Rheumatology News

TOPLINE:

The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.

METHODOLOGY:

• Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
• A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
• The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.

TAKEAWAY:

• More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
• Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
• Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
• The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.

IN PRACTICE:

“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
 

SOURCE:

Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.

LIMITATIONS:

The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
 

DISCLOSURES:

The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

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

TOPLINE:

The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.

METHODOLOGY:

• Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
• A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
• The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.

TAKEAWAY:

• More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
• Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
• Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
• The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.

IN PRACTICE:

“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
 

SOURCE:

Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.

LIMITATIONS:

The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
 

DISCLOSURES:

The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

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

TOPLINE:

The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.

METHODOLOGY:

• Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
• A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
• The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.

TAKEAWAY:

• More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
• Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
• Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
• The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.

IN PRACTICE:

“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
 

SOURCE:

Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.

LIMITATIONS:

The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
 

DISCLOSURES:

The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

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

TOPLINE:

Treatment of patients with active psoriatic arthritis with sonelokimab — an interleukin (IL)-17A- and IL-17F-inhibiting nanobody — led to a higher percentage of patients with 50% or greater improvement in American College of Rheumatology response criteria (ACR50) compared with the placebo in a phase 2 trial.

METHODOLOGY:

• Sonelokimab is a 40-kDa nanobody that binds to IL-17A, IL-17F, and albumin.
• Eligible patients were at least 18 years old with active PsA (at least three swollen and three tender joints) and had a psoriasis diagnosis.
• A total of 207 patients were randomized 1:1:1:1 to every 4 weeks receive placebo, sonelokimab 60 mg with no induction (NI) period, sonelokimab 60 mg with induction, and sonelokimab 120 mg with induction.
• Induction was once every 2 weeks up to week 8 of the trial.
• The primary endpoint was meeting ACR20 response criteria at 12 weeks.

TAKEAWAY:

• About 46% of patients in the sonelokimab 120-mg and 60-mg groups achieved ACR50, compared with 36.6% in the sonelokimab 60-mg NI group and 20% of those assigned to placebo.
• ACR20 and 90% or greater reduction in Psoriasis Area and Severity Index score response rates were higher in all three sonelokimab groups than in the placebo group.
• There were no unexpected safety findings during the trial, and no cases of inflammatory bowel disease or major cardiovascular events.
• There were two cases of oral candidiasis, which did not lead to study discontinuation.

IN PRACTICE:

These data “support further exploration in phase 3 trials of sonelokimab to evaluate its potential for the treatment of PsA,” the authors noted in the presentation.

SOURCE:

Iain B. McInnes, MD, PhD, of the University of Glasgow, Glasgow, Scotland, presented these phase 2 trial results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Congress, held in Vienna.

LIMITATIONS:

The results are from a phase 2 trial, and more research is needed.

DISCLOSURES:

MoonLake Immunotherapeutics funded the research. Dr. McInnes disclosed relationships with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Evelo, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

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

TOPLINE:

Treatment of patients with active psoriatic arthritis with sonelokimab — an interleukin (IL)-17A- and IL-17F-inhibiting nanobody — led to a higher percentage of patients with 50% or greater improvement in American College of Rheumatology response criteria (ACR50) compared with the placebo in a phase 2 trial.

METHODOLOGY:

• Sonelokimab is a 40-kDa nanobody that binds to IL-17A, IL-17F, and albumin.
• Eligible patients were at least 18 years old with active PsA (at least three swollen and three tender joints) and had a psoriasis diagnosis.
• A total of 207 patients were randomized 1:1:1:1 to every 4 weeks receive placebo, sonelokimab 60 mg with no induction (NI) period, sonelokimab 60 mg with induction, and sonelokimab 120 mg with induction.
• Induction was once every 2 weeks up to week 8 of the trial.
• The primary endpoint was meeting ACR20 response criteria at 12 weeks.

TAKEAWAY:

• About 46% of patients in the sonelokimab 120-mg and 60-mg groups achieved ACR50, compared with 36.6% in the sonelokimab 60-mg NI group and 20% of those assigned to placebo.
• ACR20 and 90% or greater reduction in Psoriasis Area and Severity Index score response rates were higher in all three sonelokimab groups than in the placebo group.
• There were no unexpected safety findings during the trial, and no cases of inflammatory bowel disease or major cardiovascular events.
• There were two cases of oral candidiasis, which did not lead to study discontinuation.

IN PRACTICE:

These data “support further exploration in phase 3 trials of sonelokimab to evaluate its potential for the treatment of PsA,” the authors noted in the presentation.

SOURCE:

Iain B. McInnes, MD, PhD, of the University of Glasgow, Glasgow, Scotland, presented these phase 2 trial results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Congress, held in Vienna.

LIMITATIONS:

The results are from a phase 2 trial, and more research is needed.

DISCLOSURES:

MoonLake Immunotherapeutics funded the research. Dr. McInnes disclosed relationships with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Evelo, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

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

TOPLINE:

Treatment of patients with active psoriatic arthritis with sonelokimab — an interleukin (IL)-17A- and IL-17F-inhibiting nanobody — led to a higher percentage of patients with 50% or greater improvement in American College of Rheumatology response criteria (ACR50) compared with the placebo in a phase 2 trial.

METHODOLOGY:

• Sonelokimab is a 40-kDa nanobody that binds to IL-17A, IL-17F, and albumin.
• Eligible patients were at least 18 years old with active PsA (at least three swollen and three tender joints) and had a psoriasis diagnosis.
• A total of 207 patients were randomized 1:1:1:1 to every 4 weeks receive placebo, sonelokimab 60 mg with no induction (NI) period, sonelokimab 60 mg with induction, and sonelokimab 120 mg with induction.
• Induction was once every 2 weeks up to week 8 of the trial.
• The primary endpoint was meeting ACR20 response criteria at 12 weeks.

TAKEAWAY:

• About 46% of patients in the sonelokimab 120-mg and 60-mg groups achieved ACR50, compared with 36.6% in the sonelokimab 60-mg NI group and 20% of those assigned to placebo.
• ACR20 and 90% or greater reduction in Psoriasis Area and Severity Index score response rates were higher in all three sonelokimab groups than in the placebo group.
• There were no unexpected safety findings during the trial, and no cases of inflammatory bowel disease or major cardiovascular events.
• There were two cases of oral candidiasis, which did not lead to study discontinuation.

IN PRACTICE:

These data “support further exploration in phase 3 trials of sonelokimab to evaluate its potential for the treatment of PsA,” the authors noted in the presentation.

SOURCE:

Iain B. McInnes, MD, PhD, of the University of Glasgow, Glasgow, Scotland, presented these phase 2 trial results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Congress, held in Vienna.

LIMITATIONS:

The results are from a phase 2 trial, and more research is needed.

DISCLOSURES:

MoonLake Immunotherapeutics funded the research. Dr. McInnes disclosed relationships with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Evelo, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

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

The Food and Drug Administration (FDA) has issued new draft guidance that does not require additional switching studies for biosimilars seeking interchangeability. These studies were previously recommended to demonstrate that switching between the biosimilar and its reference product showed no greater risk than using the reference product alone.

“The recommendations in today’s draft guidance, when finalized, will provide clarity and transparency about the FDA’s thinking and align the review and approval process with existing and emerging science,” said Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars in a statement on June 20. “We have gained valuable experience reviewing both biosimilar and interchangeable biosimilar medications over the past 10 years. Both biosimilars and interchangeable biosimilars meet the same high standard of biosimilarity for FDA approval and both are as safe and effective as the reference product.”

An interchangeable status allows a biosimilar product to be swapped with the reference product without involvement from the prescribing provider, depending on state law.

While switching studies were not required under previous FDA guidance, the 2019 document did state that the agency “expects that applications generally will include data from a switching study or studies in one or more appropriate conditions of use.”

However, of the 13 biosimilars that received interchangeability status, 9 did not include switching study data.

“Experience has shown that, for the products approved as biosimilars to date, the risk in terms of safety or diminished efficacy is insignificant following single or multiple switches between a reference product and a biosimilar product,” the FDA stated. The agency’s investigators also conducted a systematic review of switching studies, which found no differences in risk for death, serious adverse events, and treatment discontinuations in participants switched between biosimilars and reference products and those that remained on reference products.

“Additionally, today’s analytical tools can accurately evaluate the structure and effects [of] biologic products, both in the lab (in vitro) and in living organisms (in vivo) with more precision and sensitivity than switching studies,” the agency noted.

The FDA is now calling for commentary on these draft recommendations to be submitted by Aug. 20, 2024.

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

The Food and Drug Administration (FDA) has issued new draft guidance that does not require additional switching studies for biosimilars seeking interchangeability. These studies were previously recommended to demonstrate that switching between the biosimilar and its reference product showed no greater risk than using the reference product alone.

“The recommendations in today’s draft guidance, when finalized, will provide clarity and transparency about the FDA’s thinking and align the review and approval process with existing and emerging science,” said Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars in a statement on June 20. “We have gained valuable experience reviewing both biosimilar and interchangeable biosimilar medications over the past 10 years. Both biosimilars and interchangeable biosimilars meet the same high standard of biosimilarity for FDA approval and both are as safe and effective as the reference product.”

An interchangeable status allows a biosimilar product to be swapped with the reference product without involvement from the prescribing provider, depending on state law.

While switching studies were not required under previous FDA guidance, the 2019 document did state that the agency “expects that applications generally will include data from a switching study or studies in one or more appropriate conditions of use.”

However, of the 13 biosimilars that received interchangeability status, 9 did not include switching study data.

“Experience has shown that, for the products approved as biosimilars to date, the risk in terms of safety or diminished efficacy is insignificant following single or multiple switches between a reference product and a biosimilar product,” the FDA stated. The agency’s investigators also conducted a systematic review of switching studies, which found no differences in risk for death, serious adverse events, and treatment discontinuations in participants switched between biosimilars and reference products and those that remained on reference products.

“Additionally, today’s analytical tools can accurately evaluate the structure and effects [of] biologic products, both in the lab (in vitro) and in living organisms (in vivo) with more precision and sensitivity than switching studies,” the agency noted.

The FDA is now calling for commentary on these draft recommendations to be submitted by Aug. 20, 2024.

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

The Food and Drug Administration (FDA) has issued new draft guidance that does not require additional switching studies for biosimilars seeking interchangeability. These studies were previously recommended to demonstrate that switching between the biosimilar and its reference product showed no greater risk than using the reference product alone.

“The recommendations in today’s draft guidance, when finalized, will provide clarity and transparency about the FDA’s thinking and align the review and approval process with existing and emerging science,” said Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars in a statement on June 20. “We have gained valuable experience reviewing both biosimilar and interchangeable biosimilar medications over the past 10 years. Both biosimilars and interchangeable biosimilars meet the same high standard of biosimilarity for FDA approval and both are as safe and effective as the reference product.”

An interchangeable status allows a biosimilar product to be swapped with the reference product without involvement from the prescribing provider, depending on state law.

While switching studies were not required under previous FDA guidance, the 2019 document did state that the agency “expects that applications generally will include data from a switching study or studies in one or more appropriate conditions of use.”

However, of the 13 biosimilars that received interchangeability status, 9 did not include switching study data.

“Experience has shown that, for the products approved as biosimilars to date, the risk in terms of safety or diminished efficacy is insignificant following single or multiple switches between a reference product and a biosimilar product,” the FDA stated. The agency’s investigators also conducted a systematic review of switching studies, which found no differences in risk for death, serious adverse events, and treatment discontinuations in participants switched between biosimilars and reference products and those that remained on reference products.

“Additionally, today’s analytical tools can accurately evaluate the structure and effects [of] biologic products, both in the lab (in vitro) and in living organisms (in vivo) with more precision and sensitivity than switching studies,” the agency noted.

The FDA is now calling for commentary on these draft recommendations to be submitted by Aug. 20, 2024.

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

Baricitinib may be the superior choice to tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) for whom conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) have failed, according to a new study.

After 12 weeks, patients taking baricitinib achieved a 50% improvement in RA symptoms according to American College of Rheumatology response criteria (ACR50) at twice the rate as in patients assigned to receive TNF inhibitors. In addition, 75% of the baricitinib group achieved a 28-joint Disease Activity Score with C-reactive protein under 2.6, compared with less than half of patients taking TNF inhibitors.
 

Putting Safety Into the Equation

However, safety concerns also need to be considered when prescribing medication, noted Andrew Wang, MD, PhD, a rheumatologist at Yale School of Medicine in New Haven, Connecticut. He was not involved with the study, called PERFECTRA.

“This category of drugs — JAK-STAT [inhibitors] — are much newer than TNF inhibitors, CTLAs, B-cell depleters, and the other tools we have,” he said, “with relatively less real-world experience and potential downsides in the future.”

Study Details

In the study, researchers enrolled 199 patients with active RA for which previous use of at least one csDMARD had failed and randomly assigned 97 patients to receive baricitinib and the remainder to receive a TNF inhibitor: 64% started on adalimumab, 33% started on etanercept, and the rest used golimumab or infliximab.

For all patients, the suggested treatment allocation was provided via randomization lists, but physicians and patients ultimately decided treatment via shared decision-making.

Patients were diagnosed less than 5 years ago, had received no previous treatment with biologics or targeted synthetic DMARDs, and had no contraindications for TNF inhibitors or baricitinib. Researchers recruited patients from September 2019 through February 2022 across 15 health centers in the Netherlands and Belgium. The study was funded by Eli Lilly, which manufactures baricitinib, although the study was investigator initiated.

Patients were on average aged 55 years, and about two thirds were women. The average disease duration was 2 years.

At 12 weeks, 42% of the baricitinib group achieved ACR50, compared with 20% of the TNF inhibitor group. All patient-reported outcome measures showed improvement over the study period, favoring baricitinib. More patients receiving baricitinib remained on the medication overall than patients on a TNF inhibitor: At 48 weeks, 70% of patients receiving a TNF inhibitor and 80% of patients receiving baricitinib had continued taking their assigned treatment.

These results are not surprising, Wang noted, as “JAK inhibitors hit many arms of immune signaling, whereas TNF blockers just hit TNF.” However, there is a trade-off between potent, effective drugs and toxicity, he added.

“I would not be as bullish on starting baricitinib in a patient off the bat, in the same way that nobody would want to keep patients on glucocorticoids [any longer than is] minimally necessary.”

While the study was not powered to compare safety between the two drugs, there were no adverse events during the study that had not been previously reported.

“Prescribers have to be aware that cardiovascular and malignant [serious adverse events] are more frequently reported” with JAK inhibitors than with TNF inhibitors, the authors wrote. “Obviously, this has to be considered carefully in risk-benefit discussions with any individual patient.”

Dr. Wang noted that, in general, he and his colleagues would not start with a JAK inhibitor first except for special circumstances: For example, if a patient will not use an injectable medication, or for some reason, it’s impractical for the patient’s lifestyle to use medication that requires constant refrigeration.

“I think the take-home message here is these are, in general, lifelong diseases, and so a rheumatologist and their patients have to develop good relationships to monitor whether or not we’re hitting the sweet spot of keeping disease under control” while also avoiding overmedication and toxicity, he said.

One potential solution, which Dr. Wang has also done in his clinical practice, is to initiate a JAK inhibitor in patients who need it but then switch to a different modality after achieving disease control.

“You can imagine a scenario where you get them to a very low [Disease Activity Score] with baricitinib, for example, and then you switch them to a TNF inhibitor,” he said. “I can imagine that there would be ways that you could get the best of both worlds.”

PERFECTRA was financially supported by an unrestricted grant from Eli Lilly. The authors reported financial relationships with AbbVie, Eli Lilly, Galapagos, and Janssen-Cilag. Dr. Wang serves on NGM Bio’s science advisory board, consults for TCG Labs-Soleil and Seranova Bio, and has received funding from AstraZeneca.

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

Baricitinib may be the superior choice to tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) for whom conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) have failed, according to a new study.

After 12 weeks, patients taking baricitinib achieved a 50% improvement in RA symptoms according to American College of Rheumatology response criteria (ACR50) at twice the rate as in patients assigned to receive TNF inhibitors. In addition, 75% of the baricitinib group achieved a 28-joint Disease Activity Score with C-reactive protein under 2.6, compared with less than half of patients taking TNF inhibitors.
 

Putting Safety Into the Equation

However, safety concerns also need to be considered when prescribing medication, noted Andrew Wang, MD, PhD, a rheumatologist at Yale School of Medicine in New Haven, Connecticut. He was not involved with the study, called PERFECTRA.

“This category of drugs — JAK-STAT [inhibitors] — are much newer than TNF inhibitors, CTLAs, B-cell depleters, and the other tools we have,” he said, “with relatively less real-world experience and potential downsides in the future.”

Study Details

In the study, researchers enrolled 199 patients with active RA for which previous use of at least one csDMARD had failed and randomly assigned 97 patients to receive baricitinib and the remainder to receive a TNF inhibitor: 64% started on adalimumab, 33% started on etanercept, and the rest used golimumab or infliximab.

For all patients, the suggested treatment allocation was provided via randomization lists, but physicians and patients ultimately decided treatment via shared decision-making.

Patients were diagnosed less than 5 years ago, had received no previous treatment with biologics or targeted synthetic DMARDs, and had no contraindications for TNF inhibitors or baricitinib. Researchers recruited patients from September 2019 through February 2022 across 15 health centers in the Netherlands and Belgium. The study was funded by Eli Lilly, which manufactures baricitinib, although the study was investigator initiated.

Patients were on average aged 55 years, and about two thirds were women. The average disease duration was 2 years.

At 12 weeks, 42% of the baricitinib group achieved ACR50, compared with 20% of the TNF inhibitor group. All patient-reported outcome measures showed improvement over the study period, favoring baricitinib. More patients receiving baricitinib remained on the medication overall than patients on a TNF inhibitor: At 48 weeks, 70% of patients receiving a TNF inhibitor and 80% of patients receiving baricitinib had continued taking their assigned treatment.

These results are not surprising, Wang noted, as “JAK inhibitors hit many arms of immune signaling, whereas TNF blockers just hit TNF.” However, there is a trade-off between potent, effective drugs and toxicity, he added.

“I would not be as bullish on starting baricitinib in a patient off the bat, in the same way that nobody would want to keep patients on glucocorticoids [any longer than is] minimally necessary.”

While the study was not powered to compare safety between the two drugs, there were no adverse events during the study that had not been previously reported.

“Prescribers have to be aware that cardiovascular and malignant [serious adverse events] are more frequently reported” with JAK inhibitors than with TNF inhibitors, the authors wrote. “Obviously, this has to be considered carefully in risk-benefit discussions with any individual patient.”

Dr. Wang noted that, in general, he and his colleagues would not start with a JAK inhibitor first except for special circumstances: For example, if a patient will not use an injectable medication, or for some reason, it’s impractical for the patient’s lifestyle to use medication that requires constant refrigeration.

“I think the take-home message here is these are, in general, lifelong diseases, and so a rheumatologist and their patients have to develop good relationships to monitor whether or not we’re hitting the sweet spot of keeping disease under control” while also avoiding overmedication and toxicity, he said.

One potential solution, which Dr. Wang has also done in his clinical practice, is to initiate a JAK inhibitor in patients who need it but then switch to a different modality after achieving disease control.

“You can imagine a scenario where you get them to a very low [Disease Activity Score] with baricitinib, for example, and then you switch them to a TNF inhibitor,” he said. “I can imagine that there would be ways that you could get the best of both worlds.”

PERFECTRA was financially supported by an unrestricted grant from Eli Lilly. The authors reported financial relationships with AbbVie, Eli Lilly, Galapagos, and Janssen-Cilag. Dr. Wang serves on NGM Bio’s science advisory board, consults for TCG Labs-Soleil and Seranova Bio, and has received funding from AstraZeneca.

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

Baricitinib may be the superior choice to tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) for whom conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) have failed, according to a new study.

After 12 weeks, patients taking baricitinib achieved a 50% improvement in RA symptoms according to American College of Rheumatology response criteria (ACR50) at twice the rate as in patients assigned to receive TNF inhibitors. In addition, 75% of the baricitinib group achieved a 28-joint Disease Activity Score with C-reactive protein under 2.6, compared with less than half of patients taking TNF inhibitors.
 

Putting Safety Into the Equation

However, safety concerns also need to be considered when prescribing medication, noted Andrew Wang, MD, PhD, a rheumatologist at Yale School of Medicine in New Haven, Connecticut. He was not involved with the study, called PERFECTRA.

“This category of drugs — JAK-STAT [inhibitors] — are much newer than TNF inhibitors, CTLAs, B-cell depleters, and the other tools we have,” he said, “with relatively less real-world experience and potential downsides in the future.”

Study Details

In the study, researchers enrolled 199 patients with active RA for which previous use of at least one csDMARD had failed and randomly assigned 97 patients to receive baricitinib and the remainder to receive a TNF inhibitor: 64% started on adalimumab, 33% started on etanercept, and the rest used golimumab or infliximab.

For all patients, the suggested treatment allocation was provided via randomization lists, but physicians and patients ultimately decided treatment via shared decision-making.

Patients were diagnosed less than 5 years ago, had received no previous treatment with biologics or targeted synthetic DMARDs, and had no contraindications for TNF inhibitors or baricitinib. Researchers recruited patients from September 2019 through February 2022 across 15 health centers in the Netherlands and Belgium. The study was funded by Eli Lilly, which manufactures baricitinib, although the study was investigator initiated.

Patients were on average aged 55 years, and about two thirds were women. The average disease duration was 2 years.

At 12 weeks, 42% of the baricitinib group achieved ACR50, compared with 20% of the TNF inhibitor group. All patient-reported outcome measures showed improvement over the study period, favoring baricitinib. More patients receiving baricitinib remained on the medication overall than patients on a TNF inhibitor: At 48 weeks, 70% of patients receiving a TNF inhibitor and 80% of patients receiving baricitinib had continued taking their assigned treatment.

These results are not surprising, Wang noted, as “JAK inhibitors hit many arms of immune signaling, whereas TNF blockers just hit TNF.” However, there is a trade-off between potent, effective drugs and toxicity, he added.

“I would not be as bullish on starting baricitinib in a patient off the bat, in the same way that nobody would want to keep patients on glucocorticoids [any longer than is] minimally necessary.”

While the study was not powered to compare safety between the two drugs, there were no adverse events during the study that had not been previously reported.

“Prescribers have to be aware that cardiovascular and malignant [serious adverse events] are more frequently reported” with JAK inhibitors than with TNF inhibitors, the authors wrote. “Obviously, this has to be considered carefully in risk-benefit discussions with any individual patient.”

Dr. Wang noted that, in general, he and his colleagues would not start with a JAK inhibitor first except for special circumstances: For example, if a patient will not use an injectable medication, or for some reason, it’s impractical for the patient’s lifestyle to use medication that requires constant refrigeration.

“I think the take-home message here is these are, in general, lifelong diseases, and so a rheumatologist and their patients have to develop good relationships to monitor whether or not we’re hitting the sweet spot of keeping disease under control” while also avoiding overmedication and toxicity, he said.

One potential solution, which Dr. Wang has also done in his clinical practice, is to initiate a JAK inhibitor in patients who need it but then switch to a different modality after achieving disease control.

“You can imagine a scenario where you get them to a very low [Disease Activity Score] with baricitinib, for example, and then you switch them to a TNF inhibitor,” he said. “I can imagine that there would be ways that you could get the best of both worlds.”

PERFECTRA was financially supported by an unrestricted grant from Eli Lilly. The authors reported financial relationships with AbbVie, Eli Lilly, Galapagos, and Janssen-Cilag. Dr. Wang serves on NGM Bio’s science advisory board, consults for TCG Labs-Soleil and Seranova Bio, and has received funding from AstraZeneca.

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

VIENNA — People with spondyloarthritis (SpA) who have low or stable disease activity can effectively and safely be managed using a model of patient-initiated care with or without remote monitoring, suggested the results of two separate trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting. 

In the 18-month, single-center ReMonit study that included 243 people with axial SpA (axSpA), patient-initiated care was found to be noninferior for keeping them in a low-disease activity state, compared with both usual hospital follow-up and remote digital monitoring.

Meanwhile, in the 12-month, multicenter TeleSpA study, which included 200 patients with any type of SpA, the number of hospital visits needed by people who were randomly assigned to receive patient-initiated care together with asynchronous telemonitoring was significantly lower than for the usual-care group, with no detriment to the participants’ overall health outcomes or safety. Moreover, the strategy was deemed cost-effective from a healthcare provision perspective.
 

Time to Rationalize Healthcare Resources?

People with chronic rheumatic diseases such as axSpA require long-term follow-up in specialist healthcare centers, Inger Jorid Berg, MD, PhD, of Diakonhjemmet Hospital in Oslo, Norway, said when she presented the findings of the ReMonit study as a late-breaking abstract.

Sara Freeman/Medscape Medical News

“Traditionally, this has been offered as prescheduled face-to-face consultations at an outpatient clinic, but remote monitoring and patient-initiated care may allow for more targeted and efficient uses of healthcare resources,” Dr. Berg said.

“The end goal of what you’re trying to do is increase the efficiency of outpatient care and provide more patient-tailored care,” Kasper Hermans, MD, said in an interview. He presented the results of the TeleSpA study. 

Dr. Hermans, who is a rheumatology fellow and PhD candidate at Maastricht University, Maastricht, the Netherlands, observed during his presentation at EULAR 2024 that there is an increasing demand for rheumatology services but an expected shortfall in the future workforce. Thus, “sustainable alternative strategies are needed for optimizing the efficiency of care,” he said.

People need to have timely access to care, Dr. Hermans stressed, but perhaps alternatives to the traditional models of care where patients are seen routinely every 6 or 12 months are needed, particularly as prior work had suggested that around one-third of people who were seen by a rheumatologist perhaps did not need to be.

A strategy of patient-initiated care — which is where people are seen by a healthcare provider only if they feel that they need to and request a consultation — is therefore an attractive proposition, particularly if it is backed up with remote monitoring, which is what the TeleSpA study was testing.
 

Two Distinct Studies

ReMonit and TeleSpA were two distinct studies. While both were noninferiority trials and involved patient-initiated care and telemonitoring of outpatients with SpA, that is where the similarities generally end.

Notably, ReMonit included a very specific population of patients — all had a diagnosis of axSpA and were being treated with a tumor necrosis factor (TNF) inhibitor and had been on a stable dose for the last 6 months. For inclusion, they also had to have inactive disease or low disease activity, as indicated by an Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1.

ReMonit’s telemonitoring strategy involved participants completing monthly questionnaires using the Dignio smartphone app. Patients first completed the Patient Global Assessment (PGA) and noted whether they had experienced a flare in their disease. If they had a flare or their PGA score was 3 or higher, then they were asked to also complete the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI). If the BASDAI score was 4 or more, then the patient was called by a study nurse and offered a consultation.

“Patients in all three groups were recommended to take blood samples at the general practitioner’s or at the hospital every third month as a safety procedure when using TNF inhibitors,” Dr. Berg said.

The primary outcome was the proportion of people who remained with low disease activity (ASDAS < 2.1) at 6, 12, and 18 months in each of the three arms of the trial, which were patient-initiated care (n = 81), monthly remote monitoring (n = 80), or usual follow-up in the hospital every 6 months (n = 82).

TeleSpA on the other hand was a “much more pragmatic trial, much closer to actual care,” Dr. Hermans said. “We included axial spondyloarthritis, peripheral spondyloarthritis, or patients who had both axial and peripheral disease, including patients with psoriatic arthritis,” he said, adding that their inclusion was regardless of their baseline ASDAS based on C-reactive protein (ASDAS-CRP).

This means that patients who would otherwise have been classified at baseline as having high disease activity (by ASDAS-CRP or similar disease activity measures) could be included. The main proviso was that both the patient and their rheumatologist had to define the condition as being stable with an acceptable level of symptom control and no immediate plans to change treatment within the next 3 months.

TeleSpA’s remote monitoring strategy involved the use of SpA-Net, which Dr. Hermans and coinvestigators have described previously as “an ongoing, disease-specific, prospective, web-based registry for monitoring SpA in daily practice.” This captures a host of clinical and laboratory test information.

SpA-Net was used in both arms of the study. However, while the 100 participants in the standard-care arm completed questionnaires and had tests before every in-person visit that had been prescheduled with their rheumatologist, the 100 individuals in the patient-initiated care arm had no prescheduled in-person visits except for being seen at the start and end of the study. These patients were reminded via email to complete the necessary SpA-Net registry questionnaires at 6 months.

The primary outcome for TeleSpA was the total number of rheumatology visits, including both physical and telephone or video consultations, within a 1-year period. 
 

ReMonit Results

Berg reported that similar percentages of patients remained in a low disease activity state at 6, 12, and 18 months, regardless of the group that they had been randomized into, and that there was little change seen within the individual groups.

For instance, at 6, 12, and 18 months, 92%, 91%, and 92% of individuals in the patient-initiated arm had an ASDAS of < 2.1. Corresponding percentages for the usual-care arm were 96%, 93%, and 90% and for the remote-monitoring arm were 96%, 96%, and 94%.

Both patient-initiated care and remote monitoring were noninferior to usual care, and patient-initiated care was also noninferior to remote monitoring. There were no differences between the trial arms in terms of disease activity, measured using either ASDAS or BASDAI, at 6, 12, or 18 months.

Dr. Berg stated that “patient satisfaction was high in all three follow-up strategies, and there was the lowest resource use with patient-initiated care.” She concluded that “remote monitoring and patient-initiated care could be implemented in the follow-up of patients with axial spondyloarthritis and low disease activity.”
 

TeleSpA Results

In TeleSpA, people in the patient-initiated care and telemonitoring arm were seen a mean of 1.9 times over the course of the 1-year follow-up vs 2.6 for people in the usual care arm. The reduction was caused in part by the decrease in physical visits (1.4 vs 2.0) as there were the same mean number of telephone visits in each group. Overall, there was a 25.4% reduction in consultations comparing the patient-initiated care and telemonitoring arm with the usual-care arm.

Importantly, the intervention was noninferior regarding all of the predefined health outcomes: ASDAS, BASDAI, pain assessed using a visual analog scale, patient global assessment, and physician global assessment.

And more than 90% of participants in both groups reported having an overall good experience with their care.

Dr. Hermans noted after his presentation that an additional study had been performed where “we actively engaged with patients in the intervention group as well as healthcare providers to ask them what their experiences were with the intervention, how we could possibly improve it, and whether or not they thought that it was a valid approach to follow-up after the end of the study. And results were very, very reassuring.”

In terms of safety, eight serious adverse events were reported, but none were related to the study intervention, Dr. Hermans said. 

Dr. Hermans reported that there was “negligible difference” in the 1-year quality-adjusted life-years (+0.004, in favor of the intervention overall) and that, while healthcare costs were lower at €243/year for the entire intervention period, societal costs were higher, at €513/year vs usual care. The latter was thought to be “due to an unexpected rise in absenteeism that we think was most likely due to a small amount of outliers,” Dr. Hermans said. 

Nonetheless, using at willingness-to-pay threshold of €20,000/ quality-adjusted life year, he reported that the added value of patient-initiated care with remote monitoring yielded a potential net monetary benefit of +€322 from a healthcare perspective for the entire intervention period.

“We believe that these results support the fast-paced adoption of remote care interventions,” Dr. Hermans said. “In the context that I described earlier, of decreasing healthcare personnel and rising costs, we believe that this could be a valuable approach for follow-up for patients with stable axSpA.”

ReMonit was sponsored by Diakonhjemmet Hospital, and TeleSpA was sponsored by Maastricht University Medical Center, with funding from the Dutch Arthritis Society. Dr. Berg and Dr. Hermans had no relevant conflicts of interest to report.

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

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

VIENNA — People with spondyloarthritis (SpA) who have low or stable disease activity can effectively and safely be managed using a model of patient-initiated care with or without remote monitoring, suggested the results of two separate trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting. 

In the 18-month, single-center ReMonit study that included 243 people with axial SpA (axSpA), patient-initiated care was found to be noninferior for keeping them in a low-disease activity state, compared with both usual hospital follow-up and remote digital monitoring.

Meanwhile, in the 12-month, multicenter TeleSpA study, which included 200 patients with any type of SpA, the number of hospital visits needed by people who were randomly assigned to receive patient-initiated care together with asynchronous telemonitoring was significantly lower than for the usual-care group, with no detriment to the participants’ overall health outcomes or safety. Moreover, the strategy was deemed cost-effective from a healthcare provision perspective.
 

Time to Rationalize Healthcare Resources?

People with chronic rheumatic diseases such as axSpA require long-term follow-up in specialist healthcare centers, Inger Jorid Berg, MD, PhD, of Diakonhjemmet Hospital in Oslo, Norway, said when she presented the findings of the ReMonit study as a late-breaking abstract.

Sara Freeman/Medscape Medical News

“Traditionally, this has been offered as prescheduled face-to-face consultations at an outpatient clinic, but remote monitoring and patient-initiated care may allow for more targeted and efficient uses of healthcare resources,” Dr. Berg said.

“The end goal of what you’re trying to do is increase the efficiency of outpatient care and provide more patient-tailored care,” Kasper Hermans, MD, said in an interview. He presented the results of the TeleSpA study. 

Dr. Hermans, who is a rheumatology fellow and PhD candidate at Maastricht University, Maastricht, the Netherlands, observed during his presentation at EULAR 2024 that there is an increasing demand for rheumatology services but an expected shortfall in the future workforce. Thus, “sustainable alternative strategies are needed for optimizing the efficiency of care,” he said.

People need to have timely access to care, Dr. Hermans stressed, but perhaps alternatives to the traditional models of care where patients are seen routinely every 6 or 12 months are needed, particularly as prior work had suggested that around one-third of people who were seen by a rheumatologist perhaps did not need to be.

A strategy of patient-initiated care — which is where people are seen by a healthcare provider only if they feel that they need to and request a consultation — is therefore an attractive proposition, particularly if it is backed up with remote monitoring, which is what the TeleSpA study was testing.
 

Two Distinct Studies

ReMonit and TeleSpA were two distinct studies. While both were noninferiority trials and involved patient-initiated care and telemonitoring of outpatients with SpA, that is where the similarities generally end.

Notably, ReMonit included a very specific population of patients — all had a diagnosis of axSpA and were being treated with a tumor necrosis factor (TNF) inhibitor and had been on a stable dose for the last 6 months. For inclusion, they also had to have inactive disease or low disease activity, as indicated by an Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1.

ReMonit’s telemonitoring strategy involved participants completing monthly questionnaires using the Dignio smartphone app. Patients first completed the Patient Global Assessment (PGA) and noted whether they had experienced a flare in their disease. If they had a flare or their PGA score was 3 or higher, then they were asked to also complete the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI). If the BASDAI score was 4 or more, then the patient was called by a study nurse and offered a consultation.

“Patients in all three groups were recommended to take blood samples at the general practitioner’s or at the hospital every third month as a safety procedure when using TNF inhibitors,” Dr. Berg said.

The primary outcome was the proportion of people who remained with low disease activity (ASDAS < 2.1) at 6, 12, and 18 months in each of the three arms of the trial, which were patient-initiated care (n = 81), monthly remote monitoring (n = 80), or usual follow-up in the hospital every 6 months (n = 82).

TeleSpA on the other hand was a “much more pragmatic trial, much closer to actual care,” Dr. Hermans said. “We included axial spondyloarthritis, peripheral spondyloarthritis, or patients who had both axial and peripheral disease, including patients with psoriatic arthritis,” he said, adding that their inclusion was regardless of their baseline ASDAS based on C-reactive protein (ASDAS-CRP).

This means that patients who would otherwise have been classified at baseline as having high disease activity (by ASDAS-CRP or similar disease activity measures) could be included. The main proviso was that both the patient and their rheumatologist had to define the condition as being stable with an acceptable level of symptom control and no immediate plans to change treatment within the next 3 months.

TeleSpA’s remote monitoring strategy involved the use of SpA-Net, which Dr. Hermans and coinvestigators have described previously as “an ongoing, disease-specific, prospective, web-based registry for monitoring SpA in daily practice.” This captures a host of clinical and laboratory test information.

SpA-Net was used in both arms of the study. However, while the 100 participants in the standard-care arm completed questionnaires and had tests before every in-person visit that had been prescheduled with their rheumatologist, the 100 individuals in the patient-initiated care arm had no prescheduled in-person visits except for being seen at the start and end of the study. These patients were reminded via email to complete the necessary SpA-Net registry questionnaires at 6 months.

The primary outcome for TeleSpA was the total number of rheumatology visits, including both physical and telephone or video consultations, within a 1-year period. 
 

ReMonit Results

Berg reported that similar percentages of patients remained in a low disease activity state at 6, 12, and 18 months, regardless of the group that they had been randomized into, and that there was little change seen within the individual groups.

For instance, at 6, 12, and 18 months, 92%, 91%, and 92% of individuals in the patient-initiated arm had an ASDAS of < 2.1. Corresponding percentages for the usual-care arm were 96%, 93%, and 90% and for the remote-monitoring arm were 96%, 96%, and 94%.

Both patient-initiated care and remote monitoring were noninferior to usual care, and patient-initiated care was also noninferior to remote monitoring. There were no differences between the trial arms in terms of disease activity, measured using either ASDAS or BASDAI, at 6, 12, or 18 months.

Dr. Berg stated that “patient satisfaction was high in all three follow-up strategies, and there was the lowest resource use with patient-initiated care.” She concluded that “remote monitoring and patient-initiated care could be implemented in the follow-up of patients with axial spondyloarthritis and low disease activity.”
 

TeleSpA Results

In TeleSpA, people in the patient-initiated care and telemonitoring arm were seen a mean of 1.9 times over the course of the 1-year follow-up vs 2.6 for people in the usual care arm. The reduction was caused in part by the decrease in physical visits (1.4 vs 2.0) as there were the same mean number of telephone visits in each group. Overall, there was a 25.4% reduction in consultations comparing the patient-initiated care and telemonitoring arm with the usual-care arm.

Importantly, the intervention was noninferior regarding all of the predefined health outcomes: ASDAS, BASDAI, pain assessed using a visual analog scale, patient global assessment, and physician global assessment.

And more than 90% of participants in both groups reported having an overall good experience with their care.

Dr. Hermans noted after his presentation that an additional study had been performed where “we actively engaged with patients in the intervention group as well as healthcare providers to ask them what their experiences were with the intervention, how we could possibly improve it, and whether or not they thought that it was a valid approach to follow-up after the end of the study. And results were very, very reassuring.”

In terms of safety, eight serious adverse events were reported, but none were related to the study intervention, Dr. Hermans said. 

Dr. Hermans reported that there was “negligible difference” in the 1-year quality-adjusted life-years (+0.004, in favor of the intervention overall) and that, while healthcare costs were lower at €243/year for the entire intervention period, societal costs were higher, at €513/year vs usual care. The latter was thought to be “due to an unexpected rise in absenteeism that we think was most likely due to a small amount of outliers,” Dr. Hermans said. 

Nonetheless, using at willingness-to-pay threshold of €20,000/ quality-adjusted life year, he reported that the added value of patient-initiated care with remote monitoring yielded a potential net monetary benefit of +€322 from a healthcare perspective for the entire intervention period.

“We believe that these results support the fast-paced adoption of remote care interventions,” Dr. Hermans said. “In the context that I described earlier, of decreasing healthcare personnel and rising costs, we believe that this could be a valuable approach for follow-up for patients with stable axSpA.”

ReMonit was sponsored by Diakonhjemmet Hospital, and TeleSpA was sponsored by Maastricht University Medical Center, with funding from the Dutch Arthritis Society. Dr. Berg and Dr. Hermans had no relevant conflicts of interest to report.

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

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

VIENNA — People with spondyloarthritis (SpA) who have low or stable disease activity can effectively and safely be managed using a model of patient-initiated care with or without remote monitoring, suggested the results of two separate trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting. 

In the 18-month, single-center ReMonit study that included 243 people with axial SpA (axSpA), patient-initiated care was found to be noninferior for keeping them in a low-disease activity state, compared with both usual hospital follow-up and remote digital monitoring.

Meanwhile, in the 12-month, multicenter TeleSpA study, which included 200 patients with any type of SpA, the number of hospital visits needed by people who were randomly assigned to receive patient-initiated care together with asynchronous telemonitoring was significantly lower than for the usual-care group, with no detriment to the participants’ overall health outcomes or safety. Moreover, the strategy was deemed cost-effective from a healthcare provision perspective.
 

Time to Rationalize Healthcare Resources?

People with chronic rheumatic diseases such as axSpA require long-term follow-up in specialist healthcare centers, Inger Jorid Berg, MD, PhD, of Diakonhjemmet Hospital in Oslo, Norway, said when she presented the findings of the ReMonit study as a late-breaking abstract.

Sara Freeman/Medscape Medical News

“Traditionally, this has been offered as prescheduled face-to-face consultations at an outpatient clinic, but remote monitoring and patient-initiated care may allow for more targeted and efficient uses of healthcare resources,” Dr. Berg said.

“The end goal of what you’re trying to do is increase the efficiency of outpatient care and provide more patient-tailored care,” Kasper Hermans, MD, said in an interview. He presented the results of the TeleSpA study. 

Dr. Hermans, who is a rheumatology fellow and PhD candidate at Maastricht University, Maastricht, the Netherlands, observed during his presentation at EULAR 2024 that there is an increasing demand for rheumatology services but an expected shortfall in the future workforce. Thus, “sustainable alternative strategies are needed for optimizing the efficiency of care,” he said.

People need to have timely access to care, Dr. Hermans stressed, but perhaps alternatives to the traditional models of care where patients are seen routinely every 6 or 12 months are needed, particularly as prior work had suggested that around one-third of people who were seen by a rheumatologist perhaps did not need to be.

A strategy of patient-initiated care — which is where people are seen by a healthcare provider only if they feel that they need to and request a consultation — is therefore an attractive proposition, particularly if it is backed up with remote monitoring, which is what the TeleSpA study was testing.
 

Two Distinct Studies

ReMonit and TeleSpA were two distinct studies. While both were noninferiority trials and involved patient-initiated care and telemonitoring of outpatients with SpA, that is where the similarities generally end.

Notably, ReMonit included a very specific population of patients — all had a diagnosis of axSpA and were being treated with a tumor necrosis factor (TNF) inhibitor and had been on a stable dose for the last 6 months. For inclusion, they also had to have inactive disease or low disease activity, as indicated by an Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1.

ReMonit’s telemonitoring strategy involved participants completing monthly questionnaires using the Dignio smartphone app. Patients first completed the Patient Global Assessment (PGA) and noted whether they had experienced a flare in their disease. If they had a flare or their PGA score was 3 or higher, then they were asked to also complete the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI). If the BASDAI score was 4 or more, then the patient was called by a study nurse and offered a consultation.

“Patients in all three groups were recommended to take blood samples at the general practitioner’s or at the hospital every third month as a safety procedure when using TNF inhibitors,” Dr. Berg said.

The primary outcome was the proportion of people who remained with low disease activity (ASDAS < 2.1) at 6, 12, and 18 months in each of the three arms of the trial, which were patient-initiated care (n = 81), monthly remote monitoring (n = 80), or usual follow-up in the hospital every 6 months (n = 82).

TeleSpA on the other hand was a “much more pragmatic trial, much closer to actual care,” Dr. Hermans said. “We included axial spondyloarthritis, peripheral spondyloarthritis, or patients who had both axial and peripheral disease, including patients with psoriatic arthritis,” he said, adding that their inclusion was regardless of their baseline ASDAS based on C-reactive protein (ASDAS-CRP).

This means that patients who would otherwise have been classified at baseline as having high disease activity (by ASDAS-CRP or similar disease activity measures) could be included. The main proviso was that both the patient and their rheumatologist had to define the condition as being stable with an acceptable level of symptom control and no immediate plans to change treatment within the next 3 months.

TeleSpA’s remote monitoring strategy involved the use of SpA-Net, which Dr. Hermans and coinvestigators have described previously as “an ongoing, disease-specific, prospective, web-based registry for monitoring SpA in daily practice.” This captures a host of clinical and laboratory test information.

SpA-Net was used in both arms of the study. However, while the 100 participants in the standard-care arm completed questionnaires and had tests before every in-person visit that had been prescheduled with their rheumatologist, the 100 individuals in the patient-initiated care arm had no prescheduled in-person visits except for being seen at the start and end of the study. These patients were reminded via email to complete the necessary SpA-Net registry questionnaires at 6 months.

The primary outcome for TeleSpA was the total number of rheumatology visits, including both physical and telephone or video consultations, within a 1-year period. 
 

ReMonit Results

Berg reported that similar percentages of patients remained in a low disease activity state at 6, 12, and 18 months, regardless of the group that they had been randomized into, and that there was little change seen within the individual groups.

For instance, at 6, 12, and 18 months, 92%, 91%, and 92% of individuals in the patient-initiated arm had an ASDAS of < 2.1. Corresponding percentages for the usual-care arm were 96%, 93%, and 90% and for the remote-monitoring arm were 96%, 96%, and 94%.

Both patient-initiated care and remote monitoring were noninferior to usual care, and patient-initiated care was also noninferior to remote monitoring. There were no differences between the trial arms in terms of disease activity, measured using either ASDAS or BASDAI, at 6, 12, or 18 months.

Dr. Berg stated that “patient satisfaction was high in all three follow-up strategies, and there was the lowest resource use with patient-initiated care.” She concluded that “remote monitoring and patient-initiated care could be implemented in the follow-up of patients with axial spondyloarthritis and low disease activity.”
 

TeleSpA Results

In TeleSpA, people in the patient-initiated care and telemonitoring arm were seen a mean of 1.9 times over the course of the 1-year follow-up vs 2.6 for people in the usual care arm. The reduction was caused in part by the decrease in physical visits (1.4 vs 2.0) as there were the same mean number of telephone visits in each group. Overall, there was a 25.4% reduction in consultations comparing the patient-initiated care and telemonitoring arm with the usual-care arm.

Importantly, the intervention was noninferior regarding all of the predefined health outcomes: ASDAS, BASDAI, pain assessed using a visual analog scale, patient global assessment, and physician global assessment.

And more than 90% of participants in both groups reported having an overall good experience with their care.

Dr. Hermans noted after his presentation that an additional study had been performed where “we actively engaged with patients in the intervention group as well as healthcare providers to ask them what their experiences were with the intervention, how we could possibly improve it, and whether or not they thought that it was a valid approach to follow-up after the end of the study. And results were very, very reassuring.”

In terms of safety, eight serious adverse events were reported, but none were related to the study intervention, Dr. Hermans said. 

Dr. Hermans reported that there was “negligible difference” in the 1-year quality-adjusted life-years (+0.004, in favor of the intervention overall) and that, while healthcare costs were lower at €243/year for the entire intervention period, societal costs were higher, at €513/year vs usual care. The latter was thought to be “due to an unexpected rise in absenteeism that we think was most likely due to a small amount of outliers,” Dr. Hermans said. 

Nonetheless, using at willingness-to-pay threshold of €20,000/ quality-adjusted life year, he reported that the added value of patient-initiated care with remote monitoring yielded a potential net monetary benefit of +€322 from a healthcare perspective for the entire intervention period.

“We believe that these results support the fast-paced adoption of remote care interventions,” Dr. Hermans said. “In the context that I described earlier, of decreasing healthcare personnel and rising costs, we believe that this could be a valuable approach for follow-up for patients with stable axSpA.”

ReMonit was sponsored by Diakonhjemmet Hospital, and TeleSpA was sponsored by Maastricht University Medical Center, with funding from the Dutch Arthritis Society. Dr. Berg and Dr. Hermans had no relevant conflicts of interest to report.

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

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

Halifax, Nova Scotia; American Samoa; Queens, New York; Lansing, Michigan; Gurugram, India. I often ask patients where they’re from. Practicing in San Diego, the answers are a geography lesson. People from around the world come here. I sometimes add the more interesting question: How’d you end up here? Many took the three highways to San Diego: the Navy, the defense industry (like General Dynamics), or followed a partner. My Queens patient had a better answer: Super Bowl XXII. On Sunday, Jan. 31st, 1988, the Redskins played the Broncos in San Diego. John Elway and the Broncos lost, but it didn’t matter. “I was scrapin’ the ice off my windshield that Monday morning when I thought, that’s it. I’m done! I drove to the garage where I worked and quit on the spot. Then I drove home and packed my bags.”

In a paper on how to make life decisions, this guy would be Exhibit A: “Don’t overthink it.” That approach might not be suitable for everyone, or for every decision. It might actually be an example of how not to make life decisions (more on that later). But, is there a best way to go about making big life decisions?

The first treatise on this subject was a paper by one Franklin, Ben in 1772. Providing advice to a friend on how to make a career decision, Franklin argued: “My way is to divide half a sheet of paper by a line into two columns; writing over the one Pro and over the other Con.” This “moral algebra” as he called it was a framework to put rigor to a messy, organic problem.

Jeffrey Benabio, MD, MBA

The flaw in this method is that in the end you have two lists. Then what? Do the length of the lists decide? What if some factors are more important? Well, let’s add tools to help. You could use a spreadsheet and assign weights to each variable. Then sum the values and choose based on that. So if “not scraping ice off your windshield” is twice as important as “doubling your rent,” then you’ve got your answer. But what if you aren’t good at estimating how important things are? Actually, most of us are pretty awful at assigning weights to life variables – having bags of money is the consummate example. Seems important, but because of habituation, it turns out to not be sustainable. Note Exhibit B, our wealthy neighbor who owns a Lambo and G-Wagen (AMG squared, of course), who just parked a Cybertruck in his driveway. Realizing the risk of depending on peoples’ flawed judgment, companies instead use statistical modeling called bootstrap aggregating to “vote” on the weights for variables in a prediction. If you aren’t sure how important a new Rivian or walking to the beach would be, a model can answer that for you! It’s a bit disconcerting, I know. I mean, how can a model know what we’d like? Wait, isn’t that how Netflix picks stuff for you? Exactly.

Ok, so why don’t we just ask our friendly personal AI? “OK, ChatGPT, given what you know about me, where can I have it all?” Alas, here we slam into a glass wall. It seems the answer is out there but even our life-changing magical AI tools fail us. Mathematically, it is impossible to have it all. An illustrative example of this is called the economic “impossible trinity problem.” Even the most sophisticated algorithm cannot find an optional solution to some trinities such as fixed foreign exchange rate, free capital movement, and an independent monetary policy. Economists have concluded you must trade off one to have the other two. Impossible trinities are common in economics and in life. Armistead Maupin in his “Tales of the City” codifies it as Mona’s Law, the essence of which is: You cannot have the perfect job, the perfect partner, and the perfect house at the same time. (See Exhibit C, one Tom Brady).

This brings me to my final point, hard decisions are matters of the heart and experiencing life is the best way to understand its beautiful chaos. If making rash judgments is ill-advised and using technology cannot solve all problems (try asking your AI buddy for the square root of 2 as a fraction) what tools can we use? Maybe try reading more novels. They allow us to experience multiple lifetimes in a short time, which is what we need to learn what matters. Reading Dorothea’s choice at the end of “Middlemarch” is a nice example. Should she give up Lowick Manor and marry the penniless Ladislaw or keep it and use her wealth to help others? Seeing her struggle helps us understand how to answer questions like: Should I give up my academic practice or marry that guy or move to Texas? These cannot be reduced to arithmetic. The only way to know is to know as much of life as possible.

My last visit with my Queens patient was our last together. He’s divorced and moving from San Diego to Gallatin, Tennessee. “I’ve paid my last taxes to California, Doc. I decided that’s it, I’m done!” Perhaps he should have read “The Grapes of Wrath” before he set out for California in the first place.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Halifax, Nova Scotia; American Samoa; Queens, New York; Lansing, Michigan; Gurugram, India. I often ask patients where they’re from. Practicing in San Diego, the answers are a geography lesson. People from around the world come here. I sometimes add the more interesting question: How’d you end up here? Many took the three highways to San Diego: the Navy, the defense industry (like General Dynamics), or followed a partner. My Queens patient had a better answer: Super Bowl XXII. On Sunday, Jan. 31st, 1988, the Redskins played the Broncos in San Diego. John Elway and the Broncos lost, but it didn’t matter. “I was scrapin’ the ice off my windshield that Monday morning when I thought, that’s it. I’m done! I drove to the garage where I worked and quit on the spot. Then I drove home and packed my bags.”

In a paper on how to make life decisions, this guy would be Exhibit A: “Don’t overthink it.” That approach might not be suitable for everyone, or for every decision. It might actually be an example of how not to make life decisions (more on that later). But, is there a best way to go about making big life decisions?

The first treatise on this subject was a paper by one Franklin, Ben in 1772. Providing advice to a friend on how to make a career decision, Franklin argued: “My way is to divide half a sheet of paper by a line into two columns; writing over the one Pro and over the other Con.” This “moral algebra” as he called it was a framework to put rigor to a messy, organic problem.

Jeffrey Benabio, MD, MBA

The flaw in this method is that in the end you have two lists. Then what? Do the length of the lists decide? What if some factors are more important? Well, let’s add tools to help. You could use a spreadsheet and assign weights to each variable. Then sum the values and choose based on that. So if “not scraping ice off your windshield” is twice as important as “doubling your rent,” then you’ve got your answer. But what if you aren’t good at estimating how important things are? Actually, most of us are pretty awful at assigning weights to life variables – having bags of money is the consummate example. Seems important, but because of habituation, it turns out to not be sustainable. Note Exhibit B, our wealthy neighbor who owns a Lambo and G-Wagen (AMG squared, of course), who just parked a Cybertruck in his driveway. Realizing the risk of depending on peoples’ flawed judgment, companies instead use statistical modeling called bootstrap aggregating to “vote” on the weights for variables in a prediction. If you aren’t sure how important a new Rivian or walking to the beach would be, a model can answer that for you! It’s a bit disconcerting, I know. I mean, how can a model know what we’d like? Wait, isn’t that how Netflix picks stuff for you? Exactly.

Ok, so why don’t we just ask our friendly personal AI? “OK, ChatGPT, given what you know about me, where can I have it all?” Alas, here we slam into a glass wall. It seems the answer is out there but even our life-changing magical AI tools fail us. Mathematically, it is impossible to have it all. An illustrative example of this is called the economic “impossible trinity problem.” Even the most sophisticated algorithm cannot find an optional solution to some trinities such as fixed foreign exchange rate, free capital movement, and an independent monetary policy. Economists have concluded you must trade off one to have the other two. Impossible trinities are common in economics and in life. Armistead Maupin in his “Tales of the City” codifies it as Mona’s Law, the essence of which is: You cannot have the perfect job, the perfect partner, and the perfect house at the same time. (See Exhibit C, one Tom Brady).

This brings me to my final point, hard decisions are matters of the heart and experiencing life is the best way to understand its beautiful chaos. If making rash judgments is ill-advised and using technology cannot solve all problems (try asking your AI buddy for the square root of 2 as a fraction) what tools can we use? Maybe try reading more novels. They allow us to experience multiple lifetimes in a short time, which is what we need to learn what matters. Reading Dorothea’s choice at the end of “Middlemarch” is a nice example. Should she give up Lowick Manor and marry the penniless Ladislaw or keep it and use her wealth to help others? Seeing her struggle helps us understand how to answer questions like: Should I give up my academic practice or marry that guy or move to Texas? These cannot be reduced to arithmetic. The only way to know is to know as much of life as possible.

My last visit with my Queens patient was our last together. He’s divorced and moving from San Diego to Gallatin, Tennessee. “I’ve paid my last taxes to California, Doc. I decided that’s it, I’m done!” Perhaps he should have read “The Grapes of Wrath” before he set out for California in the first place.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Halifax, Nova Scotia; American Samoa; Queens, New York; Lansing, Michigan; Gurugram, India. I often ask patients where they’re from. Practicing in San Diego, the answers are a geography lesson. People from around the world come here. I sometimes add the more interesting question: How’d you end up here? Many took the three highways to San Diego: the Navy, the defense industry (like General Dynamics), or followed a partner. My Queens patient had a better answer: Super Bowl XXII. On Sunday, Jan. 31st, 1988, the Redskins played the Broncos in San Diego. John Elway and the Broncos lost, but it didn’t matter. “I was scrapin’ the ice off my windshield that Monday morning when I thought, that’s it. I’m done! I drove to the garage where I worked and quit on the spot. Then I drove home and packed my bags.”

In a paper on how to make life decisions, this guy would be Exhibit A: “Don’t overthink it.” That approach might not be suitable for everyone, or for every decision. It might actually be an example of how not to make life decisions (more on that later). But, is there a best way to go about making big life decisions?

The first treatise on this subject was a paper by one Franklin, Ben in 1772. Providing advice to a friend on how to make a career decision, Franklin argued: “My way is to divide half a sheet of paper by a line into two columns; writing over the one Pro and over the other Con.” This “moral algebra” as he called it was a framework to put rigor to a messy, organic problem.

Jeffrey Benabio, MD, MBA

The flaw in this method is that in the end you have two lists. Then what? Do the length of the lists decide? What if some factors are more important? Well, let’s add tools to help. You could use a spreadsheet and assign weights to each variable. Then sum the values and choose based on that. So if “not scraping ice off your windshield” is twice as important as “doubling your rent,” then you’ve got your answer. But what if you aren’t good at estimating how important things are? Actually, most of us are pretty awful at assigning weights to life variables – having bags of money is the consummate example. Seems important, but because of habituation, it turns out to not be sustainable. Note Exhibit B, our wealthy neighbor who owns a Lambo and G-Wagen (AMG squared, of course), who just parked a Cybertruck in his driveway. Realizing the risk of depending on peoples’ flawed judgment, companies instead use statistical modeling called bootstrap aggregating to “vote” on the weights for variables in a prediction. If you aren’t sure how important a new Rivian or walking to the beach would be, a model can answer that for you! It’s a bit disconcerting, I know. I mean, how can a model know what we’d like? Wait, isn’t that how Netflix picks stuff for you? Exactly.

Ok, so why don’t we just ask our friendly personal AI? “OK, ChatGPT, given what you know about me, where can I have it all?” Alas, here we slam into a glass wall. It seems the answer is out there but even our life-changing magical AI tools fail us. Mathematically, it is impossible to have it all. An illustrative example of this is called the economic “impossible trinity problem.” Even the most sophisticated algorithm cannot find an optional solution to some trinities such as fixed foreign exchange rate, free capital movement, and an independent monetary policy. Economists have concluded you must trade off one to have the other two. Impossible trinities are common in economics and in life. Armistead Maupin in his “Tales of the City” codifies it as Mona’s Law, the essence of which is: You cannot have the perfect job, the perfect partner, and the perfect house at the same time. (See Exhibit C, one Tom Brady).

This brings me to my final point, hard decisions are matters of the heart and experiencing life is the best way to understand its beautiful chaos. If making rash judgments is ill-advised and using technology cannot solve all problems (try asking your AI buddy for the square root of 2 as a fraction) what tools can we use? Maybe try reading more novels. They allow us to experience multiple lifetimes in a short time, which is what we need to learn what matters. Reading Dorothea’s choice at the end of “Middlemarch” is a nice example. Should she give up Lowick Manor and marry the penniless Ladislaw or keep it and use her wealth to help others? Seeing her struggle helps us understand how to answer questions like: Should I give up my academic practice or marry that guy or move to Texas? These cannot be reduced to arithmetic. The only way to know is to know as much of life as possible.

My last visit with my Queens patient was our last together. He’s divorced and moving from San Diego to Gallatin, Tennessee. “I’ve paid my last taxes to California, Doc. I decided that’s it, I’m done!” Perhaps he should have read “The Grapes of Wrath” before he set out for California in the first place.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.

“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.

“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.

Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
 

‘Therapeutic Continuums’ Aid Disease Management

Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.

A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”

Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”

He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.

The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”

Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”

Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.

To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.

The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.

He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”

For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
 

Systemic Sclerosis Research Agenda and Recommendations Align

Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.

“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”

In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”

“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
 

Remission Elusive but Getting Closer

In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.

Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.

Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”

Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.

Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.

“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”

Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.

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

VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.

“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.

“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.

Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
 

‘Therapeutic Continuums’ Aid Disease Management

Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.

A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”

Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”

He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.

The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”

Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”

Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.

To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.

The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.

He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”

For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
 

Systemic Sclerosis Research Agenda and Recommendations Align

Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.

“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”

In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”

“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
 

Remission Elusive but Getting Closer

In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.

Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.

Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”

Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.

Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.

“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”

Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.

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

VIENNA – The use of immunosuppressive and antifibrotic drugs to treat skin and lung fibrosis leads updated recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the treatment of systemic sclerosis.

“The most impactful new recommendation relates to the evidence for immunosuppressive agents and antifibrotics for the treatment of skin fibrosis and lung fibrosis,” said Francesco Del Galdo, MD, PhD, professor of experimental medicine, consultant rheumatologist, and scleroderma and connective tissue diseases specialist at Leeds Teaching Hospitals NHS Trust, Leeds, England. Dr. Del Galdo presented the update at the annual European Congress of Rheumatology.

“But there are also new recommendations, including a redefined target population for hematopoietic stem cell transplantation following cyclophosphamide, the upfront combination treatment at the time of diagnosis of pulmonary arterial hypertension [PAH], and a negative recommendation for the use of anticoagulants for pulmonary arterial hypertension,” noted Dr. Del Galdo, highlighting key updates in the 2024 recommendations.

Robert B.M. Landewé, MD, PhD, professor and rheumatologist at Amsterdam University Medical Center, Amsterdam, the Netherlands, and Zuyderland Medical Center, Heerlen, the Netherlands, co-moderated the session on EULAR recommendations. “The management of systemic sclerosis is a field in which a lot is happening,” he said. “The last update goes back to 2017, and in the meantime, many new approaches have seen the light, especially pertaining to skin fibrosis and interstitial lung disease. Six new recommendations have been coined, covering drugs like mycophenolate mofetil, nintedanib, rituximab, and tocilizumab. None of these therapies were present in the 2017 recommendations. It seems the field is now ready to further expand on targeted therapies for the management of musculoskeletal and gastrointestinal manifestations, calcinosis, and the local management of digital ulcers.”
 

‘Therapeutic Continuums’ Aid Disease Management

Dr. Del Galdo and his colleagues grouped the various interventions across what the recommendations label as evidence-backed “therapeutic continuums.” These span six of the eight different clinical manifestations of systemic sclerosis: Raynaud’s phenomenon, digital ulcers, pulmonary hypertension, musculoskeletal manifestations, skin fibrosis, interstitial lung disease (ILD), and gastrointestinal and renal crisis.

A slide showing the different strengths of evidence for various drugs across the eight manifestations illustrated the principle behind the therapeutic continuums. “These ‘therapeutic continuums’ suggest a common pathogenetic mechanism driving the various manifestations of disease,” said Dr. Del Galdo. For example, he noted, “If rituximab had a positive response in skin and in lung, it suggests that B cells play a role in the clinical manifestations of skin and lung in this disease.”

Dr. Del Galdo highlighted the new immunosuppression continuum and associated treatments for skin and lung fibrosis. “For skin involvement, the task force recommended mycophenolate, methotrexate, and rituximab, with tocilizumab having a lower level of evidence and lower recommendation strength; similarly, in interstitial lung disease, we have rituximab, mycophenolate, cyclophosphamide, and nintedanib, and these all have the highest strength of evidence. Tocilizumab is assigned one strength of evidence below the other drugs.”

He also cited the phosphodiesterase 5 inhibitor (PDE5i) drugs that are used across Raynaud’s phenomenon, digital ulcers, and pulmonary arterial hypertension, which together form a vascular therapeutic continuum.

The complexity of systemic sclerosis and multiple manifestations was a major determinant of the recommendations, Dr. Del Galdo pointed out. “The task force realized that since this is such a complex disease, we cannot recommend one treatment unconditionally. For example, with mycophenolate mofetil, what works for most patients for the skin and lung manifestations might not for someone who experiences severe diarrhea, in which mycophenolate is contraindicated. So, the highest degree of recommendation that the task force felt comfortable with was ‘should be considered.’ ”

Dr. Del Galdo stressed that the complex nature of systemic sclerosis means that “when thinking of treating one manifestation, you also always need to consider all the other clinical manifestations as experienced by the patient, and it is this multifaceted scenario that will ultimately lead to your final choice.”

Turning to new evidence around drug use, Dr. Del Galdo said that rituximab has the highest level of evidence across skin and lung manifestations, nintedanib is new in lung, and tocilizumab is new across both skin and lung.

To treat systemic sclerosis–pulmonary arterial hypertension (SSc-PAH), as long as there are no contraindications, the task force recommends using PDE5i and endothelin receptor antagonists (ERAs) at diagnosis. Data from phase 3 trials show a better outcome when the combination is established early.

The task force suggests avoiding the use of warfarin in PAH. “This is supported by a signal from two trials showing an increase in morbidity and mortality in these patients,” noted Dr. Del Galdo.

He also pointed out that selexipag and riociguat were new and important second-line additions for the treatment of PAH, and — consistent with the ERA approach — the EULAR recommendation supports frequent follow-up to establish a treat-to-target approach to maximizing clinical outcomes in SSc-PAH and SSc-ILD. “Specifically, for the first time, we recommend monitoring the effect of any chosen intervention selected within 3-6 months of starting. The evidence suggests there is a group of patients who respond and some who respond less well and who might benefit from a second-line intervention.”

For example, results of one trial support the approach of adding an antifibrotic agent to reduce progression in people with progressive lung fibrosis. “Similarly, for pulmonary hypertension, we recommend putting patients on dual treatment, and if this fails, place them on selexipag or switch the PDE5i to riociguat,” Dr. Del Galdo said.
 

Systemic Sclerosis Research Agenda and Recommendations Align

Dr. Del Galdo highlighted the value of therapeutic continuums in advancing disease understanding. “It is starting to teach us what we know and what we don’t and where do we need to build more evidence. Effectively, they determine where the gaps in therapy lie, and this starts to guide the research agenda.

“In fact, what is really interesting about this recommendation update — certainly from the perspective of disease understanding — is that we are starting to have a bird’s-eye view of the clinical manifestations of scleroderma that have so often been dealt with separately. Now we are starting to build a cumulative evidence map of this disease.”

In 2017, the research agenda largely advocated identifying immune-targeting drugs for skin and lung fibrosis, Dr. Del Galdo pointed out. “Now, we’ve done that — we’ve identified appropriate immunosuppressive drugs — and this is testimony to the importance of these recommendations because what prioritized the research agenda 10 years ago ended up informing the clinical trials and made it into the recommendations.”

“We definitely are one step forward compared to this 2017 recommendation and closer to what we would like to do,” he asserted.
 

Remission Elusive but Getting Closer

In some respects, according to Dr. Del Galdo, research and development is making relatively slow progress, especially compared with other rheumatologic diseases such as rheumatoid arthritis. “We cannot put patients with systemic sclerosis in remission yet. But I think we are one step ahead in that we’ve now established the treat-to-target approach to maximize the efficacy with which we can stall disease progression, but we cannot yet put these patients into remission,” he said. Systemic sclerosis has multiple manifestations, and fibrotic damage cannot be reversed. “Right now, the scar will remain there forever,” he noted.

Until remission is achievable, Dr. Del Galdo advises diagnosing and treating patients earlier to prevent fibrotic manifestations.

Dr. Del Galdo explained the three leading priorities on the systemic sclerosis research agenda. “There are three because it is such a complex disease. The first is considering the patient voice — this is the most important one, and the patients say they want a more holistic approach — so trialing and treating multiple manifestations together.”

Second, Dr. Del Galdo said, he would like to see a patient-reported measure developed that can capture the entire disease.

Third, from a physician’s point of view, Dr. Del Galdo said, “We want to send the patients into remission. We need to continue to further deconvolute the clinical manifestations and find the bottleneck at the beginning of the natural history of disease.

“If we can find a drug that is effective very early on, before the patients start getting the eight different manifestations with different levels of severity, then we will be on the right road, which we hope will end in remission.”

Dr. Del Galdo has served on the speakers bureau for AstraZeneca and Janssen; consulted for AstraZeneca, Boehringer Ingelheim, Capella, Chemomab, Janssen, and Mitsubishi-Tanabe; and received grant or research support from AbbVie, AstraZeneca, Boheringer Ingelheim, Capella, Chemomab, Kymab, Janssen, and Mitsubishi-Tanabe. Dr. Landewé had no relevant disclosures.

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

VIENNA — The interleukin-1 receptor antagonist (IL-1RA) canakinumab provided control of systemic juvenile idiopathic arthritis (sJIA) without the use of glucocorticoids for up to a year in most study participants after three monthly injections.

In this study of 20 patients with newly diagnosed sJIA treated off glucocorticoids, fever was controlled after a single injection in all patients, and 16 patients reached the primary outcome of remission after three injections, said Gerd Horneff, MD, PhD, Asklepios Children’s Hospital, Sankt Augustin, Germany.

Results of this open-label study, called CANAKINUMAB FIRST, were presented as late-breaking findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.

“Steroid-free, first-line treatment with canakinumab led to sustained responses in most patients, with a considerable number achieving remission,” said Dr. Horneff, adding that the observation in this group is ongoing.
 

Building on Earlier Data

The efficacy of canakinumab was previously reported in anecdotal experiences and one small patient series published 10 years ago. Dr. Horneff noted that he has offered this drug off label to patients with challenging cases.

The objective was to evaluate canakinumab as a first-line monotherapy administered in the absence of glucocorticoids. The study was open to children aged 2-18 years with active sJIA/juvenile Still disease confirmed with published criteria. All were naive to biologic or nonbiologic disease-modifying antirheumatic drugs as well as steroids.

The median age of the children was 8.4 years. A total of 60% were men. The median disease duration at the time of entry was 1.2 months. Most had fever (95%) and rash (80%) with high levels of inflammatory markers at baseline. The mean number of painful joints was 3.1, and the mean number of systemic manifestations was 2.8. No patient was without any systemic involvement, but four of the patients did not have any painful joints.

At enrollment, patients were scheduled to receive three injections of canakinumab at monthly intervals during an active treatment phase, after which they entered an observation phase lasting 40 weeks. In the event of nonresponse or flares in either phase, they were transitioned to usual care.
 

Symptoms Resolve After Single Injection

After the first injection, active joint disease and all systemic manifestations resolved in 16 (80%) of the 20 patients. Joint activity and systemic manifestations also remained controlled after the second and third injections in 16 of the 20 patients.

One patient in this series achieved inactive disease after a single injection but developed what appeared to be a treatment-related allergic reaction. He received no further treatment and was excluded from the study, although he is being followed separately.

“According to sJADAS [systemic JIA Disease Activity Score] criteria at month 3, 14 had inactive disease, three had minimal disease activity, and one patient had moderate disease activity,” Dr. Horneff said.

At week 24, or 3 months after the last injection, there was still no joint activity in 16 patients. Systemic manifestations remained controlled in 13 patients, but 1 patient by this point had a flare. Another flare occurred after this point, and other patients have not yet completed the 52-week observation period.

“Of the 10 patients who remained in the study and have completed the 52-week observation period, eight have had a drug-free remission,” Dr. Horneff said.
 

MAS Event Observed in One Patient

In addition to the allergic skin reaction, which was considered probably related to the study drug, there were three flares, one of which was a macrophage activation syndrome (MAS) event. The MAS occurred 8 weeks after the last injection, but it was managed successfully.

Of 30 infections that developed during the observation period, 18 involved the upper airway. All were treated successfully. There were also two injection-site reactions and one case of cytopenia.

Among the studies planned for follow-up, investigators will examine genomic and gene activation in relation to disease activity and the effect of canakinumab.

Comoderator of the abstract session and chair of the EULAR 2024 Abstract Selection Committee, Christian Dejaco, MD, PhD, a consultant rheumatologist and associate professor at the Medical University of Graz in Graz, Austria, suggested that these are highly encouraging data for a disease that does not currently have any approved therapies. Clearly, larger studies with a longer follow-up period are needed, but he pointed out that phase 3 trials in a rare disease like sJIA are challenging.

Because of the limited number of cases, “it will be difficult to conduct a placebo-controlled trial,” he pointed out. However, he hopes this study will provide the basis for larger studies and sufficient data to lead to an indication for this therapy.

In the meantime, he also believes that these data are likely to support empirical use in a difficult disease, even in advance of formal regulatory approval.

“We heard that canakinumab is already being used off label in JIA, and these data might encourage more of that,” he said.

Dr. Horneff reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Chugai, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, and Sobe. Dr. Dejaco reported no potential conflicts of interest.

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

VIENNA — The interleukin-1 receptor antagonist (IL-1RA) canakinumab provided control of systemic juvenile idiopathic arthritis (sJIA) without the use of glucocorticoids for up to a year in most study participants after three monthly injections.

In this study of 20 patients with newly diagnosed sJIA treated off glucocorticoids, fever was controlled after a single injection in all patients, and 16 patients reached the primary outcome of remission after three injections, said Gerd Horneff, MD, PhD, Asklepios Children’s Hospital, Sankt Augustin, Germany.

Results of this open-label study, called CANAKINUMAB FIRST, were presented as late-breaking findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.

“Steroid-free, first-line treatment with canakinumab led to sustained responses in most patients, with a considerable number achieving remission,” said Dr. Horneff, adding that the observation in this group is ongoing.
 

Building on Earlier Data

The efficacy of canakinumab was previously reported in anecdotal experiences and one small patient series published 10 years ago. Dr. Horneff noted that he has offered this drug off label to patients with challenging cases.

The objective was to evaluate canakinumab as a first-line monotherapy administered in the absence of glucocorticoids. The study was open to children aged 2-18 years with active sJIA/juvenile Still disease confirmed with published criteria. All were naive to biologic or nonbiologic disease-modifying antirheumatic drugs as well as steroids.

The median age of the children was 8.4 years. A total of 60% were men. The median disease duration at the time of entry was 1.2 months. Most had fever (95%) and rash (80%) with high levels of inflammatory markers at baseline. The mean number of painful joints was 3.1, and the mean number of systemic manifestations was 2.8. No patient was without any systemic involvement, but four of the patients did not have any painful joints.

At enrollment, patients were scheduled to receive three injections of canakinumab at monthly intervals during an active treatment phase, after which they entered an observation phase lasting 40 weeks. In the event of nonresponse or flares in either phase, they were transitioned to usual care.
 

Symptoms Resolve After Single Injection

After the first injection, active joint disease and all systemic manifestations resolved in 16 (80%) of the 20 patients. Joint activity and systemic manifestations also remained controlled after the second and third injections in 16 of the 20 patients.

One patient in this series achieved inactive disease after a single injection but developed what appeared to be a treatment-related allergic reaction. He received no further treatment and was excluded from the study, although he is being followed separately.

“According to sJADAS [systemic JIA Disease Activity Score] criteria at month 3, 14 had inactive disease, three had minimal disease activity, and one patient had moderate disease activity,” Dr. Horneff said.

At week 24, or 3 months after the last injection, there was still no joint activity in 16 patients. Systemic manifestations remained controlled in 13 patients, but 1 patient by this point had a flare. Another flare occurred after this point, and other patients have not yet completed the 52-week observation period.

“Of the 10 patients who remained in the study and have completed the 52-week observation period, eight have had a drug-free remission,” Dr. Horneff said.
 

MAS Event Observed in One Patient

In addition to the allergic skin reaction, which was considered probably related to the study drug, there were three flares, one of which was a macrophage activation syndrome (MAS) event. The MAS occurred 8 weeks after the last injection, but it was managed successfully.

Of 30 infections that developed during the observation period, 18 involved the upper airway. All were treated successfully. There were also two injection-site reactions and one case of cytopenia.

Among the studies planned for follow-up, investigators will examine genomic and gene activation in relation to disease activity and the effect of canakinumab.

Comoderator of the abstract session and chair of the EULAR 2024 Abstract Selection Committee, Christian Dejaco, MD, PhD, a consultant rheumatologist and associate professor at the Medical University of Graz in Graz, Austria, suggested that these are highly encouraging data for a disease that does not currently have any approved therapies. Clearly, larger studies with a longer follow-up period are needed, but he pointed out that phase 3 trials in a rare disease like sJIA are challenging.

Because of the limited number of cases, “it will be difficult to conduct a placebo-controlled trial,” he pointed out. However, he hopes this study will provide the basis for larger studies and sufficient data to lead to an indication for this therapy.

In the meantime, he also believes that these data are likely to support empirical use in a difficult disease, even in advance of formal regulatory approval.

“We heard that canakinumab is already being used off label in JIA, and these data might encourage more of that,” he said.

Dr. Horneff reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Chugai, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, and Sobe. Dr. Dejaco reported no potential conflicts of interest.

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

VIENNA — The interleukin-1 receptor antagonist (IL-1RA) canakinumab provided control of systemic juvenile idiopathic arthritis (sJIA) without the use of glucocorticoids for up to a year in most study participants after three monthly injections.

In this study of 20 patients with newly diagnosed sJIA treated off glucocorticoids, fever was controlled after a single injection in all patients, and 16 patients reached the primary outcome of remission after three injections, said Gerd Horneff, MD, PhD, Asklepios Children’s Hospital, Sankt Augustin, Germany.

Results of this open-label study, called CANAKINUMAB FIRST, were presented as late-breaking findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.

“Steroid-free, first-line treatment with canakinumab led to sustained responses in most patients, with a considerable number achieving remission,” said Dr. Horneff, adding that the observation in this group is ongoing.
 

Building on Earlier Data

The efficacy of canakinumab was previously reported in anecdotal experiences and one small patient series published 10 years ago. Dr. Horneff noted that he has offered this drug off label to patients with challenging cases.

The objective was to evaluate canakinumab as a first-line monotherapy administered in the absence of glucocorticoids. The study was open to children aged 2-18 years with active sJIA/juvenile Still disease confirmed with published criteria. All were naive to biologic or nonbiologic disease-modifying antirheumatic drugs as well as steroids.

The median age of the children was 8.4 years. A total of 60% were men. The median disease duration at the time of entry was 1.2 months. Most had fever (95%) and rash (80%) with high levels of inflammatory markers at baseline. The mean number of painful joints was 3.1, and the mean number of systemic manifestations was 2.8. No patient was without any systemic involvement, but four of the patients did not have any painful joints.

At enrollment, patients were scheduled to receive three injections of canakinumab at monthly intervals during an active treatment phase, after which they entered an observation phase lasting 40 weeks. In the event of nonresponse or flares in either phase, they were transitioned to usual care.
 

Symptoms Resolve After Single Injection

After the first injection, active joint disease and all systemic manifestations resolved in 16 (80%) of the 20 patients. Joint activity and systemic manifestations also remained controlled after the second and third injections in 16 of the 20 patients.

One patient in this series achieved inactive disease after a single injection but developed what appeared to be a treatment-related allergic reaction. He received no further treatment and was excluded from the study, although he is being followed separately.

“According to sJADAS [systemic JIA Disease Activity Score] criteria at month 3, 14 had inactive disease, three had minimal disease activity, and one patient had moderate disease activity,” Dr. Horneff said.

At week 24, or 3 months after the last injection, there was still no joint activity in 16 patients. Systemic manifestations remained controlled in 13 patients, but 1 patient by this point had a flare. Another flare occurred after this point, and other patients have not yet completed the 52-week observation period.

“Of the 10 patients who remained in the study and have completed the 52-week observation period, eight have had a drug-free remission,” Dr. Horneff said.
 

MAS Event Observed in One Patient

In addition to the allergic skin reaction, which was considered probably related to the study drug, there were three flares, one of which was a macrophage activation syndrome (MAS) event. The MAS occurred 8 weeks after the last injection, but it was managed successfully.

Of 30 infections that developed during the observation period, 18 involved the upper airway. All were treated successfully. There were also two injection-site reactions and one case of cytopenia.

Among the studies planned for follow-up, investigators will examine genomic and gene activation in relation to disease activity and the effect of canakinumab.

Comoderator of the abstract session and chair of the EULAR 2024 Abstract Selection Committee, Christian Dejaco, MD, PhD, a consultant rheumatologist and associate professor at the Medical University of Graz in Graz, Austria, suggested that these are highly encouraging data for a disease that does not currently have any approved therapies. Clearly, larger studies with a longer follow-up period are needed, but he pointed out that phase 3 trials in a rare disease like sJIA are challenging.

Because of the limited number of cases, “it will be difficult to conduct a placebo-controlled trial,” he pointed out. However, he hopes this study will provide the basis for larger studies and sufficient data to lead to an indication for this therapy.

In the meantime, he also believes that these data are likely to support empirical use in a difficult disease, even in advance of formal regulatory approval.

“We heard that canakinumab is already being used off label in JIA, and these data might encourage more of that,” he said.

Dr. Horneff reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Chugai, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Sanofi, and Sobe. Dr. Dejaco reported no potential conflicts of interest.

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

The Centers for Medicare & Medicaid Services (CMS) has announced the conclusion of a program that provided billions in early Medicare payments to those affected by the Change Healthcare/UnitedHealth Group cyberattack last winter. The Accelerated and Advance Payment program, which began in early March to assist hospitals and practices facing significant reimbursement delays, will stop accepting applications after July 12, 2024.

CMS reported that the program advanced more than $2.55 billion in Medicare payments to > 4200 Part A providers, including hospitals, and more than $717.18 million in payments to Part B suppliers such as physicians, nonphysician practitioners, and durable medical equipment suppliers.

According to CMS, the Medicare billing system is now functioning properly, and 96% of the early payments have been recovered. The advances were to represent ≤ 30 days of typical claims payments in a 3-month period of 2023, with full repayment expected within 90 days through “automatic recoupment from Medicare claims” — no extensions allowed.

The agency took a victory lap regarding its response. “In the face of one of the most widespread cyberattacks on the US health care industry, CMS promptly took action to get providers and suppliers access to the funds they needed to continue providing patients with vital care,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “Our efforts helped minimize the disruptive fallout from this incident, and we will remain vigilant to be ready to address future events.”

Ongoing Concerns from Health Care Organizations

Ben Teicher, an American Hospital Association spokesman, said that the organization hopes that CMS will be responsive if there’s more need for action after the advance payment program expires. The organization represents about 5000 hospitals, health care systems, and other providers.

“Our members report that the aftereffects of this event will likely be felt throughout the remainder of the year,” he said. According to Teicher, hospitals remain concerned about their ability to process claims and appeal denials, the safety of reconnecting to cyber services, and access to information needed to bill patients and reconcile payments.

In addition, hospitals are concerned about “financial support to mitigate the considerable costs incurred as a result of the cyberattack,” he said.

Charlene MacDonald, executive vice-president of public affairs at the Federation of American Hospitals, which represents more than 1000 for-profit hospitals, sent a statement to this news organization that said some providers “are still feeling the effects of care denials and delays caused by insurer inaction.

“We appreciate that the Administration acted within its authority to support providers during this unprecedented crisis and blunt these devastating impacts, especially because a vast majority of managed care companies failed to step up to the plate,” she said. “It is now time to shift our focus to holding plans accountable for using tactics to delay and deny needed patient care.”

Cyberattack Impact and Response

The ransom-based cyberattack against Change Healthcare/UnitedHealth Group targeted an electronic data interchange clearing house processing payer reimbursement systems, disrupting cash flows at hospitals and medical practices, and affecting patient access to prescriptions and life-saving therapy.

Change Healthcare — part of the UnitedHealth Group subsidiary Optum — processes half of all medical claims, according to a Department of Justice lawsuit. The American Hospital Association described the cyberattack as “the most significant and consequential incident of its kind” in US history.

By late March, UnitedHealth Group said nearly all medical and pharmacy claims were processing properly, while a deputy secretary of the US Department of Health & Human Services told clinicians that officials were focusing on the last group of clinicians who were facing cash-flow problems.

Still, a senior advisor with CMS told providers at that time that “we have heard from so many providers over the last several weeks who are really struggling to make ends meet right now or who are worried that they will not be able to make payroll in the weeks to come.”

Randy Dotinga is a freelance health/medical reporter and board member of the Association of Health Care Journalists.

A version of this article appeared on Medscape.com.

The Centers for Medicare & Medicaid Services (CMS) has announced the conclusion of a program that provided billions in early Medicare payments to those affected by the Change Healthcare/UnitedHealth Group cyberattack last winter. The Accelerated and Advance Payment program, which began in early March to assist hospitals and practices facing significant reimbursement delays, will stop accepting applications after July 12, 2024.

CMS reported that the program advanced more than $2.55 billion in Medicare payments to > 4200 Part A providers, including hospitals, and more than $717.18 million in payments to Part B suppliers such as physicians, nonphysician practitioners, and durable medical equipment suppliers.

According to CMS, the Medicare billing system is now functioning properly, and 96% of the early payments have been recovered. The advances were to represent ≤ 30 days of typical claims payments in a 3-month period of 2023, with full repayment expected within 90 days through “automatic recoupment from Medicare claims” — no extensions allowed.

The agency took a victory lap regarding its response. “In the face of one of the most widespread cyberattacks on the US health care industry, CMS promptly took action to get providers and suppliers access to the funds they needed to continue providing patients with vital care,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “Our efforts helped minimize the disruptive fallout from this incident, and we will remain vigilant to be ready to address future events.”

Ongoing Concerns from Health Care Organizations

Ben Teicher, an American Hospital Association spokesman, said that the organization hopes that CMS will be responsive if there’s more need for action after the advance payment program expires. The organization represents about 5000 hospitals, health care systems, and other providers.

“Our members report that the aftereffects of this event will likely be felt throughout the remainder of the year,” he said. According to Teicher, hospitals remain concerned about their ability to process claims and appeal denials, the safety of reconnecting to cyber services, and access to information needed to bill patients and reconcile payments.

In addition, hospitals are concerned about “financial support to mitigate the considerable costs incurred as a result of the cyberattack,” he said.

Charlene MacDonald, executive vice-president of public affairs at the Federation of American Hospitals, which represents more than 1000 for-profit hospitals, sent a statement to this news organization that said some providers “are still feeling the effects of care denials and delays caused by insurer inaction.

“We appreciate that the Administration acted within its authority to support providers during this unprecedented crisis and blunt these devastating impacts, especially because a vast majority of managed care companies failed to step up to the plate,” she said. “It is now time to shift our focus to holding plans accountable for using tactics to delay and deny needed patient care.”

Cyberattack Impact and Response

The ransom-based cyberattack against Change Healthcare/UnitedHealth Group targeted an electronic data interchange clearing house processing payer reimbursement systems, disrupting cash flows at hospitals and medical practices, and affecting patient access to prescriptions and life-saving therapy.

Change Healthcare — part of the UnitedHealth Group subsidiary Optum — processes half of all medical claims, according to a Department of Justice lawsuit. The American Hospital Association described the cyberattack as “the most significant and consequential incident of its kind” in US history.

By late March, UnitedHealth Group said nearly all medical and pharmacy claims were processing properly, while a deputy secretary of the US Department of Health & Human Services told clinicians that officials were focusing on the last group of clinicians who were facing cash-flow problems.

Still, a senior advisor with CMS told providers at that time that “we have heard from so many providers over the last several weeks who are really struggling to make ends meet right now or who are worried that they will not be able to make payroll in the weeks to come.”

Randy Dotinga is a freelance health/medical reporter and board member of the Association of Health Care Journalists.

A version of this article appeared on Medscape.com.

The Centers for Medicare & Medicaid Services (CMS) has announced the conclusion of a program that provided billions in early Medicare payments to those affected by the Change Healthcare/UnitedHealth Group cyberattack last winter. The Accelerated and Advance Payment program, which began in early March to assist hospitals and practices facing significant reimbursement delays, will stop accepting applications after July 12, 2024.

CMS reported that the program advanced more than $2.55 billion in Medicare payments to > 4200 Part A providers, including hospitals, and more than $717.18 million in payments to Part B suppliers such as physicians, nonphysician practitioners, and durable medical equipment suppliers.

According to CMS, the Medicare billing system is now functioning properly, and 96% of the early payments have been recovered. The advances were to represent ≤ 30 days of typical claims payments in a 3-month period of 2023, with full repayment expected within 90 days through “automatic recoupment from Medicare claims” — no extensions allowed.

The agency took a victory lap regarding its response. “In the face of one of the most widespread cyberattacks on the US health care industry, CMS promptly took action to get providers and suppliers access to the funds they needed to continue providing patients with vital care,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “Our efforts helped minimize the disruptive fallout from this incident, and we will remain vigilant to be ready to address future events.”

Ongoing Concerns from Health Care Organizations

Ben Teicher, an American Hospital Association spokesman, said that the organization hopes that CMS will be responsive if there’s more need for action after the advance payment program expires. The organization represents about 5000 hospitals, health care systems, and other providers.

“Our members report that the aftereffects of this event will likely be felt throughout the remainder of the year,” he said. According to Teicher, hospitals remain concerned about their ability to process claims and appeal denials, the safety of reconnecting to cyber services, and access to information needed to bill patients and reconcile payments.

In addition, hospitals are concerned about “financial support to mitigate the considerable costs incurred as a result of the cyberattack,” he said.

Charlene MacDonald, executive vice-president of public affairs at the Federation of American Hospitals, which represents more than 1000 for-profit hospitals, sent a statement to this news organization that said some providers “are still feeling the effects of care denials and delays caused by insurer inaction.

“We appreciate that the Administration acted within its authority to support providers during this unprecedented crisis and blunt these devastating impacts, especially because a vast majority of managed care companies failed to step up to the plate,” she said. “It is now time to shift our focus to holding plans accountable for using tactics to delay and deny needed patient care.”

Cyberattack Impact and Response

The ransom-based cyberattack against Change Healthcare/UnitedHealth Group targeted an electronic data interchange clearing house processing payer reimbursement systems, disrupting cash flows at hospitals and medical practices, and affecting patient access to prescriptions and life-saving therapy.

Change Healthcare — part of the UnitedHealth Group subsidiary Optum — processes half of all medical claims, according to a Department of Justice lawsuit. The American Hospital Association described the cyberattack as “the most significant and consequential incident of its kind” in US history.

By late March, UnitedHealth Group said nearly all medical and pharmacy claims were processing properly, while a deputy secretary of the US Department of Health & Human Services told clinicians that officials were focusing on the last group of clinicians who were facing cash-flow problems.

Still, a senior advisor with CMS told providers at that time that “we have heard from so many providers over the last several weeks who are really struggling to make ends meet right now or who are worried that they will not be able to make payroll in the weeks to come.”

Randy Dotinga is a freelance health/medical reporter and board member of the Association of Health Care Journalists.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Andrew N. Wilner, MD: My guest today is Dr. Jose Merino, editor in chief of the Neurology family of journals and professor of neurology and co-vice chair of education at Georgetown University in Washington, DC.

Our program today is a follow-up of Dr. Merino’s presentation at the recent American Academy of Neurology meeting in Denver, Colorado. Along with two other panelists, Dr. Merino discussed the role of open-access publication and the dangers of predatory journals. 

Jose G. Merino, MD, MPhil: Thank you for having me here. It’s a pleasure.
 

Open Access Defined

Dr. Wilner: I remember when publication in neurology was pretty straightforward. It was either the green journal or the blue journal, but things have certainly changed. I think one topic that is not clear to everyone is this concept of open access. Could you define that for us? 

Dr. Merino: Sure. Open access is a mode of publication that fosters more open or accessible science. The idea of open access is that it combines two main elements. One is that the papers that are published become immediately available to anybody with an internet connection anywhere in the world without any restrictions. 

The second important element from open access, which makes it different from other models we can talk about, is the fact that the authors retain the copyright of their work, but they give the journal and readers a license to use, reproduce, and modify the content.

This is different, for example, from instances where we have funder mandates. For example, NIH papers have to become available 6 months after publication, so they’re available to everybody but not immediately. 

Then copyright is retained, in the case of NIH employees, for example, by the government or by the journals themselves. The two elements of open access, I think, are immediate access to the material and the fact that it’s published with a Creative Commons license. 

Dr. Wilner: I remember that when a journal article was published, say, in Neurology, if you didn’t have a subscription to Neurology, you went to the library that hopefully had a subscription.

If they didn’t have it, you would write to the author and say, “Hey, I heard you have this great paper because the abstract was out there. Could you send me a reprint?” Has that whole universe evaporated? 

Dr. Merino: It depends on how the paper is published. For example, in Neurology, some of the research we publish is open access. Basically, if you have an internet connection, you can access the paper.

That’s the case for papers published in our wholly open-access journals in the Neurology family like Neurology Neuroimmunology & Neuroinflammation, Neurology Genetics, or Neurology Education. 

For other papers that are published in Neurology, not under open access, there is a paywall. For some of them, the paywall comes down after a few months based on funder mandates and so on. As I was mentioning, the NIH-funded papers are available 6 months later. 

In the first 6 months, you may have to go to your library, and if your library has a subscription, you can download it directly. [This is also true for] those that always stay behind the paywall, where you have to have a subscription or your library has to have a subscription.
 

Is Pay to Publish a Red Flag?

Dr. Wilner: I’m a professional writer. With any luck, when I write something, I get paid to write it. There’s been a long tradition in academic medicine that when you submit an article to, say, Neurology, you don’t get paid as an author for the publication. Your reward is the honor of it being published. 

Neurology supports itself in various ways, including advertising and so on. That’s been the contract: free publication for work that merits it, and the journal survives on its own. 

With open access, one of the things that’s happened is that — and I’ve published open access myself — is that I get a notification that I need to pay to have my article that I’ve slaved over published. Explain that, please. 

Dr. Merino: This is the issue with open access. As I mentioned, the paper gets published. You’re giving the journal a license to publish it. You’re retaining the copyright of your work. That means that the journal cannot make money or support itself by just publishing open access because they belong to you. 

Typically, open-access journals are not in print and don’t have much in terms of advertising. The contract is you’re giving me a license to publish it, but it’s your journal, so you’re paying a fee for the journal expenses to basically produce your paper. That’s what’s happening with open access. 

That’s been recognized with many funders, for example, with NIH funding or many of the European funders, they’re including open-access fees as part of their funding for research. Now, of course, this doesn’t help if you’re not a funded researcher or if you’re a fellow who’s doing work and so on. 

Typically, most journals will have waived fees or lower fees for these situations. The reason for the open-access fee is the fact that you’re retaining the copyright. You’re not giving it to the journal who can then use it to generate its revenue for supporting itself, the editorial staff, and so on. 

Dr. Wilner: This idea of charging for publication has created a satellite business of what are called predatory journals. How does one know if the open-access journal that I’m submitting to is really just in the business of wanting my $300 or my $900 to get published? How do I know if that’s a reasonable place to publish? 
 

Predatory Journals

Dr. Merino: That’s a big challenge that has come with this whole idea of open access and the fact that now, many journals are online only, so you’re no longer seeing a physical copy. That has given rise to the predatory journals. 

The predatory journal, by definition, is a journal that claims to be open access. They’ll take your paper and publish it, but they don’t provide all the other services that you would typically expect from the fact that you’re paying an open-access fee. This includes getting appropriate peer review, production of the manuscript, and long-term curation and storage of the manuscript. 

Many predatory journals will take your open-access fee, accept any paper that you submit, regardless of the quality, because they’re charging the fees for that. They don’t send it to real peer review, and then in a few months, the journal disappears so there’s no way for anybody to actually find your paper anymore. 

There are certain checklists. Dr. David Moher at the University of Toronto has produced some work trying to help us identify predatory journals. 

One thing I typically suggest to people who ask me this question is: Have you ever heard of this journal before? Does the journal have a track record? How far back does the story of the journal go? Is it supported by a publisher that you know? Do you know anybody who has published there? Is it something you can easily access?

If in doubt, always ask your friendly medical librarian. There used to be lists that were kept in terms of predatory journals that were being constantly updated, but those had to be shut down. As far as I understand, there were legal issues in terms of how things got on that list. 

I think that overall, if you’ve heard of it, if it’s relevant, if it’s known in your field, and if your librarian knows it, it’s probably a good legitimate open-access journal. There are many very good legitimate open-access journals. 

I mentioned the two that we have in our family, but all the other major journals have their own open-access journal within their family. There are some, like BMC or PLOS, that are completely open-access and legitimate journals. 
 

Impact Factor

Dr. Wilner: What about impact factor? Many journals boast about their impact factor. I’m not sure how to interpret that number. 

Dr. Merino: Impact factor is very interesting. The impact factor was developed by medical librarians to try to identify the journals they should be subscribing to. It’s a measure of the average citations to an average paper in the journal. 

It doesn’t tell you about specific papers. It tells you, on average, how many of the papers in this journal get cited so many times. It’s calculated by the number of articles that were cited divided by the number of articles that were published. Journals that publish many papers, like Neurology, have a hard time bringing up their impact factor beyond a certain level. 

Similarly, very small journals with one or two very highly cited papers have a very high impact factor. It’s being used as a measure, perhaps inappropriately, of how good or how reputable a journal is. We all say we don’t care about journal impact factors, but we all know our journal impact factor and we used to know it to three decimals. Now, they changed the system, and there’s only one decimal point, which makes more sense. 

This is more important, for example, for authors when deciding where to submit papers. I know that in some countries, particularly in Europe, the impact factor of the journal where you publish has an impact on your promotion decisions. 

I would say what’s even more important than the impact factor, is to say, “Well, is this the journal that fits the scope of my paper? Is this the journal that reaches the audience that I want to reach when I write my paper?” 

There are some papers, for example, that are very influential. The impact factor just captures citations. There are some papers that are very influential that may not get cited very often. There may be papers that change clinical practice. 

If you read a paper that tells you that you should be changing how you treat your patients with myasthenia based on this paper, that may not get cited. It’s a very clinically focused paper, but it’s probably more impactful than one that gets cited very much in some respect, or they make it to public policy decisions, and so on. 

I think it’s important to look more at the audience and the journal scope when you submit your papers. 

Dr. Wilner: One other technical question. The journals also say they’re indexed in PubMed or Google Scholar. If I want to publish my paper and I want it indexed where the right people are going to find it, where does it need to be indexed? 

Dr. Merino: I grew up using Index Medicus, MedlinePlus, and the Library of Science. I still do. If I need to find something, I go to PubMed. Ideally, papers are listed in MedlinePlus or can be found in PubMed. They’re not the same thing, but you can find them through them. 

That would be an important thing. Nowadays, a lot more people are using Google Scholar or Google just to identify papers. It may be a little bit less relevant, but it’s still a measure of the quality of the journal before they get indexed in some of these. For example, if you get listed in MedlinePlus, it has gone through certain quality checks by the index itself to see whether they would accept the journal or not. That’s something you want to check.

Typically, most of the large journals or the journals you and I know about are listed in more than one place, right? They’re listed in Scopus and Web of Science. They’re listed in MedlinePlus and so on. Again, if you’re submitting your paper, go somewhere where you know the journal and you’ve heard about it. 

Dr. Wilner: I’m not going to ask you about artificial intelligence. We can do that another time. I want to ask something closer to me, which is this question of publish or perish. 

There seems to be, in academics, more emphasis on the number of papers that one has published rather than their quality. How does a younger academician or one who really needs to publish cope with that? 

Dr. Merino: Many people are writing up research that may not be relevant or that may not be high quality just because you need to have a long list of papers to get promoted, for example, if you’re an academician. 

Doug Altman, who was a very influential person in the field quality of not only medical statistics but also medical publishing, had the idea that we need less research, but we need better research. 

We often receive papers where you say, well, what’s the rationale behind the question in this paper? It’s like they had a large amount of data and were trying to squeeze as much as they could out of that. I think, as a young academician, the important thing to think about is whether it is an important question that matters to you and to the field, from whatever perspective, whether it’s going to advance research, advance clinical care, or have public policy implications. 

Is this one where the answer will be important no matter what the answer is? If you’re thinking of that, your work will be well recognized, people will know you, and you’ll get invited to collaborate. I think that’s the most important thing rather than just churning out a large number of papers. 

The productivity will come from the fact that you start by saying, let me ask something that’s really meaningful to me and to the field, with a good question and using strong research methodology. 

Dr. Wilner: Thanks for that, Dr. Merino. I think that’s very valuable for all of us. This has been a great discussion. Do you have any final comments before we wrap up? 

Dr. Merino: I want to encourage people to continue reading medical journals all the time and submitting to us, again, good research and important questions with robust methodology. That’s what we’re looking for in Neurology and most serious medical journals.
 

Dr. Wilner is an associate professor of neurology at the University of Tennessee Health Science Center, Memphis. Dr. Merino is a professor in the department of neurology at Georgetown University Medical Center, Washington, DC. Dr. Wilner reported conflicts of interest with Accordant Health Services and Lulu Publishing. Dr. Merino reported no relevant conflicts of interest.

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

This transcript has been edited for clarity. 

Andrew N. Wilner, MD: My guest today is Dr. Jose Merino, editor in chief of the Neurology family of journals and professor of neurology and co-vice chair of education at Georgetown University in Washington, DC.

Our program today is a follow-up of Dr. Merino’s presentation at the recent American Academy of Neurology meeting in Denver, Colorado. Along with two other panelists, Dr. Merino discussed the role of open-access publication and the dangers of predatory journals. 

Jose G. Merino, MD, MPhil: Thank you for having me here. It’s a pleasure.
 

Open Access Defined

Dr. Wilner: I remember when publication in neurology was pretty straightforward. It was either the green journal or the blue journal, but things have certainly changed. I think one topic that is not clear to everyone is this concept of open access. Could you define that for us?