MDedge Rheumatology

VIENNA — Safe and effective options for lowering serum uric acid (sUA) in patients with gout who are refractory to conventional therapies appear to be near, judging from phase 2 and 3 trials that produced positive results at the annual European Congress of Rheumatology.

Reports from the meeting included two phase 2 studies with novel urate anion transporter 1 (URAT1) inhibitors for patients with refractory gout, in addition to extension data from the phase 3 trial program for SEL-212. In all cases, efficacy appeared to be on the same order of currently available drugs with potentially better tolerability, an important unmet need for patients with gout refractory to traditional therapies.
 

12-Month Outcomes With SEL-212

The extension data with SEL-212 follow the 6-month results presented from the DISSOLVE I and II trials at EULAR 2023. Now at 12 months, the benefits have proven to be generally sustained with no new safety signals, according to Herbert S.B. Baraf, MD, The Center for Rheumatology and Bone Research, Wheaton, Maryland.

Arthritis Foundation

SEL-212 is a drug platform involving two components delivered by intravenous infusion once monthly in sequence. The first, SEL-110, consists of tolerogenic nanoparticles containing sirolimus. The second, SEL-037, is the pegylated uricase pegadricase.

On the 1-month dosing schedule, most patients who had responded at 6 months were still responding at 12 months, and both of the two study doses of SEL-212 in the DISSOLVE trials were well tolerated over the extension, Dr. Baraf reported.

On the basis of the data so far, “this will be an effective and well tolerated therapy for refractory gout over a period of at least 12 months,” Dr. Baraf said.

The DISSOLVE I and II trials were identically designed. Patients with refractory gout, defined as failure to normalize sUA or control symptoms with a xanthine oxidase inhibitor, were randomly assigned to receive 0.15 mg SEL-212, 1.0 mg SEL-212, or placebo.

There was a stopping rule for patients who reached a sUA level < 2 mg/dL 1 hour after the infusion.

The primary endpoint was sUA level < 6 mg/dL for at least 80% of the sixth month of the 6-month trial. About 50% of patients on either dose of SEL-212 met this endpoint (vs 4% of those receiving placebo; P < .0001). There was a numerical advantage for the higher dose in both studies.

Patients who completed the 6-month trial were eligible for a 6-month extension, during which they remained on their assigned therapy, including placebo. This phase was also blinded. Patients who met the stopping rule in either the main study or extension did not take the study drug but remained in the study for final analysis.

Of the 265 patients who participated in the main phase of the study, 143 (54%) completed the 6-month extension. Most discontinuations were the result of the stopping rule. Reasons for other patients discontinuing the study included withdrawal of consent in about 10% of each treatment arm and adverse events in 13.8%, 6.8%, and 2.2% of the high-dose, low-dose, and placebo groups, respectively.

At 12 months, when the data from the two trials were pooled, the proportion of patients on therapy and responding remained at about 50% in the high-dose group and 43% in the low-dose group on an intention-to-treat analysis. Relative to the 8% response rate for placebo, the advantage for either dose was highly significant (P < .0001).

In the subgroup of patients with tophi at baseline, representing about half the study group, responses were low at 12 months, whether on high- (41%) or low-dose (43%) SEL-212. The rate of response among placebo patients with baseline tophi was 9%.
 

Safety of SEL-212

The safety over the 6-month extension did not differ substantially from that observed during the first 6 months, according to Dr. Baraf. This was reiterated in more detail by Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania. He delivered a separate safety presentation focused on DISSOLVE I.

Specifically, there were no serious adverse events thought to be related to treatment. Besides gout flares, which affected approximately 27% of patients regardless of active treatment or placebo assignment, the most common adverse effect was hypertriglyceridemia, which was observed in 5.4% of patients on active treatment vs 0% of those receiving placebo. Independent of the treatment arm, less than 5% of patients developed stomatitis or cellulitis during the 6-month extension period.

In the 6-month extension phase, there were no infusion reactions observed within 1 hour after SEL-212 administration and just two overall that occurred with low-dose SEL-212, according to Kivitz.

New Selective URAT1 Inhibitors

The other potential advance in the treatment of refractory gout is coming from newer selective URAT1 inhibitors. According to the lead investigators of two phase 2 trials evaluating a novel URAT1 inhibitor, the urate transporter protein has long been considered the most promising target for gout treatment. As this protein regulates the absorption of uric acid from the renal tubule, it has a direct uric acid–lowering effect. However, the adverse events of current agents, such as probenecid, benzbromarone, and sulfinpyrazone, have created a need for drugs with a better benefit-to-risk ratio.

In one of two multicenter phase 2 studies on refractory gout, the experimental agent ruzinurad was tested as an adjunct to the xanthine oxidase inhibitor febuxostat. In the other, the objective was to evaluate whether the experimental agent AR882 or AR882 plus allopurinol is better than allopurinol alone for reducing tophi at 12 months.
 

Ruzinurad Plus Febuxostat

In the ruzinurad trial, 151 patients with symptomatic gout and elevated sUA (> 6 mg/dL) for at least 6 weeks on stable doses of febuxostat were randomized to receive 5 mg ruzinurad, 10 mg ruzinurad, or placebo. All remained on febuxostat. In the active treatment arms, the starting ruzinurad dose was 1 mg before titrating up to the assigned target.

For the primary endpoint of sUA < 6 mg/dL at 12 weeks, the rates were 56.9%, 53.1%, and 13.7% in the high-dose, low-dose, and placebo groups, respectively (P < .0001 for both ruzinurad arms), reported Huihua Ding, MD, a clinician and researcher at Shanghai Jiao Tong University, Shanghai, China.

“Consistently, subgroup analyses based on baseline eGFR [estimated glomerular filtration rate], sUA, and tophus demonstrated superior effective of ruzinurad plus febuxostat over placebo plus febuxostat,” reported Dr. Ding, who noted that previous clinical studies suggested the potential for synergism between ruzinurad and febuxostat.

The proportion of patients achieving the more rigorous target of < 0.5 mg/dL was also higher with the higher and lower doses of ruzinurad vs placebo (43.1% and 38.8% vs 9.8%, respectively).

The proportion of patients with treatment-emergent side effects did not differ between the three groups. The most common were gout flares, which were observed in 39.2%, 49.0%, and 45.1% in the high-dose, low-dose, and placebo groups, respectively. Most adverse events were mild or moderate, and none led to treatment discontinuation.

The favorable benefit-to-risk profile of ruzinurad was attributed by Dr. Ding to its high relative selectivity and potent inhibition of URAT1, an advantage that might be relevant to avoiding side effects at higher doses.

AR882 in Patients With Tophi

In the trial with AR882, 42 patients with refractory gout and at least one subcutaneous tophus were randomized to receive 75 mg AR882, 50 mg AR882 plus allopurinol, or allopurinol alone. All drugs were taken once daily. Doses of allopurinol of up to 300 mg were permitted.

The changes in the target tophus area and crystal volume at month 6 were compared, and patients who completed this phase were invited into a 6-month extension. In the 6-month extension, 75 mg AR882 was additionally provided to those who had been in the single-agent allopurinol arm. The other arms were unchanged.

Tophi measurements were performed with calipers at regular intervals. Change from baseline in sUA levels was also an efficacy measure, according to Robert Keenan, MD, chief medical officer of Arthrosi Therapeutics, which is developing AR882.

From average baseline sUA levels of > 9 mg/dL, all three treatments reduced sUA levels by an average of at least 4.5 mg by month 3. At month 6, complete resolution of at least one target tophus was observed in 29% of the group randomized to receive 75 mg AR882 alone, 8% of those randomized to receive 50 mg AR882 plus allopurinol, and 8% of those on allopurinol alone.

At month 12, the average sUA levels were 4.3 mg/dL for 75 mg AR882, 3.7 mg/dL for 50 mg AR882 plus allopurinol, and 2.9 mg/dL for the 75 mg AR882 plus allopurinol extension-switch arm.

At the 12-month mark, the proportions of patients with complete resolution of any tophus were 50.0% for 75 mg AR882, 12.5% for 50 mg AR882 plus allopurinol, and 36.4% for the 75 mg AR882 plus allopurinol extension-switch arm, according to Dr. Keenan.

Compared with allopurinol alone at 6 months, 75 mg AR882 led to a reduction in total urate crystal volume, and this reduction was sustained at 12 months, he added.

Alone or in combination with allopurinol, AR882 was well tolerated. Gout flares were the most common adverse events, but they declined with continued AR882 treatment, according to Dr. Keenan. Diarrhea, headache, and upper respiratory infections were reported but were of mild or moderate severity.

Again, the take-home message from this study, like the other phase 2 study of a novel URAT1 inhibitor, is that these newer drugs might offer a better benefit-to-risk ratio, particularly in those with refractory disease.

“AR882 may offer improved efficacy and better safety compared to existing therapies in the treatment of patients with gout, including those with both clinically visible and subclinical crystal deposition,” Dr. Keenan said.

Dr. Baraf reported financial relationships with Horizon Therapeutics, Fresenius Kabi, Grünenthal, Olatec, Selecta Biosciences, and Sobi, which provided funding for the trials he discussed. Dr. Kivitz also reported a financial relationship with Sobi, which funded the DISSOLVE trials, along with AbbVie, Amgen, Eli Lilly, Flexion, GlaxoSmithKline, and Sanofi Regeneron. Dr. Ding reported no potential conflicts. The study she discussed was funded by Jiangsu Hengrui Pharmaceuticals. Dr. Keenan is an employee of Arthrosi Therapeutics, which provided funding for the trial he presented.

August 1, 2024 — Editor's note: This article has been updated to reflect the correct number of infusion reactions reported in the 6-month extension phase of the DISSOLVE I trial.

A version of this article appeared on Medscape.com.

VIENNA — Safe and effective options for lowering serum uric acid (sUA) in patients with gout who are refractory to conventional therapies appear to be near, judging from phase 2 and 3 trials that produced positive results at the annual European Congress of Rheumatology.

Reports from the meeting included two phase 2 studies with novel urate anion transporter 1 (URAT1) inhibitors for patients with refractory gout, in addition to extension data from the phase 3 trial program for SEL-212. In all cases, efficacy appeared to be on the same order of currently available drugs with potentially better tolerability, an important unmet need for patients with gout refractory to traditional therapies.
 

12-Month Outcomes With SEL-212

The extension data with SEL-212 follow the 6-month results presented from the DISSOLVE I and II trials at EULAR 2023. Now at 12 months, the benefits have proven to be generally sustained with no new safety signals, according to Herbert S.B. Baraf, MD, The Center for Rheumatology and Bone Research, Wheaton, Maryland.

Arthritis Foundation

SEL-212 is a drug platform involving two components delivered by intravenous infusion once monthly in sequence. The first, SEL-110, consists of tolerogenic nanoparticles containing sirolimus. The second, SEL-037, is the pegylated uricase pegadricase.

On the 1-month dosing schedule, most patients who had responded at 6 months were still responding at 12 months, and both of the two study doses of SEL-212 in the DISSOLVE trials were well tolerated over the extension, Dr. Baraf reported.

On the basis of the data so far, “this will be an effective and well tolerated therapy for refractory gout over a period of at least 12 months,” Dr. Baraf said.

The DISSOLVE I and II trials were identically designed. Patients with refractory gout, defined as failure to normalize sUA or control symptoms with a xanthine oxidase inhibitor, were randomly assigned to receive 0.15 mg SEL-212, 1.0 mg SEL-212, or placebo.

There was a stopping rule for patients who reached a sUA level < 2 mg/dL 1 hour after the infusion.

The primary endpoint was sUA level < 6 mg/dL for at least 80% of the sixth month of the 6-month trial. About 50% of patients on either dose of SEL-212 met this endpoint (vs 4% of those receiving placebo; P < .0001). There was a numerical advantage for the higher dose in both studies.

Patients who completed the 6-month trial were eligible for a 6-month extension, during which they remained on their assigned therapy, including placebo. This phase was also blinded. Patients who met the stopping rule in either the main study or extension did not take the study drug but remained in the study for final analysis.

Of the 265 patients who participated in the main phase of the study, 143 (54%) completed the 6-month extension. Most discontinuations were the result of the stopping rule. Reasons for other patients discontinuing the study included withdrawal of consent in about 10% of each treatment arm and adverse events in 13.8%, 6.8%, and 2.2% of the high-dose, low-dose, and placebo groups, respectively.

At 12 months, when the data from the two trials were pooled, the proportion of patients on therapy and responding remained at about 50% in the high-dose group and 43% in the low-dose group on an intention-to-treat analysis. Relative to the 8% response rate for placebo, the advantage for either dose was highly significant (P < .0001).

In the subgroup of patients with tophi at baseline, representing about half the study group, responses were low at 12 months, whether on high- (41%) or low-dose (43%) SEL-212. The rate of response among placebo patients with baseline tophi was 9%.
 

Safety of SEL-212

The safety over the 6-month extension did not differ substantially from that observed during the first 6 months, according to Dr. Baraf. This was reiterated in more detail by Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania. He delivered a separate safety presentation focused on DISSOLVE I.

Specifically, there were no serious adverse events thought to be related to treatment. Besides gout flares, which affected approximately 27% of patients regardless of active treatment or placebo assignment, the most common adverse effect was hypertriglyceridemia, which was observed in 5.4% of patients on active treatment vs 0% of those receiving placebo. Independent of the treatment arm, less than 5% of patients developed stomatitis or cellulitis during the 6-month extension period.

In the 6-month extension phase, there were no infusion reactions observed within 1 hour after SEL-212 administration and just two overall that occurred with low-dose SEL-212, according to Kivitz.

New Selective URAT1 Inhibitors

The other potential advance in the treatment of refractory gout is coming from newer selective URAT1 inhibitors. According to the lead investigators of two phase 2 trials evaluating a novel URAT1 inhibitor, the urate transporter protein has long been considered the most promising target for gout treatment. As this protein regulates the absorption of uric acid from the renal tubule, it has a direct uric acid–lowering effect. However, the adverse events of current agents, such as probenecid, benzbromarone, and sulfinpyrazone, have created a need for drugs with a better benefit-to-risk ratio.

In one of two multicenter phase 2 studies on refractory gout, the experimental agent ruzinurad was tested as an adjunct to the xanthine oxidase inhibitor febuxostat. In the other, the objective was to evaluate whether the experimental agent AR882 or AR882 plus allopurinol is better than allopurinol alone for reducing tophi at 12 months.
 

Ruzinurad Plus Febuxostat

In the ruzinurad trial, 151 patients with symptomatic gout and elevated sUA (> 6 mg/dL) for at least 6 weeks on stable doses of febuxostat were randomized to receive 5 mg ruzinurad, 10 mg ruzinurad, or placebo. All remained on febuxostat. In the active treatment arms, the starting ruzinurad dose was 1 mg before titrating up to the assigned target.

For the primary endpoint of sUA < 6 mg/dL at 12 weeks, the rates were 56.9%, 53.1%, and 13.7% in the high-dose, low-dose, and placebo groups, respectively (P < .0001 for both ruzinurad arms), reported Huihua Ding, MD, a clinician and researcher at Shanghai Jiao Tong University, Shanghai, China.

“Consistently, subgroup analyses based on baseline eGFR [estimated glomerular filtration rate], sUA, and tophus demonstrated superior effective of ruzinurad plus febuxostat over placebo plus febuxostat,” reported Dr. Ding, who noted that previous clinical studies suggested the potential for synergism between ruzinurad and febuxostat.

The proportion of patients achieving the more rigorous target of < 0.5 mg/dL was also higher with the higher and lower doses of ruzinurad vs placebo (43.1% and 38.8% vs 9.8%, respectively).

The proportion of patients with treatment-emergent side effects did not differ between the three groups. The most common were gout flares, which were observed in 39.2%, 49.0%, and 45.1% in the high-dose, low-dose, and placebo groups, respectively. Most adverse events were mild or moderate, and none led to treatment discontinuation.

The favorable benefit-to-risk profile of ruzinurad was attributed by Dr. Ding to its high relative selectivity and potent inhibition of URAT1, an advantage that might be relevant to avoiding side effects at higher doses.

AR882 in Patients With Tophi

In the trial with AR882, 42 patients with refractory gout and at least one subcutaneous tophus were randomized to receive 75 mg AR882, 50 mg AR882 plus allopurinol, or allopurinol alone. All drugs were taken once daily. Doses of allopurinol of up to 300 mg were permitted.

The changes in the target tophus area and crystal volume at month 6 were compared, and patients who completed this phase were invited into a 6-month extension. In the 6-month extension, 75 mg AR882 was additionally provided to those who had been in the single-agent allopurinol arm. The other arms were unchanged.

Tophi measurements were performed with calipers at regular intervals. Change from baseline in sUA levels was also an efficacy measure, according to Robert Keenan, MD, chief medical officer of Arthrosi Therapeutics, which is developing AR882.

From average baseline sUA levels of > 9 mg/dL, all three treatments reduced sUA levels by an average of at least 4.5 mg by month 3. At month 6, complete resolution of at least one target tophus was observed in 29% of the group randomized to receive 75 mg AR882 alone, 8% of those randomized to receive 50 mg AR882 plus allopurinol, and 8% of those on allopurinol alone.

At month 12, the average sUA levels were 4.3 mg/dL for 75 mg AR882, 3.7 mg/dL for 50 mg AR882 plus allopurinol, and 2.9 mg/dL for the 75 mg AR882 plus allopurinol extension-switch arm.

At the 12-month mark, the proportions of patients with complete resolution of any tophus were 50.0% for 75 mg AR882, 12.5% for 50 mg AR882 plus allopurinol, and 36.4% for the 75 mg AR882 plus allopurinol extension-switch arm, according to Dr. Keenan.

Compared with allopurinol alone at 6 months, 75 mg AR882 led to a reduction in total urate crystal volume, and this reduction was sustained at 12 months, he added.

Alone or in combination with allopurinol, AR882 was well tolerated. Gout flares were the most common adverse events, but they declined with continued AR882 treatment, according to Dr. Keenan. Diarrhea, headache, and upper respiratory infections were reported but were of mild or moderate severity.

Again, the take-home message from this study, like the other phase 2 study of a novel URAT1 inhibitor, is that these newer drugs might offer a better benefit-to-risk ratio, particularly in those with refractory disease.

“AR882 may offer improved efficacy and better safety compared to existing therapies in the treatment of patients with gout, including those with both clinically visible and subclinical crystal deposition,” Dr. Keenan said.

Dr. Baraf reported financial relationships with Horizon Therapeutics, Fresenius Kabi, Grünenthal, Olatec, Selecta Biosciences, and Sobi, which provided funding for the trials he discussed. Dr. Kivitz also reported a financial relationship with Sobi, which funded the DISSOLVE trials, along with AbbVie, Amgen, Eli Lilly, Flexion, GlaxoSmithKline, and Sanofi Regeneron. Dr. Ding reported no potential conflicts. The study she discussed was funded by Jiangsu Hengrui Pharmaceuticals. Dr. Keenan is an employee of Arthrosi Therapeutics, which provided funding for the trial he presented.

August 1, 2024 — Editor's note: This article has been updated to reflect the correct number of infusion reactions reported in the 6-month extension phase of the DISSOLVE I trial.

A version of this article appeared on Medscape.com.

VIENNA — Safe and effective options for lowering serum uric acid (sUA) in patients with gout who are refractory to conventional therapies appear to be near, judging from phase 2 and 3 trials that produced positive results at the annual European Congress of Rheumatology.

Reports from the meeting included two phase 2 studies with novel urate anion transporter 1 (URAT1) inhibitors for patients with refractory gout, in addition to extension data from the phase 3 trial program for SEL-212. In all cases, efficacy appeared to be on the same order of currently available drugs with potentially better tolerability, an important unmet need for patients with gout refractory to traditional therapies.
 

12-Month Outcomes With SEL-212

The extension data with SEL-212 follow the 6-month results presented from the DISSOLVE I and II trials at EULAR 2023. Now at 12 months, the benefits have proven to be generally sustained with no new safety signals, according to Herbert S.B. Baraf, MD, The Center for Rheumatology and Bone Research, Wheaton, Maryland.

Arthritis Foundation

SEL-212 is a drug platform involving two components delivered by intravenous infusion once monthly in sequence. The first, SEL-110, consists of tolerogenic nanoparticles containing sirolimus. The second, SEL-037, is the pegylated uricase pegadricase.

On the 1-month dosing schedule, most patients who had responded at 6 months were still responding at 12 months, and both of the two study doses of SEL-212 in the DISSOLVE trials were well tolerated over the extension, Dr. Baraf reported.

On the basis of the data so far, “this will be an effective and well tolerated therapy for refractory gout over a period of at least 12 months,” Dr. Baraf said.

The DISSOLVE I and II trials were identically designed. Patients with refractory gout, defined as failure to normalize sUA or control symptoms with a xanthine oxidase inhibitor, were randomly assigned to receive 0.15 mg SEL-212, 1.0 mg SEL-212, or placebo.

There was a stopping rule for patients who reached a sUA level < 2 mg/dL 1 hour after the infusion.

The primary endpoint was sUA level < 6 mg/dL for at least 80% of the sixth month of the 6-month trial. About 50% of patients on either dose of SEL-212 met this endpoint (vs 4% of those receiving placebo; P < .0001). There was a numerical advantage for the higher dose in both studies.

Patients who completed the 6-month trial were eligible for a 6-month extension, during which they remained on their assigned therapy, including placebo. This phase was also blinded. Patients who met the stopping rule in either the main study or extension did not take the study drug but remained in the study for final analysis.

Of the 265 patients who participated in the main phase of the study, 143 (54%) completed the 6-month extension. Most discontinuations were the result of the stopping rule. Reasons for other patients discontinuing the study included withdrawal of consent in about 10% of each treatment arm and adverse events in 13.8%, 6.8%, and 2.2% of the high-dose, low-dose, and placebo groups, respectively.

At 12 months, when the data from the two trials were pooled, the proportion of patients on therapy and responding remained at about 50% in the high-dose group and 43% in the low-dose group on an intention-to-treat analysis. Relative to the 8% response rate for placebo, the advantage for either dose was highly significant (P < .0001).

In the subgroup of patients with tophi at baseline, representing about half the study group, responses were low at 12 months, whether on high- (41%) or low-dose (43%) SEL-212. The rate of response among placebo patients with baseline tophi was 9%.
 

Safety of SEL-212

The safety over the 6-month extension did not differ substantially from that observed during the first 6 months, according to Dr. Baraf. This was reiterated in more detail by Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania. He delivered a separate safety presentation focused on DISSOLVE I.

Specifically, there were no serious adverse events thought to be related to treatment. Besides gout flares, which affected approximately 27% of patients regardless of active treatment or placebo assignment, the most common adverse effect was hypertriglyceridemia, which was observed in 5.4% of patients on active treatment vs 0% of those receiving placebo. Independent of the treatment arm, less than 5% of patients developed stomatitis or cellulitis during the 6-month extension period.

In the 6-month extension phase, there were no infusion reactions observed within 1 hour after SEL-212 administration and just two overall that occurred with low-dose SEL-212, according to Kivitz.

New Selective URAT1 Inhibitors

The other potential advance in the treatment of refractory gout is coming from newer selective URAT1 inhibitors. According to the lead investigators of two phase 2 trials evaluating a novel URAT1 inhibitor, the urate transporter protein has long been considered the most promising target for gout treatment. As this protein regulates the absorption of uric acid from the renal tubule, it has a direct uric acid–lowering effect. However, the adverse events of current agents, such as probenecid, benzbromarone, and sulfinpyrazone, have created a need for drugs with a better benefit-to-risk ratio.

In one of two multicenter phase 2 studies on refractory gout, the experimental agent ruzinurad was tested as an adjunct to the xanthine oxidase inhibitor febuxostat. In the other, the objective was to evaluate whether the experimental agent AR882 or AR882 plus allopurinol is better than allopurinol alone for reducing tophi at 12 months.
 

Ruzinurad Plus Febuxostat

In the ruzinurad trial, 151 patients with symptomatic gout and elevated sUA (> 6 mg/dL) for at least 6 weeks on stable doses of febuxostat were randomized to receive 5 mg ruzinurad, 10 mg ruzinurad, or placebo. All remained on febuxostat. In the active treatment arms, the starting ruzinurad dose was 1 mg before titrating up to the assigned target.

For the primary endpoint of sUA < 6 mg/dL at 12 weeks, the rates were 56.9%, 53.1%, and 13.7% in the high-dose, low-dose, and placebo groups, respectively (P < .0001 for both ruzinurad arms), reported Huihua Ding, MD, a clinician and researcher at Shanghai Jiao Tong University, Shanghai, China.

“Consistently, subgroup analyses based on baseline eGFR [estimated glomerular filtration rate], sUA, and tophus demonstrated superior effective of ruzinurad plus febuxostat over placebo plus febuxostat,” reported Dr. Ding, who noted that previous clinical studies suggested the potential for synergism between ruzinurad and febuxostat.

The proportion of patients achieving the more rigorous target of < 0.5 mg/dL was also higher with the higher and lower doses of ruzinurad vs placebo (43.1% and 38.8% vs 9.8%, respectively).

The proportion of patients with treatment-emergent side effects did not differ between the three groups. The most common were gout flares, which were observed in 39.2%, 49.0%, and 45.1% in the high-dose, low-dose, and placebo groups, respectively. Most adverse events were mild or moderate, and none led to treatment discontinuation.

The favorable benefit-to-risk profile of ruzinurad was attributed by Dr. Ding to its high relative selectivity and potent inhibition of URAT1, an advantage that might be relevant to avoiding side effects at higher doses.

AR882 in Patients With Tophi

In the trial with AR882, 42 patients with refractory gout and at least one subcutaneous tophus were randomized to receive 75 mg AR882, 50 mg AR882 plus allopurinol, or allopurinol alone. All drugs were taken once daily. Doses of allopurinol of up to 300 mg were permitted.

The changes in the target tophus area and crystal volume at month 6 were compared, and patients who completed this phase were invited into a 6-month extension. In the 6-month extension, 75 mg AR882 was additionally provided to those who had been in the single-agent allopurinol arm. The other arms were unchanged.

Tophi measurements were performed with calipers at regular intervals. Change from baseline in sUA levels was also an efficacy measure, according to Robert Keenan, MD, chief medical officer of Arthrosi Therapeutics, which is developing AR882.

From average baseline sUA levels of > 9 mg/dL, all three treatments reduced sUA levels by an average of at least 4.5 mg by month 3. At month 6, complete resolution of at least one target tophus was observed in 29% of the group randomized to receive 75 mg AR882 alone, 8% of those randomized to receive 50 mg AR882 plus allopurinol, and 8% of those on allopurinol alone.

At month 12, the average sUA levels were 4.3 mg/dL for 75 mg AR882, 3.7 mg/dL for 50 mg AR882 plus allopurinol, and 2.9 mg/dL for the 75 mg AR882 plus allopurinol extension-switch arm.

At the 12-month mark, the proportions of patients with complete resolution of any tophus were 50.0% for 75 mg AR882, 12.5% for 50 mg AR882 plus allopurinol, and 36.4% for the 75 mg AR882 plus allopurinol extension-switch arm, according to Dr. Keenan.

Compared with allopurinol alone at 6 months, 75 mg AR882 led to a reduction in total urate crystal volume, and this reduction was sustained at 12 months, he added.

Alone or in combination with allopurinol, AR882 was well tolerated. Gout flares were the most common adverse events, but they declined with continued AR882 treatment, according to Dr. Keenan. Diarrhea, headache, and upper respiratory infections were reported but were of mild or moderate severity.

Again, the take-home message from this study, like the other phase 2 study of a novel URAT1 inhibitor, is that these newer drugs might offer a better benefit-to-risk ratio, particularly in those with refractory disease.

“AR882 may offer improved efficacy and better safety compared to existing therapies in the treatment of patients with gout, including those with both clinically visible and subclinical crystal deposition,” Dr. Keenan said.

Dr. Baraf reported financial relationships with Horizon Therapeutics, Fresenius Kabi, Grünenthal, Olatec, Selecta Biosciences, and Sobi, which provided funding for the trials he discussed. Dr. Kivitz also reported a financial relationship with Sobi, which funded the DISSOLVE trials, along with AbbVie, Amgen, Eli Lilly, Flexion, GlaxoSmithKline, and Sanofi Regeneron. Dr. Ding reported no potential conflicts. The study she discussed was funded by Jiangsu Hengrui Pharmaceuticals. Dr. Keenan is an employee of Arthrosi Therapeutics, which provided funding for the trial he presented.

August 1, 2024 — Editor's note: This article has been updated to reflect the correct number of infusion reactions reported in the 6-month extension phase of the DISSOLVE I trial.

A version of this article appeared on Medscape.com.

TOPLINE:

A threshold of sustained lupus low disease activity state (LLDAS) or remission for 3 months significantly reduces the risk for damage accrual and flares in patients with systemic lupus erythematosus (SLE), with longer durations offering even greater protection. 

METHODOLOGY:

• This large, prospective, multicenter study aimed to quantify the impact of sustained LLDAS on irreversible damage and flares.
• It included 3449 patients (age, ≥ 18 years; 92.2% women) with SLE from 25 centers across 12 countries, analyzing a total of 37,662 visits.
• Sustained LLDAS or remission was defined as at least two consecutive visits over > 3 months in the respective state.
• The primary outcome measured was the accrual of irreversible organ damage, with flares as a key secondary outcome.

TAKEAWAY:

• During a median follow-up of 2.8 years, 80.2% of patients achieved LLDAS at least once, with 72.7% experiencing at least one episode of sustained LLDAS.
• Sustained LLDAS for > 3 months was linked to a reduced risk for damage accrual (hazard ratio [HR], 0.60; P < .0001).
• Protection from flares also increased with all durations of sustained LLDAS > 3 months (> 3 months: HR, 0.56; P < .0001; > 36 months: HR, 0.17; P < .0001).
• Longer periods of sustained LLDAS or remission were associated with significantly higher degrees of protection.

IN PRACTICE:

“These findings support the use of these treat-to-target endpoints in clinical practice and provide a practical target to aim for in SLE treatment,” the authors wrote. 

SOURCE:

The study was led by Vera Golder, MBBS, Monash University, Clayton, Australia. It was published online in The Lancet Rheumatology. 

LIMITATIONS:

While the study’s large scale and multinational cohort provided robust data, its observational design limited the ability to establish causality. The predominance of Asian ethnicity among the participants may have affected the generalizability of the findings to other populations. Additionally, the median follow-up duration of 2.8 years might not have captured long-term outcomes.

DISCLOSURES:

Some authors declared receiving grants, consulting fees, payments, and honoraria and having other ties with various sources. 

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 appeared on Medscape.com.

TOPLINE:

A threshold of sustained lupus low disease activity state (LLDAS) or remission for 3 months significantly reduces the risk for damage accrual and flares in patients with systemic lupus erythematosus (SLE), with longer durations offering even greater protection. 

METHODOLOGY:

• This large, prospective, multicenter study aimed to quantify the impact of sustained LLDAS on irreversible damage and flares.
• It included 3449 patients (age, ≥ 18 years; 92.2% women) with SLE from 25 centers across 12 countries, analyzing a total of 37,662 visits.
• Sustained LLDAS or remission was defined as at least two consecutive visits over > 3 months in the respective state.
• The primary outcome measured was the accrual of irreversible organ damage, with flares as a key secondary outcome.

TAKEAWAY:

• During a median follow-up of 2.8 years, 80.2% of patients achieved LLDAS at least once, with 72.7% experiencing at least one episode of sustained LLDAS.
• Sustained LLDAS for > 3 months was linked to a reduced risk for damage accrual (hazard ratio [HR], 0.60; P < .0001).
• Protection from flares also increased with all durations of sustained LLDAS > 3 months (> 3 months: HR, 0.56; P < .0001; > 36 months: HR, 0.17; P < .0001).
• Longer periods of sustained LLDAS or remission were associated with significantly higher degrees of protection.

IN PRACTICE:

“These findings support the use of these treat-to-target endpoints in clinical practice and provide a practical target to aim for in SLE treatment,” the authors wrote. 

SOURCE:

The study was led by Vera Golder, MBBS, Monash University, Clayton, Australia. It was published online in The Lancet Rheumatology. 

LIMITATIONS:

While the study’s large scale and multinational cohort provided robust data, its observational design limited the ability to establish causality. The predominance of Asian ethnicity among the participants may have affected the generalizability of the findings to other populations. Additionally, the median follow-up duration of 2.8 years might not have captured long-term outcomes.

DISCLOSURES:

Some authors declared receiving grants, consulting fees, payments, and honoraria and having other ties with various sources. 

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 appeared on Medscape.com.

TOPLINE:

A threshold of sustained lupus low disease activity state (LLDAS) or remission for 3 months significantly reduces the risk for damage accrual and flares in patients with systemic lupus erythematosus (SLE), with longer durations offering even greater protection. 

METHODOLOGY:

• This large, prospective, multicenter study aimed to quantify the impact of sustained LLDAS on irreversible damage and flares.
• It included 3449 patients (age, ≥ 18 years; 92.2% women) with SLE from 25 centers across 12 countries, analyzing a total of 37,662 visits.
• Sustained LLDAS or remission was defined as at least two consecutive visits over > 3 months in the respective state.
• The primary outcome measured was the accrual of irreversible organ damage, with flares as a key secondary outcome.

TAKEAWAY:

• During a median follow-up of 2.8 years, 80.2% of patients achieved LLDAS at least once, with 72.7% experiencing at least one episode of sustained LLDAS.
• Sustained LLDAS for > 3 months was linked to a reduced risk for damage accrual (hazard ratio [HR], 0.60; P < .0001).
• Protection from flares also increased with all durations of sustained LLDAS > 3 months (> 3 months: HR, 0.56; P < .0001; > 36 months: HR, 0.17; P < .0001).
• Longer periods of sustained LLDAS or remission were associated with significantly higher degrees of protection.

IN PRACTICE:

“These findings support the use of these treat-to-target endpoints in clinical practice and provide a practical target to aim for in SLE treatment,” the authors wrote. 

SOURCE:

The study was led by Vera Golder, MBBS, Monash University, Clayton, Australia. It was published online in The Lancet Rheumatology. 

LIMITATIONS:

While the study’s large scale and multinational cohort provided robust data, its observational design limited the ability to establish causality. The predominance of Asian ethnicity among the participants may have affected the generalizability of the findings to other populations. Additionally, the median follow-up duration of 2.8 years might not have captured long-term outcomes.

DISCLOSURES:

Some authors declared receiving grants, consulting fees, payments, and honoraria and having other ties with various sources. 

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 appeared on Medscape.com.

VIENNA — From a dozen or so studies and sessions devoted to the role of chimeric antigen receptor (CAR) T cells in rheumatic diseases at the annual European Congress of Rheumatology, the message was uniformly positive, supporting growing evidence that drugs in this class are heading toward a paradigm shift in refractory rheumatic diseases.

Of the reports, an update from a 15-patient case series with at least 1 year of follow-up provides “the first long-term evidence of safety and efficacy in multiple rheumatic diseases,” according to Georg Schett, MD, PhD, director of rheumatology and immunology, University of Erlangen-Nürnberg, Erlangen, Germany.

Ted Bosworth/Medscape Medical News

The report of high rates of activity and low relative risk of serious adverse events from the same series was published earlier this year in The New England Journal of Medicine when the median follow-up was 15 months. Almost all of the patients have now completed at least 1 year of follow-up and about a third have completed more than 2 years.
 

SLE Is Frequently Targeted in CAR T-Cell Studies

The three rheumatic diseases represented in this series of patients, all of whom had failed multiple previous immune suppressive treatments, were systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SSc). After the autologous T cells were harvested, they were expanded and transfected with the CD19 CAR. The proprietary investigational product, called MB-CART19.1 (Miltenyi Biotec), was administered in a single dose of one million cells per kg bodyweight.

The response rates have been, and continue to be, impressive. For the eight patients with SLE, all achieved the definition of remission in SLE criteria after one dose of treatment. Complete resolution of all major symptom types was achieved after 6 months of follow-up. So far, no patient has relapsed.

For the three patients with IIM, all reached the American College of Rheumatology–EULAR criteria for a major response. All creatine kinase levels had normalized by 3 months. In this group, there was one relapse, which occurred after 18 months of follow-up.

All four patients with SSc achieved a major response on the European Scleroderma Trials and Research (EUSTAR) group activity index. The median reduction from baseline in the EUSTAR score was 4.2 points, and this has been maintained in follow-up to date.
 

Remissions Have Persisted Off All Therapies

These remissions were achieved and maintained after a single dose of CAR T-cell therapy despite discontinuation of all immunosuppressive therapies. With the exception of the single relapse, all remissions have persisted through follow-up to date.

These responses were achieved with manageable side effects, according to Dr. Schett. The most serious adverse event was a grade 4 neutropenia that developed 4 months after receiving CAR T cells. It resolved with granulocyte colony-stimulating factor treatment. Cytokine release syndrome (CRS) has occurred in 10 patients, but it was grade 1 in eight patients and grade 2 in the others. There has been no neurotoxicity.

Almost all patients have experienced an infection during follow-up, but there has been no discernible pattern in relationship to the timing or types of infections. The most common have involved the upper respiratory tract and have been of mild severity, with cases disseminated similarly over early vs late follow-up. There was one case of pneumonia involving antibiotic treatment and a hospital stay, but it resolved.

Dr. Schett acknowledged that safety is a bigger concern in autoimmune diseases, which are often serious but rarely fatal, than in the hematologic malignancies for which CAR T cells were initially tested, but the low rates of serious adverse events in his and other early studies have supported the premise that the risks are not the same.

Asked specifically if CAR T cells can be considered a game changer in autoimmune rheumatic diseases, Dr. Schett was cautious. One reason is the CAR T cells are a complex therapy relative to biologic disease-modifying antirheumatic drugs. He thinks, therefore, that much more data are needed to confirm safety and efficacy. In addition, they are expensive, so it is not yet clear how they will be integrated with other options.

Yet, he thinks the evidence so far suggests a profound effect on the fundamental drivers of autoimmune disease. Their specific mechanism of benefit is still being evaluated, but he considers the clinical responses consistent with a “reset” hypothesis.

After a response, “we are seeing drug-free remissions in some patients as long as they have been followed,” Dr. Schett said. Based on the fact that disease control is being observed off all other therapies, “this only makes sense to me if there is some sort of immunologic reset.”
 

CAR T-Cell Studies in Autoimmune Diseases Are Proliferating

At last count, there were about 40 studies being performed with CAR T cells in various autoimmune diseases, most of which were rheumatologic disorders, according to Dr. Schett. He noted that funding is coming from multinational drug companies, small biotech startups, and investigator-initiated studies at academic centers.

At EULAR, beyond case studies and anecdotal reports, all of the clinical studies were still at the level of phase 1 or 1/2. Consistent with the data presented by Dr. Schett, the drugs have been nearly uniformly effective, with major responses persisting in patients off other therapies. Adverse events have been manageable.

Examples include a phase 1/2 multinational study with the investigational CAR T-cell therapy YTB323 (Novartis), which demonstrated acceptable safety and a strong signal of benefit in six patients with SLE. In this report, CRS was also common, but no case of CRS was more severe than grade 2. There was no neurotoxicity. Infections did occur but were of relatively mild grades and resolved with treatment.

For efficacy in the ongoing follow-up, SLE symptoms as measured with the SLE Disease Activity Index began to abate at about 14 days after the single-infusion treatment. Improvement on the Physician Global Assessment was also observed between 14 and 28 days. C3 and C4 complement levels started to rise at about 28 days. While the responses have correlated with the observed changes in biomarkers of immune function, they have endured through a median follow-up that now exceeds 6 months.
 

Complete B-Cell Depletion Is Followed by Full Recovery

“Pharmacokinetic and pharmacodynamic studies revealed peak expansion of CAR T cells approximately 13-21 days post infusion, which was accompanied by deep B-cell depletion followed by subsequent B-cell recovery,” reported Josefina Cortés-Hernández, MD, PhD, a senior lecturer at Vall d’Hebron Research Institute, Barcelona, Spain.

Dr. Schett had reported the same pattern of expansion followed by a rapid elimination of detectable CAR T cells despite the sustained clinical benefit.

Dr. Cortés-Hernández said that the signal of efficacy in the context of acceptable safety supports an expansion of clinical studies with this CAR T-cell product in SLE and perhaps other autoimmune disorders.

In another early-stage study, patients with SLE who had failed multiple prior lines of therapy have been enrolled in an ongoing study with a compound CAR (cCAR) T cell. This experimental proprietary product (iCAR Bio Therapeutics, Zhongshan, China) targets both the B-cell maturation antigen and CD19, according to Greg Deener, the chief executive officer of iCell Gene Therapeutics, New York City.

Ted Bosworth/Medscape Medical News

cCAR T-Cell Construct Targets Immune Reset

With this construct, the goal is to deplete long-lived plasma cells as well as B cells in order to achieve a more complete humoral reset. While preliminary data from the phase 1 trial were published earlier this year in Annals of the Rheumatic Diseases, Mr. Deener focused his presentation at EULAR 2024 on 12 patients with SLE and lupus nephritis, a severe form of SLE that threatens glomerular structures and can lead to end-stage liver disease.

B cells in the peripheral blood could not be detected within 10 days of the cCAR infusion, and the immunoglobulins IgM and IgA were undetectable by day 42.

However, after B-cell recovery by day 150, “flow cytometry and B-cell receptor sequencing confirmed full humoral reset was achieved,” Mr. Deener said.

The remission has been durable in 11 of the 12 patients after a mean follow-up of 458 days, Mr. Deener reported. He noted that an improvement in renal function has been observed in the majority of patients.

Like others, he reported that treatment has been relatively well tolerated. In this series of patients, there have been no cases of CRS more severe than grade 1.

Overall, the cCAR data in lupus nephritis support the hypothesis that CAR T cells are reprogramming the immune system, according to Mr. Deener.

Combined with a reasonable safety profile, the consistency of benefit from CAR T cells in autoimmune rheumatic diseases is good news, but all of the investigators who spoke at EULAR agreed that there are still many unanswered questions. Not least, it is unclear whether patients can be effectively and safely retreated when and if relapses occur. Even though Dr. Schett did report a response with retreatment following a relapse, he said that there is no conclusion to draw from a single patient.

Yet, the high rates of remissions in patients with disease refractory to other therapeutic options is highly encouraging, particularly with the manageable side effects now reported by multiple investigators using different CAR T-cell products.

“Roughly 100 patients with rheumatic diseases have been treated with CAR T-cells, and we have not seen a high-grade CRS or neurotoxicity,” he said.

Long-term efficacy is less clear. With the first clinical studies in autoimmune diseases initiated in 2021, few patients have been followed for more than 2 years. Even with the high rates of response that will certainly fuel efforts to rapidly bring these treatments forward, long-term data are now the missing piece.
 

Other Case Series Presented at EULAR

Several other abstracts reported on patients with SSc who were treated with CD19-targeting CAR T cells:

Three patients for whom autologous hematopoietic stem cell transplantation was contraindicated or unsuccessful were successfully and safely treated.

Six patients with diffuse and progressive disease achieved stable disease activity without additional immunosuppression for up to 1 year after treatment.

Dr. Schett reported no potential conflicts of interest, and the study he presented was not funded by industry. Dr. Cortés-Hernández reported a financial relationship with Novartis, which funded the study of the CAR T-cell therapy YTB323, as well as with GlaxoSmithKline, which was not involved in the study she presented.  Mr. Deener is an employee of iCell Gene Therapeutics, which provided funding for the trial he presented.

August 7, 2024 — Editor's note: This article was updated with additional disclosure information for Dr. Josefina Cortés-Hernández.

A version of this article appeared on Medscape.com.

VIENNA — From a dozen or so studies and sessions devoted to the role of chimeric antigen receptor (CAR) T cells in rheumatic diseases at the annual European Congress of Rheumatology, the message was uniformly positive, supporting growing evidence that drugs in this class are heading toward a paradigm shift in refractory rheumatic diseases.

Of the reports, an update from a 15-patient case series with at least 1 year of follow-up provides “the first long-term evidence of safety and efficacy in multiple rheumatic diseases,” according to Georg Schett, MD, PhD, director of rheumatology and immunology, University of Erlangen-Nürnberg, Erlangen, Germany.

Ted Bosworth/Medscape Medical News

The report of high rates of activity and low relative risk of serious adverse events from the same series was published earlier this year in The New England Journal of Medicine when the median follow-up was 15 months. Almost all of the patients have now completed at least 1 year of follow-up and about a third have completed more than 2 years.
 

SLE Is Frequently Targeted in CAR T-Cell Studies

The three rheumatic diseases represented in this series of patients, all of whom had failed multiple previous immune suppressive treatments, were systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SSc). After the autologous T cells were harvested, they were expanded and transfected with the CD19 CAR. The proprietary investigational product, called MB-CART19.1 (Miltenyi Biotec), was administered in a single dose of one million cells per kg bodyweight.

The response rates have been, and continue to be, impressive. For the eight patients with SLE, all achieved the definition of remission in SLE criteria after one dose of treatment. Complete resolution of all major symptom types was achieved after 6 months of follow-up. So far, no patient has relapsed.

For the three patients with IIM, all reached the American College of Rheumatology–EULAR criteria for a major response. All creatine kinase levels had normalized by 3 months. In this group, there was one relapse, which occurred after 18 months of follow-up.

All four patients with SSc achieved a major response on the European Scleroderma Trials and Research (EUSTAR) group activity index. The median reduction from baseline in the EUSTAR score was 4.2 points, and this has been maintained in follow-up to date.
 

Remissions Have Persisted Off All Therapies

These remissions were achieved and maintained after a single dose of CAR T-cell therapy despite discontinuation of all immunosuppressive therapies. With the exception of the single relapse, all remissions have persisted through follow-up to date.

These responses were achieved with manageable side effects, according to Dr. Schett. The most serious adverse event was a grade 4 neutropenia that developed 4 months after receiving CAR T cells. It resolved with granulocyte colony-stimulating factor treatment. Cytokine release syndrome (CRS) has occurred in 10 patients, but it was grade 1 in eight patients and grade 2 in the others. There has been no neurotoxicity.

Almost all patients have experienced an infection during follow-up, but there has been no discernible pattern in relationship to the timing or types of infections. The most common have involved the upper respiratory tract and have been of mild severity, with cases disseminated similarly over early vs late follow-up. There was one case of pneumonia involving antibiotic treatment and a hospital stay, but it resolved.

Dr. Schett acknowledged that safety is a bigger concern in autoimmune diseases, which are often serious but rarely fatal, than in the hematologic malignancies for which CAR T cells were initially tested, but the low rates of serious adverse events in his and other early studies have supported the premise that the risks are not the same.

Asked specifically if CAR T cells can be considered a game changer in autoimmune rheumatic diseases, Dr. Schett was cautious. One reason is the CAR T cells are a complex therapy relative to biologic disease-modifying antirheumatic drugs. He thinks, therefore, that much more data are needed to confirm safety and efficacy. In addition, they are expensive, so it is not yet clear how they will be integrated with other options.

Yet, he thinks the evidence so far suggests a profound effect on the fundamental drivers of autoimmune disease. Their specific mechanism of benefit is still being evaluated, but he considers the clinical responses consistent with a “reset” hypothesis.

After a response, “we are seeing drug-free remissions in some patients as long as they have been followed,” Dr. Schett said. Based on the fact that disease control is being observed off all other therapies, “this only makes sense to me if there is some sort of immunologic reset.”
 

CAR T-Cell Studies in Autoimmune Diseases Are Proliferating

At last count, there were about 40 studies being performed with CAR T cells in various autoimmune diseases, most of which were rheumatologic disorders, according to Dr. Schett. He noted that funding is coming from multinational drug companies, small biotech startups, and investigator-initiated studies at academic centers.

At EULAR, beyond case studies and anecdotal reports, all of the clinical studies were still at the level of phase 1 or 1/2. Consistent with the data presented by Dr. Schett, the drugs have been nearly uniformly effective, with major responses persisting in patients off other therapies. Adverse events have been manageable.

Examples include a phase 1/2 multinational study with the investigational CAR T-cell therapy YTB323 (Novartis), which demonstrated acceptable safety and a strong signal of benefit in six patients with SLE. In this report, CRS was also common, but no case of CRS was more severe than grade 2. There was no neurotoxicity. Infections did occur but were of relatively mild grades and resolved with treatment.

For efficacy in the ongoing follow-up, SLE symptoms as measured with the SLE Disease Activity Index began to abate at about 14 days after the single-infusion treatment. Improvement on the Physician Global Assessment was also observed between 14 and 28 days. C3 and C4 complement levels started to rise at about 28 days. While the responses have correlated with the observed changes in biomarkers of immune function, they have endured through a median follow-up that now exceeds 6 months.
 

Complete B-Cell Depletion Is Followed by Full Recovery

“Pharmacokinetic and pharmacodynamic studies revealed peak expansion of CAR T cells approximately 13-21 days post infusion, which was accompanied by deep B-cell depletion followed by subsequent B-cell recovery,” reported Josefina Cortés-Hernández, MD, PhD, a senior lecturer at Vall d’Hebron Research Institute, Barcelona, Spain.

Dr. Schett had reported the same pattern of expansion followed by a rapid elimination of detectable CAR T cells despite the sustained clinical benefit.

Dr. Cortés-Hernández said that the signal of efficacy in the context of acceptable safety supports an expansion of clinical studies with this CAR T-cell product in SLE and perhaps other autoimmune disorders.

In another early-stage study, patients with SLE who had failed multiple prior lines of therapy have been enrolled in an ongoing study with a compound CAR (cCAR) T cell. This experimental proprietary product (iCAR Bio Therapeutics, Zhongshan, China) targets both the B-cell maturation antigen and CD19, according to Greg Deener, the chief executive officer of iCell Gene Therapeutics, New York City.

Ted Bosworth/Medscape Medical News

cCAR T-Cell Construct Targets Immune Reset

With this construct, the goal is to deplete long-lived plasma cells as well as B cells in order to achieve a more complete humoral reset. While preliminary data from the phase 1 trial were published earlier this year in Annals of the Rheumatic Diseases, Mr. Deener focused his presentation at EULAR 2024 on 12 patients with SLE and lupus nephritis, a severe form of SLE that threatens glomerular structures and can lead to end-stage liver disease.

B cells in the peripheral blood could not be detected within 10 days of the cCAR infusion, and the immunoglobulins IgM and IgA were undetectable by day 42.

However, after B-cell recovery by day 150, “flow cytometry and B-cell receptor sequencing confirmed full humoral reset was achieved,” Mr. Deener said.

The remission has been durable in 11 of the 12 patients after a mean follow-up of 458 days, Mr. Deener reported. He noted that an improvement in renal function has been observed in the majority of patients.

Like others, he reported that treatment has been relatively well tolerated. In this series of patients, there have been no cases of CRS more severe than grade 1.

Overall, the cCAR data in lupus nephritis support the hypothesis that CAR T cells are reprogramming the immune system, according to Mr. Deener.

Combined with a reasonable safety profile, the consistency of benefit from CAR T cells in autoimmune rheumatic diseases is good news, but all of the investigators who spoke at EULAR agreed that there are still many unanswered questions. Not least, it is unclear whether patients can be effectively and safely retreated when and if relapses occur. Even though Dr. Schett did report a response with retreatment following a relapse, he said that there is no conclusion to draw from a single patient.

Yet, the high rates of remissions in patients with disease refractory to other therapeutic options is highly encouraging, particularly with the manageable side effects now reported by multiple investigators using different CAR T-cell products.

“Roughly 100 patients with rheumatic diseases have been treated with CAR T-cells, and we have not seen a high-grade CRS or neurotoxicity,” he said.

Long-term efficacy is less clear. With the first clinical studies in autoimmune diseases initiated in 2021, few patients have been followed for more than 2 years. Even with the high rates of response that will certainly fuel efforts to rapidly bring these treatments forward, long-term data are now the missing piece.
 

Other Case Series Presented at EULAR

Several other abstracts reported on patients with SSc who were treated with CD19-targeting CAR T cells:

Three patients for whom autologous hematopoietic stem cell transplantation was contraindicated or unsuccessful were successfully and safely treated.

Six patients with diffuse and progressive disease achieved stable disease activity without additional immunosuppression for up to 1 year after treatment.

Dr. Schett reported no potential conflicts of interest, and the study he presented was not funded by industry. Dr. Cortés-Hernández reported a financial relationship with Novartis, which funded the study of the CAR T-cell therapy YTB323, as well as with GlaxoSmithKline, which was not involved in the study she presented.  Mr. Deener is an employee of iCell Gene Therapeutics, which provided funding for the trial he presented.

August 7, 2024 — Editor's note: This article was updated with additional disclosure information for Dr. Josefina Cortés-Hernández.

A version of this article appeared on Medscape.com.

VIENNA — From a dozen or so studies and sessions devoted to the role of chimeric antigen receptor (CAR) T cells in rheumatic diseases at the annual European Congress of Rheumatology, the message was uniformly positive, supporting growing evidence that drugs in this class are heading toward a paradigm shift in refractory rheumatic diseases.

Of the reports, an update from a 15-patient case series with at least 1 year of follow-up provides “the first long-term evidence of safety and efficacy in multiple rheumatic diseases,” according to Georg Schett, MD, PhD, director of rheumatology and immunology, University of Erlangen-Nürnberg, Erlangen, Germany.

Ted Bosworth/Medscape Medical News

The report of high rates of activity and low relative risk of serious adverse events from the same series was published earlier this year in The New England Journal of Medicine when the median follow-up was 15 months. Almost all of the patients have now completed at least 1 year of follow-up and about a third have completed more than 2 years.
 

SLE Is Frequently Targeted in CAR T-Cell Studies

The three rheumatic diseases represented in this series of patients, all of whom had failed multiple previous immune suppressive treatments, were systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SSc). After the autologous T cells were harvested, they were expanded and transfected with the CD19 CAR. The proprietary investigational product, called MB-CART19.1 (Miltenyi Biotec), was administered in a single dose of one million cells per kg bodyweight.

The response rates have been, and continue to be, impressive. For the eight patients with SLE, all achieved the definition of remission in SLE criteria after one dose of treatment. Complete resolution of all major symptom types was achieved after 6 months of follow-up. So far, no patient has relapsed.

For the three patients with IIM, all reached the American College of Rheumatology–EULAR criteria for a major response. All creatine kinase levels had normalized by 3 months. In this group, there was one relapse, which occurred after 18 months of follow-up.

All four patients with SSc achieved a major response on the European Scleroderma Trials and Research (EUSTAR) group activity index. The median reduction from baseline in the EUSTAR score was 4.2 points, and this has been maintained in follow-up to date.
 

Remissions Have Persisted Off All Therapies

These remissions were achieved and maintained after a single dose of CAR T-cell therapy despite discontinuation of all immunosuppressive therapies. With the exception of the single relapse, all remissions have persisted through follow-up to date.

These responses were achieved with manageable side effects, according to Dr. Schett. The most serious adverse event was a grade 4 neutropenia that developed 4 months after receiving CAR T cells. It resolved with granulocyte colony-stimulating factor treatment. Cytokine release syndrome (CRS) has occurred in 10 patients, but it was grade 1 in eight patients and grade 2 in the others. There has been no neurotoxicity.

Almost all patients have experienced an infection during follow-up, but there has been no discernible pattern in relationship to the timing or types of infections. The most common have involved the upper respiratory tract and have been of mild severity, with cases disseminated similarly over early vs late follow-up. There was one case of pneumonia involving antibiotic treatment and a hospital stay, but it resolved.

Dr. Schett acknowledged that safety is a bigger concern in autoimmune diseases, which are often serious but rarely fatal, than in the hematologic malignancies for which CAR T cells were initially tested, but the low rates of serious adverse events in his and other early studies have supported the premise that the risks are not the same.

Asked specifically if CAR T cells can be considered a game changer in autoimmune rheumatic diseases, Dr. Schett was cautious. One reason is the CAR T cells are a complex therapy relative to biologic disease-modifying antirheumatic drugs. He thinks, therefore, that much more data are needed to confirm safety and efficacy. In addition, they are expensive, so it is not yet clear how they will be integrated with other options.

Yet, he thinks the evidence so far suggests a profound effect on the fundamental drivers of autoimmune disease. Their specific mechanism of benefit is still being evaluated, but he considers the clinical responses consistent with a “reset” hypothesis.

After a response, “we are seeing drug-free remissions in some patients as long as they have been followed,” Dr. Schett said. Based on the fact that disease control is being observed off all other therapies, “this only makes sense to me if there is some sort of immunologic reset.”
 

CAR T-Cell Studies in Autoimmune Diseases Are Proliferating

At last count, there were about 40 studies being performed with CAR T cells in various autoimmune diseases, most of which were rheumatologic disorders, according to Dr. Schett. He noted that funding is coming from multinational drug companies, small biotech startups, and investigator-initiated studies at academic centers.

At EULAR, beyond case studies and anecdotal reports, all of the clinical studies were still at the level of phase 1 or 1/2. Consistent with the data presented by Dr. Schett, the drugs have been nearly uniformly effective, with major responses persisting in patients off other therapies. Adverse events have been manageable.

Examples include a phase 1/2 multinational study with the investigational CAR T-cell therapy YTB323 (Novartis), which demonstrated acceptable safety and a strong signal of benefit in six patients with SLE. In this report, CRS was also common, but no case of CRS was more severe than grade 2. There was no neurotoxicity. Infections did occur but were of relatively mild grades and resolved with treatment.

For efficacy in the ongoing follow-up, SLE symptoms as measured with the SLE Disease Activity Index began to abate at about 14 days after the single-infusion treatment. Improvement on the Physician Global Assessment was also observed between 14 and 28 days. C3 and C4 complement levels started to rise at about 28 days. While the responses have correlated with the observed changes in biomarkers of immune function, they have endured through a median follow-up that now exceeds 6 months.
 

Complete B-Cell Depletion Is Followed by Full Recovery

“Pharmacokinetic and pharmacodynamic studies revealed peak expansion of CAR T cells approximately 13-21 days post infusion, which was accompanied by deep B-cell depletion followed by subsequent B-cell recovery,” reported Josefina Cortés-Hernández, MD, PhD, a senior lecturer at Vall d’Hebron Research Institute, Barcelona, Spain.

Dr. Schett had reported the same pattern of expansion followed by a rapid elimination of detectable CAR T cells despite the sustained clinical benefit.

Dr. Cortés-Hernández said that the signal of efficacy in the context of acceptable safety supports an expansion of clinical studies with this CAR T-cell product in SLE and perhaps other autoimmune disorders.

In another early-stage study, patients with SLE who had failed multiple prior lines of therapy have been enrolled in an ongoing study with a compound CAR (cCAR) T cell. This experimental proprietary product (iCAR Bio Therapeutics, Zhongshan, China) targets both the B-cell maturation antigen and CD19, according to Greg Deener, the chief executive officer of iCell Gene Therapeutics, New York City.

Ted Bosworth/Medscape Medical News

cCAR T-Cell Construct Targets Immune Reset

With this construct, the goal is to deplete long-lived plasma cells as well as B cells in order to achieve a more complete humoral reset. While preliminary data from the phase 1 trial were published earlier this year in Annals of the Rheumatic Diseases, Mr. Deener focused his presentation at EULAR 2024 on 12 patients with SLE and lupus nephritis, a severe form of SLE that threatens glomerular structures and can lead to end-stage liver disease.

B cells in the peripheral blood could not be detected within 10 days of the cCAR infusion, and the immunoglobulins IgM and IgA were undetectable by day 42.

However, after B-cell recovery by day 150, “flow cytometry and B-cell receptor sequencing confirmed full humoral reset was achieved,” Mr. Deener said.

The remission has been durable in 11 of the 12 patients after a mean follow-up of 458 days, Mr. Deener reported. He noted that an improvement in renal function has been observed in the majority of patients.

Like others, he reported that treatment has been relatively well tolerated. In this series of patients, there have been no cases of CRS more severe than grade 1.

Overall, the cCAR data in lupus nephritis support the hypothesis that CAR T cells are reprogramming the immune system, according to Mr. Deener.

Combined with a reasonable safety profile, the consistency of benefit from CAR T cells in autoimmune rheumatic diseases is good news, but all of the investigators who spoke at EULAR agreed that there are still many unanswered questions. Not least, it is unclear whether patients can be effectively and safely retreated when and if relapses occur. Even though Dr. Schett did report a response with retreatment following a relapse, he said that there is no conclusion to draw from a single patient.

Yet, the high rates of remissions in patients with disease refractory to other therapeutic options is highly encouraging, particularly with the manageable side effects now reported by multiple investigators using different CAR T-cell products.

“Roughly 100 patients with rheumatic diseases have been treated with CAR T-cells, and we have not seen a high-grade CRS or neurotoxicity,” he said.

Long-term efficacy is less clear. With the first clinical studies in autoimmune diseases initiated in 2021, few patients have been followed for more than 2 years. Even with the high rates of response that will certainly fuel efforts to rapidly bring these treatments forward, long-term data are now the missing piece.
 

Other Case Series Presented at EULAR

Several other abstracts reported on patients with SSc who were treated with CD19-targeting CAR T cells:

Three patients for whom autologous hematopoietic stem cell transplantation was contraindicated or unsuccessful were successfully and safely treated.

Six patients with diffuse and progressive disease achieved stable disease activity without additional immunosuppression for up to 1 year after treatment.

Dr. Schett reported no potential conflicts of interest, and the study he presented was not funded by industry. Dr. Cortés-Hernández reported a financial relationship with Novartis, which funded the study of the CAR T-cell therapy YTB323, as well as with GlaxoSmithKline, which was not involved in the study she presented.  Mr. Deener is an employee of iCell Gene Therapeutics, which provided funding for the trial he presented.

August 7, 2024 — Editor's note: This article was updated with additional disclosure information for Dr. Josefina Cortés-Hernández.

A version of this article appeared on Medscape.com.

TOPLINE:

Long-term, supervised exercise therapy significantly improves the functional ability and quality of life in patients with axial spondyloarthritis (axSpA) and severe functional limitations.
 

METHODOLOGY:

• This 52-week study evaluated the effectiveness of personalized exercise therapy in adults with axSpA and severe functional limitations.
• Overall, 214 participants were randomly allocated to either a personalized exercise therapy regimen or usual care for 52 weeks.
• The supervised exercise therapy regimen consisted of various exercises, patient education, goal setting, and physical activity promotion for up to 64 sessions.
• The primary endpoint was a change in the highest-ranked Patient-Specific Complaints Numeric Rating Scale (PSC1) score at 52 weeks, and secondary endpoints included measures of physical functioning and quality of life.

TAKEAWAY:

• At 52 weeks, the exercise group showed a greater improvement in the primary outcome measure (PSC1) than the usual-care group, with a mean difference of −1.8 (95% CI, −2.4 to −1.2).
• Exercise therapy led to significant improvements in functional disability and physical quality of life.
• No serious adverse events related to the intervention were reported, highlighting the safety of exercise therapy.

IN PRACTICE:

“If guided by a trained physical therapist applying a personalized approach, people with severe functional limitations due to an unfavorable course or comorbidities can be just as responsive to training as people with axSpA without severe limitations,” the authors wrote.
 

SOURCE:

The study was led by Maria A.T. van Wissen, Department of Orthopaedics, Leiden University Medical Center, Leiden, the Netherlands, and published online in Rheumatology.
 

LIMITATIONS:

The study’s reliance on self-reported data for axSpA treatment-related medication may have compromised accuracy. Additionally, the lack of information on medication changes during the study period could affect result interpretation.
 

DISCLOSURES:

The study was supported by grants from the Netherlands Organization for Health Research and Development; Ministry of Health, Welfare and Sport; Royal Dutch Society for Physical Therapy; and Dutch Arthritis Society. The authors declared no conflicts of interest.

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 appeared on Medscape.com.

TOPLINE:

Long-term, supervised exercise therapy significantly improves the functional ability and quality of life in patients with axial spondyloarthritis (axSpA) and severe functional limitations.
 

METHODOLOGY:

• This 52-week study evaluated the effectiveness of personalized exercise therapy in adults with axSpA and severe functional limitations.
• Overall, 214 participants were randomly allocated to either a personalized exercise therapy regimen or usual care for 52 weeks.
• The supervised exercise therapy regimen consisted of various exercises, patient education, goal setting, and physical activity promotion for up to 64 sessions.
• The primary endpoint was a change in the highest-ranked Patient-Specific Complaints Numeric Rating Scale (PSC1) score at 52 weeks, and secondary endpoints included measures of physical functioning and quality of life.

TAKEAWAY:

• At 52 weeks, the exercise group showed a greater improvement in the primary outcome measure (PSC1) than the usual-care group, with a mean difference of −1.8 (95% CI, −2.4 to −1.2).
• Exercise therapy led to significant improvements in functional disability and physical quality of life.
• No serious adverse events related to the intervention were reported, highlighting the safety of exercise therapy.

IN PRACTICE:

“If guided by a trained physical therapist applying a personalized approach, people with severe functional limitations due to an unfavorable course or comorbidities can be just as responsive to training as people with axSpA without severe limitations,” the authors wrote.
 

SOURCE:

The study was led by Maria A.T. van Wissen, Department of Orthopaedics, Leiden University Medical Center, Leiden, the Netherlands, and published online in Rheumatology.
 

LIMITATIONS:

The study’s reliance on self-reported data for axSpA treatment-related medication may have compromised accuracy. Additionally, the lack of information on medication changes during the study period could affect result interpretation.
 

DISCLOSURES:

The study was supported by grants from the Netherlands Organization for Health Research and Development; Ministry of Health, Welfare and Sport; Royal Dutch Society for Physical Therapy; and Dutch Arthritis Society. The authors declared no conflicts of interest.

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 appeared on Medscape.com.

TOPLINE:

Long-term, supervised exercise therapy significantly improves the functional ability and quality of life in patients with axial spondyloarthritis (axSpA) and severe functional limitations.
 

METHODOLOGY:

• This 52-week study evaluated the effectiveness of personalized exercise therapy in adults with axSpA and severe functional limitations.
• Overall, 214 participants were randomly allocated to either a personalized exercise therapy regimen or usual care for 52 weeks.
• The supervised exercise therapy regimen consisted of various exercises, patient education, goal setting, and physical activity promotion for up to 64 sessions.
• The primary endpoint was a change in the highest-ranked Patient-Specific Complaints Numeric Rating Scale (PSC1) score at 52 weeks, and secondary endpoints included measures of physical functioning and quality of life.

TAKEAWAY:

• At 52 weeks, the exercise group showed a greater improvement in the primary outcome measure (PSC1) than the usual-care group, with a mean difference of −1.8 (95% CI, −2.4 to −1.2).
• Exercise therapy led to significant improvements in functional disability and physical quality of life.
• No serious adverse events related to the intervention were reported, highlighting the safety of exercise therapy.

IN PRACTICE:

“If guided by a trained physical therapist applying a personalized approach, people with severe functional limitations due to an unfavorable course or comorbidities can be just as responsive to training as people with axSpA without severe limitations,” the authors wrote.
 

SOURCE:

The study was led by Maria A.T. van Wissen, Department of Orthopaedics, Leiden University Medical Center, Leiden, the Netherlands, and published online in Rheumatology.
 

LIMITATIONS:

The study’s reliance on self-reported data for axSpA treatment-related medication may have compromised accuracy. Additionally, the lack of information on medication changes during the study period could affect result interpretation.
 

DISCLOSURES:

The study was supported by grants from the Netherlands Organization for Health Research and Development; Ministry of Health, Welfare and Sport; Royal Dutch Society for Physical Therapy; and Dutch Arthritis Society. The authors declared no conflicts of interest.

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 appeared on Medscape.com.

Mount Sinai Health System in New York City is forcing part-time physicians to sign employment contracts that violate their labor rights, according to a June 2024 complaint by the National Labor Relations Board (NLRB). 

The complaint stems from no-poaching and confidentiality clauses in the agreements required as a condition of employment, NLRB officials alleged.

The contracts state that, for 1 year following termination, part-time physicians may not recruit, solicit, or induce to terminate the employment of any hospital system employee or independent contractor, according to a copy of the terms included in NLRB’s June 18 complaint. 

By requiring the agreements, NLRB officials claimed, Mount Sinai is “interfering with, restraining, and coercing employees” in violation of the National Labor Relations Act. The health system’s “unfair labor practices” affects commerce as outlined under the law, according to the NLRB. The Act bans employers from burdening or obstructing commerce or the free flow of commerce.

Mount Sinai did not respond to requests for comment.

The NLRB’s complaint follows a landmark decision by the Federal Trade Commission (FTC) to ban noncompete agreements nationwide. In April 2024, the FTC voted to prohibit noncompetes indefinitely in an effort to protect workers.

“Noncompete clauses keep wages low, suppress new ideas, and rob the American economy of dynamism, including from the more than 8500 new startups that would be created a year once noncompetes are banned,” FTC Chair Lina M. Khan said in a statement. “The FTC’s final rule to ban noncompetes will ensure Americans have the freedom to pursue a new job, start a new business, or bring a new idea to market.”

Business groups and agencies have since sued to challenge against the ban, including the Chamber of Commerce. The Chamber and other business groups argue that noncompete agreements are important for companies to protect trade secrets, shield recruiting investments, and hide confidential information. The lawsuits are ongoing. 
 

A Physician Blows the Whistle

An anonymous physician first alerted the NLRB to the contract language in November 2023. The doctor was required the sign the hospital system’s agreement for part-time physicians. The complaint does not say if the employee is still employed by the hospital system. 

To remedy the unfair labor practices alleged, the NLRB seeks an order requiring the health system to rescind the contract language, stop any actions against current or former employees to enforce the provisions, and make whole any employees who suffered financial losses related to the contract terms. 

The allegation against Mount Sinai is among a rising number of grievances filed with the NLRB that claim unfair labor practices. During the first 6 months of fiscal year 2024, unfair labor practice charges filed across the NLRB’s field offices increased 7% — from 9612 in 2023 to 10,278 in 2024, according to a news release. 

NLRB, meanwhile has been cracking down on anticompetitive labor practices and confidentiality provisions that prevent employees from speaking out. 

In a February 2023 decision for instance, NLRB ruled that an employer violates the National Labor Relations Act by offering severance agreements to workers that include restrictive confidentiality and nondisparagement terms. In 2022, the NLRB and the Federal Trade Commission forged a partnership to more widely combat unfair, anticompetitive, and deceptive business practices. 

“Noncompete provisions reasonably tend to chill employees in the exercise of Section 7 rights when the provisions could reasonably be construed by employees to deny them the ability to quit or change jobs by cutting off their access to other employment opportunities that they are qualified for,” NLRB General Counsel Jennifer Abruzzo said in a 2023 release. 

Ms. Abruzzo stressed in a memo that NLR Act is committed to an interagency approach to restrictions on the exercise of employee rights, “including limits to workers’ job mobility, information sharing, and referrals to other agencies.” 

Mount Sinai Health System must respond to the NLRB’s complaint by July 16, and an administrative law judge is scheduled to hear the case on September 24.

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

Mount Sinai Health System in New York City is forcing part-time physicians to sign employment contracts that violate their labor rights, according to a June 2024 complaint by the National Labor Relations Board (NLRB). 

The complaint stems from no-poaching and confidentiality clauses in the agreements required as a condition of employment, NLRB officials alleged.

The contracts state that, for 1 year following termination, part-time physicians may not recruit, solicit, or induce to terminate the employment of any hospital system employee or independent contractor, according to a copy of the terms included in NLRB’s June 18 complaint. 

By requiring the agreements, NLRB officials claimed, Mount Sinai is “interfering with, restraining, and coercing employees” in violation of the National Labor Relations Act. The health system’s “unfair labor practices” affects commerce as outlined under the law, according to the NLRB. The Act bans employers from burdening or obstructing commerce or the free flow of commerce.

Mount Sinai did not respond to requests for comment.

The NLRB’s complaint follows a landmark decision by the Federal Trade Commission (FTC) to ban noncompete agreements nationwide. In April 2024, the FTC voted to prohibit noncompetes indefinitely in an effort to protect workers.

“Noncompete clauses keep wages low, suppress new ideas, and rob the American economy of dynamism, including from the more than 8500 new startups that would be created a year once noncompetes are banned,” FTC Chair Lina M. Khan said in a statement. “The FTC’s final rule to ban noncompetes will ensure Americans have the freedom to pursue a new job, start a new business, or bring a new idea to market.”

Business groups and agencies have since sued to challenge against the ban, including the Chamber of Commerce. The Chamber and other business groups argue that noncompete agreements are important for companies to protect trade secrets, shield recruiting investments, and hide confidential information. The lawsuits are ongoing. 
 

A Physician Blows the Whistle

An anonymous physician first alerted the NLRB to the contract language in November 2023. The doctor was required the sign the hospital system’s agreement for part-time physicians. The complaint does not say if the employee is still employed by the hospital system. 

To remedy the unfair labor practices alleged, the NLRB seeks an order requiring the health system to rescind the contract language, stop any actions against current or former employees to enforce the provisions, and make whole any employees who suffered financial losses related to the contract terms. 

The allegation against Mount Sinai is among a rising number of grievances filed with the NLRB that claim unfair labor practices. During the first 6 months of fiscal year 2024, unfair labor practice charges filed across the NLRB’s field offices increased 7% — from 9612 in 2023 to 10,278 in 2024, according to a news release. 

NLRB, meanwhile has been cracking down on anticompetitive labor practices and confidentiality provisions that prevent employees from speaking out. 

In a February 2023 decision for instance, NLRB ruled that an employer violates the National Labor Relations Act by offering severance agreements to workers that include restrictive confidentiality and nondisparagement terms. In 2022, the NLRB and the Federal Trade Commission forged a partnership to more widely combat unfair, anticompetitive, and deceptive business practices. 

“Noncompete provisions reasonably tend to chill employees in the exercise of Section 7 rights when the provisions could reasonably be construed by employees to deny them the ability to quit or change jobs by cutting off their access to other employment opportunities that they are qualified for,” NLRB General Counsel Jennifer Abruzzo said in a 2023 release. 

Ms. Abruzzo stressed in a memo that NLR Act is committed to an interagency approach to restrictions on the exercise of employee rights, “including limits to workers’ job mobility, information sharing, and referrals to other agencies.” 

Mount Sinai Health System must respond to the NLRB’s complaint by July 16, and an administrative law judge is scheduled to hear the case on September 24.

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

Mount Sinai Health System in New York City is forcing part-time physicians to sign employment contracts that violate their labor rights, according to a June 2024 complaint by the National Labor Relations Board (NLRB). 

The complaint stems from no-poaching and confidentiality clauses in the agreements required as a condition of employment, NLRB officials alleged.

The contracts state that, for 1 year following termination, part-time physicians may not recruit, solicit, or induce to terminate the employment of any hospital system employee or independent contractor, according to a copy of the terms included in NLRB’s June 18 complaint. 

By requiring the agreements, NLRB officials claimed, Mount Sinai is “interfering with, restraining, and coercing employees” in violation of the National Labor Relations Act. The health system’s “unfair labor practices” affects commerce as outlined under the law, according to the NLRB. The Act bans employers from burdening or obstructing commerce or the free flow of commerce.

Mount Sinai did not respond to requests for comment.

The NLRB’s complaint follows a landmark decision by the Federal Trade Commission (FTC) to ban noncompete agreements nationwide. In April 2024, the FTC voted to prohibit noncompetes indefinitely in an effort to protect workers.

“Noncompete clauses keep wages low, suppress new ideas, and rob the American economy of dynamism, including from the more than 8500 new startups that would be created a year once noncompetes are banned,” FTC Chair Lina M. Khan said in a statement. “The FTC’s final rule to ban noncompetes will ensure Americans have the freedom to pursue a new job, start a new business, or bring a new idea to market.”

Business groups and agencies have since sued to challenge against the ban, including the Chamber of Commerce. The Chamber and other business groups argue that noncompete agreements are important for companies to protect trade secrets, shield recruiting investments, and hide confidential information. The lawsuits are ongoing. 
 

A Physician Blows the Whistle

An anonymous physician first alerted the NLRB to the contract language in November 2023. The doctor was required the sign the hospital system’s agreement for part-time physicians. The complaint does not say if the employee is still employed by the hospital system. 

To remedy the unfair labor practices alleged, the NLRB seeks an order requiring the health system to rescind the contract language, stop any actions against current or former employees to enforce the provisions, and make whole any employees who suffered financial losses related to the contract terms. 

The allegation against Mount Sinai is among a rising number of grievances filed with the NLRB that claim unfair labor practices. During the first 6 months of fiscal year 2024, unfair labor practice charges filed across the NLRB’s field offices increased 7% — from 9612 in 2023 to 10,278 in 2024, according to a news release. 

NLRB, meanwhile has been cracking down on anticompetitive labor practices and confidentiality provisions that prevent employees from speaking out. 

In a February 2023 decision for instance, NLRB ruled that an employer violates the National Labor Relations Act by offering severance agreements to workers that include restrictive confidentiality and nondisparagement terms. In 2022, the NLRB and the Federal Trade Commission forged a partnership to more widely combat unfair, anticompetitive, and deceptive business practices. 

“Noncompete provisions reasonably tend to chill employees in the exercise of Section 7 rights when the provisions could reasonably be construed by employees to deny them the ability to quit or change jobs by cutting off their access to other employment opportunities that they are qualified for,” NLRB General Counsel Jennifer Abruzzo said in a 2023 release. 

Ms. Abruzzo stressed in a memo that NLR Act is committed to an interagency approach to restrictions on the exercise of employee rights, “including limits to workers’ job mobility, information sharing, and referrals to other agencies.” 

Mount Sinai Health System must respond to the NLRB’s complaint by July 16, and an administrative law judge is scheduled to hear the case on September 24.

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

On any given day, oncologist Mark Lewis, MD, feels like he’s seesawing between two eras of technology. 

One minute, he’s working on sequencing a tumor genome. The next, he’s sifting through pages of disorganized data from a device that has been around for decades: the fax machine. 

“If two doctors’ offices aren’t on the same electronic medical record, one of the main ways to transfer records is still by fax,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “I can go from cutting-edge innovation to relying on, at best, 1980s information technology. It just boggles my mind.”

Dr. Lewis, who has posted about his frustration with fax machines, is far from alone. Oncologists are among the many specialists across the country at the mercy of telecopiers. 

According to a 2021 report by the Office of the National Coordinator for Health Information Technology, fax and mail continue to be the most common methods for hospitals and health systems to exchange care record summaries. In 2019, nearly 8 in 10 hospitals used mail or fax to send and receive health information, the report found. 

Fax machines are still commonplace across the healthcare spectrum, said Robert Havasy, MS, senior director for informatics strategy at the Healthcare Information and Management Systems Society (HIMSS). Inertia, cost, and more pressing priorities for hospitals and medical institutions contribute to the technology sticking around, he explained. 

“Post-COVID, my guess is we’re still at over 50% of healthcare practices using fax for some reason, on a daily basis,” Mr. Havasy said in an interview. “A lot of hospitals just don’t have the time, the money, or the staff to fix that problem because there’s always something a little higher up the priority chain they need to focus on.” 

If, for instance, “you’re going to do a process redesign to reduce hospital total acquired infections, your fax machine replacement might be 10th or 12th on the list. It just never gets up to 1 or 2 because it’s ‘not that much of a problem,’ ” he added.

Or is it?

Administrators may not view fax machines as a top concern, but clinicians who deal with the machines daily see it differently. 

“What worries me is we’re taking records out of an electronic storehouse [and] converting them to a paper medium,” Dr. Lewis said. “And then we are scanning into another electronic storehouse. The more steps, the more can be lost.”

And when information is lost, patient care can be compromised. 

Slower Workflows, Care Concerns

Although there are no published data on fax machine use in oncology specifically, this outdated technology does come into play in a variety of ways along the cancer care continuum. 

Radiation oncologist David R. Penberthy, MD, said patients often seek his cancer center’s expertise for second opinions, and that requires collecting patient records from many different practices. 

“Ideally, it would come electronically, but sometimes it does come by fax,” said Dr. Penberthy, program director of radiation oncology at the University of Virginia School of Medicine in Charlottesville. “The quality of the fax is not always the best. Sometimes it’s literally a fax of a fax. You’re reading something that’s very difficult to read.” 

Orders for new tests are also typically sent and received via fax temporarily while IT teams work to integrate them into the electronic health record (EHR), Dr. Penberthy said. 

Insurers and third-party laboratories often send test results back by fax as well.

“Even if I haven’t actually sent my patient out of our institution, this crucial result may only be entered back into the record as a scanned document from a fax, which is not great because it can get lost in the other results that are reported electronically,” Dr. Lewis said. The risk here is that an ordering physician won’t see these results, which can lead to delayed or overlooked care for patients, he explained.

“To me, it’s like a blind spot,” Dr. Lewis said. “Every time we use a fax, I see it actually as an opportunity for oversight and missed opportunity to collect data.”

Dr. Penberthy said faxing can slow things down at his practice, particularly if he faxes a document to another office but receives no confirmation and has to track down what happened. 

As for cybersecurity, data that are in transit during faxing are generally considered secure and compliant with the Health Insurance Portability and Accountability Act (HIPAA), said Mr. Havasy of HIMSS. However, the Privacy Rule also requires that data remain secure while at rest, which isn’t always possible, he added. 

“That’s where faxes fall down, because generally fax machines are in public, if you will, or open areas in a hospital,” he said. “They just sit on a desk. I don’t know that the next nurse who comes up and looks through that stack was the nurse who was treating the patient.” 

Important decisions or results can also be missed when sent by fax, creating headaches for physicians and care problems for patients. 

Dr. Lewis recently experienced an insurance-related fax mishap over Memorial Day weekend. He believed his patient had access to the antinausea medication he had prescribed. When Dr. Lewis happened to check the fax machine over the weekend, he found a coverage denial for the medication from the insurer but, at that point, had no recourse to appeal because it was a long holiday weekend. 

“Had the denial been sent by an electronic means that was quicker and more readily available, it would have been possible to appeal before the holiday weekend,” he said. 

Hematologist Aaron Goodman, MD, encountered a similar problem after an insurer denied coverage of an expensive cancer drug for a patient and faxed over its reason for the denial. Dr. Goodman was not directly notified that the information arrived and didn’t learn about the denial for a week, he said. 

“There’s no ‘ding’ in my inbox if something is faxed over and scanned,” said Dr. Goodman, associate professor of medicine at UC San Diego Health. “Once I realized it was denied, I was able to rectify it, but it wasted a week of a patient not getting a drug that I felt would be beneficial for them.”

Broader Health Policy Impacts

The use of outdated technology, such as fax machines, also creates ripple effects that burden the health system, health policy experts say. 

Duplicate testing and unnecessary care are top impacts, said Julia Adler-Milstein, PhD, professor of medicine and chief of the division of clinical informatics and digital transformation at the University of California, San Francisco.

Studies show that 20%-30% of the $65 billion spent annually on lab tests is used on unnecessary duplicate tests, and another estimated $30 billion is spent each year on unnecessary duplicate medical imaging. These duplicate tests may be mitigated if hospitals adopt certified EHR technology, research shows.

Still, without EHR interoperability between institutions, new providers may be unaware that tests or past labs for patients exist, leading to repeat tests, said Dr. Adler-Milstein, who researches health IT policy with a focus on EHRs. Patients can sometimes fill in the gaps, but not always. 

“Fax machines only help close information gaps if the clinician is aware of where to seek out the information and there is someone at the other organization to locate and transmit the information in a timely manner,” Dr. Adler-Milstein said. 

Old technology and poor interoperability also greatly affect data collection for disease surveillance and monitoring, said Janet Hamilton, MPH, executive director for the Council of State and Territorial Epidemiologists. This issue was keenly demonstrated during the pandemic, Ms. Hamilton said. 

“It was tragic, quite honestly,” she said. “There was such an immense amount of data that needed to be moved quickly, and that’s when computers are at their best.”

But, she said, “we didn’t have the level of systems in place to do it well.”

Specifically, the lack of electronic case reporting in place during the pandemic — where diagnoses are documented in the record and then immediately sent to the public health system — led to reports that were delayed, not made, or had missing or incomplete information, such as patients’ race and ethnicity or other health conditions, Ms. Hamilton said. 

Incomplete or missing data hampered the ability of public health officials and researchers to understand how the virus might affect different patients.

“If you had a chronic condition like cancer, you were less likely to have a positive outcome with COVID,” Ms. Hamilton said. “But because electronic case reporting was not in place, we didn’t get some of those additional pieces of information. We didn’t have people’s underlying oncology status to then say, ‘Here are individuals with these types of characteristics, and these are the things that happen if they also have a cancer.’” 

Slow, but Steady, Improvements

Efforts at the state and federal levels have targeted improved health information exchange, but progress takes time, Dr. Adler-Milstein said.

Most states have some form of health information exchange, such as statewide exchanges, regional health information organizations, or clinical data registries. Maryland is often held up as a notable example for its health information exchange, Dr. Adler-Milstein noted.

According to Maryland law, all hospitals under the jurisdiction of the Maryland Health Care Commission are required to electronically connect to the state-designated health information exchange. In 2012, Maryland became the first state to connect all its 46 acute care hospitals in the sharing of real-time data. 

The Health Information Technology for Economic and Clinical Health (HITECH) Act provided federal-enhanced Medicaid matching funds to states through 2021 to support efforts to advance electronic exchange. Nearly all states used these funds, and most have identified other sources to sustain the efforts, according to a recent US Government Accountability Office (GAO) report. However, GAO found that small and rural providers are less likely to have the financial and technological resources to participate in or maintain electronic exchange capabilities.

Nationally, several recent initiatives have targeted health data interoperability, including for cancer care. The Centers for Disease Control and Prevention’s Data Modernization Initiative is a multiyear, multi–billion-dollar effort to improve data sharing across the federal and state public health landscape. 

Meanwhile, in March 2024, the Biden-Harris administration launched United States Core Data for Interoperability Plus Cancer. The program will define a recommended minimum set of cancer-related data to be included in a patient’s EHR to enhance data exchange for research and clinical care. 

EHR vendors are also key to improving the landscape, said Dr. Adler-Milstein. Vendors such as Epic have developed strong sharing capabilities for transmitting health information from site to site, but of course, that only helps if providers have Epic, she said. 

“That’s where these national frameworks should help, because we don’t want it to break down by what EHR vendor you have,” she said. “It’s a patchwork. You can go to some places and hear success stories because they have Epic or a state health information exchange, but it’s very heterogeneous. In some places, they have nothing and are using a fax machine.”

Mr. Havasy believes fax machines will ultimately go extinct, particularly as a younger, more digitally savvy generation enters the healthcare workforce. He also foresees that the growing use of artificial intelligence will help eradicate the outdated technology. 

But, Ms. Hamilton noted, “unless we have consistent, ongoing, sustained funding, it is very hard to move off [an older] technology that can work. That’s one of the biggest barriers.” 

“Public health is about protecting the lives of every single person everywhere,” Ms. Hamilton said, “but when we don’t have the data that comes into the system, we can’t achieve our mission.”
 

A version of this article appeared on Medscape.com.

On any given day, oncologist Mark Lewis, MD, feels like he’s seesawing between two eras of technology. 

One minute, he’s working on sequencing a tumor genome. The next, he’s sifting through pages of disorganized data from a device that has been around for decades: the fax machine. 

“If two doctors’ offices aren’t on the same electronic medical record, one of the main ways to transfer records is still by fax,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “I can go from cutting-edge innovation to relying on, at best, 1980s information technology. It just boggles my mind.”

Dr. Lewis, who has posted about his frustration with fax machines, is far from alone. Oncologists are among the many specialists across the country at the mercy of telecopiers. 

According to a 2021 report by the Office of the National Coordinator for Health Information Technology, fax and mail continue to be the most common methods for hospitals and health systems to exchange care record summaries. In 2019, nearly 8 in 10 hospitals used mail or fax to send and receive health information, the report found. 

Fax machines are still commonplace across the healthcare spectrum, said Robert Havasy, MS, senior director for informatics strategy at the Healthcare Information and Management Systems Society (HIMSS). Inertia, cost, and more pressing priorities for hospitals and medical institutions contribute to the technology sticking around, he explained. 

“Post-COVID, my guess is we’re still at over 50% of healthcare practices using fax for some reason, on a daily basis,” Mr. Havasy said in an interview. “A lot of hospitals just don’t have the time, the money, or the staff to fix that problem because there’s always something a little higher up the priority chain they need to focus on.” 

If, for instance, “you’re going to do a process redesign to reduce hospital total acquired infections, your fax machine replacement might be 10th or 12th on the list. It just never gets up to 1 or 2 because it’s ‘not that much of a problem,’ ” he added.

Or is it?

Administrators may not view fax machines as a top concern, but clinicians who deal with the machines daily see it differently. 

“What worries me is we’re taking records out of an electronic storehouse [and] converting them to a paper medium,” Dr. Lewis said. “And then we are scanning into another electronic storehouse. The more steps, the more can be lost.”

And when information is lost, patient care can be compromised. 

Slower Workflows, Care Concerns

Although there are no published data on fax machine use in oncology specifically, this outdated technology does come into play in a variety of ways along the cancer care continuum. 

Radiation oncologist David R. Penberthy, MD, said patients often seek his cancer center’s expertise for second opinions, and that requires collecting patient records from many different practices. 

“Ideally, it would come electronically, but sometimes it does come by fax,” said Dr. Penberthy, program director of radiation oncology at the University of Virginia School of Medicine in Charlottesville. “The quality of the fax is not always the best. Sometimes it’s literally a fax of a fax. You’re reading something that’s very difficult to read.” 

Orders for new tests are also typically sent and received via fax temporarily while IT teams work to integrate them into the electronic health record (EHR), Dr. Penberthy said. 

Insurers and third-party laboratories often send test results back by fax as well.

“Even if I haven’t actually sent my patient out of our institution, this crucial result may only be entered back into the record as a scanned document from a fax, which is not great because it can get lost in the other results that are reported electronically,” Dr. Lewis said. The risk here is that an ordering physician won’t see these results, which can lead to delayed or overlooked care for patients, he explained.

“To me, it’s like a blind spot,” Dr. Lewis said. “Every time we use a fax, I see it actually as an opportunity for oversight and missed opportunity to collect data.”

Dr. Penberthy said faxing can slow things down at his practice, particularly if he faxes a document to another office but receives no confirmation and has to track down what happened. 

As for cybersecurity, data that are in transit during faxing are generally considered secure and compliant with the Health Insurance Portability and Accountability Act (HIPAA), said Mr. Havasy of HIMSS. However, the Privacy Rule also requires that data remain secure while at rest, which isn’t always possible, he added. 

“That’s where faxes fall down, because generally fax machines are in public, if you will, or open areas in a hospital,” he said. “They just sit on a desk. I don’t know that the next nurse who comes up and looks through that stack was the nurse who was treating the patient.” 

Important decisions or results can also be missed when sent by fax, creating headaches for physicians and care problems for patients. 

Dr. Lewis recently experienced an insurance-related fax mishap over Memorial Day weekend. He believed his patient had access to the antinausea medication he had prescribed. When Dr. Lewis happened to check the fax machine over the weekend, he found a coverage denial for the medication from the insurer but, at that point, had no recourse to appeal because it was a long holiday weekend. 

“Had the denial been sent by an electronic means that was quicker and more readily available, it would have been possible to appeal before the holiday weekend,” he said. 

Hematologist Aaron Goodman, MD, encountered a similar problem after an insurer denied coverage of an expensive cancer drug for a patient and faxed over its reason for the denial. Dr. Goodman was not directly notified that the information arrived and didn’t learn about the denial for a week, he said. 

“There’s no ‘ding’ in my inbox if something is faxed over and scanned,” said Dr. Goodman, associate professor of medicine at UC San Diego Health. “Once I realized it was denied, I was able to rectify it, but it wasted a week of a patient not getting a drug that I felt would be beneficial for them.”

Broader Health Policy Impacts

The use of outdated technology, such as fax machines, also creates ripple effects that burden the health system, health policy experts say. 

Duplicate testing and unnecessary care are top impacts, said Julia Adler-Milstein, PhD, professor of medicine and chief of the division of clinical informatics and digital transformation at the University of California, San Francisco.

Studies show that 20%-30% of the $65 billion spent annually on lab tests is used on unnecessary duplicate tests, and another estimated $30 billion is spent each year on unnecessary duplicate medical imaging. These duplicate tests may be mitigated if hospitals adopt certified EHR technology, research shows.

Still, without EHR interoperability between institutions, new providers may be unaware that tests or past labs for patients exist, leading to repeat tests, said Dr. Adler-Milstein, who researches health IT policy with a focus on EHRs. Patients can sometimes fill in the gaps, but not always. 

“Fax machines only help close information gaps if the clinician is aware of where to seek out the information and there is someone at the other organization to locate and transmit the information in a timely manner,” Dr. Adler-Milstein said. 

Old technology and poor interoperability also greatly affect data collection for disease surveillance and monitoring, said Janet Hamilton, MPH, executive director for the Council of State and Territorial Epidemiologists. This issue was keenly demonstrated during the pandemic, Ms. Hamilton said. 

“It was tragic, quite honestly,” she said. “There was such an immense amount of data that needed to be moved quickly, and that’s when computers are at their best.”

But, she said, “we didn’t have the level of systems in place to do it well.”

Specifically, the lack of electronic case reporting in place during the pandemic — where diagnoses are documented in the record and then immediately sent to the public health system — led to reports that were delayed, not made, or had missing or incomplete information, such as patients’ race and ethnicity or other health conditions, Ms. Hamilton said. 

Incomplete or missing data hampered the ability of public health officials and researchers to understand how the virus might affect different patients.

“If you had a chronic condition like cancer, you were less likely to have a positive outcome with COVID,” Ms. Hamilton said. “But because electronic case reporting was not in place, we didn’t get some of those additional pieces of information. We didn’t have people’s underlying oncology status to then say, ‘Here are individuals with these types of characteristics, and these are the things that happen if they also have a cancer.’” 

Slow, but Steady, Improvements

Efforts at the state and federal levels have targeted improved health information exchange, but progress takes time, Dr. Adler-Milstein said.

Most states have some form of health information exchange, such as statewide exchanges, regional health information organizations, or clinical data registries. Maryland is often held up as a notable example for its health information exchange, Dr. Adler-Milstein noted.

According to Maryland law, all hospitals under the jurisdiction of the Maryland Health Care Commission are required to electronically connect to the state-designated health information exchange. In 2012, Maryland became the first state to connect all its 46 acute care hospitals in the sharing of real-time data. 

The Health Information Technology for Economic and Clinical Health (HITECH) Act provided federal-enhanced Medicaid matching funds to states through 2021 to support efforts to advance electronic exchange. Nearly all states used these funds, and most have identified other sources to sustain the efforts, according to a recent US Government Accountability Office (GAO) report. However, GAO found that small and rural providers are less likely to have the financial and technological resources to participate in or maintain electronic exchange capabilities.

Nationally, several recent initiatives have targeted health data interoperability, including for cancer care. The Centers for Disease Control and Prevention’s Data Modernization Initiative is a multiyear, multi–billion-dollar effort to improve data sharing across the federal and state public health landscape. 

Meanwhile, in March 2024, the Biden-Harris administration launched United States Core Data for Interoperability Plus Cancer. The program will define a recommended minimum set of cancer-related data to be included in a patient’s EHR to enhance data exchange for research and clinical care. 

EHR vendors are also key to improving the landscape, said Dr. Adler-Milstein. Vendors such as Epic have developed strong sharing capabilities for transmitting health information from site to site, but of course, that only helps if providers have Epic, she said. 

“That’s where these national frameworks should help, because we don’t want it to break down by what EHR vendor you have,” she said. “It’s a patchwork. You can go to some places and hear success stories because they have Epic or a state health information exchange, but it’s very heterogeneous. In some places, they have nothing and are using a fax machine.”

Mr. Havasy believes fax machines will ultimately go extinct, particularly as a younger, more digitally savvy generation enters the healthcare workforce. He also foresees that the growing use of artificial intelligence will help eradicate the outdated technology. 

But, Ms. Hamilton noted, “unless we have consistent, ongoing, sustained funding, it is very hard to move off [an older] technology that can work. That’s one of the biggest barriers.” 

“Public health is about protecting the lives of every single person everywhere,” Ms. Hamilton said, “but when we don’t have the data that comes into the system, we can’t achieve our mission.”
 

A version of this article appeared on Medscape.com.

On any given day, oncologist Mark Lewis, MD, feels like he’s seesawing between two eras of technology. 

One minute, he’s working on sequencing a tumor genome. The next, he’s sifting through pages of disorganized data from a device that has been around for decades: the fax machine. 

“If two doctors’ offices aren’t on the same electronic medical record, one of the main ways to transfer records is still by fax,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “I can go from cutting-edge innovation to relying on, at best, 1980s information technology. It just boggles my mind.”

Dr. Lewis, who has posted about his frustration with fax machines, is far from alone. Oncologists are among the many specialists across the country at the mercy of telecopiers. 

According to a 2021 report by the Office of the National Coordinator for Health Information Technology, fax and mail continue to be the most common methods for hospitals and health systems to exchange care record summaries. In 2019, nearly 8 in 10 hospitals used mail or fax to send and receive health information, the report found. 

Fax machines are still commonplace across the healthcare spectrum, said Robert Havasy, MS, senior director for informatics strategy at the Healthcare Information and Management Systems Society (HIMSS). Inertia, cost, and more pressing priorities for hospitals and medical institutions contribute to the technology sticking around, he explained. 

“Post-COVID, my guess is we’re still at over 50% of healthcare practices using fax for some reason, on a daily basis,” Mr. Havasy said in an interview. “A lot of hospitals just don’t have the time, the money, or the staff to fix that problem because there’s always something a little higher up the priority chain they need to focus on.” 

If, for instance, “you’re going to do a process redesign to reduce hospital total acquired infections, your fax machine replacement might be 10th or 12th on the list. It just never gets up to 1 or 2 because it’s ‘not that much of a problem,’ ” he added.

Or is it?

Administrators may not view fax machines as a top concern, but clinicians who deal with the machines daily see it differently. 

“What worries me is we’re taking records out of an electronic storehouse [and] converting them to a paper medium,” Dr. Lewis said. “And then we are scanning into another electronic storehouse. The more steps, the more can be lost.”

And when information is lost, patient care can be compromised. 

Slower Workflows, Care Concerns

Although there are no published data on fax machine use in oncology specifically, this outdated technology does come into play in a variety of ways along the cancer care continuum. 

Radiation oncologist David R. Penberthy, MD, said patients often seek his cancer center’s expertise for second opinions, and that requires collecting patient records from many different practices. 

“Ideally, it would come electronically, but sometimes it does come by fax,” said Dr. Penberthy, program director of radiation oncology at the University of Virginia School of Medicine in Charlottesville. “The quality of the fax is not always the best. Sometimes it’s literally a fax of a fax. You’re reading something that’s very difficult to read.” 

Orders for new tests are also typically sent and received via fax temporarily while IT teams work to integrate them into the electronic health record (EHR), Dr. Penberthy said. 

Insurers and third-party laboratories often send test results back by fax as well.

“Even if I haven’t actually sent my patient out of our institution, this crucial result may only be entered back into the record as a scanned document from a fax, which is not great because it can get lost in the other results that are reported electronically,” Dr. Lewis said. The risk here is that an ordering physician won’t see these results, which can lead to delayed or overlooked care for patients, he explained.

“To me, it’s like a blind spot,” Dr. Lewis said. “Every time we use a fax, I see it actually as an opportunity for oversight and missed opportunity to collect data.”

Dr. Penberthy said faxing can slow things down at his practice, particularly if he faxes a document to another office but receives no confirmation and has to track down what happened. 

As for cybersecurity, data that are in transit during faxing are generally considered secure and compliant with the Health Insurance Portability and Accountability Act (HIPAA), said Mr. Havasy of HIMSS. However, the Privacy Rule also requires that data remain secure while at rest, which isn’t always possible, he added. 

“That’s where faxes fall down, because generally fax machines are in public, if you will, or open areas in a hospital,” he said. “They just sit on a desk. I don’t know that the next nurse who comes up and looks through that stack was the nurse who was treating the patient.” 

Important decisions or results can also be missed when sent by fax, creating headaches for physicians and care problems for patients. 

Dr. Lewis recently experienced an insurance-related fax mishap over Memorial Day weekend. He believed his patient had access to the antinausea medication he had prescribed. When Dr. Lewis happened to check the fax machine over the weekend, he found a coverage denial for the medication from the insurer but, at that point, had no recourse to appeal because it was a long holiday weekend. 

“Had the denial been sent by an electronic means that was quicker and more readily available, it would have been possible to appeal before the holiday weekend,” he said. 

Hematologist Aaron Goodman, MD, encountered a similar problem after an insurer denied coverage of an expensive cancer drug for a patient and faxed over its reason for the denial. Dr. Goodman was not directly notified that the information arrived and didn’t learn about the denial for a week, he said. 

“There’s no ‘ding’ in my inbox if something is faxed over and scanned,” said Dr. Goodman, associate professor of medicine at UC San Diego Health. “Once I realized it was denied, I was able to rectify it, but it wasted a week of a patient not getting a drug that I felt would be beneficial for them.”

Broader Health Policy Impacts

The use of outdated technology, such as fax machines, also creates ripple effects that burden the health system, health policy experts say. 

Duplicate testing and unnecessary care are top impacts, said Julia Adler-Milstein, PhD, professor of medicine and chief of the division of clinical informatics and digital transformation at the University of California, San Francisco.

Studies show that 20%-30% of the $65 billion spent annually on lab tests is used on unnecessary duplicate tests, and another estimated $30 billion is spent each year on unnecessary duplicate medical imaging. These duplicate tests may be mitigated if hospitals adopt certified EHR technology, research shows.

Still, without EHR interoperability between institutions, new providers may be unaware that tests or past labs for patients exist, leading to repeat tests, said Dr. Adler-Milstein, who researches health IT policy with a focus on EHRs. Patients can sometimes fill in the gaps, but not always. 

“Fax machines only help close information gaps if the clinician is aware of where to seek out the information and there is someone at the other organization to locate and transmit the information in a timely manner,” Dr. Adler-Milstein said. 

Old technology and poor interoperability also greatly affect data collection for disease surveillance and monitoring, said Janet Hamilton, MPH, executive director for the Council of State and Territorial Epidemiologists. This issue was keenly demonstrated during the pandemic, Ms. Hamilton said. 

“It was tragic, quite honestly,” she said. “There was such an immense amount of data that needed to be moved quickly, and that’s when computers are at their best.”

But, she said, “we didn’t have the level of systems in place to do it well.”

Specifically, the lack of electronic case reporting in place during the pandemic — where diagnoses are documented in the record and then immediately sent to the public health system — led to reports that were delayed, not made, or had missing or incomplete information, such as patients’ race and ethnicity or other health conditions, Ms. Hamilton said. 

Incomplete or missing data hampered the ability of public health officials and researchers to understand how the virus might affect different patients.

“If you had a chronic condition like cancer, you were less likely to have a positive outcome with COVID,” Ms. Hamilton said. “But because electronic case reporting was not in place, we didn’t get some of those additional pieces of information. We didn’t have people’s underlying oncology status to then say, ‘Here are individuals with these types of characteristics, and these are the things that happen if they also have a cancer.’” 

Slow, but Steady, Improvements

Efforts at the state and federal levels have targeted improved health information exchange, but progress takes time, Dr. Adler-Milstein said.

Most states have some form of health information exchange, such as statewide exchanges, regional health information organizations, or clinical data registries. Maryland is often held up as a notable example for its health information exchange, Dr. Adler-Milstein noted.

According to Maryland law, all hospitals under the jurisdiction of the Maryland Health Care Commission are required to electronically connect to the state-designated health information exchange. In 2012, Maryland became the first state to connect all its 46 acute care hospitals in the sharing of real-time data. 

The Health Information Technology for Economic and Clinical Health (HITECH) Act provided federal-enhanced Medicaid matching funds to states through 2021 to support efforts to advance electronic exchange. Nearly all states used these funds, and most have identified other sources to sustain the efforts, according to a recent US Government Accountability Office (GAO) report. However, GAO found that small and rural providers are less likely to have the financial and technological resources to participate in or maintain electronic exchange capabilities.

Nationally, several recent initiatives have targeted health data interoperability, including for cancer care. The Centers for Disease Control and Prevention’s Data Modernization Initiative is a multiyear, multi–billion-dollar effort to improve data sharing across the federal and state public health landscape. 

Meanwhile, in March 2024, the Biden-Harris administration launched United States Core Data for Interoperability Plus Cancer. The program will define a recommended minimum set of cancer-related data to be included in a patient’s EHR to enhance data exchange for research and clinical care. 

EHR vendors are also key to improving the landscape, said Dr. Adler-Milstein. Vendors such as Epic have developed strong sharing capabilities for transmitting health information from site to site, but of course, that only helps if providers have Epic, she said. 

“That’s where these national frameworks should help, because we don’t want it to break down by what EHR vendor you have,” she said. “It’s a patchwork. You can go to some places and hear success stories because they have Epic or a state health information exchange, but it’s very heterogeneous. In some places, they have nothing and are using a fax machine.”

Mr. Havasy believes fax machines will ultimately go extinct, particularly as a younger, more digitally savvy generation enters the healthcare workforce. He also foresees that the growing use of artificial intelligence will help eradicate the outdated technology. 

But, Ms. Hamilton noted, “unless we have consistent, ongoing, sustained funding, it is very hard to move off [an older] technology that can work. That’s one of the biggest barriers.” 

“Public health is about protecting the lives of every single person everywhere,” Ms. Hamilton said, “but when we don’t have the data that comes into the system, we can’t achieve our mission.”
 

A version of this article appeared on Medscape.com.

VIENNA — While there is no doubt that some people with psoriatic arthritis (PsA) have axial symptoms, data presented at the annual European Congress of Rheumatology do not appear to add much to what is already known about axial PsA or to further the cause of differentiating it from axial spondyloarthritis (axSpA).

In both the AXIS study and Reuma.pt, around one in three patients with PsA were found to have axial involvement. Notably, the percentage of people with axial PsA was found to vary according to how imaging information was interpreted in the AXIS study. Both studies were discussed during the Axial Involvement in PsA and SpA session at EULAR 2024.
 

The One-Million-Dollar Question

“So, the one-million-dollar question: What is it, really?” Philippe Carron, MD, PhD, Ghent University Hospital, Ghent, Belgium, said in the presentation that started the session. Despite PsA being described more than 60 years ago, “we still have no internationally accepted definition or a consensus on how we should define these patients and how we should screen them,” he said.

“There are some believers that it is just a form of axial SpA with concomitant psoriasis, but also some people that think that the axial PsA is a typical disease, with typical characteristics which are different from axial disease,” Dr. Carron said.

The lack of consensus makes it difficult to estimate just how many people have axial PsA. Reported prevalences range from 5% to 70%, “all caused by which criteria that you’re using to define axial involvement,” Dr. Carron added.

There are, however, two things that can be agreed upon, according to Dr. Carron. First, the prevalence of axial involvement in people with early PsA is “much, much lower” than that of more established disease. Second, exclusive axial involvement is seen in “just a minority of PsA patients.” Most people with axial disease also have peripheral disease, he added.

Imaging findings in axial PsA “are quite similar to those seen in axial SpA,” although Dr. Carron also said that there were some distinct differences. Radiographic sacroiliitis occurs in around 25%-50% of people with axial PsA, and atypical syndesmophytes are more often found in people with axial PsA than in those with axSpA.
 

Shared Characteristics

But are axial PsA and axSpA separate diseases or part of the same disease continuum? That’s a question that is still very much open for debate, said Sofia Ramiro, MD, PhD, a senior researcher at Leiden University Medical Center, Leiden, the Netherlands, and rheumatology consultant at Zuyderland Medical Center in Heerlen, the Netherlands.

While many studies have looked to answer this question, there is a big methodological problem — the studies largely cannot be compared as they have used different definitions of axSpA.

Take a patient with inflammatory back pain, psoriasis, and oligoarthritis, Dr. Ramiro said. If the patient goes to one rheumatologist, they may get a diagnosis of axSpA, but if they go to a different rheumatologist, they may get a diagnosis of axial PsA.

“This is influenced by training, expertise, by beliefs, and by belonging to ASAS [Assessment of Spondyloarthritis International Society] or to GRAPPA [Group for Research and Assessment of Psoriasis and Psoriatic Arthritis],” Dr. Ramiro suggested. It’s “a diagnostic bias” that is very difficult to overcome and makes direct comparisons between patient populations recruited into clinical studies “extremely challenging.”

To confuse matters more, axial PsA and axSpA share common characteristics: Inflammatory back pain, HLA-B27 positivity, elevated levels of C-reactive protein (CRP) or a higher erythrocyte sedimentation rate, and structural lesions in the sacroiliac joints and spine.
 

AXIS Study ‘Gives Answers’

More research into factors associated with axial PsA need to be performed to try to help define the condition and enable classification and ultimately treatment guidelines. This is where the AXIS study comes in.

The AXIS study is a joint project of ASAS and GRAPPA that was started in January 2019 with the aim of defining a homogeneous subgroup of patients who could be studied.

“The objectives of the AXIS study are to determine the frequency of axial involvement in patients with PsA; to identify the frequency of active inflammatory and structural changes on imaging; and to identify factors associated with the presence of axial involvement in PsA,” Murat Torgutalp, MD, of Charité – Universitätsmedizin Berlin, Berlin, Germany, said at EULAR 2024.

The study population consisted of 409 consecutively recruited patients diagnosed with PsA according to CASPAR (Classification for Psoriatic Arthritis) criteria; all have had PsA for up to 10 years and were untreated with biologic or targeted synthetic disease modifying drugs at the time of inclusion.

Dr. Torgutalp, who is the study’s primary research coordinator, reported that a diagnosis of PsA was made in 37% of the population when local investigators considered available clinical, laboratory, and imaging data. However, patients’ imaging data were also centrally assessed, and when the local investigators were party to the expert imaging interpretations, the percentage of people diagnosed with PsA dropped to 27%.

“When we looked at the clinical characteristics, the presence of the back pain, particularly inflammatory back pain, HLA-B27 positivity, elevated CRP, and presence of active, inflammatory and structural changes in the sacroiliac joints and spine were associated with the final conclusion on the presence of axial involvement,” Dr. Torgutalp said.

Despite the title of his presentation being “The Axis Study Gives Answers,” Dr. Torgutalp presented lots of data without giving much insight into how they might be used. He concluded that “overall, there was a trend toward overestimation of the presence of imaging changes indicative of axial involvement across all imaging modalities” by the local investigators.

Dennis McGonagle, MB, MCH, BAO, PhD, of the University of Leeds, Leeds, England,said in an interview that the AXIS study “is a noble, international effort across multiple countries to try and better understand axial PsA.”

Dr. McGonagle, who was not involved in the study, added: “A lot of data are being generated, and a lot of analysis needs to be done to drill down to get a clear message that could influence practice.”
 

Axial PsA in the Portuguese Population

Separately, Catarina Abreu, a rheumatology intern at Hospital Garcia de Orta, Almada, Portugal, presented some real-world data on axial PsA from Reuma.pt.

Of 2304 patients, 854 (37.1%) reportedly had axial PsA, which had been defined as physician-reported spondylitis or the presence of imaging findings suggestive of axial involvement. This included radiographic- or MRI-detected sacroiliitis or syndesmophytes seen on axial x-rays.

The majority (78.2%) of those with an axial PsA diagnosis had concomitant peripheral involvement, with 8.1% having exclusive axial disease.

About 70% of the axial PsA diagnoses had been made using clinical or laboratory findings alone, and 30% of diagnoses was based on imaging results. Of the latter, Ms. Abreu noted that patients who had imaging data available were more likely to be HLA-B27 positive and less likely to have dactylitis, with respective odds ratios (ORs) of 3.10 and 2.42.

Individuals with axial PsA were more likely to have enthesitis (OR, 1.92), although no data were available on whether this was axial or peripheral enthesitis. Tobacco exposure was also linked to an increased chance of having axial PsA (OR, 1.66).

Ms. Abreu noted that the “scarce number of available imaging exams” and other missing data in Reuma.pt may have led to an underdiagnosis of axial PsA.

“The difference that we found between axial and peripheral [PsA] are similar to the differences found in other studies that compared axial psoriatic arthritis with axial spondyloarthritis,” Ms. Abreu said.

“So, we leave with the question that was already left before here: If these are different diseases or just different phenotypes of the same disease, and what implications will this have in the future?” Ms. Abreu concluded.

Dr. Carron received educational grants, speaker fees, or honoraria for other consultancy work from AbbVie, UCB, Pfizer, Eli Lilly, Novartis, Janssen, and Galapagos/Alfasigma. Dr. Ramiro is an ASAS executive committee member and received research grants or consulting/speaker fees from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, and UCB. AXIS is supported by unrestricted research grants from AbbVie, Galapagos, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Torgutalp is the primary research coordinator for the study; he reported no financial conflicts of interest. The Reuma.pt registry was developed with the financial support of the pharmaceutical industry and is currently supported by AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, and Sobi. Ms. Abreu reported no financial conflicts of interest.

A version of this article appeared on Medscape.com.

VIENNA — While there is no doubt that some people with psoriatic arthritis (PsA) have axial symptoms, data presented at the annual European Congress of Rheumatology do not appear to add much to what is already known about axial PsA or to further the cause of differentiating it from axial spondyloarthritis (axSpA).

In both the AXIS study and Reuma.pt, around one in three patients with PsA were found to have axial involvement. Notably, the percentage of people with axial PsA was found to vary according to how imaging information was interpreted in the AXIS study. Both studies were discussed during the Axial Involvement in PsA and SpA session at EULAR 2024.
 

The One-Million-Dollar Question

“So, the one-million-dollar question: What is it, really?” Philippe Carron, MD, PhD, Ghent University Hospital, Ghent, Belgium, said in the presentation that started the session. Despite PsA being described more than 60 years ago, “we still have no internationally accepted definition or a consensus on how we should define these patients and how we should screen them,” he said.

“There are some believers that it is just a form of axial SpA with concomitant psoriasis, but also some people that think that the axial PsA is a typical disease, with typical characteristics which are different from axial disease,” Dr. Carron said.

The lack of consensus makes it difficult to estimate just how many people have axial PsA. Reported prevalences range from 5% to 70%, “all caused by which criteria that you’re using to define axial involvement,” Dr. Carron added.

There are, however, two things that can be agreed upon, according to Dr. Carron. First, the prevalence of axial involvement in people with early PsA is “much, much lower” than that of more established disease. Second, exclusive axial involvement is seen in “just a minority of PsA patients.” Most people with axial disease also have peripheral disease, he added.

Imaging findings in axial PsA “are quite similar to those seen in axial SpA,” although Dr. Carron also said that there were some distinct differences. Radiographic sacroiliitis occurs in around 25%-50% of people with axial PsA, and atypical syndesmophytes are more often found in people with axial PsA than in those with axSpA.
 

Shared Characteristics

But are axial PsA and axSpA separate diseases or part of the same disease continuum? That’s a question that is still very much open for debate, said Sofia Ramiro, MD, PhD, a senior researcher at Leiden University Medical Center, Leiden, the Netherlands, and rheumatology consultant at Zuyderland Medical Center in Heerlen, the Netherlands.

While many studies have looked to answer this question, there is a big methodological problem — the studies largely cannot be compared as they have used different definitions of axSpA.

Take a patient with inflammatory back pain, psoriasis, and oligoarthritis, Dr. Ramiro said. If the patient goes to one rheumatologist, they may get a diagnosis of axSpA, but if they go to a different rheumatologist, they may get a diagnosis of axial PsA.

“This is influenced by training, expertise, by beliefs, and by belonging to ASAS [Assessment of Spondyloarthritis International Society] or to GRAPPA [Group for Research and Assessment of Psoriasis and Psoriatic Arthritis],” Dr. Ramiro suggested. It’s “a diagnostic bias” that is very difficult to overcome and makes direct comparisons between patient populations recruited into clinical studies “extremely challenging.”

To confuse matters more, axial PsA and axSpA share common characteristics: Inflammatory back pain, HLA-B27 positivity, elevated levels of C-reactive protein (CRP) or a higher erythrocyte sedimentation rate, and structural lesions in the sacroiliac joints and spine.
 

AXIS Study ‘Gives Answers’

More research into factors associated with axial PsA need to be performed to try to help define the condition and enable classification and ultimately treatment guidelines. This is where the AXIS study comes in.

The AXIS study is a joint project of ASAS and GRAPPA that was started in January 2019 with the aim of defining a homogeneous subgroup of patients who could be studied.

“The objectives of the AXIS study are to determine the frequency of axial involvement in patients with PsA; to identify the frequency of active inflammatory and structural changes on imaging; and to identify factors associated with the presence of axial involvement in PsA,” Murat Torgutalp, MD, of Charité – Universitätsmedizin Berlin, Berlin, Germany, said at EULAR 2024.

The study population consisted of 409 consecutively recruited patients diagnosed with PsA according to CASPAR (Classification for Psoriatic Arthritis) criteria; all have had PsA for up to 10 years and were untreated with biologic or targeted synthetic disease modifying drugs at the time of inclusion.

Dr. Torgutalp, who is the study’s primary research coordinator, reported that a diagnosis of PsA was made in 37% of the population when local investigators considered available clinical, laboratory, and imaging data. However, patients’ imaging data were also centrally assessed, and when the local investigators were party to the expert imaging interpretations, the percentage of people diagnosed with PsA dropped to 27%.

“When we looked at the clinical characteristics, the presence of the back pain, particularly inflammatory back pain, HLA-B27 positivity, elevated CRP, and presence of active, inflammatory and structural changes in the sacroiliac joints and spine were associated with the final conclusion on the presence of axial involvement,” Dr. Torgutalp said.

Despite the title of his presentation being “The Axis Study Gives Answers,” Dr. Torgutalp presented lots of data without giving much insight into how they might be used. He concluded that “overall, there was a trend toward overestimation of the presence of imaging changes indicative of axial involvement across all imaging modalities” by the local investigators.

Dennis McGonagle, MB, MCH, BAO, PhD, of the University of Leeds, Leeds, England,said in an interview that the AXIS study “is a noble, international effort across multiple countries to try and better understand axial PsA.”

Dr. McGonagle, who was not involved in the study, added: “A lot of data are being generated, and a lot of analysis needs to be done to drill down to get a clear message that could influence practice.”
 

Axial PsA in the Portuguese Population

Separately, Catarina Abreu, a rheumatology intern at Hospital Garcia de Orta, Almada, Portugal, presented some real-world data on axial PsA from Reuma.pt.

Of 2304 patients, 854 (37.1%) reportedly had axial PsA, which had been defined as physician-reported spondylitis or the presence of imaging findings suggestive of axial involvement. This included radiographic- or MRI-detected sacroiliitis or syndesmophytes seen on axial x-rays.

The majority (78.2%) of those with an axial PsA diagnosis had concomitant peripheral involvement, with 8.1% having exclusive axial disease.

About 70% of the axial PsA diagnoses had been made using clinical or laboratory findings alone, and 30% of diagnoses was based on imaging results. Of the latter, Ms. Abreu noted that patients who had imaging data available were more likely to be HLA-B27 positive and less likely to have dactylitis, with respective odds ratios (ORs) of 3.10 and 2.42.

Individuals with axial PsA were more likely to have enthesitis (OR, 1.92), although no data were available on whether this was axial or peripheral enthesitis. Tobacco exposure was also linked to an increased chance of having axial PsA (OR, 1.66).

Ms. Abreu noted that the “scarce number of available imaging exams” and other missing data in Reuma.pt may have led to an underdiagnosis of axial PsA.

“The difference that we found between axial and peripheral [PsA] are similar to the differences found in other studies that compared axial psoriatic arthritis with axial spondyloarthritis,” Ms. Abreu said.

“So, we leave with the question that was already left before here: If these are different diseases or just different phenotypes of the same disease, and what implications will this have in the future?” Ms. Abreu concluded.

Dr. Carron received educational grants, speaker fees, or honoraria for other consultancy work from AbbVie, UCB, Pfizer, Eli Lilly, Novartis, Janssen, and Galapagos/Alfasigma. Dr. Ramiro is an ASAS executive committee member and received research grants or consulting/speaker fees from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, and UCB. AXIS is supported by unrestricted research grants from AbbVie, Galapagos, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Torgutalp is the primary research coordinator for the study; he reported no financial conflicts of interest. The Reuma.pt registry was developed with the financial support of the pharmaceutical industry and is currently supported by AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, and Sobi. Ms. Abreu reported no financial conflicts of interest.

A version of this article appeared on Medscape.com.

VIENNA — While there is no doubt that some people with psoriatic arthritis (PsA) have axial symptoms, data presented at the annual European Congress of Rheumatology do not appear to add much to what is already known about axial PsA or to further the cause of differentiating it from axial spondyloarthritis (axSpA).

In both the AXIS study and Reuma.pt, around one in three patients with PsA were found to have axial involvement. Notably, the percentage of people with axial PsA was found to vary according to how imaging information was interpreted in the AXIS study. Both studies were discussed during the Axial Involvement in PsA and SpA session at EULAR 2024.
 

The One-Million-Dollar Question

“So, the one-million-dollar question: What is it, really?” Philippe Carron, MD, PhD, Ghent University Hospital, Ghent, Belgium, said in the presentation that started the session. Despite PsA being described more than 60 years ago, “we still have no internationally accepted definition or a consensus on how we should define these patients and how we should screen them,” he said.

“There are some believers that it is just a form of axial SpA with concomitant psoriasis, but also some people that think that the axial PsA is a typical disease, with typical characteristics which are different from axial disease,” Dr. Carron said.

The lack of consensus makes it difficult to estimate just how many people have axial PsA. Reported prevalences range from 5% to 70%, “all caused by which criteria that you’re using to define axial involvement,” Dr. Carron added.

There are, however, two things that can be agreed upon, according to Dr. Carron. First, the prevalence of axial involvement in people with early PsA is “much, much lower” than that of more established disease. Second, exclusive axial involvement is seen in “just a minority of PsA patients.” Most people with axial disease also have peripheral disease, he added.

Imaging findings in axial PsA “are quite similar to those seen in axial SpA,” although Dr. Carron also said that there were some distinct differences. Radiographic sacroiliitis occurs in around 25%-50% of people with axial PsA, and atypical syndesmophytes are more often found in people with axial PsA than in those with axSpA.
 

Shared Characteristics

But are axial PsA and axSpA separate diseases or part of the same disease continuum? That’s a question that is still very much open for debate, said Sofia Ramiro, MD, PhD, a senior researcher at Leiden University Medical Center, Leiden, the Netherlands, and rheumatology consultant at Zuyderland Medical Center in Heerlen, the Netherlands.

While many studies have looked to answer this question, there is a big methodological problem — the studies largely cannot be compared as they have used different definitions of axSpA.

Take a patient with inflammatory back pain, psoriasis, and oligoarthritis, Dr. Ramiro said. If the patient goes to one rheumatologist, they may get a diagnosis of axSpA, but if they go to a different rheumatologist, they may get a diagnosis of axial PsA.

“This is influenced by training, expertise, by beliefs, and by belonging to ASAS [Assessment of Spondyloarthritis International Society] or to GRAPPA [Group for Research and Assessment of Psoriasis and Psoriatic Arthritis],” Dr. Ramiro suggested. It’s “a diagnostic bias” that is very difficult to overcome and makes direct comparisons between patient populations recruited into clinical studies “extremely challenging.”

To confuse matters more, axial PsA and axSpA share common characteristics: Inflammatory back pain, HLA-B27 positivity, elevated levels of C-reactive protein (CRP) or a higher erythrocyte sedimentation rate, and structural lesions in the sacroiliac joints and spine.
 

AXIS Study ‘Gives Answers’

More research into factors associated with axial PsA need to be performed to try to help define the condition and enable classification and ultimately treatment guidelines. This is where the AXIS study comes in.

The AXIS study is a joint project of ASAS and GRAPPA that was started in January 2019 with the aim of defining a homogeneous subgroup of patients who could be studied.

“The objectives of the AXIS study are to determine the frequency of axial involvement in patients with PsA; to identify the frequency of active inflammatory and structural changes on imaging; and to identify factors associated with the presence of axial involvement in PsA,” Murat Torgutalp, MD, of Charité – Universitätsmedizin Berlin, Berlin, Germany, said at EULAR 2024.

The study population consisted of 409 consecutively recruited patients diagnosed with PsA according to CASPAR (Classification for Psoriatic Arthritis) criteria; all have had PsA for up to 10 years and were untreated with biologic or targeted synthetic disease modifying drugs at the time of inclusion.

Dr. Torgutalp, who is the study’s primary research coordinator, reported that a diagnosis of PsA was made in 37% of the population when local investigators considered available clinical, laboratory, and imaging data. However, patients’ imaging data were also centrally assessed, and when the local investigators were party to the expert imaging interpretations, the percentage of people diagnosed with PsA dropped to 27%.

“When we looked at the clinical characteristics, the presence of the back pain, particularly inflammatory back pain, HLA-B27 positivity, elevated CRP, and presence of active, inflammatory and structural changes in the sacroiliac joints and spine were associated with the final conclusion on the presence of axial involvement,” Dr. Torgutalp said.

Despite the title of his presentation being “The Axis Study Gives Answers,” Dr. Torgutalp presented lots of data without giving much insight into how they might be used. He concluded that “overall, there was a trend toward overestimation of the presence of imaging changes indicative of axial involvement across all imaging modalities” by the local investigators.

Dennis McGonagle, MB, MCH, BAO, PhD, of the University of Leeds, Leeds, England,said in an interview that the AXIS study “is a noble, international effort across multiple countries to try and better understand axial PsA.”

Dr. McGonagle, who was not involved in the study, added: “A lot of data are being generated, and a lot of analysis needs to be done to drill down to get a clear message that could influence practice.”
 

Axial PsA in the Portuguese Population

Separately, Catarina Abreu, a rheumatology intern at Hospital Garcia de Orta, Almada, Portugal, presented some real-world data on axial PsA from Reuma.pt.

Of 2304 patients, 854 (37.1%) reportedly had axial PsA, which had been defined as physician-reported spondylitis or the presence of imaging findings suggestive of axial involvement. This included radiographic- or MRI-detected sacroiliitis or syndesmophytes seen on axial x-rays.

The majority (78.2%) of those with an axial PsA diagnosis had concomitant peripheral involvement, with 8.1% having exclusive axial disease.

About 70% of the axial PsA diagnoses had been made using clinical or laboratory findings alone, and 30% of diagnoses was based on imaging results. Of the latter, Ms. Abreu noted that patients who had imaging data available were more likely to be HLA-B27 positive and less likely to have dactylitis, with respective odds ratios (ORs) of 3.10 and 2.42.

Individuals with axial PsA were more likely to have enthesitis (OR, 1.92), although no data were available on whether this was axial or peripheral enthesitis. Tobacco exposure was also linked to an increased chance of having axial PsA (OR, 1.66).

Ms. Abreu noted that the “scarce number of available imaging exams” and other missing data in Reuma.pt may have led to an underdiagnosis of axial PsA.

“The difference that we found between axial and peripheral [PsA] are similar to the differences found in other studies that compared axial psoriatic arthritis with axial spondyloarthritis,” Ms. Abreu said.

“So, we leave with the question that was already left before here: If these are different diseases or just different phenotypes of the same disease, and what implications will this have in the future?” Ms. Abreu concluded.

Dr. Carron received educational grants, speaker fees, or honoraria for other consultancy work from AbbVie, UCB, Pfizer, Eli Lilly, Novartis, Janssen, and Galapagos/Alfasigma. Dr. Ramiro is an ASAS executive committee member and received research grants or consulting/speaker fees from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, and UCB. AXIS is supported by unrestricted research grants from AbbVie, Galapagos, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Torgutalp is the primary research coordinator for the study; he reported no financial conflicts of interest. The Reuma.pt registry was developed with the financial support of the pharmaceutical industry and is currently supported by AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, and Sobi. Ms. Abreu reported no financial conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Sedentary behavior, particularly sitting and watching television, is linked to lower odds of healthy aging, but substituting it with any physical activity — or even sleeping, in case of women with inadequate sleep — may lead to better overall health.

METHODOLOGY:

• Previous studies have shown that replacing sedentary behavior with physical activity may improve mortality outcomes, but whether this increased lifespan is accompanied by better overall health remains an unanswered question.
• To understand the impact of sedentary behavior and physical activity on healthy aging, researchers analyzed data from the prospective cohort Nurses’ Health Study.
• They included 45,176 women aged > 50 years in 1992 (mean age, 59.2 years) who were free of major chronic diseases and were followed up for 20 years.
• In 1992, validated questionnaires were used to record exposure to sedentary behavior, different levels of physical activity, and sleep. The time spent watching television was the primary exposure in the sedentary behavior category.
• The main outcome was healthy aging, defined as survival to ≥ 70 years of age and maintenance of four domains of health — being free of 11 main chronic diseases and having no impairment of subjective memory, physical function, or mental health.

TAKEAWAY:

• At 20 years of follow-up, 8.6% of the women achieved healthy aging, while 41.4% had none of the 11 chronic diseases, 16.1% had no physical function impairment, 44.1% had no mental health limitation, and 51.9% reported no memory impairment.
• For each increase of 2 hours per day spent sitting and watching television, the odds of healthy aging dropped by 12% (95% confidence interval [CI], 7%-17%).
• Conversely, every additional 2 hours per day of low-level physical activity at work upped the odds of healthy aging by 6% (95% CI, 3%-9%); furthermore, each extra hour per day of standardized moderate to vigorous physical activity (normal pace walking or the equivalent) was associated with 14% higher odds (95% CI, 11%-16%) of healthy aging.
• In a theoretical modeling analysis, individuals could increase their odds of healthy aging by replacing 1 hour of television time per day with low levels of physical activity at home and work or with moderate to vigorous levels of physical activity — or even sleeping, for those who slept for ≤ 7 hours.

IN PRACTICE:

“These findings expand on the literature reporting that replacing sedentary behavior with light or moderate to vigorous physical activity is associated with decreased mortality by suggesting that this increased lifespan might be accompanied by better overall health,” the authors wrote.

SOURCE:

Hongying Shi, PhD, Department of Epidemiology and Health Statistics, School of Public Health, Wenzhou Medical University, Wenzhou, China, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

The measures of different behaviors were self-reported and may, therefore, be less accurate than objective measurement methods. Measurement error may have attenuated the effect of low levels of physical activity. The single exposure assessment at baseline may not reflect the long-term pattern of these activities.

DISCLOSURES:

The lead author was supported by the National Social Science Foundation Project of China and the Zhejiang Provincial Philosophy and Social Sciences Planning Project. A co-author and the Nurses’ Health Study were supported by the US National Institutes of Health. The authors declared no conflicts of interest.

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

TOPLINE:

Sedentary behavior, particularly sitting and watching television, is linked to lower odds of healthy aging, but substituting it with any physical activity — or even sleeping, in case of women with inadequate sleep — may lead to better overall health.

METHODOLOGY:

• Previous studies have shown that replacing sedentary behavior with physical activity may improve mortality outcomes, but whether this increased lifespan is accompanied by better overall health remains an unanswered question.
• To understand the impact of sedentary behavior and physical activity on healthy aging, researchers analyzed data from the prospective cohort Nurses’ Health Study.
• They included 45,176 women aged > 50 years in 1992 (mean age, 59.2 years) who were free of major chronic diseases and were followed up for 20 years.
• In 1992, validated questionnaires were used to record exposure to sedentary behavior, different levels of physical activity, and sleep. The time spent watching television was the primary exposure in the sedentary behavior category.
• The main outcome was healthy aging, defined as survival to ≥ 70 years of age and maintenance of four domains of health — being free of 11 main chronic diseases and having no impairment of subjective memory, physical function, or mental health.

TAKEAWAY:

• At 20 years of follow-up, 8.6% of the women achieved healthy aging, while 41.4% had none of the 11 chronic diseases, 16.1% had no physical function impairment, 44.1% had no mental health limitation, and 51.9% reported no memory impairment.
• For each increase of 2 hours per day spent sitting and watching television, the odds of healthy aging dropped by 12% (95% confidence interval [CI], 7%-17%).
• Conversely, every additional 2 hours per day of low-level physical activity at work upped the odds of healthy aging by 6% (95% CI, 3%-9%); furthermore, each extra hour per day of standardized moderate to vigorous physical activity (normal pace walking or the equivalent) was associated with 14% higher odds (95% CI, 11%-16%) of healthy aging.
• In a theoretical modeling analysis, individuals could increase their odds of healthy aging by replacing 1 hour of television time per day with low levels of physical activity at home and work or with moderate to vigorous levels of physical activity — or even sleeping, for those who slept for ≤ 7 hours.

IN PRACTICE:

“These findings expand on the literature reporting that replacing sedentary behavior with light or moderate to vigorous physical activity is associated with decreased mortality by suggesting that this increased lifespan might be accompanied by better overall health,” the authors wrote.

SOURCE:

Hongying Shi, PhD, Department of Epidemiology and Health Statistics, School of Public Health, Wenzhou Medical University, Wenzhou, China, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

The measures of different behaviors were self-reported and may, therefore, be less accurate than objective measurement methods. Measurement error may have attenuated the effect of low levels of physical activity. The single exposure assessment at baseline may not reflect the long-term pattern of these activities.

DISCLOSURES:

The lead author was supported by the National Social Science Foundation Project of China and the Zhejiang Provincial Philosophy and Social Sciences Planning Project. A co-author and the Nurses’ Health Study were supported by the US National Institutes of Health. The authors declared no conflicts of interest.

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

TOPLINE:

Sedentary behavior, particularly sitting and watching television, is linked to lower odds of healthy aging, but substituting it with any physical activity — or even sleeping, in case of women with inadequate sleep — may lead to better overall health.

METHODOLOGY:

• Previous studies have shown that replacing sedentary behavior with physical activity may improve mortality outcomes, but whether this increased lifespan is accompanied by better overall health remains an unanswered question.
• To understand the impact of sedentary behavior and physical activity on healthy aging, researchers analyzed data from the prospective cohort Nurses’ Health Study.
• They included 45,176 women aged > 50 years in 1992 (mean age, 59.2 years) who were free of major chronic diseases and were followed up for 20 years.
• In 1992, validated questionnaires were used to record exposure to sedentary behavior, different levels of physical activity, and sleep. The time spent watching television was the primary exposure in the sedentary behavior category.
• The main outcome was healthy aging, defined as survival to ≥ 70 years of age and maintenance of four domains of health — being free of 11 main chronic diseases and having no impairment of subjective memory, physical function, or mental health.

TAKEAWAY:

• At 20 years of follow-up, 8.6% of the women achieved healthy aging, while 41.4% had none of the 11 chronic diseases, 16.1% had no physical function impairment, 44.1% had no mental health limitation, and 51.9% reported no memory impairment.
• For each increase of 2 hours per day spent sitting and watching television, the odds of healthy aging dropped by 12% (95% confidence interval [CI], 7%-17%).
• Conversely, every additional 2 hours per day of low-level physical activity at work upped the odds of healthy aging by 6% (95% CI, 3%-9%); furthermore, each extra hour per day of standardized moderate to vigorous physical activity (normal pace walking or the equivalent) was associated with 14% higher odds (95% CI, 11%-16%) of healthy aging.
• In a theoretical modeling analysis, individuals could increase their odds of healthy aging by replacing 1 hour of television time per day with low levels of physical activity at home and work or with moderate to vigorous levels of physical activity — or even sleeping, for those who slept for ≤ 7 hours.

IN PRACTICE:

“These findings expand on the literature reporting that replacing sedentary behavior with light or moderate to vigorous physical activity is associated with decreased mortality by suggesting that this increased lifespan might be accompanied by better overall health,” the authors wrote.

SOURCE:

Hongying Shi, PhD, Department of Epidemiology and Health Statistics, School of Public Health, Wenzhou Medical University, Wenzhou, China, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

The measures of different behaviors were self-reported and may, therefore, be less accurate than objective measurement methods. Measurement error may have attenuated the effect of low levels of physical activity. The single exposure assessment at baseline may not reflect the long-term pattern of these activities.

DISCLOSURES:

The lead author was supported by the National Social Science Foundation Project of China and the Zhejiang Provincial Philosophy and Social Sciences Planning Project. A co-author and the Nurses’ Health Study were supported by the US National Institutes of Health. The authors declared no conflicts of interest.

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

The Food and Drug Administration has approved ustekinumab-ttwe (Pyzchiva) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions.

In addition, the agency “provisionally determined” that the medication would be interchangeable with the reference product but that designation would not take hold until the interchangeability exclusivity period for the first approved biosimilar ustekinumab-auub (Wezlana) expires, according to a press release. This designation would, depending on state law, allow a pharmacist to substitute the biosimilar for the reference product without involving the prescribing clinician. It’s unclear when ustekinumab-auub’s interchangeability exclusivity ends.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Ustekinumab-ttwe, a human interleukin (IL)-12 and IL-23 antagonist, is indicated for the treatment of:

• Moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years or older who are candidates for phototherapy or systemic therapy 
• Active psoriatic arthritis in adults and pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease or ulcerative colitis

It is administered via subcutaneous injection in 45 mg/0.5 mL and 90 mg/mL prefilled syringes or via intravenous infusion in 130 mg/26 mL (5 mg/mL) single-dose vial. 

Developed by Samsung Bioepis, ustekinumab-ttwe will be commercialized by Sandoz in the United States. Besides ustekinumab-auub, the other ustekinumab biosimilar is ustekinumab-aekn (Selarsdi).

Ustekinumab-ttwe is expected to launch in February 2025 “in accordance with the settlement and license agreement with Janssen Biotech,” which manufacturers the reference product, Sandoz said. The other approved ustekinumab biosimilars will launch within a similar time frame.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved ustekinumab-ttwe (Pyzchiva) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions.

In addition, the agency “provisionally determined” that the medication would be interchangeable with the reference product but that designation would not take hold until the interchangeability exclusivity period for the first approved biosimilar ustekinumab-auub (Wezlana) expires, according to a press release. This designation would, depending on state law, allow a pharmacist to substitute the biosimilar for the reference product without involving the prescribing clinician. It’s unclear when ustekinumab-auub’s interchangeability exclusivity ends.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Ustekinumab-ttwe, a human interleukin (IL)-12 and IL-23 antagonist, is indicated for the treatment of:

• Moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years or older who are candidates for phototherapy or systemic therapy 
• Active psoriatic arthritis in adults and pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease or ulcerative colitis

It is administered via subcutaneous injection in 45 mg/0.5 mL and 90 mg/mL prefilled syringes or via intravenous infusion in 130 mg/26 mL (5 mg/mL) single-dose vial. 

Developed by Samsung Bioepis, ustekinumab-ttwe will be commercialized by Sandoz in the United States. Besides ustekinumab-auub, the other ustekinumab biosimilar is ustekinumab-aekn (Selarsdi).

Ustekinumab-ttwe is expected to launch in February 2025 “in accordance with the settlement and license agreement with Janssen Biotech,” which manufacturers the reference product, Sandoz said. The other approved ustekinumab biosimilars will launch within a similar time frame.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved ustekinumab-ttwe (Pyzchiva) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions.

In addition, the agency “provisionally determined” that the medication would be interchangeable with the reference product but that designation would not take hold until the interchangeability exclusivity period for the first approved biosimilar ustekinumab-auub (Wezlana) expires, according to a press release. This designation would, depending on state law, allow a pharmacist to substitute the biosimilar for the reference product without involving the prescribing clinician. It’s unclear when ustekinumab-auub’s interchangeability exclusivity ends.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Ustekinumab-ttwe, a human interleukin (IL)-12 and IL-23 antagonist, is indicated for the treatment of:

• Moderate to severe plaque psoriasis in adults and pediatric patients aged 6 years or older who are candidates for phototherapy or systemic therapy 
• Active psoriatic arthritis in adults and pediatric patients aged 6 years or older with moderately to severely active Crohn’s disease or ulcerative colitis

It is administered via subcutaneous injection in 45 mg/0.5 mL and 90 mg/mL prefilled syringes or via intravenous infusion in 130 mg/26 mL (5 mg/mL) single-dose vial. 

Developed by Samsung Bioepis, ustekinumab-ttwe will be commercialized by Sandoz in the United States. Besides ustekinumab-auub, the other ustekinumab biosimilar is ustekinumab-aekn (Selarsdi).

Ustekinumab-ttwe is expected to launch in February 2025 “in accordance with the settlement and license agreement with Janssen Biotech,” which manufacturers the reference product, Sandoz said. The other approved ustekinumab biosimilars will launch within a similar time frame.

A version of this article appeared on Medscape.com.

TOPLINE:

People with obesity who exercise while taking glucagon-like peptide 1 receptor agonists (GLP-1 RAs; liraglutide) showed increased weight loss and preserved bone health, according to a study published in JAMA Network Open.

METHODOLOGY:

• Patients were placed on an initial diet that consisted of no more than 800 calories per day for 8 weeks. Those who lost at least 5% of their starting weight were then placed into a 1-year program.
• Participants included 195 adults aged between 18 and 65 years with obesity and no diabetes, 64% of whom were women.
• They were split into four groups of interventions: Exercise only (48 patients), liraglutide only (49 patients), a combination of both (49 participants), and placebo (49 participants), for a 1-year period.
• Patients received liraglutide or volume-matched placebo as daily injections starting at 0.6 mg/d with a weekly increase until 3 mg/d was reached; exercise entailed 30-minute sessions for 4 days a week.
• Researchers studied bone health at each patient’s hip, spine, and forearm after they lost weight, by measuring bone mineral density (BMD).

TAKEAWAY:

• The overall average change in weight loss over the course of 52 weeks was 7.03 kg in the placebo group, 11.19 kg in the exercise group, 13.74 kg in the liraglutide group, and 16.88 kg in the combination group.
• After the initial low-calorie diet-induced weight loss, the placebo group regained weight, the exercise and liraglutide groups maintained weight loss, and the combination group lost additional weight.
• BMD did not change in the combination group in comparison to the placebo group at the hip (mean change, −0.006 g/cm²; 95% CI, −0.017 to 0.004 g/cm²; P = .24) or spine (−0.010 g/cm²; 95% CI, −0.025 to 0.005 g/cm²; P = .20).
• BMD of the spine in the liraglutide group decreased in comparison to the exercise group (mean change, −0.016 g/cm²; 95% CI, −0.032 to −0.001 g/cm²; P = .04) and the placebo group, in addition to decreases in the hip.

IN PRACTICE:

“Our results show that the combination of exercise and GLP-1 RA was the most effective weight loss strategy while preserving bone health,” study authors wrote.

SOURCE:

The study was led by Simon Birk Kjær Jensen, PhD, of the Department of Biomedical Sciences and Faculty of Health and Medical Sciences at the University of Copenhagen in Denmark, and published on June 25 in JAMA Network Open.

LIMITATIONS:

The study only included adults aged between 18 and 65 years without other chronic diseases and may not apply to patients who are older or have diabetes. The study sample was diverse but was conducted in Denmark, with a population of generally similar ancestry.

DISCLOSURES:

One study author reported serving on advisory boards for AstraZeneca, Boehringer Ingelheim, Bayer, and Amgen, among others. Other authors reported various financial interests, including grants, personal fees, and salaries, from Amgen, Novo Nordisk, and Abbott Lab, among others.

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

TOPLINE:

People with obesity who exercise while taking glucagon-like peptide 1 receptor agonists (GLP-1 RAs; liraglutide) showed increased weight loss and preserved bone health, according to a study published in JAMA Network Open.

METHODOLOGY:

• Patients were placed on an initial diet that consisted of no more than 800 calories per day for 8 weeks. Those who lost at least 5% of their starting weight were then placed into a 1-year program.
• Participants included 195 adults aged between 18 and 65 years with obesity and no diabetes, 64% of whom were women.
• They were split into four groups of interventions: Exercise only (48 patients), liraglutide only (49 patients), a combination of both (49 participants), and placebo (49 participants), for a 1-year period.
• Patients received liraglutide or volume-matched placebo as daily injections starting at 0.6 mg/d with a weekly increase until 3 mg/d was reached; exercise entailed 30-minute sessions for 4 days a week.
• Researchers studied bone health at each patient’s hip, spine, and forearm after they lost weight, by measuring bone mineral density (BMD).

TAKEAWAY:

• The overall average change in weight loss over the course of 52 weeks was 7.03 kg in the placebo group, 11.19 kg in the exercise group, 13.74 kg in the liraglutide group, and 16.88 kg in the combination group.
• After the initial low-calorie diet-induced weight loss, the placebo group regained weight, the exercise and liraglutide groups maintained weight loss, and the combination group lost additional weight.
• BMD did not change in the combination group in comparison to the placebo group at the hip (mean change, −0.006 g/cm²; 95% CI, −0.017 to 0.004 g/cm²; P = .24) or spine (−0.010 g/cm²; 95% CI, −0.025 to 0.005 g/cm²; P = .20).
• BMD of the spine in the liraglutide group decreased in comparison to the exercise group (mean change, −0.016 g/cm²; 95% CI, −0.032 to −0.001 g/cm²; P = .04) and the placebo group, in addition to decreases in the hip.

IN PRACTICE:

“Our results show that the combination of exercise and GLP-1 RA was the most effective weight loss strategy while preserving bone health,” study authors wrote.

SOURCE:

The study was led by Simon Birk Kjær Jensen, PhD, of the Department of Biomedical Sciences and Faculty of Health and Medical Sciences at the University of Copenhagen in Denmark, and published on June 25 in JAMA Network Open.

LIMITATIONS:

The study only included adults aged between 18 and 65 years without other chronic diseases and may not apply to patients who are older or have diabetes. The study sample was diverse but was conducted in Denmark, with a population of generally similar ancestry.

DISCLOSURES:

One study author reported serving on advisory boards for AstraZeneca, Boehringer Ingelheim, Bayer, and Amgen, among others. Other authors reported various financial interests, including grants, personal fees, and salaries, from Amgen, Novo Nordisk, and Abbott Lab, among others.

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

TOPLINE:

People with obesity who exercise while taking glucagon-like peptide 1 receptor agonists (GLP-1 RAs; liraglutide) showed increased weight loss and preserved bone health, according to a study published in JAMA Network Open.

METHODOLOGY:

• Patients were placed on an initial diet that consisted of no more than 800 calories per day for 8 weeks. Those who lost at least 5% of their starting weight were then placed into a 1-year program.
• Participants included 195 adults aged between 18 and 65 years with obesity and no diabetes, 64% of whom were women.
• They were split into four groups of interventions: Exercise only (48 patients), liraglutide only (49 patients), a combination of both (49 participants), and placebo (49 participants), for a 1-year period.
• Patients received liraglutide or volume-matched placebo as daily injections starting at 0.6 mg/d with a weekly increase until 3 mg/d was reached; exercise entailed 30-minute sessions for 4 days a week.
• Researchers studied bone health at each patient’s hip, spine, and forearm after they lost weight, by measuring bone mineral density (BMD).

TAKEAWAY:

• The overall average change in weight loss over the course of 52 weeks was 7.03 kg in the placebo group, 11.19 kg in the exercise group, 13.74 kg in the liraglutide group, and 16.88 kg in the combination group.
• After the initial low-calorie diet-induced weight loss, the placebo group regained weight, the exercise and liraglutide groups maintained weight loss, and the combination group lost additional weight.
• BMD did not change in the combination group in comparison to the placebo group at the hip (mean change, −0.006 g/cm²; 95% CI, −0.017 to 0.004 g/cm²; P = .24) or spine (−0.010 g/cm²; 95% CI, −0.025 to 0.005 g/cm²; P = .20).
• BMD of the spine in the liraglutide group decreased in comparison to the exercise group (mean change, −0.016 g/cm²; 95% CI, −0.032 to −0.001 g/cm²; P = .04) and the placebo group, in addition to decreases in the hip.

IN PRACTICE:

“Our results show that the combination of exercise and GLP-1 RA was the most effective weight loss strategy while preserving bone health,” study authors wrote.

SOURCE:

The study was led by Simon Birk Kjær Jensen, PhD, of the Department of Biomedical Sciences and Faculty of Health and Medical Sciences at the University of Copenhagen in Denmark, and published on June 25 in JAMA Network Open.

LIMITATIONS:

The study only included adults aged between 18 and 65 years without other chronic diseases and may not apply to patients who are older or have diabetes. The study sample was diverse but was conducted in Denmark, with a population of generally similar ancestry.

DISCLOSURES:

One study author reported serving on advisory boards for AstraZeneca, Boehringer Ingelheim, Bayer, and Amgen, among others. Other authors reported various financial interests, including grants, personal fees, and salaries, from Amgen, Novo Nordisk, and Abbott Lab, among others.

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