Sara Freeman

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

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

First Phase 3 Trial in China

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

Sara Freeman/Medscape Medical News

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

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

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

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

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

Standard Design

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

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

Additional Results

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

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

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

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

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

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

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

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

Another JAK in the Box?

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

First Phase 3 Trial in China

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

Sara Freeman/Medscape Medical News

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

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

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

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

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

Standard Design

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

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

Additional Results

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

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

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

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

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

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

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

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

Another JAK in the Box?

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

First Phase 3 Trial in China

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

Sara Freeman/Medscape Medical News

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

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

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

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

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

Standard Design

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

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

Additional Results

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

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

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

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

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

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

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

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

Another JAK in the Box?

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

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

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

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

A version of this article appeared on Medscape.com.

VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).

The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).

Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a late-breaking abstract presented at the at the annual European Congress of Rheumatology.
 

First JAK Trial in GCA

This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator Daniel Blockmans, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.

Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.

“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”

Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.
 

Study Details

SELECT-GCA is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.

A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.

Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.

No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.
 

Secondary Endpoints

One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.

Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (P < .0001).

Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, P = .0014).

Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).

And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.

The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.

As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.
 

‘Life-Changing’

The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.

“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”

Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”

After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”
 

Judicious Use Still Warranted

Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.

Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”

But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”

Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.

He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the ORAL [Surveillance] study; we didn’t see these problems here in this elderly population.”

The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).

The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).

Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a late-breaking abstract presented at the at the annual European Congress of Rheumatology.
 

First JAK Trial in GCA

This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator Daniel Blockmans, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.

Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.

“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”

Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.
 

Study Details

SELECT-GCA is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.

A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.

Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.

No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.
 

Secondary Endpoints

One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.

Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (P < .0001).

Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, P = .0014).

Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).

And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.

The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.

As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.
 

‘Life-Changing’

The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.

“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”

Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”

After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”
 

Judicious Use Still Warranted

Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.

Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”

But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”

Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.

He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the ORAL [Surveillance] study; we didn’t see these problems here in this elderly population.”

The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).

The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).

Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a late-breaking abstract presented at the at the annual European Congress of Rheumatology.
 

First JAK Trial in GCA

This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator Daniel Blockmans, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.

Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.

“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”

Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.
 

Study Details

SELECT-GCA is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.

A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.

Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.

No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.
 

Secondary Endpoints

One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.

Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (P < .0001).

Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, P = .0014).

Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).

And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.

The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.

As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.
 

‘Life-Changing’

The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.

“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”

Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”

After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”
 

Judicious Use Still Warranted

Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.

Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”

But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”

Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.

He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the ORAL [Surveillance] study; we didn’t see these problems here in this elderly population.”

The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

The European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology annual meeting is about to take place in Vienna, Austria. From June 12 to 15, some of the world’s leading researchers and clinicians will convene to present and learn about data on some of the new and innovative treatments for people with rheumatic and musculoskeletal diseases (RMDs) as well as to discuss how to use and optimize existing approaches. 

Ahead of the Congress, this news organization asked the Congress Committee’s Scientific Programme Chair Caroline Ospelt, MD, PhD, and Abstract Chair Christian Dejaco, MD, PhD, MBA, to discuss some of their highlights of this year’s meeting.
 

From Bench to Bedside

“For me, the beauty at EULAR is really that you have the latest on basic research, how this can be translated in clinical trials, and then the last step would be how EULAR recommends it to be used in clinical practice,” Dr. Ospelt, professor of experimental rheumatology at University Hospital Zurich, said in an interview.  

University Hospital Zurich

“So, if you go to EULAR continuously, you can actually follow the whole story of how novelty comes into clinical practice,” she added. 

In a separate interview, Dr. Dejaco, a consultant rheumatologist and associate professor at the Medical University of Graz in Austria, said: “There are several new drug trials that are going to be presented.” 

One of his highlights on the use of new drugs for the treatment of giant cell arteritis will be the phase 3 SELECT-GCA trial of the Janus kinase (JAK) inhibitor upadacitinib (LBA0001).

“It’s a trial that hopefully will lead to the approval of this drug in this indication,” Dr. Dejaco said.

EULAR

Late-Breaking Abstracts

Dr. Ospelt noted: “We had a lot of good late-breaking abstracts this year.” 

Some of these include: 

• Real-world data on the comparative effectiveness of five different classes of drugs used to treat psoriatic arthritis (PsA; LBA0002) 
• The 16-week results of a phase 2b/3 study with the novel interleukin (IL)–17A inhibitor izokibep in people with PsA (LBA0005)
• Data from the COSPIRIT-JIA trial on the efficacy and safety of ixekizumab (Taltz) in juvenile idiopathic arthritis (LBA0009)
• Phase 2 data on the safety and efficacy of the CD38-targeting monoclonal antibody daratumumab in systemic lupus erythematosus (LBA0007)
• Results of the phase 2 DAHLIAS study of the anti–neonatal Fc receptor monoclonal antibody nipocalimab in people with primary Sjögren disease (LBA0010) 
• Safety and immunogenicity data from a phase 1 study of an active anti–IL-6 immunotherapy in people with knee osteoarthritis (LBA0011)

The latter is “really interesting,” Dr. Ospelt said. As of now, there is no approved treatment for osteoarthritis, and there is no immunotherapy, “so this would be the first.” 

But it’s not just the late-breaker abstracts to look out for. Dr. Dejaco highlighted two abstracts that will be presented during the Abstract Plenary: 

• A phase 3 study of a new selective JAK1 inhibitor, SHR0302, in rheumatoid arthritis (OP0037)
• A multi-omics analysis and targeted gene-editing study in people with , which causes inflammatory and hematologic changes (OP0073)

Of the latter, he said, “this disease is still incompletely understood, and this abstract really helps to better understand the mechanisms underlying this disease.”
 

One to Watch: CAR T-Cell Therapy 

Dr. Ospelt said that the scientific program is about 80% clinical and 20% basic science overall. However, more sessions are being held jointly because data are starting to move from the bench to bedside. 

One of the basic science areas that has had “a real buzz” around it and is now producing results in the clinic is the use of chimeric antigen receptor (CAR) T cells. In one of the first, and perhaps aptly titled What Is New, or WIN, sessions of the congress, Georg Schett, MD, vice president of research at Friedrich-Alexander-Universität Erlangen-Nüremberg in Germany, will discuss the use of CAR T-cell therapy for inflammatory RMDs. There are also multiple abstract presentations on this topic. 

In-depth tissue analysis and prediction of treatment response is another interesting approach, Dr. Ospelt said. “I think that’s the way to go, that we come from the blood, we go into the tissue.” A “very nice” example of this approach will be presented during the Abstract Plenary session on Wednesday, June 12, looking at how synovial tissue macrophages may be able to give information on likely treatment response in treatment-naive rheumatoid arthritis (OP0062). There are also some further findings related to the tissue biopsy–driven treatment trial R4RA that are being presented at the meeting (OP0218, OP0242, and POS0351).
 

EULAR Highlighted Sessions

Among the highlighted sessions on the EULAR 2024 website is one on axial involvement in PsA and spondyloarthritis (SpA). 

“Axial involvement in psoriatic arthritis and peripheral involvement in axial spondyloarthritis is quite a hot topic at the moment,” Dr. Ospelt said. There are lots of questions: “How connected are they? How different are they? Do we need different treatment for axial involvement compared to peripheral involvement?” 

Another EULAR highlighted session is the 75th anniversary of glucocorticoid treatment, during which Past President of EULAR and Emeritus Professor of Rheumatology Josef S. Smolen, MD, will overview the “past, present, and future” of glucocorticoids in RMDs. Consultant rheumatologist Frank Buttgereit, MD, from the German Rheumatism Research Center in Berlin, will discuss the practicalities of using these drugs in clinical practice.

Dr. Dejaco noted: “Glucocorticoids have been one of the most important treatments for a very long time, and they’re still the most important treatment for the acute treatment of systemic inflammatory diseases.”

For a long time, there was no alternative to using steroids, he added, but steroid-sparing options now exist, and there will be data presented on a new type of drug that could potentially be used to control cortisol levels in the body (OP0335).
 

Recommendations and More

Dr. Ospelt and Dr. Dejaco both pointed out other sessions that are likely to be very popular, such as the first and second EULAR Recommendations sessions, a session on rheumatoid arthritis prevention, as well as the many presentations and sessions on digital health and nonpharmacologic interventions such as exercise. 

With over 5242 submitted abstracts, there is going to be no shortage of data being presented at EULAR 2024. Alongside the traditional abstract submission categories, this year there is a new clinical case reports category. 

“We had about 578 submissions for that category,” Dr. Dejaco said. There were 3315 abstracts submitted for the clinical research category, 812 for the basic and translational research category, 283 from health professionals in rheumatology, 152 from patient groups, and 102 in the field of pediatric rheumatology.
 

Join in On-Site, Watch on Demand 

EULAR 2024 reverts to an on-site–only meeting this year. Some of the more lighthearted yet educational elements of the program for those attending include the second edition of the EMEUNET Rheumatology Quiz and, new for this year, two escape rooms. These rooms will provide an interactive experience where small teams will have to solve rheumatologic conundrums in order to escape the room within the hour, Dr. Dejaco explained. There will also be a morning run on Friday, June 14. “It’s not a race, it’s simply to meet and run together,” Dr. Dejaco said. 

But if you cannot make the congress in person, the EULAR 2024 Livestream will be broadcasting throughout the congress. Anyone registered by June 30 will have on-demand access to the recorded content from June 17 until December 31, 2024. 

Abstracts for the meeting will be published as a supplement to Annals of the Rheumatic Diseases, the official journal of EULAR. 

Dr. Ospelt reported no relevant financial relationships. Dr. Dejaco has received consulting/speaker fees from AbbVie, Eli Lilly, Janssen, Sparrow, Novartis, Pfizer, Roche, Galapagos, and Sanofi.

A version of this article appeared on Medscape.com.

The European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology annual meeting is about to take place in Vienna, Austria. From June 12 to 15, some of the world’s leading researchers and clinicians will convene to present and learn about data on some of the new and innovative treatments for people with rheumatic and musculoskeletal diseases (RMDs) as well as to discuss how to use and optimize existing approaches. 

Ahead of the Congress, this news organization asked the Congress Committee’s Scientific Programme Chair Caroline Ospelt, MD, PhD, and Abstract Chair Christian Dejaco, MD, PhD, MBA, to discuss some of their highlights of this year’s meeting.
 

From Bench to Bedside

“For me, the beauty at EULAR is really that you have the latest on basic research, how this can be translated in clinical trials, and then the last step would be how EULAR recommends it to be used in clinical practice,” Dr. Ospelt, professor of experimental rheumatology at University Hospital Zurich, said in an interview.  

University Hospital Zurich

“So, if you go to EULAR continuously, you can actually follow the whole story of how novelty comes into clinical practice,” she added. 

In a separate interview, Dr. Dejaco, a consultant rheumatologist and associate professor at the Medical University of Graz in Austria, said: “There are several new drug trials that are going to be presented.” 

One of his highlights on the use of new drugs for the treatment of giant cell arteritis will be the phase 3 SELECT-GCA trial of the Janus kinase (JAK) inhibitor upadacitinib (LBA0001).

“It’s a trial that hopefully will lead to the approval of this drug in this indication,” Dr. Dejaco said.

EULAR

Late-Breaking Abstracts

Dr. Ospelt noted: “We had a lot of good late-breaking abstracts this year.” 

Some of these include: 

• Real-world data on the comparative effectiveness of five different classes of drugs used to treat psoriatic arthritis (PsA; LBA0002) 
• The 16-week results of a phase 2b/3 study with the novel interleukin (IL)–17A inhibitor izokibep in people with PsA (LBA0005)
• Data from the COSPIRIT-JIA trial on the efficacy and safety of ixekizumab (Taltz) in juvenile idiopathic arthritis (LBA0009)
• Phase 2 data on the safety and efficacy of the CD38-targeting monoclonal antibody daratumumab in systemic lupus erythematosus (LBA0007)
• Results of the phase 2 DAHLIAS study of the anti–neonatal Fc receptor monoclonal antibody nipocalimab in people with primary Sjögren disease (LBA0010) 
• Safety and immunogenicity data from a phase 1 study of an active anti–IL-6 immunotherapy in people with knee osteoarthritis (LBA0011)

The latter is “really interesting,” Dr. Ospelt said. As of now, there is no approved treatment for osteoarthritis, and there is no immunotherapy, “so this would be the first.” 

But it’s not just the late-breaker abstracts to look out for. Dr. Dejaco highlighted two abstracts that will be presented during the Abstract Plenary: 

• A phase 3 study of a new selective JAK1 inhibitor, SHR0302, in rheumatoid arthritis (OP0037)
• A multi-omics analysis and targeted gene-editing study in people with , which causes inflammatory and hematologic changes (OP0073)

Of the latter, he said, “this disease is still incompletely understood, and this abstract really helps to better understand the mechanisms underlying this disease.”
 

One to Watch: CAR T-Cell Therapy 

Dr. Ospelt said that the scientific program is about 80% clinical and 20% basic science overall. However, more sessions are being held jointly because data are starting to move from the bench to bedside. 

One of the basic science areas that has had “a real buzz” around it and is now producing results in the clinic is the use of chimeric antigen receptor (CAR) T cells. In one of the first, and perhaps aptly titled What Is New, or WIN, sessions of the congress, Georg Schett, MD, vice president of research at Friedrich-Alexander-Universität Erlangen-Nüremberg in Germany, will discuss the use of CAR T-cell therapy for inflammatory RMDs. There are also multiple abstract presentations on this topic. 

In-depth tissue analysis and prediction of treatment response is another interesting approach, Dr. Ospelt said. “I think that’s the way to go, that we come from the blood, we go into the tissue.” A “very nice” example of this approach will be presented during the Abstract Plenary session on Wednesday, June 12, looking at how synovial tissue macrophages may be able to give information on likely treatment response in treatment-naive rheumatoid arthritis (OP0062). There are also some further findings related to the tissue biopsy–driven treatment trial R4RA that are being presented at the meeting (OP0218, OP0242, and POS0351).
 

EULAR Highlighted Sessions

Among the highlighted sessions on the EULAR 2024 website is one on axial involvement in PsA and spondyloarthritis (SpA). 

“Axial involvement in psoriatic arthritis and peripheral involvement in axial spondyloarthritis is quite a hot topic at the moment,” Dr. Ospelt said. There are lots of questions: “How connected are they? How different are they? Do we need different treatment for axial involvement compared to peripheral involvement?” 

Another EULAR highlighted session is the 75th anniversary of glucocorticoid treatment, during which Past President of EULAR and Emeritus Professor of Rheumatology Josef S. Smolen, MD, will overview the “past, present, and future” of glucocorticoids in RMDs. Consultant rheumatologist Frank Buttgereit, MD, from the German Rheumatism Research Center in Berlin, will discuss the practicalities of using these drugs in clinical practice.

Dr. Dejaco noted: “Glucocorticoids have been one of the most important treatments for a very long time, and they’re still the most important treatment for the acute treatment of systemic inflammatory diseases.”

For a long time, there was no alternative to using steroids, he added, but steroid-sparing options now exist, and there will be data presented on a new type of drug that could potentially be used to control cortisol levels in the body (OP0335).
 

Recommendations and More

Dr. Ospelt and Dr. Dejaco both pointed out other sessions that are likely to be very popular, such as the first and second EULAR Recommendations sessions, a session on rheumatoid arthritis prevention, as well as the many presentations and sessions on digital health and nonpharmacologic interventions such as exercise. 

With over 5242 submitted abstracts, there is going to be no shortage of data being presented at EULAR 2024. Alongside the traditional abstract submission categories, this year there is a new clinical case reports category. 

“We had about 578 submissions for that category,” Dr. Dejaco said. There were 3315 abstracts submitted for the clinical research category, 812 for the basic and translational research category, 283 from health professionals in rheumatology, 152 from patient groups, and 102 in the field of pediatric rheumatology.
 

Join in On-Site, Watch on Demand 

EULAR 2024 reverts to an on-site–only meeting this year. Some of the more lighthearted yet educational elements of the program for those attending include the second edition of the EMEUNET Rheumatology Quiz and, new for this year, two escape rooms. These rooms will provide an interactive experience where small teams will have to solve rheumatologic conundrums in order to escape the room within the hour, Dr. Dejaco explained. There will also be a morning run on Friday, June 14. “It’s not a race, it’s simply to meet and run together,” Dr. Dejaco said. 

But if you cannot make the congress in person, the EULAR 2024 Livestream will be broadcasting throughout the congress. Anyone registered by June 30 will have on-demand access to the recorded content from June 17 until December 31, 2024. 

Abstracts for the meeting will be published as a supplement to Annals of the Rheumatic Diseases, the official journal of EULAR. 

Dr. Ospelt reported no relevant financial relationships. Dr. Dejaco has received consulting/speaker fees from AbbVie, Eli Lilly, Janssen, Sparrow, Novartis, Pfizer, Roche, Galapagos, and Sanofi.

A version of this article appeared on Medscape.com.

The European Alliance of Associations for Rheumatology (EULAR) 2024 European Congress of Rheumatology annual meeting is about to take place in Vienna, Austria. From June 12 to 15, some of the world’s leading researchers and clinicians will convene to present and learn about data on some of the new and innovative treatments for people with rheumatic and musculoskeletal diseases (RMDs) as well as to discuss how to use and optimize existing approaches. 

Ahead of the Congress, this news organization asked the Congress Committee’s Scientific Programme Chair Caroline Ospelt, MD, PhD, and Abstract Chair Christian Dejaco, MD, PhD, MBA, to discuss some of their highlights of this year’s meeting.
 

From Bench to Bedside

“For me, the beauty at EULAR is really that you have the latest on basic research, how this can be translated in clinical trials, and then the last step would be how EULAR recommends it to be used in clinical practice,” Dr. Ospelt, professor of experimental rheumatology at University Hospital Zurich, said in an interview.  

University Hospital Zurich

“So, if you go to EULAR continuously, you can actually follow the whole story of how novelty comes into clinical practice,” she added. 

In a separate interview, Dr. Dejaco, a consultant rheumatologist and associate professor at the Medical University of Graz in Austria, said: “There are several new drug trials that are going to be presented.” 

One of his highlights on the use of new drugs for the treatment of giant cell arteritis will be the phase 3 SELECT-GCA trial of the Janus kinase (JAK) inhibitor upadacitinib (LBA0001).

“It’s a trial that hopefully will lead to the approval of this drug in this indication,” Dr. Dejaco said.

EULAR

Late-Breaking Abstracts

Dr. Ospelt noted: “We had a lot of good late-breaking abstracts this year.” 

Some of these include: 

• Real-world data on the comparative effectiveness of five different classes of drugs used to treat psoriatic arthritis (PsA; LBA0002) 
• The 16-week results of a phase 2b/3 study with the novel interleukin (IL)–17A inhibitor izokibep in people with PsA (LBA0005)
• Data from the COSPIRIT-JIA trial on the efficacy and safety of ixekizumab (Taltz) in juvenile idiopathic arthritis (LBA0009)
• Phase 2 data on the safety and efficacy of the CD38-targeting monoclonal antibody daratumumab in systemic lupus erythematosus (LBA0007)
• Results of the phase 2 DAHLIAS study of the anti–neonatal Fc receptor monoclonal antibody nipocalimab in people with primary Sjögren disease (LBA0010) 
• Safety and immunogenicity data from a phase 1 study of an active anti–IL-6 immunotherapy in people with knee osteoarthritis (LBA0011)

The latter is “really interesting,” Dr. Ospelt said. As of now, there is no approved treatment for osteoarthritis, and there is no immunotherapy, “so this would be the first.” 

But it’s not just the late-breaker abstracts to look out for. Dr. Dejaco highlighted two abstracts that will be presented during the Abstract Plenary: 

• A phase 3 study of a new selective JAK1 inhibitor, SHR0302, in rheumatoid arthritis (OP0037)
• A multi-omics analysis and targeted gene-editing study in people with , which causes inflammatory and hematologic changes (OP0073)

Of the latter, he said, “this disease is still incompletely understood, and this abstract really helps to better understand the mechanisms underlying this disease.”
 

One to Watch: CAR T-Cell Therapy 

Dr. Ospelt said that the scientific program is about 80% clinical and 20% basic science overall. However, more sessions are being held jointly because data are starting to move from the bench to bedside. 

One of the basic science areas that has had “a real buzz” around it and is now producing results in the clinic is the use of chimeric antigen receptor (CAR) T cells. In one of the first, and perhaps aptly titled What Is New, or WIN, sessions of the congress, Georg Schett, MD, vice president of research at Friedrich-Alexander-Universität Erlangen-Nüremberg in Germany, will discuss the use of CAR T-cell therapy for inflammatory RMDs. There are also multiple abstract presentations on this topic. 

In-depth tissue analysis and prediction of treatment response is another interesting approach, Dr. Ospelt said. “I think that’s the way to go, that we come from the blood, we go into the tissue.” A “very nice” example of this approach will be presented during the Abstract Plenary session on Wednesday, June 12, looking at how synovial tissue macrophages may be able to give information on likely treatment response in treatment-naive rheumatoid arthritis (OP0062). There are also some further findings related to the tissue biopsy–driven treatment trial R4RA that are being presented at the meeting (OP0218, OP0242, and POS0351).
 

EULAR Highlighted Sessions

Among the highlighted sessions on the EULAR 2024 website is one on axial involvement in PsA and spondyloarthritis (SpA). 

“Axial involvement in psoriatic arthritis and peripheral involvement in axial spondyloarthritis is quite a hot topic at the moment,” Dr. Ospelt said. There are lots of questions: “How connected are they? How different are they? Do we need different treatment for axial involvement compared to peripheral involvement?” 

Another EULAR highlighted session is the 75th anniversary of glucocorticoid treatment, during which Past President of EULAR and Emeritus Professor of Rheumatology Josef S. Smolen, MD, will overview the “past, present, and future” of glucocorticoids in RMDs. Consultant rheumatologist Frank Buttgereit, MD, from the German Rheumatism Research Center in Berlin, will discuss the practicalities of using these drugs in clinical practice.

Dr. Dejaco noted: “Glucocorticoids have been one of the most important treatments for a very long time, and they’re still the most important treatment for the acute treatment of systemic inflammatory diseases.”

For a long time, there was no alternative to using steroids, he added, but steroid-sparing options now exist, and there will be data presented on a new type of drug that could potentially be used to control cortisol levels in the body (OP0335).
 

Recommendations and More

Dr. Ospelt and Dr. Dejaco both pointed out other sessions that are likely to be very popular, such as the first and second EULAR Recommendations sessions, a session on rheumatoid arthritis prevention, as well as the many presentations and sessions on digital health and nonpharmacologic interventions such as exercise. 

With over 5242 submitted abstracts, there is going to be no shortage of data being presented at EULAR 2024. Alongside the traditional abstract submission categories, this year there is a new clinical case reports category. 

“We had about 578 submissions for that category,” Dr. Dejaco said. There were 3315 abstracts submitted for the clinical research category, 812 for the basic and translational research category, 283 from health professionals in rheumatology, 152 from patient groups, and 102 in the field of pediatric rheumatology.
 

Join in On-Site, Watch on Demand 

EULAR 2024 reverts to an on-site–only meeting this year. Some of the more lighthearted yet educational elements of the program for those attending include the second edition of the EMEUNET Rheumatology Quiz and, new for this year, two escape rooms. These rooms will provide an interactive experience where small teams will have to solve rheumatologic conundrums in order to escape the room within the hour, Dr. Dejaco explained. There will also be a morning run on Friday, June 14. “It’s not a race, it’s simply to meet and run together,” Dr. Dejaco said. 

But if you cannot make the congress in person, the EULAR 2024 Livestream will be broadcasting throughout the congress. Anyone registered by June 30 will have on-demand access to the recorded content from June 17 until December 31, 2024. 

Abstracts for the meeting will be published as a supplement to Annals of the Rheumatic Diseases, the official journal of EULAR. 

Dr. Ospelt reported no relevant financial relationships. Dr. Dejaco has received consulting/speaker fees from AbbVie, Eli Lilly, Janssen, Sparrow, Novartis, Pfizer, Roche, Galapagos, and Sanofi.

A version of this article appeared on Medscape.com.

VIENNA — Nearly one third of anterior cruciate ligament (ACL) injuries appear to heal without surgery, according to an analysis of three-dimensional MRI data taken from the NACOX study, presented as a late-breaking poster at the OARSI 2024 World Congress. 

At 2 years after injury, three-dimensional MRI showed that 13 of 43 (30%) knees had evidence of normal, continuous ACL fibers. Moreover, a further 14 (33%) knees had a continuous ACL fiber structure following rehabilitation alone. ACL fibers were partly (16%) or completely (21%) ruptured in the remainder of cases.

Sara Freeman/Medscape Medical News

“If you think of the ACL like a rope, when there is continuity, it means those fibers have rejoined,” study coauthor Stephanie Filbay, PhD, an associate professor at the University of Melbourne in Australia, told this news organization.

“Within that, there’s a few variations of healing that we’re seeing. Some look like they’ve never been injured, while some have rejoined but appear thinner or longer than a normal ACL,” Dr. Filbay said.

She added: “What all this research is showing is that it’s happening at a much higher rate than we thought possible. And in some of the studies, it looks like ACL healing is associated with very favorable outcomes.”

At OARSI 2024, Dr. Filbay presented additional data from her and others’ research on the relationships between ACL healing and long-term functional outcomes and osteoarthritis (OA) incidence in comparisons between patients’ treatment pathways: Early ACL surgery, rehabilitation followed by delayed surgery, or rehabilitation only.
 

Healing Without Surgery

The idea that the ACL can heal without surgery is relatively recent and perhaps still not widely accepted as a concept, as Dr. Filbay explained during a plenary lecture at the congress.

Dr. Filbay explained that the ideal management of ACL injury depends on the severity of knee injury and whether someone’s knee is stable after trying nonsurgical management. Results of the ACL SNNAP trial, for example, have suggested that surgical reconstruction is superior to a rehabilitation strategy for managing non-acute ACL injuries where there are persistent symptoms of instability.

However, there have been two trials — COMPARE performed in the Netherlands and KANON performed in Sweden — that found that early surgery was no better than a strategy of initial rehabilitation with the option of having a delayed ACL surgery if needed.
 

What Happens Long Term?

Posttraumatic OA is a well-known long-term consequence of ACL injury. According to a recent meta-analysis, there is a sevenfold increased risk for OA comparing people who have and have not had an ACL injury.

ACL injury also results in OA occurring at an earlier age than in people with OA who have not had an ACL injury. This has been shown to progress at a faster rate and be associated with a longer period of disability, Dr. Filbay said at the congress, sponsored by the Osteoarthritis Research Society International.

But does the ACL really heal? Dr. Filbay thinks that it does and has been involved in several studies that have used MRI to look at how the ACL may do so.

In a recently published paper, Dr. Filbay and colleagues reported the findings from a secondary analysis of the KANON trial and found that nearly one in three (30%) of the participants who had been randomized to optional delayed surgery had MRI evidence of healing at 2 years. But when they excluded people who had delayed surgery, 53% of people managed by rehabilitation alone had evidence of healing.

The evaluation also found that those who had a healed vs non-healed ligament had better results using the Knee Injury and Osteoarthritis Outcome Score (KOOS), and that there were better outcomes at 2 years among those with ACL healing vs those who had early or delayed ACL surgery.
 

ACL Continuity and Long-Term Outcomes

At OARSI 2024, Dr. Filbay and colleagues reported an even longer-term secondary analysis of the KANON trial on the relationship between ACL healing at 5 years and outcomes at 11 years. The results were first reported in NEJM Evidence.

Dr. Filbay reported that participants with ACL continuity on MRI at 5 years actually had worse patient-reported outcomes 11 years later than those who were managed with early or delayed ACL reconstruction.

“This does not align with previous findings suggesting better 2-year outcomes compared to the surgically managed groups,” Dr. Filbay said.

However, people with ACL continuity following rehabilitation did seem to show numerically similar or fewer signs of radiographic OA at 11 years vs the surgical groups.

Radiographic OA of the tibiofemoral joint (TFJ) or patellofemoral joint (PFJ) at 11 years was observed in a respective 14% and 21% of people with ACL continuity at 5 years (n = 14) and in 22% and 11% of people with ACL discontinuity at 5 years in the rehabilitation alone group.

By comparison, radiographic OA of the TFJ or PFJ at 11 years was seen in a respective 23% and 35% of people who had rehabilitation with delayed surgery (n = 26) and in 18% and 41% of those who had early surgery (n = 49).

These are descriptive results, Dr. Filbay said, because the numbers were too small to do a statistical analysis. Further, larger, longitudinal studies will be needed.
 

Posttraumatic OA After ACL Surgery

Elsewhere at OARSI 2024, Matthew Harkey, PhD, and colleagues from Michigan State University, East Lansing, Michigan, reported data showing that nearly two thirds of people who undergo surgical reconstruction have symptoms at 6 months that could be indicative of early knee OA.

Knee symptoms indicative of OA declined to 53% at 12 months and 45% at 24 months.

“It’s a bit complex — we can’t outright say arthritis is developing, but there’s a large group of patients whose symptoms linger long after surgery,” Dr. Harkey said in a press release.

“Often, clinicians assume that these postoperative symptoms will naturally improve as patients reengage with their usual activities. However, what we’re seeing suggests these symptoms persist and likely require a targeted approach to manage or improve them,” Dr. Harkey said.

The analysis used data on 3752 individuals aged 14-40 years who were enrolled in the New Zealand ACL Registry and who completed the KOOS at 6, 12, and 24 months after having ACL reconstruction.

Dr. Harkey and team reported that one in three people had persistent early OA symptoms at 2 years, while 23% had no early OA symptoms at any timepoint.

The studies were independently supported. Dr. Filbay and Dr. Harkey had no relevant financial relationships to report.

Dr. Filbay and colleagues have developed a treatment decision aid for individuals who have sustained an ACL injury. This provides information on the different treatment options available and how they compare.

A version of this article appeared on Medscape.com.

VIENNA — Nearly one third of anterior cruciate ligament (ACL) injuries appear to heal without surgery, according to an analysis of three-dimensional MRI data taken from the NACOX study, presented as a late-breaking poster at the OARSI 2024 World Congress. 

At 2 years after injury, three-dimensional MRI showed that 13 of 43 (30%) knees had evidence of normal, continuous ACL fibers. Moreover, a further 14 (33%) knees had a continuous ACL fiber structure following rehabilitation alone. ACL fibers were partly (16%) or completely (21%) ruptured in the remainder of cases.

Sara Freeman/Medscape Medical News

“If you think of the ACL like a rope, when there is continuity, it means those fibers have rejoined,” study coauthor Stephanie Filbay, PhD, an associate professor at the University of Melbourne in Australia, told this news organization.

“Within that, there’s a few variations of healing that we’re seeing. Some look like they’ve never been injured, while some have rejoined but appear thinner or longer than a normal ACL,” Dr. Filbay said.

She added: “What all this research is showing is that it’s happening at a much higher rate than we thought possible. And in some of the studies, it looks like ACL healing is associated with very favorable outcomes.”

At OARSI 2024, Dr. Filbay presented additional data from her and others’ research on the relationships between ACL healing and long-term functional outcomes and osteoarthritis (OA) incidence in comparisons between patients’ treatment pathways: Early ACL surgery, rehabilitation followed by delayed surgery, or rehabilitation only.
 

Healing Without Surgery

The idea that the ACL can heal without surgery is relatively recent and perhaps still not widely accepted as a concept, as Dr. Filbay explained during a plenary lecture at the congress.

Dr. Filbay explained that the ideal management of ACL injury depends on the severity of knee injury and whether someone’s knee is stable after trying nonsurgical management. Results of the ACL SNNAP trial, for example, have suggested that surgical reconstruction is superior to a rehabilitation strategy for managing non-acute ACL injuries where there are persistent symptoms of instability.

However, there have been two trials — COMPARE performed in the Netherlands and KANON performed in Sweden — that found that early surgery was no better than a strategy of initial rehabilitation with the option of having a delayed ACL surgery if needed.
 

What Happens Long Term?

Posttraumatic OA is a well-known long-term consequence of ACL injury. According to a recent meta-analysis, there is a sevenfold increased risk for OA comparing people who have and have not had an ACL injury.

ACL injury also results in OA occurring at an earlier age than in people with OA who have not had an ACL injury. This has been shown to progress at a faster rate and be associated with a longer period of disability, Dr. Filbay said at the congress, sponsored by the Osteoarthritis Research Society International.

But does the ACL really heal? Dr. Filbay thinks that it does and has been involved in several studies that have used MRI to look at how the ACL may do so.

In a recently published paper, Dr. Filbay and colleagues reported the findings from a secondary analysis of the KANON trial and found that nearly one in three (30%) of the participants who had been randomized to optional delayed surgery had MRI evidence of healing at 2 years. But when they excluded people who had delayed surgery, 53% of people managed by rehabilitation alone had evidence of healing.

The evaluation also found that those who had a healed vs non-healed ligament had better results using the Knee Injury and Osteoarthritis Outcome Score (KOOS), and that there were better outcomes at 2 years among those with ACL healing vs those who had early or delayed ACL surgery.
 

ACL Continuity and Long-Term Outcomes

At OARSI 2024, Dr. Filbay and colleagues reported an even longer-term secondary analysis of the KANON trial on the relationship between ACL healing at 5 years and outcomes at 11 years. The results were first reported in NEJM Evidence.

Dr. Filbay reported that participants with ACL continuity on MRI at 5 years actually had worse patient-reported outcomes 11 years later than those who were managed with early or delayed ACL reconstruction.

“This does not align with previous findings suggesting better 2-year outcomes compared to the surgically managed groups,” Dr. Filbay said.

However, people with ACL continuity following rehabilitation did seem to show numerically similar or fewer signs of radiographic OA at 11 years vs the surgical groups.

Radiographic OA of the tibiofemoral joint (TFJ) or patellofemoral joint (PFJ) at 11 years was observed in a respective 14% and 21% of people with ACL continuity at 5 years (n = 14) and in 22% and 11% of people with ACL discontinuity at 5 years in the rehabilitation alone group.

By comparison, radiographic OA of the TFJ or PFJ at 11 years was seen in a respective 23% and 35% of people who had rehabilitation with delayed surgery (n = 26) and in 18% and 41% of those who had early surgery (n = 49).

These are descriptive results, Dr. Filbay said, because the numbers were too small to do a statistical analysis. Further, larger, longitudinal studies will be needed.
 

Posttraumatic OA After ACL Surgery

Elsewhere at OARSI 2024, Matthew Harkey, PhD, and colleagues from Michigan State University, East Lansing, Michigan, reported data showing that nearly two thirds of people who undergo surgical reconstruction have symptoms at 6 months that could be indicative of early knee OA.

Knee symptoms indicative of OA declined to 53% at 12 months and 45% at 24 months.

“It’s a bit complex — we can’t outright say arthritis is developing, but there’s a large group of patients whose symptoms linger long after surgery,” Dr. Harkey said in a press release.

“Often, clinicians assume that these postoperative symptoms will naturally improve as patients reengage with their usual activities. However, what we’re seeing suggests these symptoms persist and likely require a targeted approach to manage or improve them,” Dr. Harkey said.

The analysis used data on 3752 individuals aged 14-40 years who were enrolled in the New Zealand ACL Registry and who completed the KOOS at 6, 12, and 24 months after having ACL reconstruction.

Dr. Harkey and team reported that one in three people had persistent early OA symptoms at 2 years, while 23% had no early OA symptoms at any timepoint.

The studies were independently supported. Dr. Filbay and Dr. Harkey had no relevant financial relationships to report.

Dr. Filbay and colleagues have developed a treatment decision aid for individuals who have sustained an ACL injury. This provides information on the different treatment options available and how they compare.

A version of this article appeared on Medscape.com.

VIENNA — Nearly one third of anterior cruciate ligament (ACL) injuries appear to heal without surgery, according to an analysis of three-dimensional MRI data taken from the NACOX study, presented as a late-breaking poster at the OARSI 2024 World Congress. 

At 2 years after injury, three-dimensional MRI showed that 13 of 43 (30%) knees had evidence of normal, continuous ACL fibers. Moreover, a further 14 (33%) knees had a continuous ACL fiber structure following rehabilitation alone. ACL fibers were partly (16%) or completely (21%) ruptured in the remainder of cases.

Sara Freeman/Medscape Medical News

“If you think of the ACL like a rope, when there is continuity, it means those fibers have rejoined,” study coauthor Stephanie Filbay, PhD, an associate professor at the University of Melbourne in Australia, told this news organization.

“Within that, there’s a few variations of healing that we’re seeing. Some look like they’ve never been injured, while some have rejoined but appear thinner or longer than a normal ACL,” Dr. Filbay said.

She added: “What all this research is showing is that it’s happening at a much higher rate than we thought possible. And in some of the studies, it looks like ACL healing is associated with very favorable outcomes.”

At OARSI 2024, Dr. Filbay presented additional data from her and others’ research on the relationships between ACL healing and long-term functional outcomes and osteoarthritis (OA) incidence in comparisons between patients’ treatment pathways: Early ACL surgery, rehabilitation followed by delayed surgery, or rehabilitation only.
 

Healing Without Surgery

The idea that the ACL can heal without surgery is relatively recent and perhaps still not widely accepted as a concept, as Dr. Filbay explained during a plenary lecture at the congress.

Dr. Filbay explained that the ideal management of ACL injury depends on the severity of knee injury and whether someone’s knee is stable after trying nonsurgical management. Results of the ACL SNNAP trial, for example, have suggested that surgical reconstruction is superior to a rehabilitation strategy for managing non-acute ACL injuries where there are persistent symptoms of instability.

However, there have been two trials — COMPARE performed in the Netherlands and KANON performed in Sweden — that found that early surgery was no better than a strategy of initial rehabilitation with the option of having a delayed ACL surgery if needed.
 

What Happens Long Term?

Posttraumatic OA is a well-known long-term consequence of ACL injury. According to a recent meta-analysis, there is a sevenfold increased risk for OA comparing people who have and have not had an ACL injury.

ACL injury also results in OA occurring at an earlier age than in people with OA who have not had an ACL injury. This has been shown to progress at a faster rate and be associated with a longer period of disability, Dr. Filbay said at the congress, sponsored by the Osteoarthritis Research Society International.

But does the ACL really heal? Dr. Filbay thinks that it does and has been involved in several studies that have used MRI to look at how the ACL may do so.

In a recently published paper, Dr. Filbay and colleagues reported the findings from a secondary analysis of the KANON trial and found that nearly one in three (30%) of the participants who had been randomized to optional delayed surgery had MRI evidence of healing at 2 years. But when they excluded people who had delayed surgery, 53% of people managed by rehabilitation alone had evidence of healing.

The evaluation also found that those who had a healed vs non-healed ligament had better results using the Knee Injury and Osteoarthritis Outcome Score (KOOS), and that there were better outcomes at 2 years among those with ACL healing vs those who had early or delayed ACL surgery.
 

ACL Continuity and Long-Term Outcomes

At OARSI 2024, Dr. Filbay and colleagues reported an even longer-term secondary analysis of the KANON trial on the relationship between ACL healing at 5 years and outcomes at 11 years. The results were first reported in NEJM Evidence.

Dr. Filbay reported that participants with ACL continuity on MRI at 5 years actually had worse patient-reported outcomes 11 years later than those who were managed with early or delayed ACL reconstruction.

“This does not align with previous findings suggesting better 2-year outcomes compared to the surgically managed groups,” Dr. Filbay said.

However, people with ACL continuity following rehabilitation did seem to show numerically similar or fewer signs of radiographic OA at 11 years vs the surgical groups.

Radiographic OA of the tibiofemoral joint (TFJ) or patellofemoral joint (PFJ) at 11 years was observed in a respective 14% and 21% of people with ACL continuity at 5 years (n = 14) and in 22% and 11% of people with ACL discontinuity at 5 years in the rehabilitation alone group.

By comparison, radiographic OA of the TFJ or PFJ at 11 years was seen in a respective 23% and 35% of people who had rehabilitation with delayed surgery (n = 26) and in 18% and 41% of those who had early surgery (n = 49).

These are descriptive results, Dr. Filbay said, because the numbers were too small to do a statistical analysis. Further, larger, longitudinal studies will be needed.
 

Posttraumatic OA After ACL Surgery

Elsewhere at OARSI 2024, Matthew Harkey, PhD, and colleagues from Michigan State University, East Lansing, Michigan, reported data showing that nearly two thirds of people who undergo surgical reconstruction have symptoms at 6 months that could be indicative of early knee OA.

Knee symptoms indicative of OA declined to 53% at 12 months and 45% at 24 months.

“It’s a bit complex — we can’t outright say arthritis is developing, but there’s a large group of patients whose symptoms linger long after surgery,” Dr. Harkey said in a press release.

“Often, clinicians assume that these postoperative symptoms will naturally improve as patients reengage with their usual activities. However, what we’re seeing suggests these symptoms persist and likely require a targeted approach to manage or improve them,” Dr. Harkey said.

The analysis used data on 3752 individuals aged 14-40 years who were enrolled in the New Zealand ACL Registry and who completed the KOOS at 6, 12, and 24 months after having ACL reconstruction.

Dr. Harkey and team reported that one in three people had persistent early OA symptoms at 2 years, while 23% had no early OA symptoms at any timepoint.

The studies were independently supported. Dr. Filbay and Dr. Harkey had no relevant financial relationships to report.

Dr. Filbay and colleagues have developed a treatment decision aid for individuals who have sustained an ACL injury. This provides information on the different treatment options available and how they compare.

A version of this article appeared on Medscape.com.

VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the STEP-9 trial, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?

“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the OARSI 2024 World Congress.

Sara Freeman/Medscape Medical News

Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events by as much as 20% vs placebo, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.

“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.
 

Weight Loss Benefits

Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.

In SURMOUNT-1, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a subanalysis.

It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a viewpoint published in JAMA Internal Medicine.

“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.
 

Weight Rebound

Tonia Vincent, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.

“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.

Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.

“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.
 

Weight Loss Affects Bone

Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.

Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.

Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.

Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
 

GLP-1 and Bone Effects

Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.

Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”

The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.

These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
 

New Role for Dipeptidyl Transferase Inhibitors?

Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.

Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.

“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”

For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.

Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).

DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.

Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”
 

Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?

So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist S. Reza Jafarzadeh, DVM, PhD, suggested.

“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.

Sara Freeman/Medscape Medical News

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.

A version of this article appeared on Medscape.com .

VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the STEP-9 trial, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?

“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the OARSI 2024 World Congress.

Sara Freeman/Medscape Medical News

Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events by as much as 20% vs placebo, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.

“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.
 

Weight Loss Benefits

Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.

In SURMOUNT-1, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a subanalysis.

It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a viewpoint published in JAMA Internal Medicine.

“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.
 

Weight Rebound

Tonia Vincent, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.

“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.

Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.

“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.
 

Weight Loss Affects Bone

Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.

Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.

Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.

Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
 

GLP-1 and Bone Effects

Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.

Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”

The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.

These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
 

New Role for Dipeptidyl Transferase Inhibitors?

Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.

Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.

“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”

For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.

Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).

DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.

Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”
 

Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?

So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist S. Reza Jafarzadeh, DVM, PhD, suggested.

“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.

Sara Freeman/Medscape Medical News

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.

A version of this article appeared on Medscape.com .

VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the STEP-9 trial, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?

“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the OARSI 2024 World Congress.

Sara Freeman/Medscape Medical News

Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events by as much as 20% vs placebo, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.

“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.
 

Weight Loss Benefits

Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.

In SURMOUNT-1, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a subanalysis.

It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a viewpoint published in JAMA Internal Medicine.

“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.
 

Weight Rebound

Tonia Vincent, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.

“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.

Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.

“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.
 

Weight Loss Affects Bone

Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.

Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.

Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.

Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
 

GLP-1 and Bone Effects

Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.

Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”

The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.

These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
 

New Role for Dipeptidyl Transferase Inhibitors?

Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.

Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.

“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”

For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.

Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).

DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.

Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”
 

Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?

So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist S. Reza Jafarzadeh, DVM, PhD, suggested.

“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.

Sara Freeman/Medscape Medical News

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.

A version of this article appeared on Medscape.com .

LIVERPOOL, ENGLAND — The IRIS-RA study of the investigational monoclonal antibody drug nipocalimab in patients with rheumatoid arthritis (RA) did not meet its primary endpoint, but there could still be people with moderate to severe RA who might benefit from treatment with the drug, according to information reported at the British Society for Rheumatology annual meeting.

The primary endpoint for the phase 2A trial was the least squares mean change in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) from baseline to 12 weeks of treatment. This was reduced by −1.03 with nipocalimab and by −0.58 with placebo, giving a mean difference of just −0.45 (P = .224).

However, one of the key secondary endpoints was the proportion of patients who had 20% improvement in American College of Rheumatology response criteria (ACR20). Results for this endpoint showed a greater difference in response to nipocalimab vs placebo, with a respective 45.5% and 20.0% (P = .055) of individuals achieving ACR20.

Moreover, an analysis stratifying for anti-citrullinated protein autoantibody (ACPA) levels at baseline found that people with higher levels had a better response to nipocalimab.
 

Choice of Endpoint

“The way this study was powered was to look at a change between the treatment groups of a DAS28-CRP reduction of 1.0,” said Peter C. Taylor, BMBCh, PhD, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in Oxford, England.

DAS28-CRP was often chosen as the primary endpoint in small proof-of-concept studies, such as IRIS-RA, because it was a “measure of continuous change [that] theoretically, would allow greater sensitivity to change,” Dr. Taylor added.

Sara Freeman/Medscape Medical News

Proof of Concept

IRIS-RA was billed as a “proof-of-concept” study because it was the first time that a monoclonal antibody targeting the neonatal fragment crystallizable receptor (FcRn) was being tested in an RA population.

The study was a randomized double-blind trial in which 33 people with moderate to severe RA who had an inadequate response to tumor necrosis factor (TNF) inhibitors were treated with nipocalimab at a dose of 15 mg/kg given intravenously every 2 weeks, and 20 received a matching placebo. Participants were treated for 10 weeks, and then the primary follow-up was at 12 weeks, with additional follow-up for safety undertaken at 18 weeks.

Nipocalimab is a fully human, immunoglobulin G1 (IgG1) monoclonal antibody that is designed to selectively block the FcRn. By doing so, it essentially stops IgG from being recycled within the immune system, and this in turn lowers IgG levels. That includes potentially harmful ACPAs, among other pathogenic antibodies, Dr. Taylor and fellow investigators explained in their abstract.

“We’ve known for a long time that ACPA have prognostic value, but there’s been controversy about whether or not ACPA are actually pathogenic,” Dr. Taylor said. “So, one of the hypotheses that this study gives rise to is that by blocking FcRn, and thereby reducing, potentially, the concentration of ACPA in the blood, will we actually have efficacy in patients?”
 

Are ACPA Really Lowered?

Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in Leeds, England, questioned the reduction in antibody levels during the discussion that followed.

Although these data had not been presented, Dr. Emery observed that the reduction in IgG was actually greater than that in ACPA, “which is fairly critical. Is it feasible to look to selectively lower normal immunoglobulin over pathogenic autoantibodies?”

Dr. Emery also wanted to know if there “was a floor on the reduction of immunoglobulin” with long-term therapy, “which would be a worry.”

Dr. Taylor responded that total IgG had been reduced by about 65% and ACPA by about 40%. Why this difference exists is not yet clear. It could be because ACPA are part of complexed antibodies.

“Most of these patients are rheumatoid factor [RF]–positive,” said Taylor, pointing out that although IgM “wouldn’t normally be affected by FcRn blockade,” there was a 10% reduction in RF IgM, probably because it was complexed to IgG.

“So, the hypothesis here is that if you look at the clearance of complexes, they’re handled differently in the cytoplasm from the clearance of monomeric IgG. But that’s a hypothesis. It needs further investigation. In vitro, there’s very good, confirmatory evidence to support that. But we’ve yet to explore that more fully in vivo,” Dr. Taylor said.

As for long-term effects, Dr. Taylor responded: “All I can tell you is [that] after the 10-week intervention, that up to an 18-week observation period, immunoglobulin levels recovered very rapidly afterwards. And you mustn’t forget that other isotypes are not affected, unlike rituximab.”
 

Safety and Other Results

With regard to safety, 27 (82%) of nipocalimab- and 12 (60%) of placebo-treated participants experienced at least one treatment-emergent adverse event (TEAE). The most common, occurring in 10% or more of cases, were RA flares (36.4% for nipocalimab vs 15.0% with placebo), headache (12.1% vs 5.0%), and COVID-19 (12.1% vs 0.0%).

There were three serious TEAEs, all in the nipocalimab-treatment group: One was an infection of a burn that had been present at inclusion, another was a deep vein thrombosis that resolved with apixaban treatment, and the other was an infusion-related reaction that resolved with supportive treatment.

Another notable efficacy finding was the proportion of patients achieving DAS28-CRP remission at 12 weeks in the nipocalimab vs the placebo group was substantially greater if considering only people with high baseline ACPA levels, at a respective 40.0% vs 16.7%, when compared with the total population (21.2% vs 10.0%).

Similar findings were seen for the proportion of patients achieving an ACR50, and there were numerically greater reductions in the components of the ACR response criteria such as tender and swollen joints with nipocalimab vs placebo. All of these were exploratory observations, Dr. Taylor emphasized.
 

Combination and Further Trials

Further trials of nipocalimab are planned or are already ongoing in systemic lupus erythematosus, active lupus nephritis, Sjögren disease, and five other diseases.

In RA, nipocalimab is now being tested in combination with the TNF inhibitor certolizumab pegol (Cimzia) in the DAISY-RA trial. This is another proof-of-concept, phase 2A trial with a target accrual of 104 patients.

The IRIS-RA study was funded by Janssen Research & Development. Dr. Taylor serves as a consultant to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB and received research funding from Galapagos, among others. Dr. Emery received research grants paid to his institution from AbbVie, Bristol Myers Squibb (BMS), Pfizer, MSD, and Roche; received consultant fees from BMS, AbbVie, Pfizer, MSD, Novartis, Roche, and UCB; and has undertaken clinical trials and provided expert advice to Pfizer, MSD, AbbVie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, and Lilly.
 

A version of this article appeared on Medscape.com.

LIVERPOOL, ENGLAND — The IRIS-RA study of the investigational monoclonal antibody drug nipocalimab in patients with rheumatoid arthritis (RA) did not meet its primary endpoint, but there could still be people with moderate to severe RA who might benefit from treatment with the drug, according to information reported at the British Society for Rheumatology annual meeting.

The primary endpoint for the phase 2A trial was the least squares mean change in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) from baseline to 12 weeks of treatment. This was reduced by −1.03 with nipocalimab and by −0.58 with placebo, giving a mean difference of just −0.45 (P = .224).

However, one of the key secondary endpoints was the proportion of patients who had 20% improvement in American College of Rheumatology response criteria (ACR20). Results for this endpoint showed a greater difference in response to nipocalimab vs placebo, with a respective 45.5% and 20.0% (P = .055) of individuals achieving ACR20.

Moreover, an analysis stratifying for anti-citrullinated protein autoantibody (ACPA) levels at baseline found that people with higher levels had a better response to nipocalimab.
 

Choice of Endpoint

“The way this study was powered was to look at a change between the treatment groups of a DAS28-CRP reduction of 1.0,” said Peter C. Taylor, BMBCh, PhD, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in Oxford, England.

DAS28-CRP was often chosen as the primary endpoint in small proof-of-concept studies, such as IRIS-RA, because it was a “measure of continuous change [that] theoretically, would allow greater sensitivity to change,” Dr. Taylor added.

Sara Freeman/Medscape Medical News

Proof of Concept

IRIS-RA was billed as a “proof-of-concept” study because it was the first time that a monoclonal antibody targeting the neonatal fragment crystallizable receptor (FcRn) was being tested in an RA population.

The study was a randomized double-blind trial in which 33 people with moderate to severe RA who had an inadequate response to tumor necrosis factor (TNF) inhibitors were treated with nipocalimab at a dose of 15 mg/kg given intravenously every 2 weeks, and 20 received a matching placebo. Participants were treated for 10 weeks, and then the primary follow-up was at 12 weeks, with additional follow-up for safety undertaken at 18 weeks.

Nipocalimab is a fully human, immunoglobulin G1 (IgG1) monoclonal antibody that is designed to selectively block the FcRn. By doing so, it essentially stops IgG from being recycled within the immune system, and this in turn lowers IgG levels. That includes potentially harmful ACPAs, among other pathogenic antibodies, Dr. Taylor and fellow investigators explained in their abstract.

“We’ve known for a long time that ACPA have prognostic value, but there’s been controversy about whether or not ACPA are actually pathogenic,” Dr. Taylor said. “So, one of the hypotheses that this study gives rise to is that by blocking FcRn, and thereby reducing, potentially, the concentration of ACPA in the blood, will we actually have efficacy in patients?”
 

Are ACPA Really Lowered?

Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in Leeds, England, questioned the reduction in antibody levels during the discussion that followed.

Although these data had not been presented, Dr. Emery observed that the reduction in IgG was actually greater than that in ACPA, “which is fairly critical. Is it feasible to look to selectively lower normal immunoglobulin over pathogenic autoantibodies?”

Dr. Emery also wanted to know if there “was a floor on the reduction of immunoglobulin” with long-term therapy, “which would be a worry.”

Dr. Taylor responded that total IgG had been reduced by about 65% and ACPA by about 40%. Why this difference exists is not yet clear. It could be because ACPA are part of complexed antibodies.

“Most of these patients are rheumatoid factor [RF]–positive,” said Taylor, pointing out that although IgM “wouldn’t normally be affected by FcRn blockade,” there was a 10% reduction in RF IgM, probably because it was complexed to IgG.

“So, the hypothesis here is that if you look at the clearance of complexes, they’re handled differently in the cytoplasm from the clearance of monomeric IgG. But that’s a hypothesis. It needs further investigation. In vitro, there’s very good, confirmatory evidence to support that. But we’ve yet to explore that more fully in vivo,” Dr. Taylor said.

As for long-term effects, Dr. Taylor responded: “All I can tell you is [that] after the 10-week intervention, that up to an 18-week observation period, immunoglobulin levels recovered very rapidly afterwards. And you mustn’t forget that other isotypes are not affected, unlike rituximab.”
 

Safety and Other Results

With regard to safety, 27 (82%) of nipocalimab- and 12 (60%) of placebo-treated participants experienced at least one treatment-emergent adverse event (TEAE). The most common, occurring in 10% or more of cases, were RA flares (36.4% for nipocalimab vs 15.0% with placebo), headache (12.1% vs 5.0%), and COVID-19 (12.1% vs 0.0%).

There were three serious TEAEs, all in the nipocalimab-treatment group: One was an infection of a burn that had been present at inclusion, another was a deep vein thrombosis that resolved with apixaban treatment, and the other was an infusion-related reaction that resolved with supportive treatment.

Another notable efficacy finding was the proportion of patients achieving DAS28-CRP remission at 12 weeks in the nipocalimab vs the placebo group was substantially greater if considering only people with high baseline ACPA levels, at a respective 40.0% vs 16.7%, when compared with the total population (21.2% vs 10.0%).

Similar findings were seen for the proportion of patients achieving an ACR50, and there were numerically greater reductions in the components of the ACR response criteria such as tender and swollen joints with nipocalimab vs placebo. All of these were exploratory observations, Dr. Taylor emphasized.
 

Combination and Further Trials

Further trials of nipocalimab are planned or are already ongoing in systemic lupus erythematosus, active lupus nephritis, Sjögren disease, and five other diseases.

In RA, nipocalimab is now being tested in combination with the TNF inhibitor certolizumab pegol (Cimzia) in the DAISY-RA trial. This is another proof-of-concept, phase 2A trial with a target accrual of 104 patients.

The IRIS-RA study was funded by Janssen Research & Development. Dr. Taylor serves as a consultant to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB and received research funding from Galapagos, among others. Dr. Emery received research grants paid to his institution from AbbVie, Bristol Myers Squibb (BMS), Pfizer, MSD, and Roche; received consultant fees from BMS, AbbVie, Pfizer, MSD, Novartis, Roche, and UCB; and has undertaken clinical trials and provided expert advice to Pfizer, MSD, AbbVie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, and Lilly.
 

A version of this article appeared on Medscape.com.

LIVERPOOL, ENGLAND — The IRIS-RA study of the investigational monoclonal antibody drug nipocalimab in patients with rheumatoid arthritis (RA) did not meet its primary endpoint, but there could still be people with moderate to severe RA who might benefit from treatment with the drug, according to information reported at the British Society for Rheumatology annual meeting.

The primary endpoint for the phase 2A trial was the least squares mean change in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) from baseline to 12 weeks of treatment. This was reduced by −1.03 with nipocalimab and by −0.58 with placebo, giving a mean difference of just −0.45 (P = .224).

However, one of the key secondary endpoints was the proportion of patients who had 20% improvement in American College of Rheumatology response criteria (ACR20). Results for this endpoint showed a greater difference in response to nipocalimab vs placebo, with a respective 45.5% and 20.0% (P = .055) of individuals achieving ACR20.

Moreover, an analysis stratifying for anti-citrullinated protein autoantibody (ACPA) levels at baseline found that people with higher levels had a better response to nipocalimab.
 

Choice of Endpoint

“The way this study was powered was to look at a change between the treatment groups of a DAS28-CRP reduction of 1.0,” said Peter C. Taylor, BMBCh, PhD, the Norman Collisson chair of musculoskeletal medicine at the University of Oxford in Oxford, England.

DAS28-CRP was often chosen as the primary endpoint in small proof-of-concept studies, such as IRIS-RA, because it was a “measure of continuous change [that] theoretically, would allow greater sensitivity to change,” Dr. Taylor added.

Sara Freeman/Medscape Medical News

Proof of Concept

IRIS-RA was billed as a “proof-of-concept” study because it was the first time that a monoclonal antibody targeting the neonatal fragment crystallizable receptor (FcRn) was being tested in an RA population.

The study was a randomized double-blind trial in which 33 people with moderate to severe RA who had an inadequate response to tumor necrosis factor (TNF) inhibitors were treated with nipocalimab at a dose of 15 mg/kg given intravenously every 2 weeks, and 20 received a matching placebo. Participants were treated for 10 weeks, and then the primary follow-up was at 12 weeks, with additional follow-up for safety undertaken at 18 weeks.

Nipocalimab is a fully human, immunoglobulin G1 (IgG1) monoclonal antibody that is designed to selectively block the FcRn. By doing so, it essentially stops IgG from being recycled within the immune system, and this in turn lowers IgG levels. That includes potentially harmful ACPAs, among other pathogenic antibodies, Dr. Taylor and fellow investigators explained in their abstract.

“We’ve known for a long time that ACPA have prognostic value, but there’s been controversy about whether or not ACPA are actually pathogenic,” Dr. Taylor said. “So, one of the hypotheses that this study gives rise to is that by blocking FcRn, and thereby reducing, potentially, the concentration of ACPA in the blood, will we actually have efficacy in patients?”
 

Are ACPA Really Lowered?

Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in Leeds, England, questioned the reduction in antibody levels during the discussion that followed.

Although these data had not been presented, Dr. Emery observed that the reduction in IgG was actually greater than that in ACPA, “which is fairly critical. Is it feasible to look to selectively lower normal immunoglobulin over pathogenic autoantibodies?”

Dr. Emery also wanted to know if there “was a floor on the reduction of immunoglobulin” with long-term therapy, “which would be a worry.”

Dr. Taylor responded that total IgG had been reduced by about 65% and ACPA by about 40%. Why this difference exists is not yet clear. It could be because ACPA are part of complexed antibodies.

“Most of these patients are rheumatoid factor [RF]–positive,” said Taylor, pointing out that although IgM “wouldn’t normally be affected by FcRn blockade,” there was a 10% reduction in RF IgM, probably because it was complexed to IgG.

“So, the hypothesis here is that if you look at the clearance of complexes, they’re handled differently in the cytoplasm from the clearance of monomeric IgG. But that’s a hypothesis. It needs further investigation. In vitro, there’s very good, confirmatory evidence to support that. But we’ve yet to explore that more fully in vivo,” Dr. Taylor said.

As for long-term effects, Dr. Taylor responded: “All I can tell you is [that] after the 10-week intervention, that up to an 18-week observation period, immunoglobulin levels recovered very rapidly afterwards. And you mustn’t forget that other isotypes are not affected, unlike rituximab.”
 

Safety and Other Results

With regard to safety, 27 (82%) of nipocalimab- and 12 (60%) of placebo-treated participants experienced at least one treatment-emergent adverse event (TEAE). The most common, occurring in 10% or more of cases, were RA flares (36.4% for nipocalimab vs 15.0% with placebo), headache (12.1% vs 5.0%), and COVID-19 (12.1% vs 0.0%).

There were three serious TEAEs, all in the nipocalimab-treatment group: One was an infection of a burn that had been present at inclusion, another was a deep vein thrombosis that resolved with apixaban treatment, and the other was an infusion-related reaction that resolved with supportive treatment.

Another notable efficacy finding was the proportion of patients achieving DAS28-CRP remission at 12 weeks in the nipocalimab vs the placebo group was substantially greater if considering only people with high baseline ACPA levels, at a respective 40.0% vs 16.7%, when compared with the total population (21.2% vs 10.0%).

Similar findings were seen for the proportion of patients achieving an ACR50, and there were numerically greater reductions in the components of the ACR response criteria such as tender and swollen joints with nipocalimab vs placebo. All of these were exploratory observations, Dr. Taylor emphasized.
 

Combination and Further Trials

Further trials of nipocalimab are planned or are already ongoing in systemic lupus erythematosus, active lupus nephritis, Sjögren disease, and five other diseases.

In RA, nipocalimab is now being tested in combination with the TNF inhibitor certolizumab pegol (Cimzia) in the DAISY-RA trial. This is another proof-of-concept, phase 2A trial with a target accrual of 104 patients.

The IRIS-RA study was funded by Janssen Research & Development. Dr. Taylor serves as a consultant to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB and received research funding from Galapagos, among others. Dr. Emery received research grants paid to his institution from AbbVie, Bristol Myers Squibb (BMS), Pfizer, MSD, and Roche; received consultant fees from BMS, AbbVie, Pfizer, MSD, Novartis, Roche, and UCB; and has undertaken clinical trials and provided expert advice to Pfizer, MSD, AbbVie, BMS, UCB, Roche, Novartis, Samsung, Sandoz, and Lilly.
 

A version of this article appeared on Medscape.com.

VIENNA — Data do not back the use of diacerein or resveratrol for managing the pain of knee osteoarthritis (OA), according to the results of two well-performed, multicenter, double-blind, randomized controlled clinical trials.

During the News in Therapies session at the OARSI 2024 World Congress, the null findings of the DICKENS study and ARTHROL trial were presented alongside a reappraisal of the possible role of botulinum toxin.
 

DICKENS Study of Diacerein

“The role of diacerein in the treatment of OA is controversial,” acknowledged Dawn Aitken, PhD, associate professor at the University of Tasmania in Hobart, Tasmania, Australia. “There are only a few acceptable quality trials to date, and the results are inconsistent,” Dr. Aitken added.

Indeed, a Cochrane review performed in 2014 had concluded that there was “low-quality evidence that diacerein had a small beneficial effect on pain,” she said. The reported overall effect size on a 100-mm visual analog scale, based on a meta-analysis of 10 trials, has been just −8.65 mm, equating to just a 9% pain reduction.

Bruce Jancin/MDedge News

ARTHROL Trial of Resveratrol

Similarly, negative results were reported for resveratrol from the ARTHROL trial, with 55% of the resveratrol- and 55% of placebo-treated individuals achieving a 20% reduction in knee pain intensity at 3 months. The actual change in knee pain from baseline to 3 months was −15.7 for resveratrol and −15.2 for placebo on a numerical rating scale that went from 0 (no pain) up to 100 (worst pain).

Resveratrol is found naturally in grapes, peanuts, pine cones, and Chinese knotweed, and there is a growing body of evidence that it may have pleiotropic effects, said investigator Christelle Nguyen, PhD, MD, a professor of physical and rehabilitation medicine at Université Paris Cité, Paris, France.

It’s available in a powder form over the counter as a treatment for multiple ailments, but more recently, became available as an oral formulation. Dr. Nguyen and colleagues wanted to know if this would make a difference to OA knee pain when added to usual care.

A double-blind, multicenter, placebo-controlled randomized trial was therefore conducted that involved 142 people with knee OA who had been experiencing knee pain for at least 1 month. The participants were equally randomly allocated to receive either oral resveratrol given as two caplets of 20 mg twice daily for the first week, then once daily for a total of 6 months, or a matched placebo.

There was also no effect of resveratrol vs placebo on a host of secondary outcomes measured at 3 and 6 months.

The interpretation is that oral resveratrol may not be effective in this indication or have a biologic effect on the pain pathway, Dr. Nguyen said.

Sara Freeman/Medscape Medical News

Botulinum Toxin: Over But Not Out?

Dr. Nguyen separately reported data from a new systematic review and meta-analysis on the use of intra-articular (IA) botulinum toxin type A (BoNT-A) for knee OA pain.

Seven of the 14 randomized controlled trials included in the meta-analysis had looked specifically at knee OA outcomes in the short, intermediate, and long term.

Results showed a nonsignificant trend favoring BoNT-A use, with the standard mean difference in pain of 0.35 (−0.82; 0.12), −0.27 (−0.61; 0.08), and −0.43 (−1.12; 0.26) for short-, intermediate-, and long-term use, respectively.

In contrast, pain reductions were seen with BoNT-A in three trials that included people with OA of the shoulder or base of the thumb. This begs the question as to whether botulinum toxin may still have a role to play, Dr. Nguyen said in an interview.

“It seems like there may be a positive effect for the shoulder joint and base of the thumb,” she told this news organization.

“So, basically, we found differences between large and small to intermediate joints,” Dr. Nguyen added. “It questions the dilution of botulinum toxin into the joint. If it’s a big joint, maybe the dilution is too high,” she suggested.

This hypothesis will be tested in the upcoming RHIBOT II trial that will begin recruitment later this year. This is a follow-on from the RHIBOT trial that was published in The Lancet Rheumatology 2 years ago.

Meanwhile, the use of botulinum toxin is off-label, Dr. Nguyen said. “We use it in our clinics only when first-line treatment had failed for base of thumb OA.” It’s not offered as a stand-alone intervention, and the IA injections need to be given by someone with experience, she said.
 

Methodologically Sound Studies

Commenting on the studies, Nancy E. Lane, MD, said: “There have been small botulinum studies before but not powered enough so that you could confirm or refute hypotheses.”

Dr. Lane, endowed professor of medicine, rheumatology, and aging research and director for the Center for Musculoskeletal Health at the University of California Davis School of Medicine, Sacramento, California, added: “Similarly for resveratrol, there have been lots of studies.”

Moreover, Dr. Lane observed that the studies were “really well-designed. They were well-powered. The subjects were selected in such a way that was good rigor in the methodologic design, and there were enough people in the studies so that you could really believe the results.”

The take-home is probably that these approaches do not work, Dr. Lane said, “at least when you apply them to moderate-severe knee OA patients, they don’t seem to make a difference.”

The congress was sponsored by the Osteoarthritis Research Society International.

The DICKENS study of diacerein was an investigator-initiated trial that was funded by the National Health and Medical Research Council of Australia. TRB Chemedica International S.A. provided diacerein free of charge for the trial but was not involved in the implementation or data analysis. Dr. Aitken had no conflicts of interest to disclose.

The ARTHROL trial of oral resveratrol was funded by the French Ministry of Health and Solidarity (Ministré des Solidarités et de la Santé). Yvery Laboratory provided the resveratrol caplet and matching placebo free of charge. Dr. Nguyen has financial relationships with Actelion, Grünenthal, Ipsen, Lilly, Meda, Merz, Novartis, Preciphar, Sandoz, Takeda, Thuasne, and UCB.

Dr. Lane had no relevant conflicts of interest to declare.

A version of this article appeared on Medscape.com.

VIENNA — Data do not back the use of diacerein or resveratrol for managing the pain of knee osteoarthritis (OA), according to the results of two well-performed, multicenter, double-blind, randomized controlled clinical trials.

During the News in Therapies session at the OARSI 2024 World Congress, the null findings of the DICKENS study and ARTHROL trial were presented alongside a reappraisal of the possible role of botulinum toxin.
 

DICKENS Study of Diacerein

“The role of diacerein in the treatment of OA is controversial,” acknowledged Dawn Aitken, PhD, associate professor at the University of Tasmania in Hobart, Tasmania, Australia. “There are only a few acceptable quality trials to date, and the results are inconsistent,” Dr. Aitken added.

Indeed, a Cochrane review performed in 2014 had concluded that there was “low-quality evidence that diacerein had a small beneficial effect on pain,” she said. The reported overall effect size on a 100-mm visual analog scale, based on a meta-analysis of 10 trials, has been just −8.65 mm, equating to just a 9% pain reduction.

Bruce Jancin/MDedge News

ARTHROL Trial of Resveratrol

Similarly, negative results were reported for resveratrol from the ARTHROL trial, with 55% of the resveratrol- and 55% of placebo-treated individuals achieving a 20% reduction in knee pain intensity at 3 months. The actual change in knee pain from baseline to 3 months was −15.7 for resveratrol and −15.2 for placebo on a numerical rating scale that went from 0 (no pain) up to 100 (worst pain).

Resveratrol is found naturally in grapes, peanuts, pine cones, and Chinese knotweed, and there is a growing body of evidence that it may have pleiotropic effects, said investigator Christelle Nguyen, PhD, MD, a professor of physical and rehabilitation medicine at Université Paris Cité, Paris, France.

It’s available in a powder form over the counter as a treatment for multiple ailments, but more recently, became available as an oral formulation. Dr. Nguyen and colleagues wanted to know if this would make a difference to OA knee pain when added to usual care.

A double-blind, multicenter, placebo-controlled randomized trial was therefore conducted that involved 142 people with knee OA who had been experiencing knee pain for at least 1 month. The participants were equally randomly allocated to receive either oral resveratrol given as two caplets of 20 mg twice daily for the first week, then once daily for a total of 6 months, or a matched placebo.

There was also no effect of resveratrol vs placebo on a host of secondary outcomes measured at 3 and 6 months.

The interpretation is that oral resveratrol may not be effective in this indication or have a biologic effect on the pain pathway, Dr. Nguyen said.

Sara Freeman/Medscape Medical News

Botulinum Toxin: Over But Not Out?

Dr. Nguyen separately reported data from a new systematic review and meta-analysis on the use of intra-articular (IA) botulinum toxin type A (BoNT-A) for knee OA pain.

Seven of the 14 randomized controlled trials included in the meta-analysis had looked specifically at knee OA outcomes in the short, intermediate, and long term.

Results showed a nonsignificant trend favoring BoNT-A use, with the standard mean difference in pain of 0.35 (−0.82; 0.12), −0.27 (−0.61; 0.08), and −0.43 (−1.12; 0.26) for short-, intermediate-, and long-term use, respectively.

In contrast, pain reductions were seen with BoNT-A in three trials that included people with OA of the shoulder or base of the thumb. This begs the question as to whether botulinum toxin may still have a role to play, Dr. Nguyen said in an interview.

“It seems like there may be a positive effect for the shoulder joint and base of the thumb,” she told this news organization.

“So, basically, we found differences between large and small to intermediate joints,” Dr. Nguyen added. “It questions the dilution of botulinum toxin into the joint. If it’s a big joint, maybe the dilution is too high,” she suggested.

This hypothesis will be tested in the upcoming RHIBOT II trial that will begin recruitment later this year. This is a follow-on from the RHIBOT trial that was published in The Lancet Rheumatology 2 years ago.

Meanwhile, the use of botulinum toxin is off-label, Dr. Nguyen said. “We use it in our clinics only when first-line treatment had failed for base of thumb OA.” It’s not offered as a stand-alone intervention, and the IA injections need to be given by someone with experience, she said.
 

Methodologically Sound Studies

Commenting on the studies, Nancy E. Lane, MD, said: “There have been small botulinum studies before but not powered enough so that you could confirm or refute hypotheses.”

Dr. Lane, endowed professor of medicine, rheumatology, and aging research and director for the Center for Musculoskeletal Health at the University of California Davis School of Medicine, Sacramento, California, added: “Similarly for resveratrol, there have been lots of studies.”

Moreover, Dr. Lane observed that the studies were “really well-designed. They were well-powered. The subjects were selected in such a way that was good rigor in the methodologic design, and there were enough people in the studies so that you could really believe the results.”

The take-home is probably that these approaches do not work, Dr. Lane said, “at least when you apply them to moderate-severe knee OA patients, they don’t seem to make a difference.”

The congress was sponsored by the Osteoarthritis Research Society International.

The DICKENS study of diacerein was an investigator-initiated trial that was funded by the National Health and Medical Research Council of Australia. TRB Chemedica International S.A. provided diacerein free of charge for the trial but was not involved in the implementation or data analysis. Dr. Aitken had no conflicts of interest to disclose.

The ARTHROL trial of oral resveratrol was funded by the French Ministry of Health and Solidarity (Ministré des Solidarités et de la Santé). Yvery Laboratory provided the resveratrol caplet and matching placebo free of charge. Dr. Nguyen has financial relationships with Actelion, Grünenthal, Ipsen, Lilly, Meda, Merz, Novartis, Preciphar, Sandoz, Takeda, Thuasne, and UCB.

Dr. Lane had no relevant conflicts of interest to declare.

A version of this article appeared on Medscape.com.

VIENNA — Data do not back the use of diacerein or resveratrol for managing the pain of knee osteoarthritis (OA), according to the results of two well-performed, multicenter, double-blind, randomized controlled clinical trials.

During the News in Therapies session at the OARSI 2024 World Congress, the null findings of the DICKENS study and ARTHROL trial were presented alongside a reappraisal of the possible role of botulinum toxin.
 

DICKENS Study of Diacerein

“The role of diacerein in the treatment of OA is controversial,” acknowledged Dawn Aitken, PhD, associate professor at the University of Tasmania in Hobart, Tasmania, Australia. “There are only a few acceptable quality trials to date, and the results are inconsistent,” Dr. Aitken added.

Indeed, a Cochrane review performed in 2014 had concluded that there was “low-quality evidence that diacerein had a small beneficial effect on pain,” she said. The reported overall effect size on a 100-mm visual analog scale, based on a meta-analysis of 10 trials, has been just −8.65 mm, equating to just a 9% pain reduction.

Bruce Jancin/MDedge News

ARTHROL Trial of Resveratrol

Similarly, negative results were reported for resveratrol from the ARTHROL trial, with 55% of the resveratrol- and 55% of placebo-treated individuals achieving a 20% reduction in knee pain intensity at 3 months. The actual change in knee pain from baseline to 3 months was −15.7 for resveratrol and −15.2 for placebo on a numerical rating scale that went from 0 (no pain) up to 100 (worst pain).

Resveratrol is found naturally in grapes, peanuts, pine cones, and Chinese knotweed, and there is a growing body of evidence that it may have pleiotropic effects, said investigator Christelle Nguyen, PhD, MD, a professor of physical and rehabilitation medicine at Université Paris Cité, Paris, France.

It’s available in a powder form over the counter as a treatment for multiple ailments, but more recently, became available as an oral formulation. Dr. Nguyen and colleagues wanted to know if this would make a difference to OA knee pain when added to usual care.

A double-blind, multicenter, placebo-controlled randomized trial was therefore conducted that involved 142 people with knee OA who had been experiencing knee pain for at least 1 month. The participants were equally randomly allocated to receive either oral resveratrol given as two caplets of 20 mg twice daily for the first week, then once daily for a total of 6 months, or a matched placebo.

There was also no effect of resveratrol vs placebo on a host of secondary outcomes measured at 3 and 6 months.

The interpretation is that oral resveratrol may not be effective in this indication or have a biologic effect on the pain pathway, Dr. Nguyen said.

Sara Freeman/Medscape Medical News

Botulinum Toxin: Over But Not Out?

Dr. Nguyen separately reported data from a new systematic review and meta-analysis on the use of intra-articular (IA) botulinum toxin type A (BoNT-A) for knee OA pain.

Seven of the 14 randomized controlled trials included in the meta-analysis had looked specifically at knee OA outcomes in the short, intermediate, and long term.

Results showed a nonsignificant trend favoring BoNT-A use, with the standard mean difference in pain of 0.35 (−0.82; 0.12), −0.27 (−0.61; 0.08), and −0.43 (−1.12; 0.26) for short-, intermediate-, and long-term use, respectively.

In contrast, pain reductions were seen with BoNT-A in three trials that included people with OA of the shoulder or base of the thumb. This begs the question as to whether botulinum toxin may still have a role to play, Dr. Nguyen said in an interview.

“It seems like there may be a positive effect for the shoulder joint and base of the thumb,” she told this news organization.

“So, basically, we found differences between large and small to intermediate joints,” Dr. Nguyen added. “It questions the dilution of botulinum toxin into the joint. If it’s a big joint, maybe the dilution is too high,” she suggested.

This hypothesis will be tested in the upcoming RHIBOT II trial that will begin recruitment later this year. This is a follow-on from the RHIBOT trial that was published in The Lancet Rheumatology 2 years ago.

Meanwhile, the use of botulinum toxin is off-label, Dr. Nguyen said. “We use it in our clinics only when first-line treatment had failed for base of thumb OA.” It’s not offered as a stand-alone intervention, and the IA injections need to be given by someone with experience, she said.
 

Methodologically Sound Studies

Commenting on the studies, Nancy E. Lane, MD, said: “There have been small botulinum studies before but not powered enough so that you could confirm or refute hypotheses.”

Dr. Lane, endowed professor of medicine, rheumatology, and aging research and director for the Center for Musculoskeletal Health at the University of California Davis School of Medicine, Sacramento, California, added: “Similarly for resveratrol, there have been lots of studies.”

Moreover, Dr. Lane observed that the studies were “really well-designed. They were well-powered. The subjects were selected in such a way that was good rigor in the methodologic design, and there were enough people in the studies so that you could really believe the results.”

The take-home is probably that these approaches do not work, Dr. Lane said, “at least when you apply them to moderate-severe knee OA patients, they don’t seem to make a difference.”

The congress was sponsored by the Osteoarthritis Research Society International.

The DICKENS study of diacerein was an investigator-initiated trial that was funded by the National Health and Medical Research Council of Australia. TRB Chemedica International S.A. provided diacerein free of charge for the trial but was not involved in the implementation or data analysis. Dr. Aitken had no conflicts of interest to disclose.

The ARTHROL trial of oral resveratrol was funded by the French Ministry of Health and Solidarity (Ministré des Solidarités et de la Santé). Yvery Laboratory provided the resveratrol caplet and matching placebo free of charge. Dr. Nguyen has financial relationships with Actelion, Grünenthal, Ipsen, Lilly, Meda, Merz, Novartis, Preciphar, Sandoz, Takeda, Thuasne, and UCB.

Dr. Lane had no relevant conflicts of interest to declare.

A version of this article appeared on Medscape.com.

LIVERPOOL, ENGLAND — Four in five people with rheumatoid arthritis (RA) fall into “at risk” categories for the initiation of Janus kinase (JAK) inhibitors set by the European Medicines Agency (EMA), according to data from the long-running British Society for Rheumatology (BSR) Biologics Register in RA (BSRBR-RA).

The EMA decided in January 2023 to implement measures to reduce the risk for serious side effects with JAK inhibitors in the treatment of chronic inflammatory diseases. The EMA’s recommendations advise that JAK inhibitors “should be used in the following patients only if no suitable treatment alternatives are available: those aged 65 years or above, those at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past, and those at increased risk of cancer.” The guidance also says to use JAK inhibitors “with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism [VTE]) ... [and that] the doses should be reduced in patient groups who are at risk of VTE, cancer, or major cardiovascular problems, where possible.”

To gauge the potential impact of the EMA’s decision, researchers analyzed BSRBR-RA data from 1341 individuals with RA who had started treatment with a JAK inhibitor before the agency issued its new recommendations. Among these individuals, 1075 (80.2%) met ≥ 1 EMA risk criterion. Half (54%) were current or past smokers, 44% had an increased risk for major cardiovascular events such as heart attack or stroke, 39% were 65 years or older, and 10% had an increased risk for cancer.

Nearly half (49%) of the study population who met ≥ 1 EMA risk criterion had received only one (31%) or no (18%) prior biologic disease-modifying antirheumatic drug (bDMARD), Zixing Tian, a PhD student at the University of Manchester in England, reported at the  annual meeting of the British Society for Rheumatology. Of the remainder, 23% had received two prior bDMARDs, and 28% had previously received three or more bDMARDs.

Sara Freeman/Medscape Medical News

Considerable Implications

There are potentially two ways of interpreting these data, suggested Ken Baker, BMBCh, PhD, senior clinical fellow and honorary consultant rheumatologist at Newcastle University in Newcastle upon Tyne, England.

“One is that rheumatologists starting these treatments are throwing caution to the wind and ignoring all guidance,” Dr. Baker said.

“The second is perhaps that the EMA guidance is difficult to implement in practice when it involves lots of the comorbidities and risk factors that commonly affect patients with rheumatoid arthritis.”

Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in England, also commented on the findings.

Were Cautions Warranted?

Like the US Food and Drug Administration, the EMA has concerns over the use of JAK inhibitors because of the drugs’ potential to increase the risk for serious side effects such as VTE, major adverse cardiovascular events, cancer, and all-cause mortality relative to tumor necrosis factor–alpha inhibitors.

Initially, the EMA issued cautions that only related to the use of tofacitinib (Xeljanz), which was the first JAK inhibitor to gain approval for RA and other chronic inflammatory diseases in Europe, but this expanded to include baricitinib (Olumiant) and most recently any member of the drug class, including abrocitinib (Cibinqo), filgotinib (Jyseleca), and upadacitinib (Rinvoq).

The EMA has done a responsible job of looking at the available data and issuing cautions to protect the populations of patients who may be exposed to these drugs, Peter C. Taylor, BMBCh, PhD, told this news organization. However, they are also severely restricting the populations of patients who can be treated with them. “It’s a complicated situation,” he said.

Shared Decision

“The issue for benefit and risk is there for any drug we use,” said Dr. Taylor, noting that there are over-the-counter drugs that can be “far more dangerous” than JAK inhibitors in terms of cardiovascular risk.

“In my opinion, the really key thing is to be able to communicate the issues with integrity, in a manner that the patient understands, to make sure that the risk is acceptable to them,” Dr. Taylor said.

It is all about optimizing treatment for an individual and proactively managing any other factors that may increase their personal risk for unwanted effects, Maya Buch, MBChB, PhD, professor of rheumatology and honorary consultant rheumatologist at the University of Manchester, said during a debate at the meeting.

“We still have unmet needs for our patient population. Patients aren’t achieving the goals and endpoints that we need,” Dr. Buch said.

“Don’t lose sight of the positive attributes that we’ve seen with JAK inhibitors,” she advised.

“We presume we know what the patient thinks when it comes to a matter of risk assessment, but it is always about tailoring treatment to that individual, and we are sometimes surprised in terms of what the patients want, even in the face of apparent higher risk,” Dr. Buch added.
 

Judicious Use

Iain McInnes, MBChB, PhD, observed during the same debate that it was “hard to argue that drugs are generally unsafe when they have already been approved. It’s also challenging to suggest they are not useful when they are being used.”

Sara Freeman/Medscape Medical News

Dr. McInnes, honorary consultant rheumatologist and vice principal and head of the College of Medical Veterinary & Life Sciences at the University of Glasgow in Scotland, pointed out that the EMA warnings assume that all JAK inhibitors are the same, but is that really the case? This is complex biochemistry, and could newer JAK inhibitors have an improved safety profile?

“There is no free ride in the immune system, and we should bear that in mind,” Dr. McInnes said. “These drugs work ... but we are absolutely flitting along the boundaries of the safety/efficacy window.”

Dr. McInnes told this news organization that clinicians do have to be cautious.

“There’s a paradox in that the very age group that the regulators are now asking us to be cautious about prescribing is pushing JAK inhibitors later and later in the disease course,” he said. This is a time when people would already have other risks for cardiovascular and other events.

“Overall, if used within the regulatory advice, Janus kinase inhibitors are a really useful drug class.”

The BSRBR-RA is funded by a grant from the BSR. The BSR currently receives funding from AbbVie, Amgen, Celltrion, Eli Lilly, Pfizer, Samsung Bioepis, Sanofi, and Sandoz and in the past from Hospira, Merck Sharp & Dohme (MSD), Roche, SOBI, and UCB. This income finances a wholly separate contract between the BSR and the University of Manchester to host the BSRBR-RA. All decisions concerning study design, data capture, analyses, interpretation, and publication are made autonomously of any industrial contribution. Ms. Tian had no conflicts of interest to report. Dr. Emery disclosed ties to AbbVie, Bristol Myers Squibb (BMS), Eli Lilly, Pfizer, MSD, Novartis, Roche, Sandoz, Samsung, and UCB. Dr. Taylor disclosed ties to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB. Dr. Buch disclosed ties to Gilead, AbbVie, Arxx Therapeutics, Boehringer Ingelheim, CESAS Medical, Galapagos, Gilead, MediStreams, and Pfizer. Dr. McInnes disclosed ties to AbbVie, AstraZeneca, Boehringer Ingelheim, Compugen, Cabaletta Bio, Causeway, Dexterra, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, and UCB.

A version of this article appeared on Medscape.com .

LIVERPOOL, ENGLAND — Four in five people with rheumatoid arthritis (RA) fall into “at risk” categories for the initiation of Janus kinase (JAK) inhibitors set by the European Medicines Agency (EMA), according to data from the long-running British Society for Rheumatology (BSR) Biologics Register in RA (BSRBR-RA).

The EMA decided in January 2023 to implement measures to reduce the risk for serious side effects with JAK inhibitors in the treatment of chronic inflammatory diseases. The EMA’s recommendations advise that JAK inhibitors “should be used in the following patients only if no suitable treatment alternatives are available: those aged 65 years or above, those at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past, and those at increased risk of cancer.” The guidance also says to use JAK inhibitors “with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism [VTE]) ... [and that] the doses should be reduced in patient groups who are at risk of VTE, cancer, or major cardiovascular problems, where possible.”

To gauge the potential impact of the EMA’s decision, researchers analyzed BSRBR-RA data from 1341 individuals with RA who had started treatment with a JAK inhibitor before the agency issued its new recommendations. Among these individuals, 1075 (80.2%) met ≥ 1 EMA risk criterion. Half (54%) were current or past smokers, 44% had an increased risk for major cardiovascular events such as heart attack or stroke, 39% were 65 years or older, and 10% had an increased risk for cancer.

Nearly half (49%) of the study population who met ≥ 1 EMA risk criterion had received only one (31%) or no (18%) prior biologic disease-modifying antirheumatic drug (bDMARD), Zixing Tian, a PhD student at the University of Manchester in England, reported at the  annual meeting of the British Society for Rheumatology. Of the remainder, 23% had received two prior bDMARDs, and 28% had previously received three or more bDMARDs.

Sara Freeman/Medscape Medical News

Considerable Implications

There are potentially two ways of interpreting these data, suggested Ken Baker, BMBCh, PhD, senior clinical fellow and honorary consultant rheumatologist at Newcastle University in Newcastle upon Tyne, England.

“One is that rheumatologists starting these treatments are throwing caution to the wind and ignoring all guidance,” Dr. Baker said.

“The second is perhaps that the EMA guidance is difficult to implement in practice when it involves lots of the comorbidities and risk factors that commonly affect patients with rheumatoid arthritis.”

Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in England, also commented on the findings.

Were Cautions Warranted?

Like the US Food and Drug Administration, the EMA has concerns over the use of JAK inhibitors because of the drugs’ potential to increase the risk for serious side effects such as VTE, major adverse cardiovascular events, cancer, and all-cause mortality relative to tumor necrosis factor–alpha inhibitors.

Initially, the EMA issued cautions that only related to the use of tofacitinib (Xeljanz), which was the first JAK inhibitor to gain approval for RA and other chronic inflammatory diseases in Europe, but this expanded to include baricitinib (Olumiant) and most recently any member of the drug class, including abrocitinib (Cibinqo), filgotinib (Jyseleca), and upadacitinib (Rinvoq).

The EMA has done a responsible job of looking at the available data and issuing cautions to protect the populations of patients who may be exposed to these drugs, Peter C. Taylor, BMBCh, PhD, told this news organization. However, they are also severely restricting the populations of patients who can be treated with them. “It’s a complicated situation,” he said.

Shared Decision

“The issue for benefit and risk is there for any drug we use,” said Dr. Taylor, noting that there are over-the-counter drugs that can be “far more dangerous” than JAK inhibitors in terms of cardiovascular risk.

“In my opinion, the really key thing is to be able to communicate the issues with integrity, in a manner that the patient understands, to make sure that the risk is acceptable to them,” Dr. Taylor said.

It is all about optimizing treatment for an individual and proactively managing any other factors that may increase their personal risk for unwanted effects, Maya Buch, MBChB, PhD, professor of rheumatology and honorary consultant rheumatologist at the University of Manchester, said during a debate at the meeting.

“We still have unmet needs for our patient population. Patients aren’t achieving the goals and endpoints that we need,” Dr. Buch said.

“Don’t lose sight of the positive attributes that we’ve seen with JAK inhibitors,” she advised.

“We presume we know what the patient thinks when it comes to a matter of risk assessment, but it is always about tailoring treatment to that individual, and we are sometimes surprised in terms of what the patients want, even in the face of apparent higher risk,” Dr. Buch added.
 

Judicious Use

Iain McInnes, MBChB, PhD, observed during the same debate that it was “hard to argue that drugs are generally unsafe when they have already been approved. It’s also challenging to suggest they are not useful when they are being used.”

Sara Freeman/Medscape Medical News

Dr. McInnes, honorary consultant rheumatologist and vice principal and head of the College of Medical Veterinary & Life Sciences at the University of Glasgow in Scotland, pointed out that the EMA warnings assume that all JAK inhibitors are the same, but is that really the case? This is complex biochemistry, and could newer JAK inhibitors have an improved safety profile?

“There is no free ride in the immune system, and we should bear that in mind,” Dr. McInnes said. “These drugs work ... but we are absolutely flitting along the boundaries of the safety/efficacy window.”

Dr. McInnes told this news organization that clinicians do have to be cautious.

“There’s a paradox in that the very age group that the regulators are now asking us to be cautious about prescribing is pushing JAK inhibitors later and later in the disease course,” he said. This is a time when people would already have other risks for cardiovascular and other events.

“Overall, if used within the regulatory advice, Janus kinase inhibitors are a really useful drug class.”

The BSRBR-RA is funded by a grant from the BSR. The BSR currently receives funding from AbbVie, Amgen, Celltrion, Eli Lilly, Pfizer, Samsung Bioepis, Sanofi, and Sandoz and in the past from Hospira, Merck Sharp & Dohme (MSD), Roche, SOBI, and UCB. This income finances a wholly separate contract between the BSR and the University of Manchester to host the BSRBR-RA. All decisions concerning study design, data capture, analyses, interpretation, and publication are made autonomously of any industrial contribution. Ms. Tian had no conflicts of interest to report. Dr. Emery disclosed ties to AbbVie, Bristol Myers Squibb (BMS), Eli Lilly, Pfizer, MSD, Novartis, Roche, Sandoz, Samsung, and UCB. Dr. Taylor disclosed ties to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB. Dr. Buch disclosed ties to Gilead, AbbVie, Arxx Therapeutics, Boehringer Ingelheim, CESAS Medical, Galapagos, Gilead, MediStreams, and Pfizer. Dr. McInnes disclosed ties to AbbVie, AstraZeneca, Boehringer Ingelheim, Compugen, Cabaletta Bio, Causeway, Dexterra, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, and UCB.

A version of this article appeared on Medscape.com .

LIVERPOOL, ENGLAND — Four in five people with rheumatoid arthritis (RA) fall into “at risk” categories for the initiation of Janus kinase (JAK) inhibitors set by the European Medicines Agency (EMA), according to data from the long-running British Society for Rheumatology (BSR) Biologics Register in RA (BSRBR-RA).

The EMA decided in January 2023 to implement measures to reduce the risk for serious side effects with JAK inhibitors in the treatment of chronic inflammatory diseases. The EMA’s recommendations advise that JAK inhibitors “should be used in the following patients only if no suitable treatment alternatives are available: those aged 65 years or above, those at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past, and those at increased risk of cancer.” The guidance also says to use JAK inhibitors “with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism [VTE]) ... [and that] the doses should be reduced in patient groups who are at risk of VTE, cancer, or major cardiovascular problems, where possible.”

To gauge the potential impact of the EMA’s decision, researchers analyzed BSRBR-RA data from 1341 individuals with RA who had started treatment with a JAK inhibitor before the agency issued its new recommendations. Among these individuals, 1075 (80.2%) met ≥ 1 EMA risk criterion. Half (54%) were current or past smokers, 44% had an increased risk for major cardiovascular events such as heart attack or stroke, 39% were 65 years or older, and 10% had an increased risk for cancer.

Nearly half (49%) of the study population who met ≥ 1 EMA risk criterion had received only one (31%) or no (18%) prior biologic disease-modifying antirheumatic drug (bDMARD), Zixing Tian, a PhD student at the University of Manchester in England, reported at the  annual meeting of the British Society for Rheumatology. Of the remainder, 23% had received two prior bDMARDs, and 28% had previously received three or more bDMARDs.

Sara Freeman/Medscape Medical News

Considerable Implications

There are potentially two ways of interpreting these data, suggested Ken Baker, BMBCh, PhD, senior clinical fellow and honorary consultant rheumatologist at Newcastle University in Newcastle upon Tyne, England.

“One is that rheumatologists starting these treatments are throwing caution to the wind and ignoring all guidance,” Dr. Baker said.

“The second is perhaps that the EMA guidance is difficult to implement in practice when it involves lots of the comorbidities and risk factors that commonly affect patients with rheumatoid arthritis.”

Paul Emery, MD, Versus Arthritis professor of rheumatology and director of the Leeds Biomedical Research Centre at the University of Leeds in England, also commented on the findings.

Were Cautions Warranted?

Like the US Food and Drug Administration, the EMA has concerns over the use of JAK inhibitors because of the drugs’ potential to increase the risk for serious side effects such as VTE, major adverse cardiovascular events, cancer, and all-cause mortality relative to tumor necrosis factor–alpha inhibitors.

Initially, the EMA issued cautions that only related to the use of tofacitinib (Xeljanz), which was the first JAK inhibitor to gain approval for RA and other chronic inflammatory diseases in Europe, but this expanded to include baricitinib (Olumiant) and most recently any member of the drug class, including abrocitinib (Cibinqo), filgotinib (Jyseleca), and upadacitinib (Rinvoq).

The EMA has done a responsible job of looking at the available data and issuing cautions to protect the populations of patients who may be exposed to these drugs, Peter C. Taylor, BMBCh, PhD, told this news organization. However, they are also severely restricting the populations of patients who can be treated with them. “It’s a complicated situation,” he said.

Shared Decision

“The issue for benefit and risk is there for any drug we use,” said Dr. Taylor, noting that there are over-the-counter drugs that can be “far more dangerous” than JAK inhibitors in terms of cardiovascular risk.

“In my opinion, the really key thing is to be able to communicate the issues with integrity, in a manner that the patient understands, to make sure that the risk is acceptable to them,” Dr. Taylor said.

It is all about optimizing treatment for an individual and proactively managing any other factors that may increase their personal risk for unwanted effects, Maya Buch, MBChB, PhD, professor of rheumatology and honorary consultant rheumatologist at the University of Manchester, said during a debate at the meeting.

“We still have unmet needs for our patient population. Patients aren’t achieving the goals and endpoints that we need,” Dr. Buch said.

“Don’t lose sight of the positive attributes that we’ve seen with JAK inhibitors,” she advised.

“We presume we know what the patient thinks when it comes to a matter of risk assessment, but it is always about tailoring treatment to that individual, and we are sometimes surprised in terms of what the patients want, even in the face of apparent higher risk,” Dr. Buch added.
 

Judicious Use

Iain McInnes, MBChB, PhD, observed during the same debate that it was “hard to argue that drugs are generally unsafe when they have already been approved. It’s also challenging to suggest they are not useful when they are being used.”

Sara Freeman/Medscape Medical News

Dr. McInnes, honorary consultant rheumatologist and vice principal and head of the College of Medical Veterinary & Life Sciences at the University of Glasgow in Scotland, pointed out that the EMA warnings assume that all JAK inhibitors are the same, but is that really the case? This is complex biochemistry, and could newer JAK inhibitors have an improved safety profile?

“There is no free ride in the immune system, and we should bear that in mind,” Dr. McInnes said. “These drugs work ... but we are absolutely flitting along the boundaries of the safety/efficacy window.”

Dr. McInnes told this news organization that clinicians do have to be cautious.

“There’s a paradox in that the very age group that the regulators are now asking us to be cautious about prescribing is pushing JAK inhibitors later and later in the disease course,” he said. This is a time when people would already have other risks for cardiovascular and other events.

“Overall, if used within the regulatory advice, Janus kinase inhibitors are a really useful drug class.”

The BSRBR-RA is funded by a grant from the BSR. The BSR currently receives funding from AbbVie, Amgen, Celltrion, Eli Lilly, Pfizer, Samsung Bioepis, Sanofi, and Sandoz and in the past from Hospira, Merck Sharp & Dohme (MSD), Roche, SOBI, and UCB. This income finances a wholly separate contract between the BSR and the University of Manchester to host the BSRBR-RA. All decisions concerning study design, data capture, analyses, interpretation, and publication are made autonomously of any industrial contribution. Ms. Tian had no conflicts of interest to report. Dr. Emery disclosed ties to AbbVie, Bristol Myers Squibb (BMS), Eli Lilly, Pfizer, MSD, Novartis, Roche, Sandoz, Samsung, and UCB. Dr. Taylor disclosed ties to AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, Aqtual, and UCB. Dr. Buch disclosed ties to Gilead, AbbVie, Arxx Therapeutics, Boehringer Ingelheim, CESAS Medical, Galapagos, Gilead, MediStreams, and Pfizer. Dr. McInnes disclosed ties to AbbVie, AstraZeneca, Boehringer Ingelheim, Compugen, Cabaletta Bio, Causeway, Dexterra, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, and UCB.

A version of this article appeared on Medscape.com .

VIENNA — Encouraging primary or secondary analyses of trial data for the use of several novel injectables and gene therapy for knee osteoarthritis (OA) were reported at the OARSI 2024 World Congress.

Of all the approaches discussed during the News in Therapies session at OARSI 2024, the most intriguing was the use of the placental extract PTP-001 (MOTYS, Bioventus), session chair Nancy E. Lane, MD, of the University of California Davis School of Medicine, Sacramento, California, told this news organization.

Other notable presentations of data from trials of investigational agents for knee OA included an update from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate; a phase 2 trial of pentosan polysulfate sodium (PPS), a non-opioid, semi-synthetic xylose-based polysaccharide; and an update on phase 2 study results for XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant of interleukin 10 (IL-10).
 

PTP-001 (MOTYS)

Indeed, promising results were seen in a phase 2 trial testing a single intra-articular (IA) injection of PTP-001 vs an IA saline placebo in just over 200 individuals with symptomatic knee OA. Results of this dose-finding study were presented by Alessandra Pavesio, senior vice president and the chief science officer of Bioventus/Doron Therapeutics, Durham, North Carolina.

Ms. Pavesio reported there were decreases in knee pain and improvements in knee function, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). These changes were seen after 26 weeks of treatment with PTP-001 given at either a low (100 mg, n = 74) or high (200 mg, n = 40) dose.

Sara Freeman/Medscape Medical News

Novel Fluticasone Delivery

In the same session, James A. Helliwell, MD, cofounder, director, and chief executive officer of Eupraxia Pharmaceuticals in Victoria, British Columbia, Canada, presented updated data from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate.

Dr. Helliwell, a cardiothoracic anesthesiologist, explained that EP-104IAR uses proprietary technology to form fluticasone into a crystal that can then be injected directly into the joint. This then slowly diffuses out to provide a highly localized treatment.

The SPRINGBOARD trial recruited just over 300 individuals with moderate knee OA and moderate to severe WOMAC pain and randomly allocated 164 to a single IA injection of EP-104IAR and 164 to a matching vehicle injection as a placebo. The latter was a slightly viscous substance that behaved like hyaluronic acid, Dr. Helliwell said.

The LSM change in total WOMAC score from baseline to week 12 showed a greater improvement with EP-104IAR than with placebo in a per protocol analysis (−2.79 vs −2.07; P = .002). Similar results were seen for the WOMAC subscales of pain (−2.97 vs −2.24; P = .003), function (−2.64 vs −1.99; P = .005), and stiffness (−2.85 vs −2.05; P = .001).

These differences persisted, Dr. Helliwell reported, out to a 20-week assessment for total WOMAC score, function, and stiffness and out to a 15-week assessment for WOMAC pain.

It’s probably no surprise that a steroid works, Dr. Helliwell said, noting that the safety profile of EP-104IAR may be better than that of regular IA steroid injection because it has “few off-target” effects. He reported that there were “minimal, clinically insignificant, and transient effects” of EP-104IAR on serum cortisol. There was no effect on glucose metabolism, even in patients with diabetes, he said.

“There is a group of our patients that we give long-acting steroids to in the joint, so it looked like [the EP-104IAR] safety profile was really good,” Dr. Lane told this news organization. However, she added: “I’m worried about the price tag associated with it.”
 

PPS

Although it perhaps can’t be described as a novel injectable per se, Mukesh Ahuja, MBBS, global clinical head of osteoarthritis at Paradigm Biopharmaceuticals, presented results of the novel use of PPS.

“PPS is a non-opioid, semi-synthetic xylose-based polysaccharide that is derived from beechwood trees,” Dr. Ahuja said. “It has a long-track record for treating pain, inflammation, and thrombosis in humans.”

Sara Freeman/Medscape Medical News

Gene Therapy

Elsewhere at OARSI 2024, updated data were reported on XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant (v) of IL-10.

Howard Rutman, MD, MBA, chief medical officer of Xalud Therapeutics, reported data from a patient subgroup analysis of a phase 2 trial, which evaluated the effects of single and repeat IA injections of XT-150.

Previously, it was found that a single dose of XT-150 (0.15 mg/mL or 0.45 mg/mL) given as a 1-mL IA injection did not meet its primary endpoint of a greater proportion of patients achieving a 30% or more improvement in WOMAC pain at 180 days vs a matching placebo.

Sara Freeman/Medscape Medical News

The Best Is Yet to Come?

“There’s a lot of things cooking that haven’t been presented here [at OARSI],” Dr. Lane observed.

“We are figuring out how to regenerate cartilage, and it’s a little different than throwing some stem cells in there. There’s some ground-breaking stuff [coming], it just takes us a while.”

Dr. Lane also noted that researchers were “really figuring out” how joints become painful, which will be a major step in figuring out how to make them less painful for patients.

“We’re making a lot of progress in ways that I don’t think we previously thought of, for example, the weight loss drugs. They probably have a central pain reduction effect, I think there’s a little overlap with the opioid receptors, so that’s pretty exciting. So, we’re getting there,” Dr. Lane said.

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Lane had no relevant conflicts to declare. The trial of PTP-001 (MOTYS) was funded by Bioventus. Ms. Pavesio is an employee of Doron Therapeutics, a subsidiary of Bioventus. The SPRINGBOARD trial with EP-104IAR was funded by Eupraxia Pharmaceuticals. Dr. Helliwell is an employee and stockholder of Eupraxia Pharmaceuticals. The trial of PPS was funded by Paradigm Biopharmaceuticals. Dr. Ahuja is an employee and stockholder of Paradigm Biopharmaceuticals and holds stock in ChitogenX. The trial of XT-150 was funded by Xalud Therapeutics. Dr. Rutman is an employee and equity holder of the company.
 

A version of this article appeared on Medscape.com.

VIENNA — Encouraging primary or secondary analyses of trial data for the use of several novel injectables and gene therapy for knee osteoarthritis (OA) were reported at the OARSI 2024 World Congress.

Of all the approaches discussed during the News in Therapies session at OARSI 2024, the most intriguing was the use of the placental extract PTP-001 (MOTYS, Bioventus), session chair Nancy E. Lane, MD, of the University of California Davis School of Medicine, Sacramento, California, told this news organization.

Other notable presentations of data from trials of investigational agents for knee OA included an update from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate; a phase 2 trial of pentosan polysulfate sodium (PPS), a non-opioid, semi-synthetic xylose-based polysaccharide; and an update on phase 2 study results for XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant of interleukin 10 (IL-10).
 

PTP-001 (MOTYS)

Indeed, promising results were seen in a phase 2 trial testing a single intra-articular (IA) injection of PTP-001 vs an IA saline placebo in just over 200 individuals with symptomatic knee OA. Results of this dose-finding study were presented by Alessandra Pavesio, senior vice president and the chief science officer of Bioventus/Doron Therapeutics, Durham, North Carolina.

Ms. Pavesio reported there were decreases in knee pain and improvements in knee function, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). These changes were seen after 26 weeks of treatment with PTP-001 given at either a low (100 mg, n = 74) or high (200 mg, n = 40) dose.

Sara Freeman/Medscape Medical News

Novel Fluticasone Delivery

In the same session, James A. Helliwell, MD, cofounder, director, and chief executive officer of Eupraxia Pharmaceuticals in Victoria, British Columbia, Canada, presented updated data from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate.

Dr. Helliwell, a cardiothoracic anesthesiologist, explained that EP-104IAR uses proprietary technology to form fluticasone into a crystal that can then be injected directly into the joint. This then slowly diffuses out to provide a highly localized treatment.

The SPRINGBOARD trial recruited just over 300 individuals with moderate knee OA and moderate to severe WOMAC pain and randomly allocated 164 to a single IA injection of EP-104IAR and 164 to a matching vehicle injection as a placebo. The latter was a slightly viscous substance that behaved like hyaluronic acid, Dr. Helliwell said.

The LSM change in total WOMAC score from baseline to week 12 showed a greater improvement with EP-104IAR than with placebo in a per protocol analysis (−2.79 vs −2.07; P = .002). Similar results were seen for the WOMAC subscales of pain (−2.97 vs −2.24; P = .003), function (−2.64 vs −1.99; P = .005), and stiffness (−2.85 vs −2.05; P = .001).

These differences persisted, Dr. Helliwell reported, out to a 20-week assessment for total WOMAC score, function, and stiffness and out to a 15-week assessment for WOMAC pain.

It’s probably no surprise that a steroid works, Dr. Helliwell said, noting that the safety profile of EP-104IAR may be better than that of regular IA steroid injection because it has “few off-target” effects. He reported that there were “minimal, clinically insignificant, and transient effects” of EP-104IAR on serum cortisol. There was no effect on glucose metabolism, even in patients with diabetes, he said.

“There is a group of our patients that we give long-acting steroids to in the joint, so it looked like [the EP-104IAR] safety profile was really good,” Dr. Lane told this news organization. However, she added: “I’m worried about the price tag associated with it.”
 

PPS

Although it perhaps can’t be described as a novel injectable per se, Mukesh Ahuja, MBBS, global clinical head of osteoarthritis at Paradigm Biopharmaceuticals, presented results of the novel use of PPS.

“PPS is a non-opioid, semi-synthetic xylose-based polysaccharide that is derived from beechwood trees,” Dr. Ahuja said. “It has a long-track record for treating pain, inflammation, and thrombosis in humans.”

Sara Freeman/Medscape Medical News

Gene Therapy

Elsewhere at OARSI 2024, updated data were reported on XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant (v) of IL-10.

Howard Rutman, MD, MBA, chief medical officer of Xalud Therapeutics, reported data from a patient subgroup analysis of a phase 2 trial, which evaluated the effects of single and repeat IA injections of XT-150.

Previously, it was found that a single dose of XT-150 (0.15 mg/mL or 0.45 mg/mL) given as a 1-mL IA injection did not meet its primary endpoint of a greater proportion of patients achieving a 30% or more improvement in WOMAC pain at 180 days vs a matching placebo.

Sara Freeman/Medscape Medical News

The Best Is Yet to Come?

“There’s a lot of things cooking that haven’t been presented here [at OARSI],” Dr. Lane observed.

“We are figuring out how to regenerate cartilage, and it’s a little different than throwing some stem cells in there. There’s some ground-breaking stuff [coming], it just takes us a while.”

Dr. Lane also noted that researchers were “really figuring out” how joints become painful, which will be a major step in figuring out how to make them less painful for patients.

“We’re making a lot of progress in ways that I don’t think we previously thought of, for example, the weight loss drugs. They probably have a central pain reduction effect, I think there’s a little overlap with the opioid receptors, so that’s pretty exciting. So, we’re getting there,” Dr. Lane said.

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Lane had no relevant conflicts to declare. The trial of PTP-001 (MOTYS) was funded by Bioventus. Ms. Pavesio is an employee of Doron Therapeutics, a subsidiary of Bioventus. The SPRINGBOARD trial with EP-104IAR was funded by Eupraxia Pharmaceuticals. Dr. Helliwell is an employee and stockholder of Eupraxia Pharmaceuticals. The trial of PPS was funded by Paradigm Biopharmaceuticals. Dr. Ahuja is an employee and stockholder of Paradigm Biopharmaceuticals and holds stock in ChitogenX. The trial of XT-150 was funded by Xalud Therapeutics. Dr. Rutman is an employee and equity holder of the company.
 

A version of this article appeared on Medscape.com.

VIENNA — Encouraging primary or secondary analyses of trial data for the use of several novel injectables and gene therapy for knee osteoarthritis (OA) were reported at the OARSI 2024 World Congress.

Of all the approaches discussed during the News in Therapies session at OARSI 2024, the most intriguing was the use of the placental extract PTP-001 (MOTYS, Bioventus), session chair Nancy E. Lane, MD, of the University of California Davis School of Medicine, Sacramento, California, told this news organization.

Other notable presentations of data from trials of investigational agents for knee OA included an update from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate; a phase 2 trial of pentosan polysulfate sodium (PPS), a non-opioid, semi-synthetic xylose-based polysaccharide; and an update on phase 2 study results for XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant of interleukin 10 (IL-10).
 

PTP-001 (MOTYS)

Indeed, promising results were seen in a phase 2 trial testing a single intra-articular (IA) injection of PTP-001 vs an IA saline placebo in just over 200 individuals with symptomatic knee OA. Results of this dose-finding study were presented by Alessandra Pavesio, senior vice president and the chief science officer of Bioventus/Doron Therapeutics, Durham, North Carolina.

Ms. Pavesio reported there were decreases in knee pain and improvements in knee function, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). These changes were seen after 26 weeks of treatment with PTP-001 given at either a low (100 mg, n = 74) or high (200 mg, n = 40) dose.

Sara Freeman/Medscape Medical News

Novel Fluticasone Delivery

In the same session, James A. Helliwell, MD, cofounder, director, and chief executive officer of Eupraxia Pharmaceuticals in Victoria, British Columbia, Canada, presented updated data from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate.

Dr. Helliwell, a cardiothoracic anesthesiologist, explained that EP-104IAR uses proprietary technology to form fluticasone into a crystal that can then be injected directly into the joint. This then slowly diffuses out to provide a highly localized treatment.

The SPRINGBOARD trial recruited just over 300 individuals with moderate knee OA and moderate to severe WOMAC pain and randomly allocated 164 to a single IA injection of EP-104IAR and 164 to a matching vehicle injection as a placebo. The latter was a slightly viscous substance that behaved like hyaluronic acid, Dr. Helliwell said.

The LSM change in total WOMAC score from baseline to week 12 showed a greater improvement with EP-104IAR than with placebo in a per protocol analysis (−2.79 vs −2.07; P = .002). Similar results were seen for the WOMAC subscales of pain (−2.97 vs −2.24; P = .003), function (−2.64 vs −1.99; P = .005), and stiffness (−2.85 vs −2.05; P = .001).

These differences persisted, Dr. Helliwell reported, out to a 20-week assessment for total WOMAC score, function, and stiffness and out to a 15-week assessment for WOMAC pain.

It’s probably no surprise that a steroid works, Dr. Helliwell said, noting that the safety profile of EP-104IAR may be better than that of regular IA steroid injection because it has “few off-target” effects. He reported that there were “minimal, clinically insignificant, and transient effects” of EP-104IAR on serum cortisol. There was no effect on glucose metabolism, even in patients with diabetes, he said.

“There is a group of our patients that we give long-acting steroids to in the joint, so it looked like [the EP-104IAR] safety profile was really good,” Dr. Lane told this news organization. However, she added: “I’m worried about the price tag associated with it.”
 

PPS

Although it perhaps can’t be described as a novel injectable per se, Mukesh Ahuja, MBBS, global clinical head of osteoarthritis at Paradigm Biopharmaceuticals, presented results of the novel use of PPS.

“PPS is a non-opioid, semi-synthetic xylose-based polysaccharide that is derived from beechwood trees,” Dr. Ahuja said. “It has a long-track record for treating pain, inflammation, and thrombosis in humans.”

Sara Freeman/Medscape Medical News

Gene Therapy

Elsewhere at OARSI 2024, updated data were reported on XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant (v) of IL-10.

Howard Rutman, MD, MBA, chief medical officer of Xalud Therapeutics, reported data from a patient subgroup analysis of a phase 2 trial, which evaluated the effects of single and repeat IA injections of XT-150.

Previously, it was found that a single dose of XT-150 (0.15 mg/mL or 0.45 mg/mL) given as a 1-mL IA injection did not meet its primary endpoint of a greater proportion of patients achieving a 30% or more improvement in WOMAC pain at 180 days vs a matching placebo.

Sara Freeman/Medscape Medical News

The Best Is Yet to Come?

“There’s a lot of things cooking that haven’t been presented here [at OARSI],” Dr. Lane observed.

“We are figuring out how to regenerate cartilage, and it’s a little different than throwing some stem cells in there. There’s some ground-breaking stuff [coming], it just takes us a while.”

Dr. Lane also noted that researchers were “really figuring out” how joints become painful, which will be a major step in figuring out how to make them less painful for patients.

“We’re making a lot of progress in ways that I don’t think we previously thought of, for example, the weight loss drugs. They probably have a central pain reduction effect, I think there’s a little overlap with the opioid receptors, so that’s pretty exciting. So, we’re getting there,” Dr. Lane said.

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Lane had no relevant conflicts to declare. The trial of PTP-001 (MOTYS) was funded by Bioventus. Ms. Pavesio is an employee of Doron Therapeutics, a subsidiary of Bioventus. The SPRINGBOARD trial with EP-104IAR was funded by Eupraxia Pharmaceuticals. Dr. Helliwell is an employee and stockholder of Eupraxia Pharmaceuticals. The trial of PPS was funded by Paradigm Biopharmaceuticals. Dr. Ahuja is an employee and stockholder of Paradigm Biopharmaceuticals and holds stock in ChitogenX. The trial of XT-150 was funded by Xalud Therapeutics. Dr. Rutman is an employee and equity holder of the company.
 

A version of this article appeared on Medscape.com.

LIVERPOOL, ENGLAND — An updated guideline from the British Society for Rheumatology (BSR) on the management of Sjögren disease asks rheumatologists and other clinicians caring for patients with the condition to “do the little things well” rather than overly focusing on rheumatologic treatments. The guideline’s new format provides recommendations for specific clinical questions and now also includes recommendations for managing the disease in children and adolescents. 

“The original guideline was published in 2017, and things move on very rapidly,” consultant rheumatologist Elizabeth Price, MBBCh, PhD, said ahead of her presentation of the updated guideline at the annual meeting of the British Society for Rheumatology.

Sara Freeman/Medscape Medical News

What’s in a Name?

The BSR guideline on the management of adult and juvenile onset Sjögren disease is published in Rheumatology and is available via the BSR website, where it is accompanied by a short summary sheet. 

The most notable change perhaps is the name the guideline now uses, Dr. Price said at BSR 2024. “We have been bold and called it Sjögren disease.” Previously, the guideline used the term primary Sjögren’s syndrome, but there has been a “move away from using eponymous syndromes and dropping s’s and apostrophes,” she explained. 

Another significant change is that advice on managing Sjögren disease in children and adolescents is now included where appropriate, meaning that the British guideline is now the first to cover Sjögren disease “across the ages,” Dr. Price said.

A pediatric/adolescent rheumatologist joined the guideline working group, which already consisted of several adult rheumatologists, ophthalmologists, and a dentistry consultant. The group now comprises 22 members total, including a general practitioner, an oncologist, a renal physician, an occupational therapist, two patients with Sjögren disease, and a librarian.
 

Confirming the Diagnosis

The first questions asked to help form the new recommendations were around confirming a diagnosis of Sjögren disease, such as what is the diagnostic accuracy of antinuclear antibodies (ANAs), extractable nuclear antigens (ENAs), and other novel antigens in Sjögren disease? And what is the diagnostic accuracy of salivary gland ultrasound, imaging in general, and salivary gland or lacrimal gland biopsies? 

The resulting recommendations advised not to measure ANAs in the absence of clinical indicators of Sjögren disease or any other connective tissue disease but to use it to screen if there was a clinical suspicion. And ENAs should be measured even if the ANAs were negative and there is a high index of suspicion. 

In terms of imaging, ultrasound of the salivary glands was thought to be useful, but other imaging was not recommended for routine practice at the current time. Minor lip but not lacrimal gland biopsies were recommended if clinical and serologic features were not enough to make a diagnosis.
 

Lymphoma Worries

The 2017 version of the guideline did not include information about lymphoma, but this is the thing that most patients with Sjögren disease will worry about, Dr. Price said. “They all look it up on YouTube, they all come back and tell me that they are really worried they’ll develop it.”

The question that was therefore posed was whether there were any measurable biomarkers that could predict the development of lymphoma in adults and children. Seven predictors were found, the strongest being a low level of complement C4 alone or together with low levels of C3. Other predictors were salivary gland enlargement, lymphadenopathy, anti-Ro/La and rheumatoid factor autoantibodies, cryoglobulinemia, monoclonal gammopathy, and a high focus score. 

All of these predictors put someone in a higher risk category for lymphoma. If two or fewer of those features are present, the lifetime risk is “probably below 2%,” Dr. Price said. However, if all seven are present, the lifetime risk is “approaching 100%.”

The recommendation made on the basis of these findings is that people with Sjögren disease need to be offered early further investigation if they present with any new salivary gland swelling or other symptoms that might suggest the development of lymphoma. In this regard, a labial salivary gland biopsy might provide additional prognostic information.
 

‘Do the Little Things Well’

“You have to do the little things well,” Dr. Price said. “Many of the patients [who] come to see me for a second opinion have not been prescribed the right eye drops, have not been given advice on dental care,” with their management taking “too much on the rheumatological treatments.”

Rheumatologists are of course not trained or expected to be experts in ophthalmology or dentistry, but “you need to look at their mouth and you do need to examine their eyes, and you do need to give them some advice,” Dr. Price advised.

Thankfully, that is where the updated guidelines should help, with a recommendation that people with Sjögren disease should use preservative-free eye drops every 2-3 hours.

“It’s vital you avoid preservatives, because preservatives flatten the corneal surface and reduce the surface area and can cause inflammation in their own right,” Dr. Price cautioned, adding that there are plenty of suitable eye drop formulations available. 

In regard to helping with dry mouth symptoms, the recommendation is to use a saliva substitute for symptomatic relief. For vaginal dryness, the recommendation is to consider advising topical nonhormonal vaginal moisturizers plus estrogen creams or pessaries in peri- or postmenopausal women with significant vaginal dryness. 

“Very important, however, is to maintain a neutral pH, an alkaline environment in the mouth because acid damages dental enamel,” Dr. Price said. Conversely, an acidic vaginal moisturizer is needed to treat vaginal dryness. 

Dental hygiene is important. Regular brushing with a fluoride-based toothpaste is advised. The use of xylitol-containing products has been shown to reduce bacteria known to increase the risk for dental decay. Telling patients not to eat between meals is also simple but important advice. 

“We do recommend that patients are assessed holistically,” Dr. Price said, noting that they should be offered access to cognitive-behavioral therapy and exercise therapies to help with the symptoms of fatigue and joint pain.
 

Watch Out for Comorbidities

Sjögren disease is associated with many comorbidities, some of which might be predicted from the age and demographics of the people who are normally affected. 

“This is on the whole an older, female population, so you see a lot of osteoarthritis, gastroesophageal reflux, and hypertension,” Dr. Price said. “However, you may not be aware that 1 in 5 of these patients develop thyroid disease,” and there is a higher rate of celiac disease and primary biliary cholangitis than is seen in the general background population. 

The recommendation, therefore, is to “be aware of and consider screening for commonly associated conditions, as guided by age and/or clinical presentation.” As such, it’s recommended that baseline and repeated investigations that look for signs of comorbidity are performed, such as thyroid function assessment and liver function tests, to name two.
 

Treatment Recommendations

As in the original guideline, the treatment of systemic disease is discussed, but the advice has been overhauled with the availability of new data. 

The updated guidance notes that a trial of hydroxychloroquine for 6-12 months is the recommended treatment approach for people with fatigue and systemic symptoms. 

Systemic steroids may be used in the short-term for specific indications but should not be offered routinely. 

Conventional immunosuppressive or biologic drugs and immunoglobulins are not currently recommended outside of managing specific systemic complications.

In juvenile cases, the treatment of recurrent swollen parotid glands that are not due to infection or stone disease should include a short course of a nonsteroidal anti-inflammatory drug or a short course of oral steroids. This should be combined with massage followed by washouts with saline or steroids. In refractory cases, escalation to anti–B-cell–targeted therapies may be considered in select situations.
 

View on Updates

Patient advocate Bridget Crampton, who leads the helpline team at Sjögren’s UK (formerly the British Sjögren’s Syndrome Association), commented on the importance of the guidelines during a roundtable held by the BSR. 

“I think it will help [patients] make better use of their own appointments. So, they’ll know what treatments might be offered. They’ll know what they want to talk about at their appointments,” she said. 

Ms. Crampton, who has lived with Sjögren disease herself for the past 20 years, added: “I think it’s important for patients that we have guidelines like this. It means that all clinicians can easily access information. My hope is that it might standardize care across the UK a little bit more.” 

No specific funding was received to create the guidelines, be that from any bodies in the public, commercial, or not-for-profit sectors. No conflicts of interests were expressed by any of the experts quoted in this article.

A version of this article appeared on Medscape.com.

LIVERPOOL, ENGLAND — An updated guideline from the British Society for Rheumatology (BSR) on the management of Sjögren disease asks rheumatologists and other clinicians caring for patients with the condition to “do the little things well” rather than overly focusing on rheumatologic treatments. The guideline’s new format provides recommendations for specific clinical questions and now also includes recommendations for managing the disease in children and adolescents. 

“The original guideline was published in 2017, and things move on very rapidly,” consultant rheumatologist Elizabeth Price, MBBCh, PhD, said ahead of her presentation of the updated guideline at the annual meeting of the British Society for Rheumatology.

Sara Freeman/Medscape Medical News

What’s in a Name?

The BSR guideline on the management of adult and juvenile onset Sjögren disease is published in Rheumatology and is available via the BSR website, where it is accompanied by a short summary sheet. 

The most notable change perhaps is the name the guideline now uses, Dr. Price said at BSR 2024. “We have been bold and called it Sjögren disease.” Previously, the guideline used the term primary Sjögren’s syndrome, but there has been a “move away from using eponymous syndromes and dropping s’s and apostrophes,” she explained. 

Another significant change is that advice on managing Sjögren disease in children and adolescents is now included where appropriate, meaning that the British guideline is now the first to cover Sjögren disease “across the ages,” Dr. Price said.

A pediatric/adolescent rheumatologist joined the guideline working group, which already consisted of several adult rheumatologists, ophthalmologists, and a dentistry consultant. The group now comprises 22 members total, including a general practitioner, an oncologist, a renal physician, an occupational therapist, two patients with Sjögren disease, and a librarian.
 

Confirming the Diagnosis

The first questions asked to help form the new recommendations were around confirming a diagnosis of Sjögren disease, such as what is the diagnostic accuracy of antinuclear antibodies (ANAs), extractable nuclear antigens (ENAs), and other novel antigens in Sjögren disease? And what is the diagnostic accuracy of salivary gland ultrasound, imaging in general, and salivary gland or lacrimal gland biopsies? 

The resulting recommendations advised not to measure ANAs in the absence of clinical indicators of Sjögren disease or any other connective tissue disease but to use it to screen if there was a clinical suspicion. And ENAs should be measured even if the ANAs were negative and there is a high index of suspicion. 

In terms of imaging, ultrasound of the salivary glands was thought to be useful, but other imaging was not recommended for routine practice at the current time. Minor lip but not lacrimal gland biopsies were recommended if clinical and serologic features were not enough to make a diagnosis.
 

Lymphoma Worries

The 2017 version of the guideline did not include information about lymphoma, but this is the thing that most patients with Sjögren disease will worry about, Dr. Price said. “They all look it up on YouTube, they all come back and tell me that they are really worried they’ll develop it.”

The question that was therefore posed was whether there were any measurable biomarkers that could predict the development of lymphoma in adults and children. Seven predictors were found, the strongest being a low level of complement C4 alone or together with low levels of C3. Other predictors were salivary gland enlargement, lymphadenopathy, anti-Ro/La and rheumatoid factor autoantibodies, cryoglobulinemia, monoclonal gammopathy, and a high focus score. 

All of these predictors put someone in a higher risk category for lymphoma. If two or fewer of those features are present, the lifetime risk is “probably below 2%,” Dr. Price said. However, if all seven are present, the lifetime risk is “approaching 100%.”

The recommendation made on the basis of these findings is that people with Sjögren disease need to be offered early further investigation if they present with any new salivary gland swelling or other symptoms that might suggest the development of lymphoma. In this regard, a labial salivary gland biopsy might provide additional prognostic information.
 

‘Do the Little Things Well’

“You have to do the little things well,” Dr. Price said. “Many of the patients [who] come to see me for a second opinion have not been prescribed the right eye drops, have not been given advice on dental care,” with their management taking “too much on the rheumatological treatments.”

Rheumatologists are of course not trained or expected to be experts in ophthalmology or dentistry, but “you need to look at their mouth and you do need to examine their eyes, and you do need to give them some advice,” Dr. Price advised.

Thankfully, that is where the updated guidelines should help, with a recommendation that people with Sjögren disease should use preservative-free eye drops every 2-3 hours.

“It’s vital you avoid preservatives, because preservatives flatten the corneal surface and reduce the surface area and can cause inflammation in their own right,” Dr. Price cautioned, adding that there are plenty of suitable eye drop formulations available. 

In regard to helping with dry mouth symptoms, the recommendation is to use a saliva substitute for symptomatic relief. For vaginal dryness, the recommendation is to consider advising topical nonhormonal vaginal moisturizers plus estrogen creams or pessaries in peri- or postmenopausal women with significant vaginal dryness. 

“Very important, however, is to maintain a neutral pH, an alkaline environment in the mouth because acid damages dental enamel,” Dr. Price said. Conversely, an acidic vaginal moisturizer is needed to treat vaginal dryness. 

Dental hygiene is important. Regular brushing with a fluoride-based toothpaste is advised. The use of xylitol-containing products has been shown to reduce bacteria known to increase the risk for dental decay. Telling patients not to eat between meals is also simple but important advice. 

“We do recommend that patients are assessed holistically,” Dr. Price said, noting that they should be offered access to cognitive-behavioral therapy and exercise therapies to help with the symptoms of fatigue and joint pain.
 

Watch Out for Comorbidities

Sjögren disease is associated with many comorbidities, some of which might be predicted from the age and demographics of the people who are normally affected. 

“This is on the whole an older, female population, so you see a lot of osteoarthritis, gastroesophageal reflux, and hypertension,” Dr. Price said. “However, you may not be aware that 1 in 5 of these patients develop thyroid disease,” and there is a higher rate of celiac disease and primary biliary cholangitis than is seen in the general background population. 

The recommendation, therefore, is to “be aware of and consider screening for commonly associated conditions, as guided by age and/or clinical presentation.” As such, it’s recommended that baseline and repeated investigations that look for signs of comorbidity are performed, such as thyroid function assessment and liver function tests, to name two.
 

Treatment Recommendations

As in the original guideline, the treatment of systemic disease is discussed, but the advice has been overhauled with the availability of new data. 

The updated guidance notes that a trial of hydroxychloroquine for 6-12 months is the recommended treatment approach for people with fatigue and systemic symptoms. 

Systemic steroids may be used in the short-term for specific indications but should not be offered routinely. 

Conventional immunosuppressive or biologic drugs and immunoglobulins are not currently recommended outside of managing specific systemic complications.

In juvenile cases, the treatment of recurrent swollen parotid glands that are not due to infection or stone disease should include a short course of a nonsteroidal anti-inflammatory drug or a short course of oral steroids. This should be combined with massage followed by washouts with saline or steroids. In refractory cases, escalation to anti–B-cell–targeted therapies may be considered in select situations.
 

View on Updates

Patient advocate Bridget Crampton, who leads the helpline team at Sjögren’s UK (formerly the British Sjögren’s Syndrome Association), commented on the importance of the guidelines during a roundtable held by the BSR. 

“I think it will help [patients] make better use of their own appointments. So, they’ll know what treatments might be offered. They’ll know what they want to talk about at their appointments,” she said. 

Ms. Crampton, who has lived with Sjögren disease herself for the past 20 years, added: “I think it’s important for patients that we have guidelines like this. It means that all clinicians can easily access information. My hope is that it might standardize care across the UK a little bit more.” 

No specific funding was received to create the guidelines, be that from any bodies in the public, commercial, or not-for-profit sectors. No conflicts of interests were expressed by any of the experts quoted in this article.

A version of this article appeared on Medscape.com.

LIVERPOOL, ENGLAND — An updated guideline from the British Society for Rheumatology (BSR) on the management of Sjögren disease asks rheumatologists and other clinicians caring for patients with the condition to “do the little things well” rather than overly focusing on rheumatologic treatments. The guideline’s new format provides recommendations for specific clinical questions and now also includes recommendations for managing the disease in children and adolescents. 

“The original guideline was published in 2017, and things move on very rapidly,” consultant rheumatologist Elizabeth Price, MBBCh, PhD, said ahead of her presentation of the updated guideline at the annual meeting of the British Society for Rheumatology.

Sara Freeman/Medscape Medical News

What’s in a Name?

The BSR guideline on the management of adult and juvenile onset Sjögren disease is published in Rheumatology and is available via the BSR website, where it is accompanied by a short summary sheet. 

The most notable change perhaps is the name the guideline now uses, Dr. Price said at BSR 2024. “We have been bold and called it Sjögren disease.” Previously, the guideline used the term primary Sjögren’s syndrome, but there has been a “move away from using eponymous syndromes and dropping s’s and apostrophes,” she explained. 

Another significant change is that advice on managing Sjögren disease in children and adolescents is now included where appropriate, meaning that the British guideline is now the first to cover Sjögren disease “across the ages,” Dr. Price said.

A pediatric/adolescent rheumatologist joined the guideline working group, which already consisted of several adult rheumatologists, ophthalmologists, and a dentistry consultant. The group now comprises 22 members total, including a general practitioner, an oncologist, a renal physician, an occupational therapist, two patients with Sjögren disease, and a librarian.
 

Confirming the Diagnosis

The first questions asked to help form the new recommendations were around confirming a diagnosis of Sjögren disease, such as what is the diagnostic accuracy of antinuclear antibodies (ANAs), extractable nuclear antigens (ENAs), and other novel antigens in Sjögren disease? And what is the diagnostic accuracy of salivary gland ultrasound, imaging in general, and salivary gland or lacrimal gland biopsies? 

The resulting recommendations advised not to measure ANAs in the absence of clinical indicators of Sjögren disease or any other connective tissue disease but to use it to screen if there was a clinical suspicion. And ENAs should be measured even if the ANAs were negative and there is a high index of suspicion. 

In terms of imaging, ultrasound of the salivary glands was thought to be useful, but other imaging was not recommended for routine practice at the current time. Minor lip but not lacrimal gland biopsies were recommended if clinical and serologic features were not enough to make a diagnosis.
 

Lymphoma Worries

The 2017 version of the guideline did not include information about lymphoma, but this is the thing that most patients with Sjögren disease will worry about, Dr. Price said. “They all look it up on YouTube, they all come back and tell me that they are really worried they’ll develop it.”

The question that was therefore posed was whether there were any measurable biomarkers that could predict the development of lymphoma in adults and children. Seven predictors were found, the strongest being a low level of complement C4 alone or together with low levels of C3. Other predictors were salivary gland enlargement, lymphadenopathy, anti-Ro/La and rheumatoid factor autoantibodies, cryoglobulinemia, monoclonal gammopathy, and a high focus score. 

All of these predictors put someone in a higher risk category for lymphoma. If two or fewer of those features are present, the lifetime risk is “probably below 2%,” Dr. Price said. However, if all seven are present, the lifetime risk is “approaching 100%.”

The recommendation made on the basis of these findings is that people with Sjögren disease need to be offered early further investigation if they present with any new salivary gland swelling or other symptoms that might suggest the development of lymphoma. In this regard, a labial salivary gland biopsy might provide additional prognostic information.
 

‘Do the Little Things Well’

“You have to do the little things well,” Dr. Price said. “Many of the patients [who] come to see me for a second opinion have not been prescribed the right eye drops, have not been given advice on dental care,” with their management taking “too much on the rheumatological treatments.”

Rheumatologists are of course not trained or expected to be experts in ophthalmology or dentistry, but “you need to look at their mouth and you do need to examine their eyes, and you do need to give them some advice,” Dr. Price advised.

Thankfully, that is where the updated guidelines should help, with a recommendation that people with Sjögren disease should use preservative-free eye drops every 2-3 hours.

“It’s vital you avoid preservatives, because preservatives flatten the corneal surface and reduce the surface area and can cause inflammation in their own right,” Dr. Price cautioned, adding that there are plenty of suitable eye drop formulations available. 

In regard to helping with dry mouth symptoms, the recommendation is to use a saliva substitute for symptomatic relief. For vaginal dryness, the recommendation is to consider advising topical nonhormonal vaginal moisturizers plus estrogen creams or pessaries in peri- or postmenopausal women with significant vaginal dryness. 

“Very important, however, is to maintain a neutral pH, an alkaline environment in the mouth because acid damages dental enamel,” Dr. Price said. Conversely, an acidic vaginal moisturizer is needed to treat vaginal dryness. 

Dental hygiene is important. Regular brushing with a fluoride-based toothpaste is advised. The use of xylitol-containing products has been shown to reduce bacteria known to increase the risk for dental decay. Telling patients not to eat between meals is also simple but important advice. 

“We do recommend that patients are assessed holistically,” Dr. Price said, noting that they should be offered access to cognitive-behavioral therapy and exercise therapies to help with the symptoms of fatigue and joint pain.
 

Watch Out for Comorbidities

Sjögren disease is associated with many comorbidities, some of which might be predicted from the age and demographics of the people who are normally affected. 

“This is on the whole an older, female population, so you see a lot of osteoarthritis, gastroesophageal reflux, and hypertension,” Dr. Price said. “However, you may not be aware that 1 in 5 of these patients develop thyroid disease,” and there is a higher rate of celiac disease and primary biliary cholangitis than is seen in the general background population. 

The recommendation, therefore, is to “be aware of and consider screening for commonly associated conditions, as guided by age and/or clinical presentation.” As such, it’s recommended that baseline and repeated investigations that look for signs of comorbidity are performed, such as thyroid function assessment and liver function tests, to name two.
 

Treatment Recommendations

As in the original guideline, the treatment of systemic disease is discussed, but the advice has been overhauled with the availability of new data. 

The updated guidance notes that a trial of hydroxychloroquine for 6-12 months is the recommended treatment approach for people with fatigue and systemic symptoms. 

Systemic steroids may be used in the short-term for specific indications but should not be offered routinely. 

Conventional immunosuppressive or biologic drugs and immunoglobulins are not currently recommended outside of managing specific systemic complications.

In juvenile cases, the treatment of recurrent swollen parotid glands that are not due to infection or stone disease should include a short course of a nonsteroidal anti-inflammatory drug or a short course of oral steroids. This should be combined with massage followed by washouts with saline or steroids. In refractory cases, escalation to anti–B-cell–targeted therapies may be considered in select situations.
 

View on Updates

Patient advocate Bridget Crampton, who leads the helpline team at Sjögren’s UK (formerly the British Sjögren’s Syndrome Association), commented on the importance of the guidelines during a roundtable held by the BSR. 

“I think it will help [patients] make better use of their own appointments. So, they’ll know what treatments might be offered. They’ll know what they want to talk about at their appointments,” she said. 

Ms. Crampton, who has lived with Sjögren disease herself for the past 20 years, added: “I think it’s important for patients that we have guidelines like this. It means that all clinicians can easily access information. My hope is that it might standardize care across the UK a little bit more.” 

No specific funding was received to create the guidelines, be that from any bodies in the public, commercial, or not-for-profit sectors. No conflicts of interests were expressed by any of the experts quoted in this article.

A version of this article appeared on Medscape.com.