation software, and extra time for medical students to complete written exams.

Neurodivergent physicians have also called for increased diversity of senior leadership and utilizing “cognitive apprenticeship models,” where employees explain their thought processes and receive timely feedback.

But far too often, there is little intervention until a doctor reaches a crisis point. “I look forward to the day when we don’t have to wait until people are profoundly depleted to discover how their brains work,” says Dr. Houser.

Beyond logistical and structural changes in the medical field, Dr. Grosjean speaks of the simple need to listen to colleagues with an open mind and believe them when they express their feelings and experiences. “Everyone has a role to play in challenging stigma, misconceptions, and stereotypes,” Ms. McVey agrees. Ask yourself the old question, she suggests: “If not me, then who? If not now, then when?”

A version of this article first appeared on Medscape.com.

Some 15%-20% of the world’s population are neurodivergent, with conditions such as autism, dyslexia, Tourette syndrome, attention-deficit/hyperactivity disorder (ADHD), and others. With different strengths and challenges around learning, engaging socially, or completing certain tasks, neurodivergent people can face barriers in the workforce.

Meanwhile, studies suggest that neurodivergent people may be overrepresented in STEM fields such as medicine. The medical field may self-select for traits associated with neurodivergent conditions, researchers say, including a hyperfocus on intense interests, pattern recognition, increased curiosity and empathy, and thinking quickly under pressure.

But neurodivergent physicians report difficult, even damaging, experiences in the healthcare field. They struggle with stigma, a culture of nondisclosure, and lack of accommodations, which can lead to burnout and poor mental health.

“The medical system and the mental health system are some of the spaces that are holding on tightly to some of the outdated understandings of things like autism and ADHD,” says Megan Anna Neff, PsyD, a psychologist with autism and ADHD based in Portland, Oregon.

Situations can get dire: A 2023 survey of more than 200 autistic doctors from several countries found that 77% had considered suicide and 24% had attempted it.

But here’s the crux of it: Many neurodivergent doctors believe their unique ways of thinking and outside-the-box creativity are skills and strengths that can benefit the field. And they say making medicine more inclusive — and better understanding how a neurodivergent physician’s brain works — would allow them to thrive.
 

Blending In and Breaking Down

The exact number of neurodivergent physicians in the workforce remains unknown. Existing studies are small and focus mainly on autism. But researchers believe the percentage could be higher than we think, because neurodiversity can be underidentified.

Although autism can sometimes be diagnosed as early as 18 months, it’s not uncommon to receive a diagnosis well into adulthood. “Like many late-identified autistic adults, I got my autism diagnosis in the context of autistic burnout,” says Melissa Houser, MD, a primary care physician who received a diagnosis in 2021. Dr. Houser, who uses the pronouns she/they, explains that her experience is common, “a consequence of chronically having your life’s demands exceed your capacity.”

Dr. Houser, who also has ADHD and dyslexia, among other neurodivergent conditions, says that before her diagnosis, she worked in a traditional practice setting. Eventually, she began to notice intense dysregulation and fatigue. “I began to have a lot more difficulties with communication and my motor planning and sequencing,” Dr. Houser says. “I was sleep-deprived, and my needs were not being met. I was in a situation where I had a complete lack of autonomy over my practice.”

Deep in burnout, Dr. Houser says she lost her ability to “mask,” a term used to describe how some neurodivergent people work to “blend in” with societal expectations. This led to further communication breakdowns with her supervisor. Finally, Dr. Houser saw a psychiatrist.

Shortly after her diagnosis, Dr. Houser quit her job and founded All Brains Belong, a nonprofit that provides neurodiversity-affirming medical care, education, and advocacy. Research has found that people with autism are at increased risk for physical health conditions, including immune conditions, gastrointestinal disorders, metabolic conditions, and increased mortality in hospital settings. Understanding these connections can “mean the difference between life and death” for neurodivergent patients, Dr. Houser says.

Yet, in a 2015 study that assessed providers’ ability to recognize autism, a high proportion were not aware that they had patients with autism spectrum disorder, and most reported lacking both the skills and the tools to care for them.
 

 

 

Different as a Doctor and a Patient

Bernadette Grosjean, MD, a retired associate professor of psychiatry at David Geffen School of Medicine at UCLA and a distinguished Fellow of the American Psychiatric Association, also found insight into lifelong experiences as both a doctor and a patient with her autism diagnosis, which came when she was 61.

“Looking back, I was a smart kid but kind of clumsy and different in other ways,” Dr. Grosjean says. According to a 2021 survey by Cambridge University, autistic individuals are significantly more likely to identify as LGBTQ+, and Dr. Grosjean, who is gay, says that not being fully accepted by family or friends played a role in her struggles with mental health issues.

Throughout her mental health treatment, Dr. Grosjean felt as though her providers “were expecting from me things that I didn’t know how to do or fix. I didn’t know how to be a ‘good’ patient,” she recalls.

As a psychiatrist, Dr. Grosjean started to notice that many of the women she treated for borderline personality disorder, which is categorized by unstable relationships and emotions, were autistic. “I then started asking lots of questions about myself — the fact that I’ve always been very sensitive or that I’ve been accused of being both hypersensitive and not having emotions, and I understood a lot.”

When Dr. Grosjean came across Autistic Doctors International, a group of over 800 autistic doctors worldwide, she says, “I found my tribe.” She now serves as the US lead for psychiatry for the group, which is focused on support, advocacy, research, and education around neurodiversity.

Psychiatric comorbidities can accompany neurodivergent conditions. But a growing body of research, including a 2022 study published in the European Archives of Psychiatry and Clinical Neuroscience, indicates that autism and ADHD are frequently misdiagnosed as depression or anxiety.

Dr. Neff was unaware of her conditions until one of her children was diagnosed with autism in 2021. She started to research it. “As I was learning about autism and girls, I was like, ‘Oh, my gosh, this is me,’ ” Dr. Neff recalls. Within a few weeks, she had her own diagnosis.

In hindsight, Dr. Neff has more clarity regarding her struggles in the traditional medical space. She had found it difficult to fit patients into short appointment windows and keep their notes concise. Although she loved hospital work, the environment had been overwhelming and led to burnout.
 

‘A Deficit-Based Lens’

Dr. Houser believes that too often, autism is viewed through a “deficit-based lens.” Stressors like sensory overload, changes in routine, or unexpected events can exacerbate behavioral challenges for neurodivergent people in the workplace. The DSM-5 criteria for autism, she points out, are largely based on autistic “stress behaviors.”

The result, Dr. Houser says, is that neurodivergent doctors are judged by their response to stressors that put them at a disadvantage rather than their capabilities under more positive circumstances. “The more dysregulated someone is,” she says, “the more likely they are to manifest those observable behaviors.”

Dr. Neff notes that medicine is a very “sensory overwhelming work environment.” Working in ob.gyn. and primary care clinics, she remembers often coming home with a headache and a low-grade fever. “I had no idea why, but I now realize it’s because I was so sensory sick.”

Fearing for her job, Dr. Neff intentionally waited until she was in private practice to disclose her neurodiversity. “I don’t think it would have been received well if I was in a hospital system,” she says. “There’s a lot of invalidation that can come when someone chooses to self-disclose, and their colleagues don’t have a framework in mind to understand.” In one instance, after revealing her diagnosis, she remembers a well-known researcher telling her she wasn’t autistic.
Dr. Grosjean has also had former colleagues invalidate her diagnosis, something she says “keeps people quiet.”
 

 

 

Understanding the Neurodivergent Brain

The general lack of education on how neurodivergent brains work, physicians with these conditions say, means they are not often recognized for how they can function with certain accommodations and how they could contribute in unique ways if their workplace challenges were reduced.

“What we know about autistic brains is that we are systems-thinking pattern matchers,” says Dr. Houser, who formed an interdisciplinary task force to explore medical conditions that are more common in autistic people. Through that comprehensive approach, she has worked to find best practices to treat the constellation of conditions that can arise among these patients. “My autistic brain allowed me to do that,” Dr. Houser says.

Catriona McVey, a medical student in the United Kingdom and creator of the blog Attention Deficit Doctor, points out that “ADHD brains are interest-driven; they can be very focused when you’re doing something enjoyable or new due to increased dopaminergic stimulation.” Ms. McVey speaks from personal experience. “I’ve hyperfocused before on an essay that interested me for over 10 hours,” she recalls, “so I imagine if I was interested in surgery, I could easily hyperfocus on a long operation.” 

Empathy is another key part of medical practice. Contrary to stereotypes of neurodivergent people lacking empathy, current research suggests this isn’t true. A concept known as the “double empathy problem,” a term coined by British researcher Damian Milton in 2012, challenges the misconception that autistic people do not have empathy, explains Dr. Grosjean.

Mr. Milton theorized that there are two types of empathy: emotional, when you feel someone else’s pain, and cognitive, which involves critical thinking to understand someone’s emotions or thoughts. “Autistic people have, in general, a lot of emotional empathy,” Dr. Grosjean says, “but the cognitive empathy they don’t have as well.”

Dr. Neff has experienced this in her practice. “I will often feel what my clients are feeling as they’re feeling it,” she says, adding that she has always had an innate ability to analyze and connect with clients. She’s good at observing the interplay of health conditions, incorporating biology, psychology, and social conceptualizations of issues, with nuance. She feels that recognizing behavioral patterns or psychological triggers in her patients helps her see them holistically and provide better care. “That was a skill even before I realized I was autistic, but I always thought it was just intuitive to everyone,” she says. 
 

Support Can Lead to Success

The Americans with Disabilities Act requires employers to provide reasonable accommodations to neurodivergent employees. However, getting those accommodations involves disclosure, which many physicians have reasons to avoid.

It also means more work. Requesting and putting adjustments in place can take a lot of time and energy to organize. Ms. McVey says they can be “long-winded, multistep tasks” that are not very compatible with ADHD. “Some doctors report that service pressures and funding are used as excuses to refuse adjustments,” she adds. 

Ms. McVey lists several workplace accommodations that could be helpful, including flexible working hours, a quiet space to complete paperwork, dictation software, and extra time for medical students to complete written exams.

Neurodivergent physicians have also called for increased diversity of senior leadership and utilizing “cognitive apprenticeship models,” where employees explain their thought processes and receive timely feedback.

But far too often, there is little intervention until a doctor reaches a crisis point. “I look forward to the day when we don’t have to wait until people are profoundly depleted to discover how their brains work,” says Dr. Houser.

Beyond logistical and structural changes in the medical field, Dr. Grosjean speaks of the simple need to listen to colleagues with an open mind and believe them when they express their feelings and experiences. “Everyone has a role to play in challenging stigma, misconceptions, and stereotypes,” Ms. McVey agrees. Ask yourself the old question, she suggests: “If not me, then who? If not now, then when?”

A version of this article first appeared on Medscape.com.

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US Hospitals Prone to Cyberattacks Like One That Impacted Patient Care at Ascension, Experts Say

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Fri, 06/21/2024 - 14:19

In the wake of a debilitating cyberattack against one of the nation’s largest health care systems, Marvin Ruckle, a nurse at an Ascension hospital in Wichita, Kansas, said he had a frightening experience: He nearly gave a baby “the wrong dose of narcotic” because of confusing paperwork.

Ruckle, who has worked in the neonatal intensive care unit at Ascension Via Christi St. Joseph for two decades, said it was “hard to decipher which was the correct dose” on the medication record. He’d “never seen that happen,” he said, “when we were on the computer system” before the cyberattack.

A May 8 ransomware attack against Ascension, a Catholic health system with 140 hospitals in at least 10 states, locked providers out of systems that track and coordinate nearly every aspect of patient care. They include its systems for electronic health records, some phones, and ones “utilized to order certain tests, procedures and medications,” the company said in a May 9 statement.

More than a dozen doctors and nurses who work for the sprawling health system told Michigan Public and KFF Health News that patient care at its hospitals across the nation was compromised in the fallout of the cyberattack over the past several weeks. Clinicians working for hospitals in three states described harrowing lapses, including delayed or lost lab results, medication errors, and an absence of routine safety checks via technology to prevent potentially fatal mistakes.

Despite a precipitous rise in cyberattacks against the health sector in recent years, a weeks-long disruption of this magnitude is beyond what most health systems are prepared for, said John S. Clark, an associate chief pharmacy officer at the University of Michigan health system.

“I don’t believe that anyone is fully prepared,” he said. Most emergency management plans “are designed around long-term downtimes that are into one, two, or three days.”

Ascension in a public statement May 9 said its care teams were “trained for these kinds of disruptions,” but did not respond to questions in early June about whether it had prepared for longer periods of downtime. Ascension said June 14 it had restored access to electronic health records across its network, but that patient “medical records and other information collected between May 8” and when the service was restored “may be temporarily inaccessible as we work to update the portal with information collected during the system downtime.”

Ruckle said he “had no training” for the cyberattack.
 

Back to Paper

Lisa Watson, an intensive care unit nurse at Ascension Via Christi St. Francis hospital in Wichita, described her own close call. She said she nearly administered the wrong medication to a critically ill patient because she couldn’t scan it as she normally would. “My patient probably would have passed away had I not caught it,” she said.

Watson is no stranger to using paper for patients’ medical charts, saying she did so “for probably half of my career,” before electronic health records became ubiquitous in hospitals. What happened after the cyberattack was “by no means the same.”

“When we paper-charted, we had systems in place to get those orders to other departments in a timely manner,” she said, “and those have all gone away.”

Melissa LaRue, an ICU nurse at Ascension Saint Agnes Hospital in Baltimore, described a close call with “administering the wrong dosage” of a patient’s blood pressure medication. “Luckily,” she said, it was “triple-checked and remedied before that could happen. But I think the potential for harm is there when you have so much information and paperwork that you have to go through.”

Clinicians say their hospitals have relied on slapdash workarounds, using handwritten notes, faxes, sticky notes, and basic computer spreadsheets — many devised on the fly by doctors and nurses — to care for patients.

More than a dozen other nurses and doctors, some of them without union protections, at Ascension hospitals in Michigan recounted situations in which they say patient care was compromised. Those clinicians spoke on the condition that they not be named for fear of retaliation by their employer.

An Ascension hospital emergency room doctor in Detroit said a man on the city’s east side was given a dangerous narcotic intended for another patient because of a paperwork mix-up. As a result, the patient’s breathing slowed to the point that he had to be put on a ventilator. “We intubated him and we sent him to the ICU because he got the wrong medication.”

A nurse in a Michigan Ascension hospital ER said a woman with low blood sugar and “altered mental status” went into cardiac arrest and died after staff said they waited four hours for lab results they needed to determine how to treat her, but never received. “If I started having crushing chest pain in the middle of work and thought I was having a big one, I would grab someone to drive me down the street to another hospital,” the same ER nurse said.

Similar concerns reportedly led a travel nurse at an Ascension hospital in Indiana to quit. “I just want to warn those patients that are coming to any of the Ascension facilities that there will be delays in care. There is potential for error and for harm,” Justin Neisser told CBS4 in Indianapolis in May.

Several nurses and doctors at Ascension hospitals said they feared the errors they’ve witnessed since the cyberattack began could threaten their professional licenses. “This is how a RaDonda Vaught happens,” one nurse said, referring to the Tennessee nurse who was convicted of criminally negligent homicide in 2022 for a fatal drug error.

Reporters were not able to review records to verify clinicians’ claims because of privacy laws surrounding patients’ medical information that apply to health care professionals.

Ascension declined to answer questions about claims that care has been affected by the ransomware attack. “As we have made clear throughout this cyber attack which has impacted our system and our dedicated clinical providers, caring for our patients is our highest priority,” Sean Fitzpatrick, Ascension’s vice president of external communications, said via email on June 3. “We are confident that our care providers in our hospitals and facilities continue to provide quality medical care.”

The federal government requires hospitals to protect patients’ sensitive health data, according to cybersecurity experts. However, there are no federal requirements for hospitals to prevent or prepare for cyberattacks that could compromise their electronic systems.
 

 

 

Hospitals: ‘The No.1 Target of Ransomware’

“We’ve started to think about these as public health issues and disasters on the scale of earthquakes or hurricanes,” said Jeff Tully, a co-director of the Center for Healthcare Cybersecurity at the University of California-San Diego. “These types of cybersecurity incidents should be thought of as a matter of when, and not if.”

Josh Corman, a cybersecurity expert and advocate, said ransom crews regard hospitals as the perfect prey: “They have terrible security and they’ll pay. So almost immediately, hospitals went to the No. 1 target of ransomware.”

In 2023, the health sector experienced the largest share of ransomware attacks of 16 infrastructure sectors considered vital to national security or safety, according to an FBI report on internet crimes. In March, the federal Department of Health and Human Services said reported large breaches involving ransomware had jumped by 264% over the past five years.

A cyberattack this year on Change Healthcare, a unit of UnitedHealth Group’s Optum division that processes billions of health care transactions every year, crippled the business of providers, pharmacies, and hospitals.

In May, UnitedHealth Group CEO Andrew Witty told lawmakers the company paid a $22 million ransom as a result of the Change Healthcare attack — which occurred after hackers accessed a company portal that didn’t have multifactor authentication, a basic cybersecurity tool.

The Biden administration in recent months has pushed to bolster health care cybersecurity standards, but it’s not clear which new measures will be required.

In January, HHS nudged companies to improve email security, add multifactor authentication, and institute cybersecurity training and testing, among other voluntary measures. The Centers for Medicare & Medicaid Services is expected to release new requirements for hospitals, but the scope and timing are unclear. The same is true of an update HHS is expected to make to patient privacy regulations.

HHS said the voluntary measures “will inform the creation of new enforceable cybersecurity standards,” department spokesperson Jeff Nesbit said in a statement.

“The recent cyberattack at Ascension only underscores the need for everyone in the health care ecosystem to do their part to secure their systems and protect patients,” Nesbit said.

Meanwhile, lobbyists for the hospital industry contend cybersecurity mandates or penalties are misplaced and would curtail hospitals’ resources to fend off attacks.

“Hospitals and health systems are not the primary source of cyber risk exposure facing the health care sector,” the American Hospital Association, the largest lobbying group for U.S. hospitals, said in an April statement prepared for U.S. House lawmakers. Most large data breaches that hit hospitals in 2023 originated with third-party “business associates” or other health entities, including CMS itself, the AHA statement said.

Hospitals consolidating into large multistate health systems face increased risk of data breaches and ransomware attacks, according to one study. Ascension in 2022 was the third-largest hospital chain in the U.S. by number of beds, according to the most recent data from the federal Agency for Healthcare Research and Quality.

And while cybersecurity regulations can quickly become outdated, they can at least make it clear that if health systems fail to implement basic protections there “should be consequences for that,” Jim Bagian, a former director of the National Center for Patient Safety at the Veterans Health Administration, told Michigan Public’s Stateside.

Patients can pay the price when lapses occur. Those in hospital care face a greater likelihood of death during a cyberattack, according to researchers at the University of Minnesota School of Public Health.

Workers concerned about patient safety at Ascension hospitals in Michigan have called for the company to make changes.

“We implore Ascension to recognize the internal problems that continue to plague its hospitals, both publicly and transparently,” said Dina Carlisle, a nurse and the president of the OPEIU Local 40 union, which represents nurses at Ascension Providence Rochester. At least 125 staff members at that Ascension hospital have signed a petition asking administrators to temporarily reduce elective surgeries and nonemergency patient admissions, like under the protocols many hospitals adopted early in the covid-19 pandemic.

Watson, the Kansas ICU nurse, said in late May that nurses had urged management to bring in more nurses to help manage the workflow. “Everything that we say has fallen on deaf ears,” she said.

“It is very hard to be a nurse at Ascension right now,” Watson said in late May. “It is very hard to be a patient at Ascension right now.”

If you’re a patient or worker at an Ascension hospital and would like to tell KFF Health News about your experiences, click here to share your story with us.
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

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In the wake of a debilitating cyberattack against one of the nation’s largest health care systems, Marvin Ruckle, a nurse at an Ascension hospital in Wichita, Kansas, said he had a frightening experience: He nearly gave a baby “the wrong dose of narcotic” because of confusing paperwork.

Ruckle, who has worked in the neonatal intensive care unit at Ascension Via Christi St. Joseph for two decades, said it was “hard to decipher which was the correct dose” on the medication record. He’d “never seen that happen,” he said, “when we were on the computer system” before the cyberattack.

A May 8 ransomware attack against Ascension, a Catholic health system with 140 hospitals in at least 10 states, locked providers out of systems that track and coordinate nearly every aspect of patient care. They include its systems for electronic health records, some phones, and ones “utilized to order certain tests, procedures and medications,” the company said in a May 9 statement.

More than a dozen doctors and nurses who work for the sprawling health system told Michigan Public and KFF Health News that patient care at its hospitals across the nation was compromised in the fallout of the cyberattack over the past several weeks. Clinicians working for hospitals in three states described harrowing lapses, including delayed or lost lab results, medication errors, and an absence of routine safety checks via technology to prevent potentially fatal mistakes.

Despite a precipitous rise in cyberattacks against the health sector in recent years, a weeks-long disruption of this magnitude is beyond what most health systems are prepared for, said John S. Clark, an associate chief pharmacy officer at the University of Michigan health system.

“I don’t believe that anyone is fully prepared,” he said. Most emergency management plans “are designed around long-term downtimes that are into one, two, or three days.”

Ascension in a public statement May 9 said its care teams were “trained for these kinds of disruptions,” but did not respond to questions in early June about whether it had prepared for longer periods of downtime. Ascension said June 14 it had restored access to electronic health records across its network, but that patient “medical records and other information collected between May 8” and when the service was restored “may be temporarily inaccessible as we work to update the portal with information collected during the system downtime.”

Ruckle said he “had no training” for the cyberattack.
 

Back to Paper

Lisa Watson, an intensive care unit nurse at Ascension Via Christi St. Francis hospital in Wichita, described her own close call. She said she nearly administered the wrong medication to a critically ill patient because she couldn’t scan it as she normally would. “My patient probably would have passed away had I not caught it,” she said.

Watson is no stranger to using paper for patients’ medical charts, saying she did so “for probably half of my career,” before electronic health records became ubiquitous in hospitals. What happened after the cyberattack was “by no means the same.”

“When we paper-charted, we had systems in place to get those orders to other departments in a timely manner,” she said, “and those have all gone away.”

Melissa LaRue, an ICU nurse at Ascension Saint Agnes Hospital in Baltimore, described a close call with “administering the wrong dosage” of a patient’s blood pressure medication. “Luckily,” she said, it was “triple-checked and remedied before that could happen. But I think the potential for harm is there when you have so much information and paperwork that you have to go through.”

Clinicians say their hospitals have relied on slapdash workarounds, using handwritten notes, faxes, sticky notes, and basic computer spreadsheets — many devised on the fly by doctors and nurses — to care for patients.

More than a dozen other nurses and doctors, some of them without union protections, at Ascension hospitals in Michigan recounted situations in which they say patient care was compromised. Those clinicians spoke on the condition that they not be named for fear of retaliation by their employer.

An Ascension hospital emergency room doctor in Detroit said a man on the city’s east side was given a dangerous narcotic intended for another patient because of a paperwork mix-up. As a result, the patient’s breathing slowed to the point that he had to be put on a ventilator. “We intubated him and we sent him to the ICU because he got the wrong medication.”

A nurse in a Michigan Ascension hospital ER said a woman with low blood sugar and “altered mental status” went into cardiac arrest and died after staff said they waited four hours for lab results they needed to determine how to treat her, but never received. “If I started having crushing chest pain in the middle of work and thought I was having a big one, I would grab someone to drive me down the street to another hospital,” the same ER nurse said.

Similar concerns reportedly led a travel nurse at an Ascension hospital in Indiana to quit. “I just want to warn those patients that are coming to any of the Ascension facilities that there will be delays in care. There is potential for error and for harm,” Justin Neisser told CBS4 in Indianapolis in May.

Several nurses and doctors at Ascension hospitals said they feared the errors they’ve witnessed since the cyberattack began could threaten their professional licenses. “This is how a RaDonda Vaught happens,” one nurse said, referring to the Tennessee nurse who was convicted of criminally negligent homicide in 2022 for a fatal drug error.

Reporters were not able to review records to verify clinicians’ claims because of privacy laws surrounding patients’ medical information that apply to health care professionals.

Ascension declined to answer questions about claims that care has been affected by the ransomware attack. “As we have made clear throughout this cyber attack which has impacted our system and our dedicated clinical providers, caring for our patients is our highest priority,” Sean Fitzpatrick, Ascension’s vice president of external communications, said via email on June 3. “We are confident that our care providers in our hospitals and facilities continue to provide quality medical care.”

The federal government requires hospitals to protect patients’ sensitive health data, according to cybersecurity experts. However, there are no federal requirements for hospitals to prevent or prepare for cyberattacks that could compromise their electronic systems.
 

 

 

Hospitals: ‘The No.1 Target of Ransomware’

“We’ve started to think about these as public health issues and disasters on the scale of earthquakes or hurricanes,” said Jeff Tully, a co-director of the Center for Healthcare Cybersecurity at the University of California-San Diego. “These types of cybersecurity incidents should be thought of as a matter of when, and not if.”

Josh Corman, a cybersecurity expert and advocate, said ransom crews regard hospitals as the perfect prey: “They have terrible security and they’ll pay. So almost immediately, hospitals went to the No. 1 target of ransomware.”

In 2023, the health sector experienced the largest share of ransomware attacks of 16 infrastructure sectors considered vital to national security or safety, according to an FBI report on internet crimes. In March, the federal Department of Health and Human Services said reported large breaches involving ransomware had jumped by 264% over the past five years.

A cyberattack this year on Change Healthcare, a unit of UnitedHealth Group’s Optum division that processes billions of health care transactions every year, crippled the business of providers, pharmacies, and hospitals.

In May, UnitedHealth Group CEO Andrew Witty told lawmakers the company paid a $22 million ransom as a result of the Change Healthcare attack — which occurred after hackers accessed a company portal that didn’t have multifactor authentication, a basic cybersecurity tool.

The Biden administration in recent months has pushed to bolster health care cybersecurity standards, but it’s not clear which new measures will be required.

In January, HHS nudged companies to improve email security, add multifactor authentication, and institute cybersecurity training and testing, among other voluntary measures. The Centers for Medicare & Medicaid Services is expected to release new requirements for hospitals, but the scope and timing are unclear. The same is true of an update HHS is expected to make to patient privacy regulations.

HHS said the voluntary measures “will inform the creation of new enforceable cybersecurity standards,” department spokesperson Jeff Nesbit said in a statement.

“The recent cyberattack at Ascension only underscores the need for everyone in the health care ecosystem to do their part to secure their systems and protect patients,” Nesbit said.

Meanwhile, lobbyists for the hospital industry contend cybersecurity mandates or penalties are misplaced and would curtail hospitals’ resources to fend off attacks.

“Hospitals and health systems are not the primary source of cyber risk exposure facing the health care sector,” the American Hospital Association, the largest lobbying group for U.S. hospitals, said in an April statement prepared for U.S. House lawmakers. Most large data breaches that hit hospitals in 2023 originated with third-party “business associates” or other health entities, including CMS itself, the AHA statement said.

Hospitals consolidating into large multistate health systems face increased risk of data breaches and ransomware attacks, according to one study. Ascension in 2022 was the third-largest hospital chain in the U.S. by number of beds, according to the most recent data from the federal Agency for Healthcare Research and Quality.

And while cybersecurity regulations can quickly become outdated, they can at least make it clear that if health systems fail to implement basic protections there “should be consequences for that,” Jim Bagian, a former director of the National Center for Patient Safety at the Veterans Health Administration, told Michigan Public’s Stateside.

Patients can pay the price when lapses occur. Those in hospital care face a greater likelihood of death during a cyberattack, according to researchers at the University of Minnesota School of Public Health.

Workers concerned about patient safety at Ascension hospitals in Michigan have called for the company to make changes.

“We implore Ascension to recognize the internal problems that continue to plague its hospitals, both publicly and transparently,” said Dina Carlisle, a nurse and the president of the OPEIU Local 40 union, which represents nurses at Ascension Providence Rochester. At least 125 staff members at that Ascension hospital have signed a petition asking administrators to temporarily reduce elective surgeries and nonemergency patient admissions, like under the protocols many hospitals adopted early in the covid-19 pandemic.

Watson, the Kansas ICU nurse, said in late May that nurses had urged management to bring in more nurses to help manage the workflow. “Everything that we say has fallen on deaf ears,” she said.

“It is very hard to be a nurse at Ascension right now,” Watson said in late May. “It is very hard to be a patient at Ascension right now.”

If you’re a patient or worker at an Ascension hospital and would like to tell KFF Health News about your experiences, click here to share your story with us.
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

In the wake of a debilitating cyberattack against one of the nation’s largest health care systems, Marvin Ruckle, a nurse at an Ascension hospital in Wichita, Kansas, said he had a frightening experience: He nearly gave a baby “the wrong dose of narcotic” because of confusing paperwork.

Ruckle, who has worked in the neonatal intensive care unit at Ascension Via Christi St. Joseph for two decades, said it was “hard to decipher which was the correct dose” on the medication record. He’d “never seen that happen,” he said, “when we were on the computer system” before the cyberattack.

A May 8 ransomware attack against Ascension, a Catholic health system with 140 hospitals in at least 10 states, locked providers out of systems that track and coordinate nearly every aspect of patient care. They include its systems for electronic health records, some phones, and ones “utilized to order certain tests, procedures and medications,” the company said in a May 9 statement.

More than a dozen doctors and nurses who work for the sprawling health system told Michigan Public and KFF Health News that patient care at its hospitals across the nation was compromised in the fallout of the cyberattack over the past several weeks. Clinicians working for hospitals in three states described harrowing lapses, including delayed or lost lab results, medication errors, and an absence of routine safety checks via technology to prevent potentially fatal mistakes.

Despite a precipitous rise in cyberattacks against the health sector in recent years, a weeks-long disruption of this magnitude is beyond what most health systems are prepared for, said John S. Clark, an associate chief pharmacy officer at the University of Michigan health system.

“I don’t believe that anyone is fully prepared,” he said. Most emergency management plans “are designed around long-term downtimes that are into one, two, or three days.”

Ascension in a public statement May 9 said its care teams were “trained for these kinds of disruptions,” but did not respond to questions in early June about whether it had prepared for longer periods of downtime. Ascension said June 14 it had restored access to electronic health records across its network, but that patient “medical records and other information collected between May 8” and when the service was restored “may be temporarily inaccessible as we work to update the portal with information collected during the system downtime.”

Ruckle said he “had no training” for the cyberattack.
 

Back to Paper

Lisa Watson, an intensive care unit nurse at Ascension Via Christi St. Francis hospital in Wichita, described her own close call. She said she nearly administered the wrong medication to a critically ill patient because she couldn’t scan it as she normally would. “My patient probably would have passed away had I not caught it,” she said.

Watson is no stranger to using paper for patients’ medical charts, saying she did so “for probably half of my career,” before electronic health records became ubiquitous in hospitals. What happened after the cyberattack was “by no means the same.”

“When we paper-charted, we had systems in place to get those orders to other departments in a timely manner,” she said, “and those have all gone away.”

Melissa LaRue, an ICU nurse at Ascension Saint Agnes Hospital in Baltimore, described a close call with “administering the wrong dosage” of a patient’s blood pressure medication. “Luckily,” she said, it was “triple-checked and remedied before that could happen. But I think the potential for harm is there when you have so much information and paperwork that you have to go through.”

Clinicians say their hospitals have relied on slapdash workarounds, using handwritten notes, faxes, sticky notes, and basic computer spreadsheets — many devised on the fly by doctors and nurses — to care for patients.

More than a dozen other nurses and doctors, some of them without union protections, at Ascension hospitals in Michigan recounted situations in which they say patient care was compromised. Those clinicians spoke on the condition that they not be named for fear of retaliation by their employer.

An Ascension hospital emergency room doctor in Detroit said a man on the city’s east side was given a dangerous narcotic intended for another patient because of a paperwork mix-up. As a result, the patient’s breathing slowed to the point that he had to be put on a ventilator. “We intubated him and we sent him to the ICU because he got the wrong medication.”

A nurse in a Michigan Ascension hospital ER said a woman with low blood sugar and “altered mental status” went into cardiac arrest and died after staff said they waited four hours for lab results they needed to determine how to treat her, but never received. “If I started having crushing chest pain in the middle of work and thought I was having a big one, I would grab someone to drive me down the street to another hospital,” the same ER nurse said.

Similar concerns reportedly led a travel nurse at an Ascension hospital in Indiana to quit. “I just want to warn those patients that are coming to any of the Ascension facilities that there will be delays in care. There is potential for error and for harm,” Justin Neisser told CBS4 in Indianapolis in May.

Several nurses and doctors at Ascension hospitals said they feared the errors they’ve witnessed since the cyberattack began could threaten their professional licenses. “This is how a RaDonda Vaught happens,” one nurse said, referring to the Tennessee nurse who was convicted of criminally negligent homicide in 2022 for a fatal drug error.

Reporters were not able to review records to verify clinicians’ claims because of privacy laws surrounding patients’ medical information that apply to health care professionals.

Ascension declined to answer questions about claims that care has been affected by the ransomware attack. “As we have made clear throughout this cyber attack which has impacted our system and our dedicated clinical providers, caring for our patients is our highest priority,” Sean Fitzpatrick, Ascension’s vice president of external communications, said via email on June 3. “We are confident that our care providers in our hospitals and facilities continue to provide quality medical care.”

The federal government requires hospitals to protect patients’ sensitive health data, according to cybersecurity experts. However, there are no federal requirements for hospitals to prevent or prepare for cyberattacks that could compromise their electronic systems.
 

 

 

Hospitals: ‘The No.1 Target of Ransomware’

“We’ve started to think about these as public health issues and disasters on the scale of earthquakes or hurricanes,” said Jeff Tully, a co-director of the Center for Healthcare Cybersecurity at the University of California-San Diego. “These types of cybersecurity incidents should be thought of as a matter of when, and not if.”

Josh Corman, a cybersecurity expert and advocate, said ransom crews regard hospitals as the perfect prey: “They have terrible security and they’ll pay. So almost immediately, hospitals went to the No. 1 target of ransomware.”

In 2023, the health sector experienced the largest share of ransomware attacks of 16 infrastructure sectors considered vital to national security or safety, according to an FBI report on internet crimes. In March, the federal Department of Health and Human Services said reported large breaches involving ransomware had jumped by 264% over the past five years.

A cyberattack this year on Change Healthcare, a unit of UnitedHealth Group’s Optum division that processes billions of health care transactions every year, crippled the business of providers, pharmacies, and hospitals.

In May, UnitedHealth Group CEO Andrew Witty told lawmakers the company paid a $22 million ransom as a result of the Change Healthcare attack — which occurred after hackers accessed a company portal that didn’t have multifactor authentication, a basic cybersecurity tool.

The Biden administration in recent months has pushed to bolster health care cybersecurity standards, but it’s not clear which new measures will be required.

In January, HHS nudged companies to improve email security, add multifactor authentication, and institute cybersecurity training and testing, among other voluntary measures. The Centers for Medicare & Medicaid Services is expected to release new requirements for hospitals, but the scope and timing are unclear. The same is true of an update HHS is expected to make to patient privacy regulations.

HHS said the voluntary measures “will inform the creation of new enforceable cybersecurity standards,” department spokesperson Jeff Nesbit said in a statement.

“The recent cyberattack at Ascension only underscores the need for everyone in the health care ecosystem to do their part to secure their systems and protect patients,” Nesbit said.

Meanwhile, lobbyists for the hospital industry contend cybersecurity mandates or penalties are misplaced and would curtail hospitals’ resources to fend off attacks.

“Hospitals and health systems are not the primary source of cyber risk exposure facing the health care sector,” the American Hospital Association, the largest lobbying group for U.S. hospitals, said in an April statement prepared for U.S. House lawmakers. Most large data breaches that hit hospitals in 2023 originated with third-party “business associates” or other health entities, including CMS itself, the AHA statement said.

Hospitals consolidating into large multistate health systems face increased risk of data breaches and ransomware attacks, according to one study. Ascension in 2022 was the third-largest hospital chain in the U.S. by number of beds, according to the most recent data from the federal Agency for Healthcare Research and Quality.

And while cybersecurity regulations can quickly become outdated, they can at least make it clear that if health systems fail to implement basic protections there “should be consequences for that,” Jim Bagian, a former director of the National Center for Patient Safety at the Veterans Health Administration, told Michigan Public’s Stateside.

Patients can pay the price when lapses occur. Those in hospital care face a greater likelihood of death during a cyberattack, according to researchers at the University of Minnesota School of Public Health.

Workers concerned about patient safety at Ascension hospitals in Michigan have called for the company to make changes.

“We implore Ascension to recognize the internal problems that continue to plague its hospitals, both publicly and transparently,” said Dina Carlisle, a nurse and the president of the OPEIU Local 40 union, which represents nurses at Ascension Providence Rochester. At least 125 staff members at that Ascension hospital have signed a petition asking administrators to temporarily reduce elective surgeries and nonemergency patient admissions, like under the protocols many hospitals adopted early in the covid-19 pandemic.

Watson, the Kansas ICU nurse, said in late May that nurses had urged management to bring in more nurses to help manage the workflow. “Everything that we say has fallen on deaf ears,” she said.

“It is very hard to be a nurse at Ascension right now,” Watson said in late May. “It is very hard to be a patient at Ascension right now.”

If you’re a patient or worker at an Ascension hospital and would like to tell KFF Health News about your experiences, click here to share your story with us.
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

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Should You Offer Medical Credit Cards?

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Thu, 06/20/2024 - 16:36

Editor’s note: This is Dr. Eastern’s last “Managing Your Practice” column for Dermatology News. After his first column was published in 1986, Dr. Eastern continued writing his column monthly until the mid-1990s, resuming in 2005. In total, he has written over 300 columns on topics relevant to medical practice, ranging from hiring employees, selling and merging practices, complying with OSHA, and avoiding embezzlement, to electronic health records, burnout, medical assistants, negative online reviews, artificial intelligence in the office, and more. In the future, he will continue to provide commentary on practice issues with an occasional guest editorial.

Medicare reimbursement cuts, increasing overhead and staff salaries, and inflation have made running a profitable private practice increasingly challenging, particularly for rural and smaller offices. Medical credit cards are an increasingly popular choice to fill this gap.

Unlike a conventional credit card, a medical credit card is used only to pay for medical services.

alexialex/Getty Images

Traditionally, these cards were used to help cover procedures insurance didn’t cover — such as cosmetic procedures — but over the years, they have been expanded to cover other healthcare charges, mostly for patients who are paying out of pocket due to inadequate insurance or other reasons.

Advantages for physicians include immediate payment from the credit card company and reduced billing and collection costs. Patients are also less likely to delay or defer treatment if they can charge the payment and pay it back in installments.

The first step in offering medical credit cards is signing up with one or more third-party card companies. CareCredit is the most common provider in the medical credit card market. Other vendors include Wells Fargo, AccessOne, Alphaeon Credit, and iCare Financial. (As always, I have no financial interest in any product or service mentioned in this column.) A member of your staff signs patients up, and the credit card company checks their credit. If approved, the card company pays you your fee and assumes responsibility for collecting from the patient.

The interest charge on medical credit cards is often deferred for a period of time, typically between 6 and 24 months. If patients pay off the debt within this time, they can avoid paying interest. But, like other credit cards, if they make late payments or have an unpaid balance once the promotional period ends, they may end up with interest and fees totaling 25%-30% or more. It is important to make it very clear to your patients that payments are interest-free only if they are all made on time and within the promotional period.

Dr. Joseph S. Eastern

According to a Consumer Financial Protection Bureau report released earlier this year, deferred interest medical credit cards or loans were used to pay nearly $23 billion in healthcare expenses from 2018 to 2020. Individuals unable to complete payment during the promotional period paid $1 billion in deferred interest payments during that period.

Despite the growing popularity of medical credit cards among physicians, it is worth noting that some consumer groups view them as predatory financial products, marketed toward people in tough financial situations. A coalition of 60 health advocacy groups has urged the Biden Administration to ban deferred interest medical credit cards. So there is that much more reason to choose candidates for medical credit cards carefully, and to make them fully aware of what obligations they are assuming.

Patients who do not think they can pay off the balance within the interest-free time frame should probably be advised to pursue an alternative payment method, such as using a conventional credit card, taking out a personal or home-equity loan, or borrowing from a retirement savings account. Some physicians are willing to negotiate a reduced fee for patients who agree to pay cash at the time of service.

Those who do choose to apply for a medical credit card should be informed of their options, which can vary considerably depending on the product and the third-party vendor. Some medical credit products can be used only for elective procedures, but some can be used more broadly for various medical expenses. Check to make sure that each patient’s financing option can be used for his or her desired medical service.



Some payment products can only be used at specific practices or groups, while others can be used at a variety of medical offices and hospitals. If a patient arrives with a medical credit card already in hand, confirm that it is one that your office accepts.

Interest rates generally vary with each card and vendor. Make patients aware of when interest rates start accruing and if the plan offers a fixed or variable APR, or if it charges compounding interest. Confirm if there is a deferred interest option, and if so, for how long.

Different medical credit products also have varying fees and payment schedules. See that each patient reads the terms of the agreement to understand when interest may start to accrue or change, as well as when certain fees may apply. Understanding when the payments are due will help them avoid additional fees, including late fees. Some medical payment plans may also have administrative or processing fees. If so, patients should be made aware of them.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, New Jersey. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

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Editor’s note: This is Dr. Eastern’s last “Managing Your Practice” column for Dermatology News. After his first column was published in 1986, Dr. Eastern continued writing his column monthly until the mid-1990s, resuming in 2005. In total, he has written over 300 columns on topics relevant to medical practice, ranging from hiring employees, selling and merging practices, complying with OSHA, and avoiding embezzlement, to electronic health records, burnout, medical assistants, negative online reviews, artificial intelligence in the office, and more. In the future, he will continue to provide commentary on practice issues with an occasional guest editorial.

Medicare reimbursement cuts, increasing overhead and staff salaries, and inflation have made running a profitable private practice increasingly challenging, particularly for rural and smaller offices. Medical credit cards are an increasingly popular choice to fill this gap.

Unlike a conventional credit card, a medical credit card is used only to pay for medical services.

alexialex/Getty Images

Traditionally, these cards were used to help cover procedures insurance didn’t cover — such as cosmetic procedures — but over the years, they have been expanded to cover other healthcare charges, mostly for patients who are paying out of pocket due to inadequate insurance or other reasons.

Advantages for physicians include immediate payment from the credit card company and reduced billing and collection costs. Patients are also less likely to delay or defer treatment if they can charge the payment and pay it back in installments.

The first step in offering medical credit cards is signing up with one or more third-party card companies. CareCredit is the most common provider in the medical credit card market. Other vendors include Wells Fargo, AccessOne, Alphaeon Credit, and iCare Financial. (As always, I have no financial interest in any product or service mentioned in this column.) A member of your staff signs patients up, and the credit card company checks their credit. If approved, the card company pays you your fee and assumes responsibility for collecting from the patient.

The interest charge on medical credit cards is often deferred for a period of time, typically between 6 and 24 months. If patients pay off the debt within this time, they can avoid paying interest. But, like other credit cards, if they make late payments or have an unpaid balance once the promotional period ends, they may end up with interest and fees totaling 25%-30% or more. It is important to make it very clear to your patients that payments are interest-free only if they are all made on time and within the promotional period.

Dr. Joseph S. Eastern

According to a Consumer Financial Protection Bureau report released earlier this year, deferred interest medical credit cards or loans were used to pay nearly $23 billion in healthcare expenses from 2018 to 2020. Individuals unable to complete payment during the promotional period paid $1 billion in deferred interest payments during that period.

Despite the growing popularity of medical credit cards among physicians, it is worth noting that some consumer groups view them as predatory financial products, marketed toward people in tough financial situations. A coalition of 60 health advocacy groups has urged the Biden Administration to ban deferred interest medical credit cards. So there is that much more reason to choose candidates for medical credit cards carefully, and to make them fully aware of what obligations they are assuming.

Patients who do not think they can pay off the balance within the interest-free time frame should probably be advised to pursue an alternative payment method, such as using a conventional credit card, taking out a personal or home-equity loan, or borrowing from a retirement savings account. Some physicians are willing to negotiate a reduced fee for patients who agree to pay cash at the time of service.

Those who do choose to apply for a medical credit card should be informed of their options, which can vary considerably depending on the product and the third-party vendor. Some medical credit products can be used only for elective procedures, but some can be used more broadly for various medical expenses. Check to make sure that each patient’s financing option can be used for his or her desired medical service.



Some payment products can only be used at specific practices or groups, while others can be used at a variety of medical offices and hospitals. If a patient arrives with a medical credit card already in hand, confirm that it is one that your office accepts.

Interest rates generally vary with each card and vendor. Make patients aware of when interest rates start accruing and if the plan offers a fixed or variable APR, or if it charges compounding interest. Confirm if there is a deferred interest option, and if so, for how long.

Different medical credit products also have varying fees and payment schedules. See that each patient reads the terms of the agreement to understand when interest may start to accrue or change, as well as when certain fees may apply. Understanding when the payments are due will help them avoid additional fees, including late fees. Some medical payment plans may also have administrative or processing fees. If so, patients should be made aware of them.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, New Jersey. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Editor’s note: This is Dr. Eastern’s last “Managing Your Practice” column for Dermatology News. After his first column was published in 1986, Dr. Eastern continued writing his column monthly until the mid-1990s, resuming in 2005. In total, he has written over 300 columns on topics relevant to medical practice, ranging from hiring employees, selling and merging practices, complying with OSHA, and avoiding embezzlement, to electronic health records, burnout, medical assistants, negative online reviews, artificial intelligence in the office, and more. In the future, he will continue to provide commentary on practice issues with an occasional guest editorial.

Medicare reimbursement cuts, increasing overhead and staff salaries, and inflation have made running a profitable private practice increasingly challenging, particularly for rural and smaller offices. Medical credit cards are an increasingly popular choice to fill this gap.

Unlike a conventional credit card, a medical credit card is used only to pay for medical services.

alexialex/Getty Images

Traditionally, these cards were used to help cover procedures insurance didn’t cover — such as cosmetic procedures — but over the years, they have been expanded to cover other healthcare charges, mostly for patients who are paying out of pocket due to inadequate insurance or other reasons.

Advantages for physicians include immediate payment from the credit card company and reduced billing and collection costs. Patients are also less likely to delay or defer treatment if they can charge the payment and pay it back in installments.

The first step in offering medical credit cards is signing up with one or more third-party card companies. CareCredit is the most common provider in the medical credit card market. Other vendors include Wells Fargo, AccessOne, Alphaeon Credit, and iCare Financial. (As always, I have no financial interest in any product or service mentioned in this column.) A member of your staff signs patients up, and the credit card company checks their credit. If approved, the card company pays you your fee and assumes responsibility for collecting from the patient.

The interest charge on medical credit cards is often deferred for a period of time, typically between 6 and 24 months. If patients pay off the debt within this time, they can avoid paying interest. But, like other credit cards, if they make late payments or have an unpaid balance once the promotional period ends, they may end up with interest and fees totaling 25%-30% or more. It is important to make it very clear to your patients that payments are interest-free only if they are all made on time and within the promotional period.

Dr. Joseph S. Eastern

According to a Consumer Financial Protection Bureau report released earlier this year, deferred interest medical credit cards or loans were used to pay nearly $23 billion in healthcare expenses from 2018 to 2020. Individuals unable to complete payment during the promotional period paid $1 billion in deferred interest payments during that period.

Despite the growing popularity of medical credit cards among physicians, it is worth noting that some consumer groups view them as predatory financial products, marketed toward people in tough financial situations. A coalition of 60 health advocacy groups has urged the Biden Administration to ban deferred interest medical credit cards. So there is that much more reason to choose candidates for medical credit cards carefully, and to make them fully aware of what obligations they are assuming.

Patients who do not think they can pay off the balance within the interest-free time frame should probably be advised to pursue an alternative payment method, such as using a conventional credit card, taking out a personal or home-equity loan, or borrowing from a retirement savings account. Some physicians are willing to negotiate a reduced fee for patients who agree to pay cash at the time of service.

Those who do choose to apply for a medical credit card should be informed of their options, which can vary considerably depending on the product and the third-party vendor. Some medical credit products can be used only for elective procedures, but some can be used more broadly for various medical expenses. Check to make sure that each patient’s financing option can be used for his or her desired medical service.



Some payment products can only be used at specific practices or groups, while others can be used at a variety of medical offices and hospitals. If a patient arrives with a medical credit card already in hand, confirm that it is one that your office accepts.

Interest rates generally vary with each card and vendor. Make patients aware of when interest rates start accruing and if the plan offers a fixed or variable APR, or if it charges compounding interest. Confirm if there is a deferred interest option, and if so, for how long.

Different medical credit products also have varying fees and payment schedules. See that each patient reads the terms of the agreement to understand when interest may start to accrue or change, as well as when certain fees may apply. Understanding when the payments are due will help them avoid additional fees, including late fees. Some medical payment plans may also have administrative or processing fees. If so, patients should be made aware of them.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, New Jersey. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

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Latest Izokibep Trial for PsA Shows Promise But Misses on Enthesitis

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Thu, 06/20/2024 - 15:12

— The investigational interleukin (IL)-17 inhibitor izokibep hit its mark when it came to improving overall disease activity in people with active psoriatic arthritis (PsA) in a phase 2b/3 trial, but it was no better than placebo at reducing inflammation of the entheses. 

This apparent and unexpected lack of effect in the entheses was a key talking point after Philip J. Mease, MD, presented the late-breaking trial findings at the annual European Congress of Rheumatology.

Sara Freeman/Medscape Medical News
Dr. Philip J. Mease

At just 18.6 kilodaltons in size, izokibep is just “one tenth the size of a standard monoclonal antibody” and is classed as a small protein therapeutic, Dr. Mease said. It has a “very tight” binding affinity for IL-17A, and because it also binds to albumin, it has a prolonged half-life compared with other IL-17 inhibitors. Potentially, it should be able to “penetrate into difficult areas,” such as the entheses, he said.
 

Prespecified Enthesitis Analysis

However, results of a prespecified secondary analysis conducted in 209 of the 343 trial participants who had received treatment showed no significant difference in the proportions with enthesis resolution at 16 weeks, defined as a Leeds Enthesitis Index (LEI) of 0.

Comparing two dosing regimens of izokibep 160 mg once weekly (QW) vs every other week (Q2W) with placebo, enthesitis resolution was seen in 45%, 56%, and 47%, respectively, of patients.

The LEI is “sometimes subject to problems with evaluation because of placebo response, which is what we see here,” noted Dr. Mease, director of rheumatology research at the Providence Swedish Medical Center and a rheumatology professor at the University of Washington School of Medicine in Seattle.

An exploratory analysis showed that there was a better response for izokibep vs placebo if the analysis included only patients with higher LEI scores at baseline, at 8.0% (n = 12) for placebo, 22.0% (n = 9) for izokibep 160 mg QW, and 50.0% (n = 12) for izokibep 160 mg Q2W.
 

Main Efficacy Data

The primary endpoint for the trial was the proportion of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks. This showed a clear advantage for treatment with izokibep 160 QW and Q2W compared with placebo, with a respective 40%, 43%, and 15% of patients meeting this endpoint.

Corresponding ACR20 response rates were 59%, 64%, and 35%, respectively; ACR70 response rates were a respective 25%, 23%, and 5%.

In addition to ACR70, izokibep 160 QW and Q2W met a number of other “high hurdle” efficacy endpoints better than did placebo, Dr. Mease reported. A 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI90) was achieved by a respective 64%, 58%, and 12% of patients, and a 100% reduction in this index (PASI100) was achieved by a respective 51%, 47%, and 12%. And 41%, 42%, and 14% of patients, respectively, met the criteria for minimal disease activity.
 

 

 

Patient Population

Mease pointed out during his presentation that the trial included patients with adult-onset PsA that had been ongoing for ≥ 6 months. Patients had to have at least three tender or swollen joints and an inadequate response, intolerance, or contraindication to commonly used front-line therapies such as nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and tumor necrosis factor inhibitors (TNFi).

In fact, around half of the participants across the three treatment arms had received prior csDMARDs, and almost a quarter had received a TNFi.

The mean duration of disease was around 7 years, the average age was about 50 years, and the majority of the participants were White individuals. There were more women than men in the placebo vs the izokibep arms (43.4% vs about 60.0%).
 

Adverse Events

Injection site reactions were the most common adverse events, most of which were mild to moderate. Very few (< 1% to 4%) led to any need to discontinue the drug.

Serious adverse events occurred at low rates in all study arms: 0.8% for placebo, 2.7% for izokibep QW, and 1.8% for izokibep Q2W.

One patient each (0.9%) in the izokibep arms developed ulcerative colitis, whereas none in the placebo group did. Only two patients developed candidiasis. One was in the placebo group and had a skin infection, and the other was an oral infection in the QW izokibep arm.

There were no cases of uveitis, suicidal ideation, or deaths reported.
 

Comments on the Study

During the discussion that followed the presentation, Walter P. Maksymowych, MBChB, of the University of Alberta in Edmonton, Alberta, Canada, addressed the dosing regimens used.

Dr. Walter P. Maksymowych

“Looking at the side effect profile and then looking at the response rate, comparing the weekly dosing and every 2 weeks, do you think, in hindsight, you might be remiss that there wasn’t an additional dosing on a monthly basis, especially since this is a construct that is meant to prolong the half-life of the molecule?” he asked, adding that perhaps this should be something to consider in future studies.

Mease responded that there had been a fourth dosing arm in the trial — izokibep 80 mg once a month — but because there were only eight patients, the data were not sufficiently robust to analyze. 

Commenting on the study, Laura C. Coates, MBChB, PhD, said: “It’s a pretty standard phase 2b/3 study,” and the outcomes were not wildly different from what has been seen with other IL-17A inhibitors.

“In phase 2, the enthesitis data looked really good; in phase 3, the enthesitis data looks the same as for any other IL-17 inhibitor,” Dr. Coates said.

Dr. Laura C. Coates


More and longer-term data are needed to see if “the theoretical biological difference in the drug design translates to a different clinical outcome or whether it’s another IL-17,” added Dr. Coates, a clinician scientist and senior clinical research fellow at the University of Oxford in England.

Dennis McGonagle, MB MCH BAO, PhD, of the University of Leeds, England, also picked up on the enthesitis data, echoing the conclusion that the phase 2 enthesitis data were “spectacular” and noting that “it’s a real inversion of what was expected, given the small molecule.”

The study was funded by Acelyrin. Dr. Mease disclosed ties with Acelyrin and other pharmaceutical companies. Dr. Maksymowych, Dr. Coates, and Dr. McGonagle reported having a variety of financial relationships with pharmaceutical companies outside of this study.
 

A version of this article appeared on Medscape.com.

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— The investigational interleukin (IL)-17 inhibitor izokibep hit its mark when it came to improving overall disease activity in people with active psoriatic arthritis (PsA) in a phase 2b/3 trial, but it was no better than placebo at reducing inflammation of the entheses. 

This apparent and unexpected lack of effect in the entheses was a key talking point after Philip J. Mease, MD, presented the late-breaking trial findings at the annual European Congress of Rheumatology.

Sara Freeman/Medscape Medical News
Dr. Philip J. Mease

At just 18.6 kilodaltons in size, izokibep is just “one tenth the size of a standard monoclonal antibody” and is classed as a small protein therapeutic, Dr. Mease said. It has a “very tight” binding affinity for IL-17A, and because it also binds to albumin, it has a prolonged half-life compared with other IL-17 inhibitors. Potentially, it should be able to “penetrate into difficult areas,” such as the entheses, he said.
 

Prespecified Enthesitis Analysis

However, results of a prespecified secondary analysis conducted in 209 of the 343 trial participants who had received treatment showed no significant difference in the proportions with enthesis resolution at 16 weeks, defined as a Leeds Enthesitis Index (LEI) of 0.

Comparing two dosing regimens of izokibep 160 mg once weekly (QW) vs every other week (Q2W) with placebo, enthesitis resolution was seen in 45%, 56%, and 47%, respectively, of patients.

The LEI is “sometimes subject to problems with evaluation because of placebo response, which is what we see here,” noted Dr. Mease, director of rheumatology research at the Providence Swedish Medical Center and a rheumatology professor at the University of Washington School of Medicine in Seattle.

An exploratory analysis showed that there was a better response for izokibep vs placebo if the analysis included only patients with higher LEI scores at baseline, at 8.0% (n = 12) for placebo, 22.0% (n = 9) for izokibep 160 mg QW, and 50.0% (n = 12) for izokibep 160 mg Q2W.
 

Main Efficacy Data

The primary endpoint for the trial was the proportion of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks. This showed a clear advantage for treatment with izokibep 160 QW and Q2W compared with placebo, with a respective 40%, 43%, and 15% of patients meeting this endpoint.

Corresponding ACR20 response rates were 59%, 64%, and 35%, respectively; ACR70 response rates were a respective 25%, 23%, and 5%.

In addition to ACR70, izokibep 160 QW and Q2W met a number of other “high hurdle” efficacy endpoints better than did placebo, Dr. Mease reported. A 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI90) was achieved by a respective 64%, 58%, and 12% of patients, and a 100% reduction in this index (PASI100) was achieved by a respective 51%, 47%, and 12%. And 41%, 42%, and 14% of patients, respectively, met the criteria for minimal disease activity.
 

 

 

Patient Population

Mease pointed out during his presentation that the trial included patients with adult-onset PsA that had been ongoing for ≥ 6 months. Patients had to have at least three tender or swollen joints and an inadequate response, intolerance, or contraindication to commonly used front-line therapies such as nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and tumor necrosis factor inhibitors (TNFi).

In fact, around half of the participants across the three treatment arms had received prior csDMARDs, and almost a quarter had received a TNFi.

The mean duration of disease was around 7 years, the average age was about 50 years, and the majority of the participants were White individuals. There were more women than men in the placebo vs the izokibep arms (43.4% vs about 60.0%).
 

Adverse Events

Injection site reactions were the most common adverse events, most of which were mild to moderate. Very few (< 1% to 4%) led to any need to discontinue the drug.

Serious adverse events occurred at low rates in all study arms: 0.8% for placebo, 2.7% for izokibep QW, and 1.8% for izokibep Q2W.

One patient each (0.9%) in the izokibep arms developed ulcerative colitis, whereas none in the placebo group did. Only two patients developed candidiasis. One was in the placebo group and had a skin infection, and the other was an oral infection in the QW izokibep arm.

There were no cases of uveitis, suicidal ideation, or deaths reported.
 

Comments on the Study

During the discussion that followed the presentation, Walter P. Maksymowych, MBChB, of the University of Alberta in Edmonton, Alberta, Canada, addressed the dosing regimens used.

Dr. Walter P. Maksymowych

“Looking at the side effect profile and then looking at the response rate, comparing the weekly dosing and every 2 weeks, do you think, in hindsight, you might be remiss that there wasn’t an additional dosing on a monthly basis, especially since this is a construct that is meant to prolong the half-life of the molecule?” he asked, adding that perhaps this should be something to consider in future studies.

Mease responded that there had been a fourth dosing arm in the trial — izokibep 80 mg once a month — but because there were only eight patients, the data were not sufficiently robust to analyze. 

Commenting on the study, Laura C. Coates, MBChB, PhD, said: “It’s a pretty standard phase 2b/3 study,” and the outcomes were not wildly different from what has been seen with other IL-17A inhibitors.

“In phase 2, the enthesitis data looked really good; in phase 3, the enthesitis data looks the same as for any other IL-17 inhibitor,” Dr. Coates said.

Dr. Laura C. Coates


More and longer-term data are needed to see if “the theoretical biological difference in the drug design translates to a different clinical outcome or whether it’s another IL-17,” added Dr. Coates, a clinician scientist and senior clinical research fellow at the University of Oxford in England.

Dennis McGonagle, MB MCH BAO, PhD, of the University of Leeds, England, also picked up on the enthesitis data, echoing the conclusion that the phase 2 enthesitis data were “spectacular” and noting that “it’s a real inversion of what was expected, given the small molecule.”

The study was funded by Acelyrin. Dr. Mease disclosed ties with Acelyrin and other pharmaceutical companies. Dr. Maksymowych, Dr. Coates, and Dr. McGonagle reported having a variety of financial relationships with pharmaceutical companies outside of this study.
 

A version of this article appeared on Medscape.com.

— The investigational interleukin (IL)-17 inhibitor izokibep hit its mark when it came to improving overall disease activity in people with active psoriatic arthritis (PsA) in a phase 2b/3 trial, but it was no better than placebo at reducing inflammation of the entheses. 

This apparent and unexpected lack of effect in the entheses was a key talking point after Philip J. Mease, MD, presented the late-breaking trial findings at the annual European Congress of Rheumatology.

Sara Freeman/Medscape Medical News
Dr. Philip J. Mease

At just 18.6 kilodaltons in size, izokibep is just “one tenth the size of a standard monoclonal antibody” and is classed as a small protein therapeutic, Dr. Mease said. It has a “very tight” binding affinity for IL-17A, and because it also binds to albumin, it has a prolonged half-life compared with other IL-17 inhibitors. Potentially, it should be able to “penetrate into difficult areas,” such as the entheses, he said.
 

Prespecified Enthesitis Analysis

However, results of a prespecified secondary analysis conducted in 209 of the 343 trial participants who had received treatment showed no significant difference in the proportions with enthesis resolution at 16 weeks, defined as a Leeds Enthesitis Index (LEI) of 0.

Comparing two dosing regimens of izokibep 160 mg once weekly (QW) vs every other week (Q2W) with placebo, enthesitis resolution was seen in 45%, 56%, and 47%, respectively, of patients.

The LEI is “sometimes subject to problems with evaluation because of placebo response, which is what we see here,” noted Dr. Mease, director of rheumatology research at the Providence Swedish Medical Center and a rheumatology professor at the University of Washington School of Medicine in Seattle.

An exploratory analysis showed that there was a better response for izokibep vs placebo if the analysis included only patients with higher LEI scores at baseline, at 8.0% (n = 12) for placebo, 22.0% (n = 9) for izokibep 160 mg QW, and 50.0% (n = 12) for izokibep 160 mg Q2W.
 

Main Efficacy Data

The primary endpoint for the trial was the proportion of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks. This showed a clear advantage for treatment with izokibep 160 QW and Q2W compared with placebo, with a respective 40%, 43%, and 15% of patients meeting this endpoint.

Corresponding ACR20 response rates were 59%, 64%, and 35%, respectively; ACR70 response rates were a respective 25%, 23%, and 5%.

In addition to ACR70, izokibep 160 QW and Q2W met a number of other “high hurdle” efficacy endpoints better than did placebo, Dr. Mease reported. A 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI90) was achieved by a respective 64%, 58%, and 12% of patients, and a 100% reduction in this index (PASI100) was achieved by a respective 51%, 47%, and 12%. And 41%, 42%, and 14% of patients, respectively, met the criteria for minimal disease activity.
 

 

 

Patient Population

Mease pointed out during his presentation that the trial included patients with adult-onset PsA that had been ongoing for ≥ 6 months. Patients had to have at least three tender or swollen joints and an inadequate response, intolerance, or contraindication to commonly used front-line therapies such as nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and tumor necrosis factor inhibitors (TNFi).

In fact, around half of the participants across the three treatment arms had received prior csDMARDs, and almost a quarter had received a TNFi.

The mean duration of disease was around 7 years, the average age was about 50 years, and the majority of the participants were White individuals. There were more women than men in the placebo vs the izokibep arms (43.4% vs about 60.0%).
 

Adverse Events

Injection site reactions were the most common adverse events, most of which were mild to moderate. Very few (< 1% to 4%) led to any need to discontinue the drug.

Serious adverse events occurred at low rates in all study arms: 0.8% for placebo, 2.7% for izokibep QW, and 1.8% for izokibep Q2W.

One patient each (0.9%) in the izokibep arms developed ulcerative colitis, whereas none in the placebo group did. Only two patients developed candidiasis. One was in the placebo group and had a skin infection, and the other was an oral infection in the QW izokibep arm.

There were no cases of uveitis, suicidal ideation, or deaths reported.
 

Comments on the Study

During the discussion that followed the presentation, Walter P. Maksymowych, MBChB, of the University of Alberta in Edmonton, Alberta, Canada, addressed the dosing regimens used.

Dr. Walter P. Maksymowych

“Looking at the side effect profile and then looking at the response rate, comparing the weekly dosing and every 2 weeks, do you think, in hindsight, you might be remiss that there wasn’t an additional dosing on a monthly basis, especially since this is a construct that is meant to prolong the half-life of the molecule?” he asked, adding that perhaps this should be something to consider in future studies.

Mease responded that there had been a fourth dosing arm in the trial — izokibep 80 mg once a month — but because there were only eight patients, the data were not sufficiently robust to analyze. 

Commenting on the study, Laura C. Coates, MBChB, PhD, said: “It’s a pretty standard phase 2b/3 study,” and the outcomes were not wildly different from what has been seen with other IL-17A inhibitors.

“In phase 2, the enthesitis data looked really good; in phase 3, the enthesitis data looks the same as for any other IL-17 inhibitor,” Dr. Coates said.

Dr. Laura C. Coates


More and longer-term data are needed to see if “the theoretical biological difference in the drug design translates to a different clinical outcome or whether it’s another IL-17,” added Dr. Coates, a clinician scientist and senior clinical research fellow at the University of Oxford in England.

Dennis McGonagle, MB MCH BAO, PhD, of the University of Leeds, England, also picked up on the enthesitis data, echoing the conclusion that the phase 2 enthesitis data were “spectacular” and noting that “it’s a real inversion of what was expected, given the small molecule.”

The study was funded by Acelyrin. Dr. Mease disclosed ties with Acelyrin and other pharmaceutical companies. Dr. Maksymowych, Dr. Coates, and Dr. McGonagle reported having a variety of financial relationships with pharmaceutical companies outside of this study.
 

A version of this article appeared on Medscape.com.

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Selective JAK 1 Inhibitor for RA Proves Promising in Phase 3 Trial

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— The highly selective oral Janus kinase (JAK) inhibitor SHR0302 (ivarmacitinib) enables more patients with active rheumatoid arthritis to meet American College of Rheumatology (ACR) response criteria than placebo, the results of a phase 3 trial showed.

After 24 weeks of daily treatment, the primary endpoint of an ACR20 response was met by 40.4% of those who had been given placebo, 70.4% who had received a 4-mg dose, and 75.1% given an 8-mg dose. At the same time point, ACR50 responses were a respective 15.4%, 46.0%, and 57.1%, and ACR70 responses were 6.9%, 22.2%, and 31.7%. All analyses comparing SHR0302 vs placebo were highly significant (P < .0001).
 

First Phase 3 Trial in China

“This is the first highly selective JAK inhibitor originally developed, and a phase 3 clinical trial conducted, [exclusively] in China,” Jinjing Liu, from the department of rheumatology at Peking Union Medical College Hospital in Beijing, China, said in an interview.

Sara Freeman/Medscape Medical News
Jinjing Liu

Ms. Liu presented the results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, during the Abstract Plenary, which highlights the best-scored abstracts of the meeting.

“We are working our best to provide more choices for Chinese patients,” Ms. Liu said, which includes lowering the financial cost of treatments. A locally developed JAK inhibitor could potentially be a much cheaper option than other alternatives that are currently available, she said.

But it is more than that, Ms. Liu said. “The selectivity of SHR0302 for JAK 1 is nine times greater than for JAK 2, so it surpasses either tofacitinib or baricitinib.” The theory is that this higher selectivity for JAK 1 over JAK 2 could lead to fewer adverse events (AEs).

“Maybe it will result in lower JAK 2–associated hematologic side effects,” Ms. Liu said.

“We have noticed that, throughout the clinical trial, the most commonly reported AEs in the drug groups were upper extremity infection [21.7%-22.8% vs 13.8% for placebo] and hyperlipidemia [12.2%-15.3% vs 5.3%].” And for the control group, she said that anemia was the second highest reported AE, at 11.7% vs 6.3% and 7.4% for SHR0302 4 and 8 mg, respectively.
 

Standard Design

The trial design was typical for a phase 3 study: Multicenter, randomized, placebo controlled, and double blind for the first 24 weeks, followed by an extension period out to 52 weeks. For inclusion in the study, patients had to be aged 18-75 years and have active rheumatoid arthritis and an inadequate response to previous treatment with conventional synthetic disease-modifying antirheumatic drugs.

Of 1085 patients who were initially screened, 566 were randomly allocated to receive placebo (n = 188), SHR0302 4 mg (n = 189), or SHR0302 8 mg (n = 189). The average age of patients was 51 years, and 13.3% of patients were older than 65 years.
 

Additional Results

Alongside improvements in ACR responses, Ms Liu reported that a significantly higher proportion of patients treated with SHR0302 vs placebo achieved a Disease Activity Score in 28 joints based on C-reactive protein less than 2.6 (29.6% with 4 mg and 39.2% with 8 mg vs 4.2% with placebo; both P < .0001) and at least 3.2 (57.1% and 46.0% vs 15.4%; both P < .0001) at 24 weeks.

There were also greater improvements seen in Health Assessment Questionnaire-Disability Index, 36-item Short-Form (SF36) physical component summary, and SF36 mental component summary scores for active vs placebo treatment.

As for AEs, there were no surprises. During the main 24-week trial period, 81.5%, 90.5%, and 79.3% of patients treated with SHR0302 4 and 8 mg and placebo, respectively, experienced any AE.

Infection-related treatment-emergent adverse effects occurred slightly more often in the SHR0302-treated groups (40.2% for 4 mg and 40.7% for 8 mg) than in the placebo group (34.0%). There was a single case of serious infection that required treatment in the SHR0302 8 mg–treated group but no cases of systemic opportunistic infection.

There was one thromboembolic event and one major cardiovascular event in the 24-week period, both occurring in patients treated with SHR0302 8 mg. There were also single cases of each reported during the extension phase of the trial, but both were in the placebo arm.

Two cases of liver function abnormality — one each in the SHR0302 4- and 8-mg groups — were recorded during the main part of the trial and two cases — both in the SHR0302 4-mg group — during the extension phase.

As for malignancy, there was a single, newly diagnosed case in the SHR0302 4 mg group in the first part of the trial and two cases, both in the SHR0302 4-mg group, during the extension phase.

“We hope this [JAK inhibitor] will be for everybody. But, you know, if it’s for patients, globally, more clinical trials would be required,” Ms. Liu said in an interview. The future, she added, was to start accumulating some real-world data and perhaps do a trial comparing SHR0302 with another JAK inhibitor or a tumor necrosis factor inhibitor.
 

Another JAK in the Box?

Following her presentation, Ms. Liu at EULAR 2024 was quizzed as to why there were so many screening failures. She responded that she did not have the full data to answer the question but noted that some patients in her center had been worried about being randomized to a placebo. This trial has also been conducted during the COVID-19 pandemic, so that may have been a contributing factor with patients unable to get to their follow-up appointments.

Dr. Iain B. McInnes

Iain B. McInnes, MD, PhD, vice principal, professor of rheumatology, and head of the College of Medical, Veterinary & Life Sciences at the University of Glasgow, Glasgow, Scotland, commented on the study, saying: “The JAK field is in evolution. We need to understand the broader toxicities. There is an unexplained mechanism driving potential cardiovascular and malignant risk in a small proportion of patients receiving the drugs.”

Dr. McInnes added, “It’s really unclear whether the solution is going to be greater selectivity and potency, or whether we need to think really about selecting the right patients for a JAK inhibitor.”

The study was funded by Jiangsu Hengrui Pharmaceuticals. Two of the 18 authors of the abstract were employees of the sponsoring company, but Ms. Liu reported having no conflicts of interest. Dr. McInnes reported serving on speaker’s bureaus for AbbVie and UCB; receiving consulting fees received from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Eli Lilly, Evelo, Gilead, Janssen, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB; and receiving grant/research support from GlaxoSmithKline, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, and UCB.

A version of this article appeared on Medscape.com.

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— The highly selective oral Janus kinase (JAK) inhibitor SHR0302 (ivarmacitinib) enables more patients with active rheumatoid arthritis to meet American College of Rheumatology (ACR) response criteria than placebo, the results of a phase 3 trial showed.

After 24 weeks of daily treatment, the primary endpoint of an ACR20 response was met by 40.4% of those who had been given placebo, 70.4% who had received a 4-mg dose, and 75.1% given an 8-mg dose. At the same time point, ACR50 responses were a respective 15.4%, 46.0%, and 57.1%, and ACR70 responses were 6.9%, 22.2%, and 31.7%. All analyses comparing SHR0302 vs placebo were highly significant (P < .0001).
 

First Phase 3 Trial in China

“This is the first highly selective JAK inhibitor originally developed, and a phase 3 clinical trial conducted, [exclusively] in China,” Jinjing Liu, from the department of rheumatology at Peking Union Medical College Hospital in Beijing, China, said in an interview.

Sara Freeman/Medscape Medical News
Jinjing Liu

Ms. Liu presented the results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, during the Abstract Plenary, which highlights the best-scored abstracts of the meeting.

“We are working our best to provide more choices for Chinese patients,” Ms. Liu said, which includes lowering the financial cost of treatments. A locally developed JAK inhibitor could potentially be a much cheaper option than other alternatives that are currently available, she said.

But it is more than that, Ms. Liu said. “The selectivity of SHR0302 for JAK 1 is nine times greater than for JAK 2, so it surpasses either tofacitinib or baricitinib.” The theory is that this higher selectivity for JAK 1 over JAK 2 could lead to fewer adverse events (AEs).

“Maybe it will result in lower JAK 2–associated hematologic side effects,” Ms. Liu said.

“We have noticed that, throughout the clinical trial, the most commonly reported AEs in the drug groups were upper extremity infection [21.7%-22.8% vs 13.8% for placebo] and hyperlipidemia [12.2%-15.3% vs 5.3%].” And for the control group, she said that anemia was the second highest reported AE, at 11.7% vs 6.3% and 7.4% for SHR0302 4 and 8 mg, respectively.
 

Standard Design

The trial design was typical for a phase 3 study: Multicenter, randomized, placebo controlled, and double blind for the first 24 weeks, followed by an extension period out to 52 weeks. For inclusion in the study, patients had to be aged 18-75 years and have active rheumatoid arthritis and an inadequate response to previous treatment with conventional synthetic disease-modifying antirheumatic drugs.

Of 1085 patients who were initially screened, 566 were randomly allocated to receive placebo (n = 188), SHR0302 4 mg (n = 189), or SHR0302 8 mg (n = 189). The average age of patients was 51 years, and 13.3% of patients were older than 65 years.
 

Additional Results

Alongside improvements in ACR responses, Ms Liu reported that a significantly higher proportion of patients treated with SHR0302 vs placebo achieved a Disease Activity Score in 28 joints based on C-reactive protein less than 2.6 (29.6% with 4 mg and 39.2% with 8 mg vs 4.2% with placebo; both P < .0001) and at least 3.2 (57.1% and 46.0% vs 15.4%; both P < .0001) at 24 weeks.

There were also greater improvements seen in Health Assessment Questionnaire-Disability Index, 36-item Short-Form (SF36) physical component summary, and SF36 mental component summary scores for active vs placebo treatment.

As for AEs, there were no surprises. During the main 24-week trial period, 81.5%, 90.5%, and 79.3% of patients treated with SHR0302 4 and 8 mg and placebo, respectively, experienced any AE.

Infection-related treatment-emergent adverse effects occurred slightly more often in the SHR0302-treated groups (40.2% for 4 mg and 40.7% for 8 mg) than in the placebo group (34.0%). There was a single case of serious infection that required treatment in the SHR0302 8 mg–treated group but no cases of systemic opportunistic infection.

There was one thromboembolic event and one major cardiovascular event in the 24-week period, both occurring in patients treated with SHR0302 8 mg. There were also single cases of each reported during the extension phase of the trial, but both were in the placebo arm.

Two cases of liver function abnormality — one each in the SHR0302 4- and 8-mg groups — were recorded during the main part of the trial and two cases — both in the SHR0302 4-mg group — during the extension phase.

As for malignancy, there was a single, newly diagnosed case in the SHR0302 4 mg group in the first part of the trial and two cases, both in the SHR0302 4-mg group, during the extension phase.

“We hope this [JAK inhibitor] will be for everybody. But, you know, if it’s for patients, globally, more clinical trials would be required,” Ms. Liu said in an interview. The future, she added, was to start accumulating some real-world data and perhaps do a trial comparing SHR0302 with another JAK inhibitor or a tumor necrosis factor inhibitor.
 

Another JAK in the Box?

Following her presentation, Ms. Liu at EULAR 2024 was quizzed as to why there were so many screening failures. She responded that she did not have the full data to answer the question but noted that some patients in her center had been worried about being randomized to a placebo. This trial has also been conducted during the COVID-19 pandemic, so that may have been a contributing factor with patients unable to get to their follow-up appointments.

Dr. Iain B. McInnes

Iain B. McInnes, MD, PhD, vice principal, professor of rheumatology, and head of the College of Medical, Veterinary & Life Sciences at the University of Glasgow, Glasgow, Scotland, commented on the study, saying: “The JAK field is in evolution. We need to understand the broader toxicities. There is an unexplained mechanism driving potential cardiovascular and malignant risk in a small proportion of patients receiving the drugs.”

Dr. McInnes added, “It’s really unclear whether the solution is going to be greater selectivity and potency, or whether we need to think really about selecting the right patients for a JAK inhibitor.”

The study was funded by Jiangsu Hengrui Pharmaceuticals. Two of the 18 authors of the abstract were employees of the sponsoring company, but Ms. Liu reported having no conflicts of interest. Dr. McInnes reported serving on speaker’s bureaus for AbbVie and UCB; receiving consulting fees received from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Eli Lilly, Evelo, Gilead, Janssen, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB; and receiving grant/research support from GlaxoSmithKline, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, and UCB.

A version of this article appeared on Medscape.com.

— The highly selective oral Janus kinase (JAK) inhibitor SHR0302 (ivarmacitinib) enables more patients with active rheumatoid arthritis to meet American College of Rheumatology (ACR) response criteria than placebo, the results of a phase 3 trial showed.

After 24 weeks of daily treatment, the primary endpoint of an ACR20 response was met by 40.4% of those who had been given placebo, 70.4% who had received a 4-mg dose, and 75.1% given an 8-mg dose. At the same time point, ACR50 responses were a respective 15.4%, 46.0%, and 57.1%, and ACR70 responses were 6.9%, 22.2%, and 31.7%. All analyses comparing SHR0302 vs placebo were highly significant (P < .0001).
 

First Phase 3 Trial in China

“This is the first highly selective JAK inhibitor originally developed, and a phase 3 clinical trial conducted, [exclusively] in China,” Jinjing Liu, from the department of rheumatology at Peking Union Medical College Hospital in Beijing, China, said in an interview.

Sara Freeman/Medscape Medical News
Jinjing Liu

Ms. Liu presented the results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, during the Abstract Plenary, which highlights the best-scored abstracts of the meeting.

“We are working our best to provide more choices for Chinese patients,” Ms. Liu said, which includes lowering the financial cost of treatments. A locally developed JAK inhibitor could potentially be a much cheaper option than other alternatives that are currently available, she said.

But it is more than that, Ms. Liu said. “The selectivity of SHR0302 for JAK 1 is nine times greater than for JAK 2, so it surpasses either tofacitinib or baricitinib.” The theory is that this higher selectivity for JAK 1 over JAK 2 could lead to fewer adverse events (AEs).

“Maybe it will result in lower JAK 2–associated hematologic side effects,” Ms. Liu said.

“We have noticed that, throughout the clinical trial, the most commonly reported AEs in the drug groups were upper extremity infection [21.7%-22.8% vs 13.8% for placebo] and hyperlipidemia [12.2%-15.3% vs 5.3%].” And for the control group, she said that anemia was the second highest reported AE, at 11.7% vs 6.3% and 7.4% for SHR0302 4 and 8 mg, respectively.
 

Standard Design

The trial design was typical for a phase 3 study: Multicenter, randomized, placebo controlled, and double blind for the first 24 weeks, followed by an extension period out to 52 weeks. For inclusion in the study, patients had to be aged 18-75 years and have active rheumatoid arthritis and an inadequate response to previous treatment with conventional synthetic disease-modifying antirheumatic drugs.

Of 1085 patients who were initially screened, 566 were randomly allocated to receive placebo (n = 188), SHR0302 4 mg (n = 189), or SHR0302 8 mg (n = 189). The average age of patients was 51 years, and 13.3% of patients were older than 65 years.
 

Additional Results

Alongside improvements in ACR responses, Ms Liu reported that a significantly higher proportion of patients treated with SHR0302 vs placebo achieved a Disease Activity Score in 28 joints based on C-reactive protein less than 2.6 (29.6% with 4 mg and 39.2% with 8 mg vs 4.2% with placebo; both P < .0001) and at least 3.2 (57.1% and 46.0% vs 15.4%; both P < .0001) at 24 weeks.

There were also greater improvements seen in Health Assessment Questionnaire-Disability Index, 36-item Short-Form (SF36) physical component summary, and SF36 mental component summary scores for active vs placebo treatment.

As for AEs, there were no surprises. During the main 24-week trial period, 81.5%, 90.5%, and 79.3% of patients treated with SHR0302 4 and 8 mg and placebo, respectively, experienced any AE.

Infection-related treatment-emergent adverse effects occurred slightly more often in the SHR0302-treated groups (40.2% for 4 mg and 40.7% for 8 mg) than in the placebo group (34.0%). There was a single case of serious infection that required treatment in the SHR0302 8 mg–treated group but no cases of systemic opportunistic infection.

There was one thromboembolic event and one major cardiovascular event in the 24-week period, both occurring in patients treated with SHR0302 8 mg. There were also single cases of each reported during the extension phase of the trial, but both were in the placebo arm.

Two cases of liver function abnormality — one each in the SHR0302 4- and 8-mg groups — were recorded during the main part of the trial and two cases — both in the SHR0302 4-mg group — during the extension phase.

As for malignancy, there was a single, newly diagnosed case in the SHR0302 4 mg group in the first part of the trial and two cases, both in the SHR0302 4-mg group, during the extension phase.

“We hope this [JAK inhibitor] will be for everybody. But, you know, if it’s for patients, globally, more clinical trials would be required,” Ms. Liu said in an interview. The future, she added, was to start accumulating some real-world data and perhaps do a trial comparing SHR0302 with another JAK inhibitor or a tumor necrosis factor inhibitor.
 

Another JAK in the Box?

Following her presentation, Ms. Liu at EULAR 2024 was quizzed as to why there were so many screening failures. She responded that she did not have the full data to answer the question but noted that some patients in her center had been worried about being randomized to a placebo. This trial has also been conducted during the COVID-19 pandemic, so that may have been a contributing factor with patients unable to get to their follow-up appointments.

Dr. Iain B. McInnes

Iain B. McInnes, MD, PhD, vice principal, professor of rheumatology, and head of the College of Medical, Veterinary & Life Sciences at the University of Glasgow, Glasgow, Scotland, commented on the study, saying: “The JAK field is in evolution. We need to understand the broader toxicities. There is an unexplained mechanism driving potential cardiovascular and malignant risk in a small proportion of patients receiving the drugs.”

Dr. McInnes added, “It’s really unclear whether the solution is going to be greater selectivity and potency, or whether we need to think really about selecting the right patients for a JAK inhibitor.”

The study was funded by Jiangsu Hengrui Pharmaceuticals. Two of the 18 authors of the abstract were employees of the sponsoring company, but Ms. Liu reported having no conflicts of interest. Dr. McInnes reported serving on speaker’s bureaus for AbbVie and UCB; receiving consulting fees received from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Eli Lilly, Evelo, Gilead, Janssen, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB; and receiving grant/research support from GlaxoSmithKline, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, and UCB.

A version of this article appeared on Medscape.com.

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