Rheumatology

VIENNA — Nipocalimab, iscalimab, and tibulizumab, but not lusvertikimab, appear to be promising new agents for Sjögren disease that warrant further investigation, suggest the results of four separate early clinical trials reported at the recent annual European Congress of Rheumatology (EULAR).

This is potentially good news for patients, as discovering new treatments that work for managing the various symptoms of Sjögren disease is a high priority, Jacques-Eric Gottenberg, MD, PhD, said when he presented the results of the phase 2 DAHLIAS study of nipocalimab during a late-breaking abstract session.

“All patients suffer from high burden of symptoms — pain, fatigue, and dryness; nearly 50% of patients have systemic complications; mortality is increased, so there is a high unmet need since no specific drug has been accepted so far,” said Dr. Gottenberg, who works at Strasbourg University Hospital in Strasbourg, France.

“The pathogenesis of the disease involves high B-cell activation, resulting in high IgG levels, and secretion of autoantibodies,” such as anti-Ro, anti-La, anti-Sjögren’s syndrome type A (anti-SSA), and anti-Sjögren’s syndrome type B antibodies, Dr. Gottenberg said.

Thus, one approach to reducing the disease burden is to try to lower circulating immunoglobulin G (IgG) levels and IgG-associated autoantibodies, which is how the monoclonal antibody nipocalimab works. Nipocalimab essentially blocks the interaction of IgG with the neonatal fragment crystallizable receptor and has already been shown to have efficacy in other autoimmune conditions such as myasthenia gravis and fetal and neonatal hemolytic disease, although not as hoped in rheumatoid arthritis.
 

The DAHLIAS Phase 2 Study

Now, results from the DAHLIAS study show that nipocalimab may also work in Sjögren disease, with significant improvement vs placebo seen in the primary endpoint of the total EULAR Sjögren’s Syndrome Disease Activity Index (clinESSDAI) at 24 weeks for one of the two doses of the drug that were tested.

The multicenter, placebo-controlled, double-blind study was conducted in 163 patients with moderate to severely active primary Sjögren disease. The latter was determined by having a clinESSDAI of 6 or higher and seropositivity for anti-Ro60, anti-Ro52, or both autoantibodies.

Dr. Gottenberg reported that the mean age of patients was 48 years; the majority (92.6%) were women and of White ethnicity (90.8%). The baseline clinESSDAI was a mean of 9.9; 98.1% had anti-Ro60, 80.6% had anti-Ro52, and 71.9% had anti-La antibodies.

In addition to standard of care, patients were randomly allocated to receive intravenous treatment every 2 weeks with nipocalimab 5 mg/kg or 15 mg/kg, or placebo.

At 24 weeks, the least squares mean (LSM) change in clinESSDAI from baseline was −3.74 for placebo, −4.08 for nipocalimab 5 mg/kg (P = not significant vs placebo), and −6.40 for nipocalimab 15 mg/kg (P = .02 vs placebo).

Nipocalimab 15 mg/kg also “demonstrated similar and consistent trends in other key efficacy endpoints,” Dr. Gottenberg said. This included improvements in the ESSDAI and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and composite measures such as the Sjögren’s Tool for Assessing Response (STAR), Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS), and the Disease Activity Level. There were also improvements in the unstimulated salivary flow rate.

Safety findings showed no new concerns, with adverse events reported in 62.5% of placebo-treated patients and by 79.2% and 79.6% of patients receiving nipocalimab 5 mg/kg and 15 mg/kg, respectively. Serious adverse events were reported in a respective 5.4%, 7.5%, and 7.4%, including severe infections or infections requiring intravenous anti-infectives in 1.8%, 3.8%, and 1.9% of participants, although none was thought to be related to the study treatment. No opportunistic infections or any deaths were reported.

Thomas Schindler, PhD, senior clinical scientist at F. Hoffmann-La Roche Ltd., in Basel, Switzerland, commented from the audience: “This was a very impressive set of results, and I’m very surprised that its safety profile is so benign.”

Dr. Schindler wanted to know if there were any changes in the serum albumin level and if this manifested as any laboratory abnormalities, but there were no reported cases of severe hypoalbuminemia in the study.
 

The TWINSS Phase 2 Study

Similarly hopeful results were reported for iscalimab, a fully human IgG1 anti-CD40 monoclonal antibody that is given by subcutaneous injection, during a clinical abstracts session. Xavier Mariette, MD, PhD, head of the Rheumatology Department at Bicêtre Hospital, Paris-Saclay University in Paris, France, reported updated results of the phase 2b dose-ranging TWINSS study, showing sustained benefits at 48 weeks. The primary endpoint results at 24 weeks were recently published in The Lancet.

TWINSS was set up to assess the safety and efficacy of iscalimab given every 2 weeks vs placebo in two distinct cohorts of patients with Sjögren disease — one with moderate to severe disease with both systemic and symptomatic involvement and the other with low systemic involvement but high symptom burden.

Whereas patients in the first cohort who had moderate to severe disease (n = 173) were randomly allocated to one of three doses (150, 300, and 600 mg) of iscalimab or placebo for the initial 24 weeks, those in the second cohort (n = 100) were randomly allocated to a 600-mg dose or placebo. After the double-blind period ended, patients taking iscalimab continued on the dose they were taking for another 24 weeks, with those in the placebo arms switching to the 600-mg dose in cohort 1 and the 300-mg dose in cohort 2.

Topline results for those in cohort 1 with moderate to severe Sjögren disease were that the significant improvements in ESSDAI that had been seen at week 24 were maintained in those who continued iscalimab and improved in those who had switched from placebo.

LSM change from baseline in ESSDAI vs placebo at week 24 had been −3.0, −1.4, and −2.9 for the 150-, 300-, and 600-mg doses of iscalimab, respectively. Results at week 48 were a respective −7.6, −5.7, and −7.9. The LSM change for the placebo-treated patients who had switched to the 600-mg dose was −6.7.

Dr. Mariette reported “consistent improvement” in patient-reported outcomes, including ESSPRI, the Sjögren’s Syndrome Symptom Diary, Functional Assessment of Chronic Illness Therapy-Fatigue measure, and the Impact of Dry Eye on Everyday Life instrument. There was also a significant improvement in stimulated salivary flow rates.

Similar benefits were seen in the second cohort of patients who did not have systemic involvement but had a high burden of symptoms, with improved ESSPRI scores of a LSM change from baseline vs placebo of −2.29 for patients continuing iscalimab 600 mg treatment and −1.14 for those taking the 300-mg dose after being treated with placebo. Improvements were also seen in the other patient-reported outcomes used.

Regarding safety, Dr. Mariette reported that there were “no specific issues” seen in the patients who switched from placebo to iscalimab, either at the 300-mg or 600-mg dose. Any adverse event occurred in around 80% of placebo-treated patients and roughly 90% of those given iscalimab, and serious adverse events occurred in 11.4%, 14.3%, and 11.4% pf patients treated with iscalimab 150, 300, and 600 mg, and 4.9% of those given placebo and then 600 mg iscalimab.

“The safety seems equivalent to patients having received iscalimab from the beginning of the trial,” Dr. Mariette said, adding “the risk-benefit [analysis] seems positive in patients up to week 48.”
 

Phase 1 Trial of Tibulizumab

Further positive early trial results were reported by Michael Howell, PhD, chief scientific officer for Zura Bio, a biotech company based in Henderson, Nevada. During a poster tour at EULAR 2024, Dr. Howell presented some preliminary findings from a phase 1 trial of tibulizumab, a dual antagonist of interleukin (IL)-17A and the B-cell–activating factor (BAFF) engineered by fusing elements of ixekizumab (Taltz) and tabalumab together.

“The headline result for me is that the molecule does what it’s supposed to,” Dr. Howell told this news organization. “We have potent engagement of the IL-17 and BAFF pathways, and this sets the tone for additional exploration in rheumatologic diseases where there’s known activation of those two pathways,” he said.

Dr. Howell reported that total B-cell counts and lower levels of type 1 T helper cells were seen during the trial.

Over the years, Dr. Howell, an immunologist, has been involved in the development of many therapeutics, such as risankizumab (Skyrizi) and spesolimab (Spevigo).

“When I look at the molecules and the opportunity we have to do broader antagonism of pathways in a safe aspect, this is probably one of the most exciting,” he said.

The trial he presented included 25 people with a confirmed diagnosis of Sjögren disease and anti-SSA or anti-SSB antibodies. Patients received tibulizumab or a placebo for a total of 12 weeks via a subcutaneous injection. Various doses were tested: 30 mg, 100 mg, or 300 mg every 4 weeks, or 300 mg every 2 weeks.

Serum levels of both BAFF and IL-17A increased as expected in the tibulizumab-treated patients, and Dr. Howell reported that “it’s well tolerated. There’s no adverse event profile that caused any concern.”

As a phase 1 study, it was not powered to look at efficacy, but there were positive signals, Dr. Howell said, meaning that the drug is likely to be tested further in a phase 2 trial.
 

Lusvertikimab Phase 2 Trial

During the same poster tour, the null findings of a phase 2 trial of the anti-IL-7 monoclonal antibody lusvertikimab were presented by Benjamin Fisher, MD, professor of rheumatology at Birmingham University in Birmingham, England.

Dr. Fisher told this news organization: “It’s a negative study, at least over the 3-month period that we’ve studied it.” Whether longer durations of treatment may be needed is a question that currently cannot be answered, he added.

A total of 48 patients with Sjögren disease had been included in the trial from 19 different centers in Europe, the United States, and Australia. The mean age of the participants was 53.7 years, 87% were women, and the mean duration of disease was 5.0 years. Baseline ESSDAI and ESSPRI were 12.1 and 7.0, respectively. Half were receiving other background treatment, and 72.9% were anti-Ro or anti-SSA positive.

Lusvertikimab 750 mg or a matching placebo was given via intravenous infusion at weeks 0, 2, 4, 7, and 10.

The primary endpoint was the mean change in ESSDAI from baseline to week 13, which was the same, at −3.9, in both groups. There was also no significant difference between the groups in any of the other secondary endpoints that were used, including ESSPRI, Schirmer’s test, the ocular staining score, salivary flow rate, physician and patient global assessment, assessment of fatigue, quality of life, or the composite measures STAR and CRESS.

“This isn’t going anywhere,” said Dr. Fisher, asking what was going to happen next and if this meant the end of IL-7-focused therapy.

“For years, there’s been quite a lot of interest in this,” Dr. Fisher said. Sjögren disease is characterized by a sort of focal inflammation of the saliva glands, which is composed of both T and B cells in the early stages, probably a T-cell component and a B-cell component, he explained.

“IL-7 is thought to be an important cytokine for homeostasis of the T-cell compartment, so for maintenance of T central memory and effector memory cells,” he said. “So, the idea is that, if you block IL-7, you switch off T cells, and you may rebalance the immune system towards a more regulatory phenotype. Just that it didn’t work,” Dr. Fisher said.

“There’s large unmet need,” he said. “Sjögren’s is associated with poor health-related quality of life, [and] a large part that is symptom-driven — dryness and fatigue — which we have no real interventions yet for patients; there’s no licensed therapeutics for it.”

Dr. Fisher cited ianalumab as one of the front-runners for becoming the first licensed treatment for Sjögren disease. The novel BAFF-targeting antibody is already in phase 3 trials and is also showing promise for the treatment of systemic lupus erythematosus.

“Then there are CD40-targeting drugs; the ones most advanced are dazodalibep and iscalimab.” Commenting on the potential of iscalimab, Dr. Fisher said that it “seems to work — it improves systemic disease activity; it also leads to some symptomatic improvement, which has been difficult to demonstrate in Sjögren’s.”

Dr. Fisher added that “the nipocalimab data looks interesting, as do data on TYK2 inhibition.”

The DAHLIAS study was funded by Janssen Research & Development. Dr. Gottenberg has consulted for AbbVie, Bristol Myers Squibb (BMS), Galapagos, Gilead, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and UCB. The TWINSS study was funded by Novartis. Dr. Mariette has consulted for BMS, Galapagos, GlaxoSmithKline, Novartis, Pfizer, and Servier. The tibulizumab phase 1 study was funded by Eli Lilly & Company. Dr. Howell is an employee of the developer, Zura Bio. The Institut de Recherches Internationales Servier sponsored the lusvertikimab trial. Dr. Fisher has consulted for Novartis, Roche, BMS, Galapagos, Janssen, Servier, UCB, and Sanofi and received funding to his institution for collaborative research from Janssen, Celgene, Galapagos, and Servier.
 

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

VIENNA — Nipocalimab, iscalimab, and tibulizumab, but not lusvertikimab, appear to be promising new agents for Sjögren disease that warrant further investigation, suggest the results of four separate early clinical trials reported at the recent annual European Congress of Rheumatology (EULAR).

This is potentially good news for patients, as discovering new treatments that work for managing the various symptoms of Sjögren disease is a high priority, Jacques-Eric Gottenberg, MD, PhD, said when he presented the results of the phase 2 DAHLIAS study of nipocalimab during a late-breaking abstract session.

“All patients suffer from high burden of symptoms — pain, fatigue, and dryness; nearly 50% of patients have systemic complications; mortality is increased, so there is a high unmet need since no specific drug has been accepted so far,” said Dr. Gottenberg, who works at Strasbourg University Hospital in Strasbourg, France.

“The pathogenesis of the disease involves high B-cell activation, resulting in high IgG levels, and secretion of autoantibodies,” such as anti-Ro, anti-La, anti-Sjögren’s syndrome type A (anti-SSA), and anti-Sjögren’s syndrome type B antibodies, Dr. Gottenberg said.

Thus, one approach to reducing the disease burden is to try to lower circulating immunoglobulin G (IgG) levels and IgG-associated autoantibodies, which is how the monoclonal antibody nipocalimab works. Nipocalimab essentially blocks the interaction of IgG with the neonatal fragment crystallizable receptor and has already been shown to have efficacy in other autoimmune conditions such as myasthenia gravis and fetal and neonatal hemolytic disease, although not as hoped in rheumatoid arthritis.
 

The DAHLIAS Phase 2 Study

Now, results from the DAHLIAS study show that nipocalimab may also work in Sjögren disease, with significant improvement vs placebo seen in the primary endpoint of the total EULAR Sjögren’s Syndrome Disease Activity Index (clinESSDAI) at 24 weeks for one of the two doses of the drug that were tested.

The multicenter, placebo-controlled, double-blind study was conducted in 163 patients with moderate to severely active primary Sjögren disease. The latter was determined by having a clinESSDAI of 6 or higher and seropositivity for anti-Ro60, anti-Ro52, or both autoantibodies.

Dr. Gottenberg reported that the mean age of patients was 48 years; the majority (92.6%) were women and of White ethnicity (90.8%). The baseline clinESSDAI was a mean of 9.9; 98.1% had anti-Ro60, 80.6% had anti-Ro52, and 71.9% had anti-La antibodies.

In addition to standard of care, patients were randomly allocated to receive intravenous treatment every 2 weeks with nipocalimab 5 mg/kg or 15 mg/kg, or placebo.

At 24 weeks, the least squares mean (LSM) change in clinESSDAI from baseline was −3.74 for placebo, −4.08 for nipocalimab 5 mg/kg (P = not significant vs placebo), and −6.40 for nipocalimab 15 mg/kg (P = .02 vs placebo).

Nipocalimab 15 mg/kg also “demonstrated similar and consistent trends in other key efficacy endpoints,” Dr. Gottenberg said. This included improvements in the ESSDAI and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and composite measures such as the Sjögren’s Tool for Assessing Response (STAR), Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS), and the Disease Activity Level. There were also improvements in the unstimulated salivary flow rate.

Safety findings showed no new concerns, with adverse events reported in 62.5% of placebo-treated patients and by 79.2% and 79.6% of patients receiving nipocalimab 5 mg/kg and 15 mg/kg, respectively. Serious adverse events were reported in a respective 5.4%, 7.5%, and 7.4%, including severe infections or infections requiring intravenous anti-infectives in 1.8%, 3.8%, and 1.9% of participants, although none was thought to be related to the study treatment. No opportunistic infections or any deaths were reported.

Thomas Schindler, PhD, senior clinical scientist at F. Hoffmann-La Roche Ltd., in Basel, Switzerland, commented from the audience: “This was a very impressive set of results, and I’m very surprised that its safety profile is so benign.”

Dr. Schindler wanted to know if there were any changes in the serum albumin level and if this manifested as any laboratory abnormalities, but there were no reported cases of severe hypoalbuminemia in the study.
 

The TWINSS Phase 2 Study

Similarly hopeful results were reported for iscalimab, a fully human IgG1 anti-CD40 monoclonal antibody that is given by subcutaneous injection, during a clinical abstracts session. Xavier Mariette, MD, PhD, head of the Rheumatology Department at Bicêtre Hospital, Paris-Saclay University in Paris, France, reported updated results of the phase 2b dose-ranging TWINSS study, showing sustained benefits at 48 weeks. The primary endpoint results at 24 weeks were recently published in The Lancet.

TWINSS was set up to assess the safety and efficacy of iscalimab given every 2 weeks vs placebo in two distinct cohorts of patients with Sjögren disease — one with moderate to severe disease with both systemic and symptomatic involvement and the other with low systemic involvement but high symptom burden.

Whereas patients in the first cohort who had moderate to severe disease (n = 173) were randomly allocated to one of three doses (150, 300, and 600 mg) of iscalimab or placebo for the initial 24 weeks, those in the second cohort (n = 100) were randomly allocated to a 600-mg dose or placebo. After the double-blind period ended, patients taking iscalimab continued on the dose they were taking for another 24 weeks, with those in the placebo arms switching to the 600-mg dose in cohort 1 and the 300-mg dose in cohort 2.

Topline results for those in cohort 1 with moderate to severe Sjögren disease were that the significant improvements in ESSDAI that had been seen at week 24 were maintained in those who continued iscalimab and improved in those who had switched from placebo.

LSM change from baseline in ESSDAI vs placebo at week 24 had been −3.0, −1.4, and −2.9 for the 150-, 300-, and 600-mg doses of iscalimab, respectively. Results at week 48 were a respective −7.6, −5.7, and −7.9. The LSM change for the placebo-treated patients who had switched to the 600-mg dose was −6.7.

Dr. Mariette reported “consistent improvement” in patient-reported outcomes, including ESSPRI, the Sjögren’s Syndrome Symptom Diary, Functional Assessment of Chronic Illness Therapy-Fatigue measure, and the Impact of Dry Eye on Everyday Life instrument. There was also a significant improvement in stimulated salivary flow rates.

Similar benefits were seen in the second cohort of patients who did not have systemic involvement but had a high burden of symptoms, with improved ESSPRI scores of a LSM change from baseline vs placebo of −2.29 for patients continuing iscalimab 600 mg treatment and −1.14 for those taking the 300-mg dose after being treated with placebo. Improvements were also seen in the other patient-reported outcomes used.

Regarding safety, Dr. Mariette reported that there were “no specific issues” seen in the patients who switched from placebo to iscalimab, either at the 300-mg or 600-mg dose. Any adverse event occurred in around 80% of placebo-treated patients and roughly 90% of those given iscalimab, and serious adverse events occurred in 11.4%, 14.3%, and 11.4% pf patients treated with iscalimab 150, 300, and 600 mg, and 4.9% of those given placebo and then 600 mg iscalimab.

“The safety seems equivalent to patients having received iscalimab from the beginning of the trial,” Dr. Mariette said, adding “the risk-benefit [analysis] seems positive in patients up to week 48.”
 

Phase 1 Trial of Tibulizumab

Further positive early trial results were reported by Michael Howell, PhD, chief scientific officer for Zura Bio, a biotech company based in Henderson, Nevada. During a poster tour at EULAR 2024, Dr. Howell presented some preliminary findings from a phase 1 trial of tibulizumab, a dual antagonist of interleukin (IL)-17A and the B-cell–activating factor (BAFF) engineered by fusing elements of ixekizumab (Taltz) and tabalumab together.

“The headline result for me is that the molecule does what it’s supposed to,” Dr. Howell told this news organization. “We have potent engagement of the IL-17 and BAFF pathways, and this sets the tone for additional exploration in rheumatologic diseases where there’s known activation of those two pathways,” he said.

Dr. Howell reported that total B-cell counts and lower levels of type 1 T helper cells were seen during the trial.

Over the years, Dr. Howell, an immunologist, has been involved in the development of many therapeutics, such as risankizumab (Skyrizi) and spesolimab (Spevigo).

“When I look at the molecules and the opportunity we have to do broader antagonism of pathways in a safe aspect, this is probably one of the most exciting,” he said.

The trial he presented included 25 people with a confirmed diagnosis of Sjögren disease and anti-SSA or anti-SSB antibodies. Patients received tibulizumab or a placebo for a total of 12 weeks via a subcutaneous injection. Various doses were tested: 30 mg, 100 mg, or 300 mg every 4 weeks, or 300 mg every 2 weeks.

Serum levels of both BAFF and IL-17A increased as expected in the tibulizumab-treated patients, and Dr. Howell reported that “it’s well tolerated. There’s no adverse event profile that caused any concern.”

As a phase 1 study, it was not powered to look at efficacy, but there were positive signals, Dr. Howell said, meaning that the drug is likely to be tested further in a phase 2 trial.
 

Lusvertikimab Phase 2 Trial

During the same poster tour, the null findings of a phase 2 trial of the anti-IL-7 monoclonal antibody lusvertikimab were presented by Benjamin Fisher, MD, professor of rheumatology at Birmingham University in Birmingham, England.

Dr. Fisher told this news organization: “It’s a negative study, at least over the 3-month period that we’ve studied it.” Whether longer durations of treatment may be needed is a question that currently cannot be answered, he added.

A total of 48 patients with Sjögren disease had been included in the trial from 19 different centers in Europe, the United States, and Australia. The mean age of the participants was 53.7 years, 87% were women, and the mean duration of disease was 5.0 years. Baseline ESSDAI and ESSPRI were 12.1 and 7.0, respectively. Half were receiving other background treatment, and 72.9% were anti-Ro or anti-SSA positive.

Lusvertikimab 750 mg or a matching placebo was given via intravenous infusion at weeks 0, 2, 4, 7, and 10.

The primary endpoint was the mean change in ESSDAI from baseline to week 13, which was the same, at −3.9, in both groups. There was also no significant difference between the groups in any of the other secondary endpoints that were used, including ESSPRI, Schirmer’s test, the ocular staining score, salivary flow rate, physician and patient global assessment, assessment of fatigue, quality of life, or the composite measures STAR and CRESS.

“This isn’t going anywhere,” said Dr. Fisher, asking what was going to happen next and if this meant the end of IL-7-focused therapy.

“For years, there’s been quite a lot of interest in this,” Dr. Fisher said. Sjögren disease is characterized by a sort of focal inflammation of the saliva glands, which is composed of both T and B cells in the early stages, probably a T-cell component and a B-cell component, he explained.

“IL-7 is thought to be an important cytokine for homeostasis of the T-cell compartment, so for maintenance of T central memory and effector memory cells,” he said. “So, the idea is that, if you block IL-7, you switch off T cells, and you may rebalance the immune system towards a more regulatory phenotype. Just that it didn’t work,” Dr. Fisher said.

“There’s large unmet need,” he said. “Sjögren’s is associated with poor health-related quality of life, [and] a large part that is symptom-driven — dryness and fatigue — which we have no real interventions yet for patients; there’s no licensed therapeutics for it.”

Dr. Fisher cited ianalumab as one of the front-runners for becoming the first licensed treatment for Sjögren disease. The novel BAFF-targeting antibody is already in phase 3 trials and is also showing promise for the treatment of systemic lupus erythematosus.

“Then there are CD40-targeting drugs; the ones most advanced are dazodalibep and iscalimab.” Commenting on the potential of iscalimab, Dr. Fisher said that it “seems to work — it improves systemic disease activity; it also leads to some symptomatic improvement, which has been difficult to demonstrate in Sjögren’s.”

Dr. Fisher added that “the nipocalimab data looks interesting, as do data on TYK2 inhibition.”

The DAHLIAS study was funded by Janssen Research & Development. Dr. Gottenberg has consulted for AbbVie, Bristol Myers Squibb (BMS), Galapagos, Gilead, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and UCB. The TWINSS study was funded by Novartis. Dr. Mariette has consulted for BMS, Galapagos, GlaxoSmithKline, Novartis, Pfizer, and Servier. The tibulizumab phase 1 study was funded by Eli Lilly & Company. Dr. Howell is an employee of the developer, Zura Bio. The Institut de Recherches Internationales Servier sponsored the lusvertikimab trial. Dr. Fisher has consulted for Novartis, Roche, BMS, Galapagos, Janssen, Servier, UCB, and Sanofi and received funding to his institution for collaborative research from Janssen, Celgene, Galapagos, and Servier.
 

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

VIENNA — Nipocalimab, iscalimab, and tibulizumab, but not lusvertikimab, appear to be promising new agents for Sjögren disease that warrant further investigation, suggest the results of four separate early clinical trials reported at the recent annual European Congress of Rheumatology (EULAR).

This is potentially good news for patients, as discovering new treatments that work for managing the various symptoms of Sjögren disease is a high priority, Jacques-Eric Gottenberg, MD, PhD, said when he presented the results of the phase 2 DAHLIAS study of nipocalimab during a late-breaking abstract session.

“All patients suffer from high burden of symptoms — pain, fatigue, and dryness; nearly 50% of patients have systemic complications; mortality is increased, so there is a high unmet need since no specific drug has been accepted so far,” said Dr. Gottenberg, who works at Strasbourg University Hospital in Strasbourg, France.

“The pathogenesis of the disease involves high B-cell activation, resulting in high IgG levels, and secretion of autoantibodies,” such as anti-Ro, anti-La, anti-Sjögren’s syndrome type A (anti-SSA), and anti-Sjögren’s syndrome type B antibodies, Dr. Gottenberg said.

Thus, one approach to reducing the disease burden is to try to lower circulating immunoglobulin G (IgG) levels and IgG-associated autoantibodies, which is how the monoclonal antibody nipocalimab works. Nipocalimab essentially blocks the interaction of IgG with the neonatal fragment crystallizable receptor and has already been shown to have efficacy in other autoimmune conditions such as myasthenia gravis and fetal and neonatal hemolytic disease, although not as hoped in rheumatoid arthritis.
 

The DAHLIAS Phase 2 Study

Now, results from the DAHLIAS study show that nipocalimab may also work in Sjögren disease, with significant improvement vs placebo seen in the primary endpoint of the total EULAR Sjögren’s Syndrome Disease Activity Index (clinESSDAI) at 24 weeks for one of the two doses of the drug that were tested.

The multicenter, placebo-controlled, double-blind study was conducted in 163 patients with moderate to severely active primary Sjögren disease. The latter was determined by having a clinESSDAI of 6 or higher and seropositivity for anti-Ro60, anti-Ro52, or both autoantibodies.

Dr. Gottenberg reported that the mean age of patients was 48 years; the majority (92.6%) were women and of White ethnicity (90.8%). The baseline clinESSDAI was a mean of 9.9; 98.1% had anti-Ro60, 80.6% had anti-Ro52, and 71.9% had anti-La antibodies.

In addition to standard of care, patients were randomly allocated to receive intravenous treatment every 2 weeks with nipocalimab 5 mg/kg or 15 mg/kg, or placebo.

At 24 weeks, the least squares mean (LSM) change in clinESSDAI from baseline was −3.74 for placebo, −4.08 for nipocalimab 5 mg/kg (P = not significant vs placebo), and −6.40 for nipocalimab 15 mg/kg (P = .02 vs placebo).

Nipocalimab 15 mg/kg also “demonstrated similar and consistent trends in other key efficacy endpoints,” Dr. Gottenberg said. This included improvements in the ESSDAI and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) and composite measures such as the Sjögren’s Tool for Assessing Response (STAR), Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS), and the Disease Activity Level. There were also improvements in the unstimulated salivary flow rate.

Safety findings showed no new concerns, with adverse events reported in 62.5% of placebo-treated patients and by 79.2% and 79.6% of patients receiving nipocalimab 5 mg/kg and 15 mg/kg, respectively. Serious adverse events were reported in a respective 5.4%, 7.5%, and 7.4%, including severe infections or infections requiring intravenous anti-infectives in 1.8%, 3.8%, and 1.9% of participants, although none was thought to be related to the study treatment. No opportunistic infections or any deaths were reported.

Thomas Schindler, PhD, senior clinical scientist at F. Hoffmann-La Roche Ltd., in Basel, Switzerland, commented from the audience: “This was a very impressive set of results, and I’m very surprised that its safety profile is so benign.”

Dr. Schindler wanted to know if there were any changes in the serum albumin level and if this manifested as any laboratory abnormalities, but there were no reported cases of severe hypoalbuminemia in the study.
 

The TWINSS Phase 2 Study

Similarly hopeful results were reported for iscalimab, a fully human IgG1 anti-CD40 monoclonal antibody that is given by subcutaneous injection, during a clinical abstracts session. Xavier Mariette, MD, PhD, head of the Rheumatology Department at Bicêtre Hospital, Paris-Saclay University in Paris, France, reported updated results of the phase 2b dose-ranging TWINSS study, showing sustained benefits at 48 weeks. The primary endpoint results at 24 weeks were recently published in The Lancet.

TWINSS was set up to assess the safety and efficacy of iscalimab given every 2 weeks vs placebo in two distinct cohorts of patients with Sjögren disease — one with moderate to severe disease with both systemic and symptomatic involvement and the other with low systemic involvement but high symptom burden.

Whereas patients in the first cohort who had moderate to severe disease (n = 173) were randomly allocated to one of three doses (150, 300, and 600 mg) of iscalimab or placebo for the initial 24 weeks, those in the second cohort (n = 100) were randomly allocated to a 600-mg dose or placebo. After the double-blind period ended, patients taking iscalimab continued on the dose they were taking for another 24 weeks, with those in the placebo arms switching to the 600-mg dose in cohort 1 and the 300-mg dose in cohort 2.

Topline results for those in cohort 1 with moderate to severe Sjögren disease were that the significant improvements in ESSDAI that had been seen at week 24 were maintained in those who continued iscalimab and improved in those who had switched from placebo.

LSM change from baseline in ESSDAI vs placebo at week 24 had been −3.0, −1.4, and −2.9 for the 150-, 300-, and 600-mg doses of iscalimab, respectively. Results at week 48 were a respective −7.6, −5.7, and −7.9. The LSM change for the placebo-treated patients who had switched to the 600-mg dose was −6.7.

Dr. Mariette reported “consistent improvement” in patient-reported outcomes, including ESSPRI, the Sjögren’s Syndrome Symptom Diary, Functional Assessment of Chronic Illness Therapy-Fatigue measure, and the Impact of Dry Eye on Everyday Life instrument. There was also a significant improvement in stimulated salivary flow rates.

Similar benefits were seen in the second cohort of patients who did not have systemic involvement but had a high burden of symptoms, with improved ESSPRI scores of a LSM change from baseline vs placebo of −2.29 for patients continuing iscalimab 600 mg treatment and −1.14 for those taking the 300-mg dose after being treated with placebo. Improvements were also seen in the other patient-reported outcomes used.

Regarding safety, Dr. Mariette reported that there were “no specific issues” seen in the patients who switched from placebo to iscalimab, either at the 300-mg or 600-mg dose. Any adverse event occurred in around 80% of placebo-treated patients and roughly 90% of those given iscalimab, and serious adverse events occurred in 11.4%, 14.3%, and 11.4% pf patients treated with iscalimab 150, 300, and 600 mg, and 4.9% of those given placebo and then 600 mg iscalimab.

“The safety seems equivalent to patients having received iscalimab from the beginning of the trial,” Dr. Mariette said, adding “the risk-benefit [analysis] seems positive in patients up to week 48.”
 

Phase 1 Trial of Tibulizumab

Further positive early trial results were reported by Michael Howell, PhD, chief scientific officer for Zura Bio, a biotech company based in Henderson, Nevada. During a poster tour at EULAR 2024, Dr. Howell presented some preliminary findings from a phase 1 trial of tibulizumab, a dual antagonist of interleukin (IL)-17A and the B-cell–activating factor (BAFF) engineered by fusing elements of ixekizumab (Taltz) and tabalumab together.

“The headline result for me is that the molecule does what it’s supposed to,” Dr. Howell told this news organization. “We have potent engagement of the IL-17 and BAFF pathways, and this sets the tone for additional exploration in rheumatologic diseases where there’s known activation of those two pathways,” he said.

Dr. Howell reported that total B-cell counts and lower levels of type 1 T helper cells were seen during the trial.

Over the years, Dr. Howell, an immunologist, has been involved in the development of many therapeutics, such as risankizumab (Skyrizi) and spesolimab (Spevigo).

“When I look at the molecules and the opportunity we have to do broader antagonism of pathways in a safe aspect, this is probably one of the most exciting,” he said.

The trial he presented included 25 people with a confirmed diagnosis of Sjögren disease and anti-SSA or anti-SSB antibodies. Patients received tibulizumab or a placebo for a total of 12 weeks via a subcutaneous injection. Various doses were tested: 30 mg, 100 mg, or 300 mg every 4 weeks, or 300 mg every 2 weeks.

Serum levels of both BAFF and IL-17A increased as expected in the tibulizumab-treated patients, and Dr. Howell reported that “it’s well tolerated. There’s no adverse event profile that caused any concern.”

As a phase 1 study, it was not powered to look at efficacy, but there were positive signals, Dr. Howell said, meaning that the drug is likely to be tested further in a phase 2 trial.
 

Lusvertikimab Phase 2 Trial

During the same poster tour, the null findings of a phase 2 trial of the anti-IL-7 monoclonal antibody lusvertikimab were presented by Benjamin Fisher, MD, professor of rheumatology at Birmingham University in Birmingham, England.

Dr. Fisher told this news organization: “It’s a negative study, at least over the 3-month period that we’ve studied it.” Whether longer durations of treatment may be needed is a question that currently cannot be answered, he added.

A total of 48 patients with Sjögren disease had been included in the trial from 19 different centers in Europe, the United States, and Australia. The mean age of the participants was 53.7 years, 87% were women, and the mean duration of disease was 5.0 years. Baseline ESSDAI and ESSPRI were 12.1 and 7.0, respectively. Half were receiving other background treatment, and 72.9% were anti-Ro or anti-SSA positive.

Lusvertikimab 750 mg or a matching placebo was given via intravenous infusion at weeks 0, 2, 4, 7, and 10.

The primary endpoint was the mean change in ESSDAI from baseline to week 13, which was the same, at −3.9, in both groups. There was also no significant difference between the groups in any of the other secondary endpoints that were used, including ESSPRI, Schirmer’s test, the ocular staining score, salivary flow rate, physician and patient global assessment, assessment of fatigue, quality of life, or the composite measures STAR and CRESS.

“This isn’t going anywhere,” said Dr. Fisher, asking what was going to happen next and if this meant the end of IL-7-focused therapy.

“For years, there’s been quite a lot of interest in this,” Dr. Fisher said. Sjögren disease is characterized by a sort of focal inflammation of the saliva glands, which is composed of both T and B cells in the early stages, probably a T-cell component and a B-cell component, he explained.

“IL-7 is thought to be an important cytokine for homeostasis of the T-cell compartment, so for maintenance of T central memory and effector memory cells,” he said. “So, the idea is that, if you block IL-7, you switch off T cells, and you may rebalance the immune system towards a more regulatory phenotype. Just that it didn’t work,” Dr. Fisher said.

“There’s large unmet need,” he said. “Sjögren’s is associated with poor health-related quality of life, [and] a large part that is symptom-driven — dryness and fatigue — which we have no real interventions yet for patients; there’s no licensed therapeutics for it.”

Dr. Fisher cited ianalumab as one of the front-runners for becoming the first licensed treatment for Sjögren disease. The novel BAFF-targeting antibody is already in phase 3 trials and is also showing promise for the treatment of systemic lupus erythematosus.

“Then there are CD40-targeting drugs; the ones most advanced are dazodalibep and iscalimab.” Commenting on the potential of iscalimab, Dr. Fisher said that it “seems to work — it improves systemic disease activity; it also leads to some symptomatic improvement, which has been difficult to demonstrate in Sjögren’s.”

Dr. Fisher added that “the nipocalimab data looks interesting, as do data on TYK2 inhibition.”

The DAHLIAS study was funded by Janssen Research & Development. Dr. Gottenberg has consulted for AbbVie, Bristol Myers Squibb (BMS), Galapagos, Gilead, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and UCB. The TWINSS study was funded by Novartis. Dr. Mariette has consulted for BMS, Galapagos, GlaxoSmithKline, Novartis, Pfizer, and Servier. The tibulizumab phase 1 study was funded by Eli Lilly & Company. Dr. Howell is an employee of the developer, Zura Bio. The Institut de Recherches Internationales Servier sponsored the lusvertikimab trial. Dr. Fisher has consulted for Novartis, Roche, BMS, Galapagos, Janssen, Servier, UCB, and Sanofi and received funding to his institution for collaborative research from Janssen, Celgene, Galapagos, and Servier.
 

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

TOPLINE:

Chronic exposure to air pollutants such as fine particulate matter ≤ 2.5 μm in diameter (PM_2.5), particulate matter ≤ 10 μm in diameter (PM₁₀), nitrogen dioxide (NO₂), and nitrogen oxides (NO_X) increased the risk for systemic lupus erythematosus (SLE) onset. The risk was highest among those with high genetic risk and high air-pollution exposure. 

METHODOLOGY:

• Researchers prospectively investigated the association between long-term exposure to air pollutants and incident SLE in 459,815 participants from the UK Biobank.
• A land-use regression model was used to quantify the annual average air pollution concentrations, including PM_2.5, PM₁₀, NO₂, and NO_X.
• The genetic susceptibility to lupus was assessed using polygenic risk scores (PRS), and the participants were classified into low–, intermediate–, or high–genetic-risk groups based on the tertiles of PRS.
• The joint effect of air pollutants and genetic susceptibility to lupus on the risk for incident SLE was evaluated, with the reference group consisting of participants with a low genetic risk and low exposure to air pollution.

TAKEAWAY: 

• Over a median follow-up period of 11.77 years, 399 new cases of SLE were identified.
• The odds of developing SLE were higher among participants with high genetic risk than among those with low genetic risk (hazard ratio [HR], 3.45; P < .001 for trend).
• The risk for developing SLE was even higher among participants with a high genetic risk and high exposure to PM_2.5 (adjusted HR [aHR], 4.16; 95% CI, 2.67-6.49), PM₁₀ (aHR, 5.31; 95% CI, 3.30-8.55), NO₂ (aHR, 5.61; 95% CI, 3.45-9.13), and NO_X (aHR, 4.80; 95% CI, 3.00-7.66) than among with those with a low genetic risk and low exposure to air pollutants.

IN PRACTICE:

“Findings can inform the development of stricter air quality regulations to mitigate exposure to harmful pollutants, thereby reducing the risk of SLE,” the authors wrote. 

SOURCE:

The study was led by Meiqi Xing, MASc, Huazhong University of Science and Technology, Wuhan, China. It was published online in Arthritis & Rheumatology.

LIMITATIONS:

The study participants were enrolled voluntarily, which may have led to selection bias because they might have been healthier or more health conscious. The study did not consider the specific components of air pollutants, particularly particulate matter, which may have varying effects on the incidence of SLE. Other air pollutants such as ozone, sulfur dioxide, and carbon monoxide were not included in the analysis.

DISCLOSURES:

This study did not disclose any funding source. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Chronic exposure to air pollutants such as fine particulate matter ≤ 2.5 μm in diameter (PM_2.5), particulate matter ≤ 10 μm in diameter (PM₁₀), nitrogen dioxide (NO₂), and nitrogen oxides (NO_X) increased the risk for systemic lupus erythematosus (SLE) onset. The risk was highest among those with high genetic risk and high air-pollution exposure. 

METHODOLOGY:

• Researchers prospectively investigated the association between long-term exposure to air pollutants and incident SLE in 459,815 participants from the UK Biobank.
• A land-use regression model was used to quantify the annual average air pollution concentrations, including PM_2.5, PM₁₀, NO₂, and NO_X.
• The genetic susceptibility to lupus was assessed using polygenic risk scores (PRS), and the participants were classified into low–, intermediate–, or high–genetic-risk groups based on the tertiles of PRS.
• The joint effect of air pollutants and genetic susceptibility to lupus on the risk for incident SLE was evaluated, with the reference group consisting of participants with a low genetic risk and low exposure to air pollution.

TAKEAWAY: 

• Over a median follow-up period of 11.77 years, 399 new cases of SLE were identified.
• The odds of developing SLE were higher among participants with high genetic risk than among those with low genetic risk (hazard ratio [HR], 3.45; P < .001 for trend).
• The risk for developing SLE was even higher among participants with a high genetic risk and high exposure to PM_2.5 (adjusted HR [aHR], 4.16; 95% CI, 2.67-6.49), PM₁₀ (aHR, 5.31; 95% CI, 3.30-8.55), NO₂ (aHR, 5.61; 95% CI, 3.45-9.13), and NO_X (aHR, 4.80; 95% CI, 3.00-7.66) than among with those with a low genetic risk and low exposure to air pollutants.

IN PRACTICE:

“Findings can inform the development of stricter air quality regulations to mitigate exposure to harmful pollutants, thereby reducing the risk of SLE,” the authors wrote. 

SOURCE:

The study was led by Meiqi Xing, MASc, Huazhong University of Science and Technology, Wuhan, China. It was published online in Arthritis & Rheumatology.

LIMITATIONS:

The study participants were enrolled voluntarily, which may have led to selection bias because they might have been healthier or more health conscious. The study did not consider the specific components of air pollutants, particularly particulate matter, which may have varying effects on the incidence of SLE. Other air pollutants such as ozone, sulfur dioxide, and carbon monoxide were not included in the analysis.

DISCLOSURES:

This study did not disclose any funding source. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Chronic exposure to air pollutants such as fine particulate matter ≤ 2.5 μm in diameter (PM_2.5), particulate matter ≤ 10 μm in diameter (PM₁₀), nitrogen dioxide (NO₂), and nitrogen oxides (NO_X) increased the risk for systemic lupus erythematosus (SLE) onset. The risk was highest among those with high genetic risk and high air-pollution exposure. 

METHODOLOGY:

• Researchers prospectively investigated the association between long-term exposure to air pollutants and incident SLE in 459,815 participants from the UK Biobank.
• A land-use regression model was used to quantify the annual average air pollution concentrations, including PM_2.5, PM₁₀, NO₂, and NO_X.
• The genetic susceptibility to lupus was assessed using polygenic risk scores (PRS), and the participants were classified into low–, intermediate–, or high–genetic-risk groups based on the tertiles of PRS.
• The joint effect of air pollutants and genetic susceptibility to lupus on the risk for incident SLE was evaluated, with the reference group consisting of participants with a low genetic risk and low exposure to air pollution.

TAKEAWAY: 

• Over a median follow-up period of 11.77 years, 399 new cases of SLE were identified.
• The odds of developing SLE were higher among participants with high genetic risk than among those with low genetic risk (hazard ratio [HR], 3.45; P < .001 for trend).
• The risk for developing SLE was even higher among participants with a high genetic risk and high exposure to PM_2.5 (adjusted HR [aHR], 4.16; 95% CI, 2.67-6.49), PM₁₀ (aHR, 5.31; 95% CI, 3.30-8.55), NO₂ (aHR, 5.61; 95% CI, 3.45-9.13), and NO_X (aHR, 4.80; 95% CI, 3.00-7.66) than among with those with a low genetic risk and low exposure to air pollutants.

IN PRACTICE:

“Findings can inform the development of stricter air quality regulations to mitigate exposure to harmful pollutants, thereby reducing the risk of SLE,” the authors wrote. 

SOURCE:

The study was led by Meiqi Xing, MASc, Huazhong University of Science and Technology, Wuhan, China. It was published online in Arthritis & Rheumatology.

LIMITATIONS:

The study participants were enrolled voluntarily, which may have led to selection bias because they might have been healthier or more health conscious. The study did not consider the specific components of air pollutants, particularly particulate matter, which may have varying effects on the incidence of SLE. Other air pollutants such as ozone, sulfur dioxide, and carbon monoxide were not included in the analysis.

DISCLOSURES:

This study did not disclose any funding source. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

About 40% of patients with osteoarthritis (OA) and 36% with rheumatoid arthritis (RA) screened positive for anxiety, depression, and/or fibromyalgia as part of routine visits to an academic medical center, and these comorbidities were linked to poorer patient status measures, highlighting the need for routine screening in clinical practice. 

METHODOLOGY:

• This retrospective cross-sectional study analyzed the prevalence of anxiety, depression, and fibromyalgia in 366 patients with OA (mean age, 66.6 years) and 488 patients with RA (mean age, 56.9 years) who were in routine care at an academic center from 2011 to 2022.
• All participants were required to have complete Multidimensional Health Assessment Questionnaire (MDHAQ) data available for the analysis.
• The MDHAQ included indices to assess the overall patient status and screen for anxiety, depression, and fibromyalgia.
• The overall patient status was measured using the Routine Assessment of Patient Index Data 3 (RAPID3), which comprised the physical function, pain, and patient global scores.
• The prevalence of each comorbidity and its association with patient status was analyzed using unadjusted and age-adjusted odds ratios (ORs) and 95% CIs.

TAKEAWAY:

• Among the patients with OA, 40.4% were screened positive for at least one of the three indices indicating patient distress (anxiety, depression, and fibromyalgia). Among patients with RA, the proportion was 36.3%.
• Among the patients who screened positive for at least one index, about 20% screened positive for all three indices related to anxiety, depression, and fibromyalgia.
• In patients with OA, a poorer patient status (RAPID3, ≥ 12 vs < 12) increased the likelihood of anxiety (OR, 3.93; 95% CI, 2.24-7.23), depression (OR, 3.79; 95% CI, 2.01-7.73), and fibromyalgia (OR, 6.70; 95% CI, 3.36-14.99).
• Similarly, the odds of all three comorbidities increased in the patients with RA who had worsened patient status.

IN PRACTICE:

“Screening for [anxiety, depression, and/or fibromyalgia] can be incorporated feasibly into routine clinical care using a single MDHAQ to better inform health professionals concerning patient status, prognosis, and response to treatments,” the authors wrote.

SOURCE:

The study was led by Juan Schmukler, MD, Rush University Medical Center, Chicago, and was published online on July 16, 2024, in ACR Open Rheumatology. 

LIMITATIONS:

The analyses were cross-sectional, and whether anxiety, depression, and fibromyalgia had preceded or followed the onset of OA or RA was not known. Information on the clinical variables associated with anxiety, depression, and fibromyalgia, such as body mass index, medication history, and other comorbid conditions, was not available. All the patients were seen at a single rheumatology site, which may have limited the generalizability of the observations. 

DISCLOSURES:

This study did not disclose any sources of funding. One author disclosed receiving grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One author reported numerous financial relationships with companies in the medical industry, and another reported holding a copyright and trademark on MDHAQ and RAPID3. 

This article was created using several editorial tools, including AI, as a part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

About 40% of patients with osteoarthritis (OA) and 36% with rheumatoid arthritis (RA) screened positive for anxiety, depression, and/or fibromyalgia as part of routine visits to an academic medical center, and these comorbidities were linked to poorer patient status measures, highlighting the need for routine screening in clinical practice. 

METHODOLOGY:

• This retrospective cross-sectional study analyzed the prevalence of anxiety, depression, and fibromyalgia in 366 patients with OA (mean age, 66.6 years) and 488 patients with RA (mean age, 56.9 years) who were in routine care at an academic center from 2011 to 2022.
• All participants were required to have complete Multidimensional Health Assessment Questionnaire (MDHAQ) data available for the analysis.
• The MDHAQ included indices to assess the overall patient status and screen for anxiety, depression, and fibromyalgia.
• The overall patient status was measured using the Routine Assessment of Patient Index Data 3 (RAPID3), which comprised the physical function, pain, and patient global scores.
• The prevalence of each comorbidity and its association with patient status was analyzed using unadjusted and age-adjusted odds ratios (ORs) and 95% CIs.

TAKEAWAY:

• Among the patients with OA, 40.4% were screened positive for at least one of the three indices indicating patient distress (anxiety, depression, and fibromyalgia). Among patients with RA, the proportion was 36.3%.
• Among the patients who screened positive for at least one index, about 20% screened positive for all three indices related to anxiety, depression, and fibromyalgia.
• In patients with OA, a poorer patient status (RAPID3, ≥ 12 vs < 12) increased the likelihood of anxiety (OR, 3.93; 95% CI, 2.24-7.23), depression (OR, 3.79; 95% CI, 2.01-7.73), and fibromyalgia (OR, 6.70; 95% CI, 3.36-14.99).
• Similarly, the odds of all three comorbidities increased in the patients with RA who had worsened patient status.

IN PRACTICE:

“Screening for [anxiety, depression, and/or fibromyalgia] can be incorporated feasibly into routine clinical care using a single MDHAQ to better inform health professionals concerning patient status, prognosis, and response to treatments,” the authors wrote.

SOURCE:

The study was led by Juan Schmukler, MD, Rush University Medical Center, Chicago, and was published online on July 16, 2024, in ACR Open Rheumatology. 

LIMITATIONS:

The analyses were cross-sectional, and whether anxiety, depression, and fibromyalgia had preceded or followed the onset of OA or RA was not known. Information on the clinical variables associated with anxiety, depression, and fibromyalgia, such as body mass index, medication history, and other comorbid conditions, was not available. All the patients were seen at a single rheumatology site, which may have limited the generalizability of the observations. 

DISCLOSURES:

This study did not disclose any sources of funding. One author disclosed receiving grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One author reported numerous financial relationships with companies in the medical industry, and another reported holding a copyright and trademark on MDHAQ and RAPID3. 

This article was created using several editorial tools, including AI, as a part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

About 40% of patients with osteoarthritis (OA) and 36% with rheumatoid arthritis (RA) screened positive for anxiety, depression, and/or fibromyalgia as part of routine visits to an academic medical center, and these comorbidities were linked to poorer patient status measures, highlighting the need for routine screening in clinical practice. 

METHODOLOGY:

• This retrospective cross-sectional study analyzed the prevalence of anxiety, depression, and fibromyalgia in 366 patients with OA (mean age, 66.6 years) and 488 patients with RA (mean age, 56.9 years) who were in routine care at an academic center from 2011 to 2022.
• All participants were required to have complete Multidimensional Health Assessment Questionnaire (MDHAQ) data available for the analysis.
• The MDHAQ included indices to assess the overall patient status and screen for anxiety, depression, and fibromyalgia.
• The overall patient status was measured using the Routine Assessment of Patient Index Data 3 (RAPID3), which comprised the physical function, pain, and patient global scores.
• The prevalence of each comorbidity and its association with patient status was analyzed using unadjusted and age-adjusted odds ratios (ORs) and 95% CIs.

TAKEAWAY:

• Among the patients with OA, 40.4% were screened positive for at least one of the three indices indicating patient distress (anxiety, depression, and fibromyalgia). Among patients with RA, the proportion was 36.3%.
• Among the patients who screened positive for at least one index, about 20% screened positive for all three indices related to anxiety, depression, and fibromyalgia.
• In patients with OA, a poorer patient status (RAPID3, ≥ 12 vs < 12) increased the likelihood of anxiety (OR, 3.93; 95% CI, 2.24-7.23), depression (OR, 3.79; 95% CI, 2.01-7.73), and fibromyalgia (OR, 6.70; 95% CI, 3.36-14.99).
• Similarly, the odds of all three comorbidities increased in the patients with RA who had worsened patient status.

IN PRACTICE:

“Screening for [anxiety, depression, and/or fibromyalgia] can be incorporated feasibly into routine clinical care using a single MDHAQ to better inform health professionals concerning patient status, prognosis, and response to treatments,” the authors wrote.

SOURCE:

The study was led by Juan Schmukler, MD, Rush University Medical Center, Chicago, and was published online on July 16, 2024, in ACR Open Rheumatology. 

LIMITATIONS:

The analyses were cross-sectional, and whether anxiety, depression, and fibromyalgia had preceded or followed the onset of OA or RA was not known. Information on the clinical variables associated with anxiety, depression, and fibromyalgia, such as body mass index, medication history, and other comorbid conditions, was not available. All the patients were seen at a single rheumatology site, which may have limited the generalizability of the observations. 

DISCLOSURES:

This study did not disclose any sources of funding. One author disclosed receiving grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One author reported numerous financial relationships with companies in the medical industry, and another reported holding a copyright and trademark on MDHAQ and RAPID3. 

This article was created using several editorial tools, including AI, as a part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

More gastrointestinal and nervous symptom adverse events (AEs) are linked to apremilast than deucravacitinib, which is associated with more cutaneous AEs, according to a retrospective comparison using US Food and Drug Administration (FDA) data.

METHODOLOGY:

• To evaluate the adverse events associated with apremilast, an oral phosphodiesterase-4 (PDE4) inhibitor, and deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor, data were drawn from the FDA’s Adverse Event Reporting System database.
• The Medex_UIMA_1.8.3 system was used to standardize drug names, and MedDRA terminology was used to encode, categorize, and localize signals.
• AE event signals were grouped by skin and subcutaneous tissue disorders, gastrointestinal disorders, infections and infestations, and nervous system disorders.

TAKEAWAY:

• There were 95,734 AE reports for apremilast and 760 AE reports for deucravacitinib, and AEs were found to be significant over time.
• The more common cutaneous AEs were psoriasis recurrence and acne (associated with apremilast) and skin burning and erythema (associated with deucravacitinib).
• The more common gastrointestinal AEs were diarrhea and nausea (apremilast) and mouth ulceration (deucravacitinib).
• Deucravacitinib-related pruritus and rash, as well as apremilast-related tension headache, were more common in women than men; deucravacitinib-related skin burning was more common in men.

IN PRACTICE:

The results “can help the doctors to choose the right treatment options based on the baseline characteristics of different patients,” said Yuanyuan Xu, a graduate student in the Department of Dermatology, Sichuan University, Chengdu, China.

SOURCE:

Mr. Xu presented the study as a poster at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2024 annual meeting.

LIMITATIONS:

The study was retrospective and cannot prove causality, and there were far fewer AE reports related to deucravacitinib, likely because the drug was introduced more recently.

DISCLOSURES:

The study received no funding, and the authors had no relevant financial disclosures.

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

TOPLINE:

More gastrointestinal and nervous symptom adverse events (AEs) are linked to apremilast than deucravacitinib, which is associated with more cutaneous AEs, according to a retrospective comparison using US Food and Drug Administration (FDA) data.

METHODOLOGY:

• To evaluate the adverse events associated with apremilast, an oral phosphodiesterase-4 (PDE4) inhibitor, and deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor, data were drawn from the FDA’s Adverse Event Reporting System database.
• The Medex_UIMA_1.8.3 system was used to standardize drug names, and MedDRA terminology was used to encode, categorize, and localize signals.
• AE event signals were grouped by skin and subcutaneous tissue disorders, gastrointestinal disorders, infections and infestations, and nervous system disorders.

TAKEAWAY:

• There were 95,734 AE reports for apremilast and 760 AE reports for deucravacitinib, and AEs were found to be significant over time.
• The more common cutaneous AEs were psoriasis recurrence and acne (associated with apremilast) and skin burning and erythema (associated with deucravacitinib).
• The more common gastrointestinal AEs were diarrhea and nausea (apremilast) and mouth ulceration (deucravacitinib).
• Deucravacitinib-related pruritus and rash, as well as apremilast-related tension headache, were more common in women than men; deucravacitinib-related skin burning was more common in men.

IN PRACTICE:

The results “can help the doctors to choose the right treatment options based on the baseline characteristics of different patients,” said Yuanyuan Xu, a graduate student in the Department of Dermatology, Sichuan University, Chengdu, China.

SOURCE:

Mr. Xu presented the study as a poster at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2024 annual meeting.

LIMITATIONS:

The study was retrospective and cannot prove causality, and there were far fewer AE reports related to deucravacitinib, likely because the drug was introduced more recently.

DISCLOSURES:

The study received no funding, and the authors had no relevant financial disclosures.

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

TOPLINE:

More gastrointestinal and nervous symptom adverse events (AEs) are linked to apremilast than deucravacitinib, which is associated with more cutaneous AEs, according to a retrospective comparison using US Food and Drug Administration (FDA) data.

METHODOLOGY:

• To evaluate the adverse events associated with apremilast, an oral phosphodiesterase-4 (PDE4) inhibitor, and deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor, data were drawn from the FDA’s Adverse Event Reporting System database.
• The Medex_UIMA_1.8.3 system was used to standardize drug names, and MedDRA terminology was used to encode, categorize, and localize signals.
• AE event signals were grouped by skin and subcutaneous tissue disorders, gastrointestinal disorders, infections and infestations, and nervous system disorders.

TAKEAWAY:

• There were 95,734 AE reports for apremilast and 760 AE reports for deucravacitinib, and AEs were found to be significant over time.
• The more common cutaneous AEs were psoriasis recurrence and acne (associated with apremilast) and skin burning and erythema (associated with deucravacitinib).
• The more common gastrointestinal AEs were diarrhea and nausea (apremilast) and mouth ulceration (deucravacitinib).
• Deucravacitinib-related pruritus and rash, as well as apremilast-related tension headache, were more common in women than men; deucravacitinib-related skin burning was more common in men.

IN PRACTICE:

The results “can help the doctors to choose the right treatment options based on the baseline characteristics of different patients,” said Yuanyuan Xu, a graduate student in the Department of Dermatology, Sichuan University, Chengdu, China.

SOURCE:

Mr. Xu presented the study as a poster at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2024 annual meeting.

LIMITATIONS:

The study was retrospective and cannot prove causality, and there were far fewer AE reports related to deucravacitinib, likely because the drug was introduced more recently.

DISCLOSURES:

The study received no funding, and the authors had no relevant financial disclosures.

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

TOPLINE:

Rates of major adverse cardiovascular events (MACE) do not differ significantly among individual biologics used for psoriasis or psoriatic arthritis (PsA), a database analysis finds. 

METHODOLOGY:

• Data from the TriNetX health records database included 32,758 patients treated with TNF inhibitors (TNFi, 62.9%), interleukin-17 inhibitors (IL-17i, 15.4%), IL-23i (10.7%), and IL-12i/IL-23i (10.7%).
• The researchers calculated time-dependent risk for MACE using multinomial Cox proportional hazard ratios. The reference was TNFi exposure.
• Subset analyses compared MACE in patients with and without existing cardiovascular disease.

TAKEAWAY:

• Compared with TNFi use, there was no difference in the incidence of MACE events in the IL-17i, IL-23i, or IL-12i/IL-23i group.
• There were also no significant differences between biologic groups in the incidence of congestive heart failure, myocardial infarction, or cerebral vascular accident/stroke.

IN PRACTICE:

Despite some concern about increased risk for MACE with TNFi use, this study suggests no special risk for patients with psoriasis or PsA associated with TNFi vs other biologics. “Given our results, as it pertains to MACE, prescribers shouldn’t favor any one biologic class over another,” said lead investigator Shikha Singla, MD, medical director of the Psoriatic Arthritis Program at Medical College of Wisconsin in Milwaukee, Wisconsin.

SOURCE:

Bonit Gill, MD, a second-year fellow at Medical College of Wisconsin, presented the study as a poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. 

LIMITATIONS:

The study’s retrospective nature makes it impossible to prove causation and the patients included in the study were from Wisconsin, which may limit generalizability.

DISCLOSURES:

Dr. Gill had no relevant financial disclosures. Other study authors participated in trials or consulted for AbbVie, AstraZeneca, Novartis, Eli Lilly, Janssen, and UCB.

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

TOPLINE:

Rates of major adverse cardiovascular events (MACE) do not differ significantly among individual biologics used for psoriasis or psoriatic arthritis (PsA), a database analysis finds. 

METHODOLOGY:

• Data from the TriNetX health records database included 32,758 patients treated with TNF inhibitors (TNFi, 62.9%), interleukin-17 inhibitors (IL-17i, 15.4%), IL-23i (10.7%), and IL-12i/IL-23i (10.7%).
• The researchers calculated time-dependent risk for MACE using multinomial Cox proportional hazard ratios. The reference was TNFi exposure.
• Subset analyses compared MACE in patients with and without existing cardiovascular disease.

TAKEAWAY:

• Compared with TNFi use, there was no difference in the incidence of MACE events in the IL-17i, IL-23i, or IL-12i/IL-23i group.
• There were also no significant differences between biologic groups in the incidence of congestive heart failure, myocardial infarction, or cerebral vascular accident/stroke.

IN PRACTICE:

Despite some concern about increased risk for MACE with TNFi use, this study suggests no special risk for patients with psoriasis or PsA associated with TNFi vs other biologics. “Given our results, as it pertains to MACE, prescribers shouldn’t favor any one biologic class over another,” said lead investigator Shikha Singla, MD, medical director of the Psoriatic Arthritis Program at Medical College of Wisconsin in Milwaukee, Wisconsin.

SOURCE:

Bonit Gill, MD, a second-year fellow at Medical College of Wisconsin, presented the study as a poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. 

LIMITATIONS:

The study’s retrospective nature makes it impossible to prove causation and the patients included in the study were from Wisconsin, which may limit generalizability.

DISCLOSURES:

Dr. Gill had no relevant financial disclosures. Other study authors participated in trials or consulted for AbbVie, AstraZeneca, Novartis, Eli Lilly, Janssen, and UCB.

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

TOPLINE:

Rates of major adverse cardiovascular events (MACE) do not differ significantly among individual biologics used for psoriasis or psoriatic arthritis (PsA), a database analysis finds. 

METHODOLOGY:

• Data from the TriNetX health records database included 32,758 patients treated with TNF inhibitors (TNFi, 62.9%), interleukin-17 inhibitors (IL-17i, 15.4%), IL-23i (10.7%), and IL-12i/IL-23i (10.7%).
• The researchers calculated time-dependent risk for MACE using multinomial Cox proportional hazard ratios. The reference was TNFi exposure.
• Subset analyses compared MACE in patients with and without existing cardiovascular disease.

TAKEAWAY:

• Compared with TNFi use, there was no difference in the incidence of MACE events in the IL-17i, IL-23i, or IL-12i/IL-23i group.
• There were also no significant differences between biologic groups in the incidence of congestive heart failure, myocardial infarction, or cerebral vascular accident/stroke.

IN PRACTICE:

Despite some concern about increased risk for MACE with TNFi use, this study suggests no special risk for patients with psoriasis or PsA associated with TNFi vs other biologics. “Given our results, as it pertains to MACE, prescribers shouldn’t favor any one biologic class over another,” said lead investigator Shikha Singla, MD, medical director of the Psoriatic Arthritis Program at Medical College of Wisconsin in Milwaukee, Wisconsin.

SOURCE:

Bonit Gill, MD, a second-year fellow at Medical College of Wisconsin, presented the study as a poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. 

LIMITATIONS:

The study’s retrospective nature makes it impossible to prove causation and the patients included in the study were from Wisconsin, which may limit generalizability.

DISCLOSURES:

Dr. Gill had no relevant financial disclosures. Other study authors participated in trials or consulted for AbbVie, AstraZeneca, Novartis, Eli Lilly, Janssen, and UCB.

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

Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.

“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.

At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.

But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.

Sara Freeman/MDedge News

Societies Agree: Discontinue as Fast as Possible

GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.

Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.

Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.

Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.

The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.

EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.

For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.

EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.
 

Low-Dose Approach Gains Ground

While saying he’d be the first physician to eliminate GCs whenever possible, Dr. Buttgereit made the case before the EULAR Congress that GCs in low doses could still play a role in treatment.

Many physicians believe that very low doses between 2 and 4 mg/d are a realistic therapy option for RA, he said, adding that a mean daily usage < 5 mg could be used over a longer period with relatively low risk.

Several studies he coauthored tested the 5-mg approach. The GLORIA trial compared 5 mg/d prednisolone and placebo in 451 patients aged 65 years and older with active RA over the course of 2 years. The researchers found that patients on prednisolone had a mean Disease Activity Score in 28 joints (DAS28) that was 0.37 points lower and mean joint damage score that was 1.7 points lower than those of patients on placebo, suggesting that the GC had long-term benefits in these patients with RA.

The tradeoff was a 24% increase in the risk of having at least one adverse event of special interest, but most of these events were non-severe infections, Dr. Buttgereit said.

Another study, the SEMIRA trial, assigned 128 patients to a continued regimen of prednisone 5 mg/d for 24 weeks. Another group of 131 patients received a tapered-prednisone regimen. All patients received tocilizumab 162 mg with or without csDMARDs, maintained at stable doses.

Patients in the first cohort achieved superior disease activity control than those in the tapered regimen group. “The side effects showed that in the tapering prednisone group, there were more treatment-emergent adverse effects in this double-blind trial as compared to the continued prednisone group,” Dr. Buttgereit said.

One limitation of the SEMIRA trial was that it studied the effect of tocilizumab as a GC-sparing agent, and it didn’t consider using a tumor necrosis factor or Janus kinase (JAK) inhibitor, which might have a more potent effect on pain and GC dose reduction, Dr. Adami said. “Why do we need to use glucocorticoids if we know they might be detrimental, if we know there might be some other option in our armamentarium?”

Other studies have shown that low-dose GC protocols can be used with standard treatment, according to Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh School of Medicine.

“Examples of this are the LoVAS and PEXIVAS studies for antineutrophil cytoplasmic antibody-associated [ANCA] vasculitis. This has been highlighted in existing treatment recommendations for ANCA vasculitis and systemic lupus erythematosus nephritis,” Dr. Sattui said.

Debating the Toxicity Threshold

Are low GC dosages significantly associated with adverse events like mortality, cardiovascular, or diabetes risk? It depends on who you ask.

Much of the toxicity data on GCs come from inadequately powered or controlled studies and often refer to doses that currently are considered too high, Dr. Buttgereit said. His presentation highlighted a study from Hong Kong, a time-varying analysis of GC dose and incident risk for major adverse cardiovascular events (MACE) in more than 12,000 patients with RA. Researchers found that GC regimens ≥ 5 mg/d significantly increased the risk for MACE. Comparatively, doses below this threshold did not confer excessive risk, he said.

Low-dose GCs are lesser toxic than high-dose GCs, noted Joan Merrill, MD, a professor with the Arthritis and Clinical Immunology Research Program at The University of Oklahoma Health Sciences Center, Oklahoma City. “There may be less weight gain, less chance of acne, and less risk for all the slower, more organ-threatening side effects.”

Bianca Nogrady/MDedge News

Tapering Options Across Diseases

Rheumatologists in the field continue to navigate GC-tapering options and treatment combinations that reduce the cumulative use of GCs over time, finding their own solutions based on the conditions they treat.

In his EULAR presentation, Dr. Buttgereit suggested that current therapeutic approaches for RA may be too narrow when they don’t consider the possibility of including very low doses of GCs.

For RA, “why shouldn’t we not do a combination of something like methotrexate plus a JAK inhibitor or a biological,” plus a very low dose of GCs < 5 mg/d, he asked.

However, Dr. Adami said he generally avoids GCs if RA disease activity is not severe (based on DAS28) and if the patient has a visual analog scale pain score < 7. “Nonetheless, even in patients with more severe disease, I would avoid GCs for more than 3 months. Usually, 1 month of steroids, tapered rapidly and discontinued.”

All patients should receive an appropriate treat-to-target strategy with csDMARDs and biologics if needed, he added.

A patient coming to clinic with difficult-to-treat RA who chronically uses GCs deserves special attention. The priority is bone protection with an anti-osteoporosis medication. “I found that JAK inhibitors, in some cases, help with the discontinuation of steroids, especially in those with residual pain. Therefore, I would think of switching medication,” Dr. Adami said.

For polymyalgia rheumatica, most clinicians will likely try to taper GCs around 52 weeks, similar to ACR/EULAR guidelines, according to Robert F. Spiera, MD, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, New York City.

Hospital for Special Surgery

What to Consider for AI Symptoms

Clinicians also need to address AI in patients who are coming off GCs, Dr. Sattui said. He advised that symptoms suggestive of AI, including malaise, fatigue, nausea, and muscle and/or joint pain, should guide testing.

Even in the absence of symptoms, clinicians should consider assessing patients who have been on high doses for prolonged periods or obese or older adults who might be at a high risk for AI. “Signs to consider include weight loss, hypotension, or orthostatism,” he said.

Differentiating between AI symptoms and symptoms from the underlying disease can be a challenge. This requires a physical exam and workup, including morning serum cortisol. Collaboration with endocrinology colleagues and other treating providers is important, as well as patient education of symptoms and monitoring for possible adjustments in treating AI and other acute diseases, he said.

Dr. Smolen received research grants from AbbVie, AstraZeneca, Galapagos, and Eli Lilly. Dr. Adami received speaker fees and/or was a consultant for Galapagos, Theramex, Amgen, Eli Lilly, UCB, Fresenius Kabi, Bristol Myers Squibb, Abiogen, and Pfizer. Dr. Buttgereit’s disclosures included AbbVie, AstraZeneca, Grünenthal, Horizon Therapeutics, Mundipharma, Pfizer, and Roche. Dr. Merrill had no relevant disclosures. Dr. Spiera has been a consultant for Roche-Genentech, GlaxoSmithKline, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie. Dr. Sattui reported receiving research support from AstraZeneca and GlaxoSmithKline (clinical trials), receiving consulting fees from Sanofi (funds toward research support), serving on advisory boards for Sanofi and Amgen (funds toward research support), and receiving speaker fees from Fresenius Kabi (funds toward research support).
 

A version of this article appeared on Medscape.com.

Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.

“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.

At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.

But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.

Sara Freeman/MDedge News

Societies Agree: Discontinue as Fast as Possible

GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.

Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.

Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.

Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.

The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.

EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.

For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.

EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.
 

Low-Dose Approach Gains Ground

While saying he’d be the first physician to eliminate GCs whenever possible, Dr. Buttgereit made the case before the EULAR Congress that GCs in low doses could still play a role in treatment.

Many physicians believe that very low doses between 2 and 4 mg/d are a realistic therapy option for RA, he said, adding that a mean daily usage < 5 mg could be used over a longer period with relatively low risk.

Several studies he coauthored tested the 5-mg approach. The GLORIA trial compared 5 mg/d prednisolone and placebo in 451 patients aged 65 years and older with active RA over the course of 2 years. The researchers found that patients on prednisolone had a mean Disease Activity Score in 28 joints (DAS28) that was 0.37 points lower and mean joint damage score that was 1.7 points lower than those of patients on placebo, suggesting that the GC had long-term benefits in these patients with RA.

The tradeoff was a 24% increase in the risk of having at least one adverse event of special interest, but most of these events were non-severe infections, Dr. Buttgereit said.

Another study, the SEMIRA trial, assigned 128 patients to a continued regimen of prednisone 5 mg/d for 24 weeks. Another group of 131 patients received a tapered-prednisone regimen. All patients received tocilizumab 162 mg with or without csDMARDs, maintained at stable doses.

Patients in the first cohort achieved superior disease activity control than those in the tapered regimen group. “The side effects showed that in the tapering prednisone group, there were more treatment-emergent adverse effects in this double-blind trial as compared to the continued prednisone group,” Dr. Buttgereit said.

One limitation of the SEMIRA trial was that it studied the effect of tocilizumab as a GC-sparing agent, and it didn’t consider using a tumor necrosis factor or Janus kinase (JAK) inhibitor, which might have a more potent effect on pain and GC dose reduction, Dr. Adami said. “Why do we need to use glucocorticoids if we know they might be detrimental, if we know there might be some other option in our armamentarium?”

Other studies have shown that low-dose GC protocols can be used with standard treatment, according to Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh School of Medicine.

“Examples of this are the LoVAS and PEXIVAS studies for antineutrophil cytoplasmic antibody-associated [ANCA] vasculitis. This has been highlighted in existing treatment recommendations for ANCA vasculitis and systemic lupus erythematosus nephritis,” Dr. Sattui said.

Debating the Toxicity Threshold

Are low GC dosages significantly associated with adverse events like mortality, cardiovascular, or diabetes risk? It depends on who you ask.

Much of the toxicity data on GCs come from inadequately powered or controlled studies and often refer to doses that currently are considered too high, Dr. Buttgereit said. His presentation highlighted a study from Hong Kong, a time-varying analysis of GC dose and incident risk for major adverse cardiovascular events (MACE) in more than 12,000 patients with RA. Researchers found that GC regimens ≥ 5 mg/d significantly increased the risk for MACE. Comparatively, doses below this threshold did not confer excessive risk, he said.

Low-dose GCs are lesser toxic than high-dose GCs, noted Joan Merrill, MD, a professor with the Arthritis and Clinical Immunology Research Program at The University of Oklahoma Health Sciences Center, Oklahoma City. “There may be less weight gain, less chance of acne, and less risk for all the slower, more organ-threatening side effects.”

Bianca Nogrady/MDedge News

Tapering Options Across Diseases

Rheumatologists in the field continue to navigate GC-tapering options and treatment combinations that reduce the cumulative use of GCs over time, finding their own solutions based on the conditions they treat.

In his EULAR presentation, Dr. Buttgereit suggested that current therapeutic approaches for RA may be too narrow when they don’t consider the possibility of including very low doses of GCs.

For RA, “why shouldn’t we not do a combination of something like methotrexate plus a JAK inhibitor or a biological,” plus a very low dose of GCs < 5 mg/d, he asked.

However, Dr. Adami said he generally avoids GCs if RA disease activity is not severe (based on DAS28) and if the patient has a visual analog scale pain score < 7. “Nonetheless, even in patients with more severe disease, I would avoid GCs for more than 3 months. Usually, 1 month of steroids, tapered rapidly and discontinued.”

All patients should receive an appropriate treat-to-target strategy with csDMARDs and biologics if needed, he added.

A patient coming to clinic with difficult-to-treat RA who chronically uses GCs deserves special attention. The priority is bone protection with an anti-osteoporosis medication. “I found that JAK inhibitors, in some cases, help with the discontinuation of steroids, especially in those with residual pain. Therefore, I would think of switching medication,” Dr. Adami said.

For polymyalgia rheumatica, most clinicians will likely try to taper GCs around 52 weeks, similar to ACR/EULAR guidelines, according to Robert F. Spiera, MD, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, New York City.

Hospital for Special Surgery

What to Consider for AI Symptoms

Clinicians also need to address AI in patients who are coming off GCs, Dr. Sattui said. He advised that symptoms suggestive of AI, including malaise, fatigue, nausea, and muscle and/or joint pain, should guide testing.

Even in the absence of symptoms, clinicians should consider assessing patients who have been on high doses for prolonged periods or obese or older adults who might be at a high risk for AI. “Signs to consider include weight loss, hypotension, or orthostatism,” he said.

Differentiating between AI symptoms and symptoms from the underlying disease can be a challenge. This requires a physical exam and workup, including morning serum cortisol. Collaboration with endocrinology colleagues and other treating providers is important, as well as patient education of symptoms and monitoring for possible adjustments in treating AI and other acute diseases, he said.

Dr. Smolen received research grants from AbbVie, AstraZeneca, Galapagos, and Eli Lilly. Dr. Adami received speaker fees and/or was a consultant for Galapagos, Theramex, Amgen, Eli Lilly, UCB, Fresenius Kabi, Bristol Myers Squibb, Abiogen, and Pfizer. Dr. Buttgereit’s disclosures included AbbVie, AstraZeneca, Grünenthal, Horizon Therapeutics, Mundipharma, Pfizer, and Roche. Dr. Merrill had no relevant disclosures. Dr. Spiera has been a consultant for Roche-Genentech, GlaxoSmithKline, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie. Dr. Sattui reported receiving research support from AstraZeneca and GlaxoSmithKline (clinical trials), receiving consulting fees from Sanofi (funds toward research support), serving on advisory boards for Sanofi and Amgen (funds toward research support), and receiving speaker fees from Fresenius Kabi (funds toward research support).
 

A version of this article appeared on Medscape.com.

Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.

“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.

At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.

But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.

Sara Freeman/MDedge News

Societies Agree: Discontinue as Fast as Possible

GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.

Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.

Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.

Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.

The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.

EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.

For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.

EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.
 

Low-Dose Approach Gains Ground

While saying he’d be the first physician to eliminate GCs whenever possible, Dr. Buttgereit made the case before the EULAR Congress that GCs in low doses could still play a role in treatment.

Many physicians believe that very low doses between 2 and 4 mg/d are a realistic therapy option for RA, he said, adding that a mean daily usage < 5 mg could be used over a longer period with relatively low risk.

Several studies he coauthored tested the 5-mg approach. The GLORIA trial compared 5 mg/d prednisolone and placebo in 451 patients aged 65 years and older with active RA over the course of 2 years. The researchers found that patients on prednisolone had a mean Disease Activity Score in 28 joints (DAS28) that was 0.37 points lower and mean joint damage score that was 1.7 points lower than those of patients on placebo, suggesting that the GC had long-term benefits in these patients with RA.

The tradeoff was a 24% increase in the risk of having at least one adverse event of special interest, but most of these events were non-severe infections, Dr. Buttgereit said.

Another study, the SEMIRA trial, assigned 128 patients to a continued regimen of prednisone 5 mg/d for 24 weeks. Another group of 131 patients received a tapered-prednisone regimen. All patients received tocilizumab 162 mg with or without csDMARDs, maintained at stable doses.

Patients in the first cohort achieved superior disease activity control than those in the tapered regimen group. “The side effects showed that in the tapering prednisone group, there were more treatment-emergent adverse effects in this double-blind trial as compared to the continued prednisone group,” Dr. Buttgereit said.

One limitation of the SEMIRA trial was that it studied the effect of tocilizumab as a GC-sparing agent, and it didn’t consider using a tumor necrosis factor or Janus kinase (JAK) inhibitor, which might have a more potent effect on pain and GC dose reduction, Dr. Adami said. “Why do we need to use glucocorticoids if we know they might be detrimental, if we know there might be some other option in our armamentarium?”

Other studies have shown that low-dose GC protocols can be used with standard treatment, according to Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh School of Medicine.

“Examples of this are the LoVAS and PEXIVAS studies for antineutrophil cytoplasmic antibody-associated [ANCA] vasculitis. This has been highlighted in existing treatment recommendations for ANCA vasculitis and systemic lupus erythematosus nephritis,” Dr. Sattui said.

Debating the Toxicity Threshold

Are low GC dosages significantly associated with adverse events like mortality, cardiovascular, or diabetes risk? It depends on who you ask.

Much of the toxicity data on GCs come from inadequately powered or controlled studies and often refer to doses that currently are considered too high, Dr. Buttgereit said. His presentation highlighted a study from Hong Kong, a time-varying analysis of GC dose and incident risk for major adverse cardiovascular events (MACE) in more than 12,000 patients with RA. Researchers found that GC regimens ≥ 5 mg/d significantly increased the risk for MACE. Comparatively, doses below this threshold did not confer excessive risk, he said.

Low-dose GCs are lesser toxic than high-dose GCs, noted Joan Merrill, MD, a professor with the Arthritis and Clinical Immunology Research Program at The University of Oklahoma Health Sciences Center, Oklahoma City. “There may be less weight gain, less chance of acne, and less risk for all the slower, more organ-threatening side effects.”

Bianca Nogrady/MDedge News

Tapering Options Across Diseases

Rheumatologists in the field continue to navigate GC-tapering options and treatment combinations that reduce the cumulative use of GCs over time, finding their own solutions based on the conditions they treat.

In his EULAR presentation, Dr. Buttgereit suggested that current therapeutic approaches for RA may be too narrow when they don’t consider the possibility of including very low doses of GCs.

For RA, “why shouldn’t we not do a combination of something like methotrexate plus a JAK inhibitor or a biological,” plus a very low dose of GCs < 5 mg/d, he asked.

However, Dr. Adami said he generally avoids GCs if RA disease activity is not severe (based on DAS28) and if the patient has a visual analog scale pain score < 7. “Nonetheless, even in patients with more severe disease, I would avoid GCs for more than 3 months. Usually, 1 month of steroids, tapered rapidly and discontinued.”

All patients should receive an appropriate treat-to-target strategy with csDMARDs and biologics if needed, he added.

A patient coming to clinic with difficult-to-treat RA who chronically uses GCs deserves special attention. The priority is bone protection with an anti-osteoporosis medication. “I found that JAK inhibitors, in some cases, help with the discontinuation of steroids, especially in those with residual pain. Therefore, I would think of switching medication,” Dr. Adami said.

For polymyalgia rheumatica, most clinicians will likely try to taper GCs around 52 weeks, similar to ACR/EULAR guidelines, according to Robert F. Spiera, MD, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, New York City.

Hospital for Special Surgery

What to Consider for AI Symptoms

Clinicians also need to address AI in patients who are coming off GCs, Dr. Sattui said. He advised that symptoms suggestive of AI, including malaise, fatigue, nausea, and muscle and/or joint pain, should guide testing.

Even in the absence of symptoms, clinicians should consider assessing patients who have been on high doses for prolonged periods or obese or older adults who might be at a high risk for AI. “Signs to consider include weight loss, hypotension, or orthostatism,” he said.

Differentiating between AI symptoms and symptoms from the underlying disease can be a challenge. This requires a physical exam and workup, including morning serum cortisol. Collaboration with endocrinology colleagues and other treating providers is important, as well as patient education of symptoms and monitoring for possible adjustments in treating AI and other acute diseases, he said.

Dr. Smolen received research grants from AbbVie, AstraZeneca, Galapagos, and Eli Lilly. Dr. Adami received speaker fees and/or was a consultant for Galapagos, Theramex, Amgen, Eli Lilly, UCB, Fresenius Kabi, Bristol Myers Squibb, Abiogen, and Pfizer. Dr. Buttgereit’s disclosures included AbbVie, AstraZeneca, Grünenthal, Horizon Therapeutics, Mundipharma, Pfizer, and Roche. Dr. Merrill had no relevant disclosures. Dr. Spiera has been a consultant for Roche-Genentech, GlaxoSmithKline, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie. Dr. Sattui reported receiving research support from AstraZeneca and GlaxoSmithKline (clinical trials), receiving consulting fees from Sanofi (funds toward research support), serving on advisory boards for Sanofi and Amgen (funds toward research support), and receiving speaker fees from Fresenius Kabi (funds toward research support).
 

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

SEATTLE — Tissue resident memory (TRM) T cells are a hot topic lately in the treatment of psoriasis. These cells reside in the skin and other tissues and promote the inflammatory response, likely contributing to psoriasis symptoms. In fact, flare-ups often recur at the same site, a phenomenon that might be driven by these resident memory cells, according to Liv Eidsmo, MD, PhD.

This has led to their use as biomarkers in clinical trials for new therapies, but TRM T cells have a complex biology that is far from fully understood, Dr. Eidsmo said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “With time, we’re understanding that the regulation of the functionality is more complicated than we thought, so following these cells as a positive outcome of a clinical trial is a little bit premature,” said Dr. Eidsmo, who is a consultant dermatologist at the University of Copenhagen, Copenhagen, Denmark.

Treatment strategies focus on inhibition of interleukin (IL)-23, which is an activator of TRM T cells and probably keeps them alive, according to Dr. Eidsmo. “The hope is that these cells can be silenced by IL-23 inhibition, which is a great idea, and it probably works. It’s just a matter of what is the readout of long-term remission, because the big challenge in the clinical world is when do we stop these expensive biological treatments? When can we feel secure that patients are in deep remission?” she asked.

TRM cells are also far from the only immune cells involved in psoriasis. Others include keratinocytes, Langerhans cells, and fibroblasts. Dr. Eidsmo referenced a recent spatial analysis that used single-cell and spatial RNA sequencing to identify the localization of specific cell populations and inflammatory pathways within psoriasis lesions and epidermal compartments as well as also suggested crosstalk links between cell types. Epigenetic changes in stem cells may also maintain a lower threshold for tissue inflammation.

Dr. Eidsmo advised caution in eliminating TRM T cells, which play a key role in protecting against melanoma and other cancers, especially later in life. “We don’t want to get rid of them. We want to have the right balance.”

She noted a study in her own lab that mapped TRM T cells in healthy epidermis and found that they could be renewed from both circulating precursors and cells within the epidermis. “So getting rid of the mature TRM T cells will most likely just lead to a new generation of the same subset.”

Other data show that there are a wide range of subsets of TRM T cells, and she recommended focusing on the functionality of TRM T cells rather than sheer numbers. “This is something we’re working on now: Can we change the functionality [of TRM T cells], rather than eradicate them and hope for the best in the next generation? Can we change the functionality of the T cells we already have in the skin?”

There is also epigenetic data in TRM T cells, keratinocytes, stem cells, and other cells thus suggesting complexity and plasticity in the system that remains poorly understood. 

Taken together, the research is at too early of a stage to be clinically useful, said Dr. Eidsmo. “We need to go back to the drawing board and just realize what we need to measure, and with the new techniques coming out, maybe spatial [measurement] at a high resolution, we can find biomarkers that better dictate the future of this. Be a little bit wary when you read the outcomes from the clinical trials that are ongoing, because right now, it’s a bit of a race between different biologics. These cells are used as a readout of efficacy of the treatments, and we’re not quite there yet.”

During the Q&A session after the presentation, one audience member asked about the heterogeneity of cells found within the skin of patients with psoriasis and pointed out that many proinflammatory cells likely play a role in tumor control. Dr. Eidsmo responded that her group’s analysis of a large database of patients with metastatic melanoma found that a factor that is important to the development of TRM T cells was strongly correlated to survival in patients with metastatic melanoma receiving immune checkpoint blockade. “So we really don’t want to eradicate them,” she said.

Also during the Q&A, Iain McInnes, MD, PhD, commented about the need to understand the previous events that drove the creation of memory T cells. “For me, the question is about the hierarchy, the primacy of what really drives the memory. In the infectious world, we’re trained to think [that memory responses] are T cell driven memory, but I wonder whether you have an idea of whether the T cell is responding to other memories, particularly in the stroma. Because certainly in the arthropathies, we have really good evidence now of epigenetic change in the synovial stroma and subsets,” said Dr. McInnes, who is director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Glasgow, Scotland.

Dr. Eidsmo responded that she believes responses are different among different individuals. “We know too little about how these two systems interact with one another. I think the TRM T cells are very good at amplifying the stroma to recruit cells in. I think we need to think of two-step therapies. You need to normalize this [stromal] environment. How you can do that, I don’t know.”

Dr. McInnes agreed. “As a myeloid doctor, I strongly believe that perpetuators are innate and the adaptive is following on. But how do we test that? That’s really hard,” he said. 

Dr. Eidsmo did not list any disclosures. Dr. McInnes has financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer, Compugen, Cabaletta, Causeway, Dextera, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, Versus Arthritis, MRC, and UCB. 

SEATTLE — Tissue resident memory (TRM) T cells are a hot topic lately in the treatment of psoriasis. These cells reside in the skin and other tissues and promote the inflammatory response, likely contributing to psoriasis symptoms. In fact, flare-ups often recur at the same site, a phenomenon that might be driven by these resident memory cells, according to Liv Eidsmo, MD, PhD.

This has led to their use as biomarkers in clinical trials for new therapies, but TRM T cells have a complex biology that is far from fully understood, Dr. Eidsmo said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “With time, we’re understanding that the regulation of the functionality is more complicated than we thought, so following these cells as a positive outcome of a clinical trial is a little bit premature,” said Dr. Eidsmo, who is a consultant dermatologist at the University of Copenhagen, Copenhagen, Denmark.

Treatment strategies focus on inhibition of interleukin (IL)-23, which is an activator of TRM T cells and probably keeps them alive, according to Dr. Eidsmo. “The hope is that these cells can be silenced by IL-23 inhibition, which is a great idea, and it probably works. It’s just a matter of what is the readout of long-term remission, because the big challenge in the clinical world is when do we stop these expensive biological treatments? When can we feel secure that patients are in deep remission?” she asked.

TRM cells are also far from the only immune cells involved in psoriasis. Others include keratinocytes, Langerhans cells, and fibroblasts. Dr. Eidsmo referenced a recent spatial analysis that used single-cell and spatial RNA sequencing to identify the localization of specific cell populations and inflammatory pathways within psoriasis lesions and epidermal compartments as well as also suggested crosstalk links between cell types. Epigenetic changes in stem cells may also maintain a lower threshold for tissue inflammation.

Dr. Eidsmo advised caution in eliminating TRM T cells, which play a key role in protecting against melanoma and other cancers, especially later in life. “We don’t want to get rid of them. We want to have the right balance.”

She noted a study in her own lab that mapped TRM T cells in healthy epidermis and found that they could be renewed from both circulating precursors and cells within the epidermis. “So getting rid of the mature TRM T cells will most likely just lead to a new generation of the same subset.”

Other data show that there are a wide range of subsets of TRM T cells, and she recommended focusing on the functionality of TRM T cells rather than sheer numbers. “This is something we’re working on now: Can we change the functionality [of TRM T cells], rather than eradicate them and hope for the best in the next generation? Can we change the functionality of the T cells we already have in the skin?”

There is also epigenetic data in TRM T cells, keratinocytes, stem cells, and other cells thus suggesting complexity and plasticity in the system that remains poorly understood. 

Taken together, the research is at too early of a stage to be clinically useful, said Dr. Eidsmo. “We need to go back to the drawing board and just realize what we need to measure, and with the new techniques coming out, maybe spatial [measurement] at a high resolution, we can find biomarkers that better dictate the future of this. Be a little bit wary when you read the outcomes from the clinical trials that are ongoing, because right now, it’s a bit of a race between different biologics. These cells are used as a readout of efficacy of the treatments, and we’re not quite there yet.”

During the Q&A session after the presentation, one audience member asked about the heterogeneity of cells found within the skin of patients with psoriasis and pointed out that many proinflammatory cells likely play a role in tumor control. Dr. Eidsmo responded that her group’s analysis of a large database of patients with metastatic melanoma found that a factor that is important to the development of TRM T cells was strongly correlated to survival in patients with metastatic melanoma receiving immune checkpoint blockade. “So we really don’t want to eradicate them,” she said.

Also during the Q&A, Iain McInnes, MD, PhD, commented about the need to understand the previous events that drove the creation of memory T cells. “For me, the question is about the hierarchy, the primacy of what really drives the memory. In the infectious world, we’re trained to think [that memory responses] are T cell driven memory, but I wonder whether you have an idea of whether the T cell is responding to other memories, particularly in the stroma. Because certainly in the arthropathies, we have really good evidence now of epigenetic change in the synovial stroma and subsets,” said Dr. McInnes, who is director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Glasgow, Scotland.

Dr. Eidsmo responded that she believes responses are different among different individuals. “We know too little about how these two systems interact with one another. I think the TRM T cells are very good at amplifying the stroma to recruit cells in. I think we need to think of two-step therapies. You need to normalize this [stromal] environment. How you can do that, I don’t know.”

Dr. McInnes agreed. “As a myeloid doctor, I strongly believe that perpetuators are innate and the adaptive is following on. But how do we test that? That’s really hard,” he said. 

Dr. Eidsmo did not list any disclosures. Dr. McInnes has financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer, Compugen, Cabaletta, Causeway, Dextera, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, Versus Arthritis, MRC, and UCB. 

SEATTLE — Tissue resident memory (TRM) T cells are a hot topic lately in the treatment of psoriasis. These cells reside in the skin and other tissues and promote the inflammatory response, likely contributing to psoriasis symptoms. In fact, flare-ups often recur at the same site, a phenomenon that might be driven by these resident memory cells, according to Liv Eidsmo, MD, PhD.

This has led to their use as biomarkers in clinical trials for new therapies, but TRM T cells have a complex biology that is far from fully understood, Dr. Eidsmo said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “With time, we’re understanding that the regulation of the functionality is more complicated than we thought, so following these cells as a positive outcome of a clinical trial is a little bit premature,” said Dr. Eidsmo, who is a consultant dermatologist at the University of Copenhagen, Copenhagen, Denmark.

Treatment strategies focus on inhibition of interleukin (IL)-23, which is an activator of TRM T cells and probably keeps them alive, according to Dr. Eidsmo. “The hope is that these cells can be silenced by IL-23 inhibition, which is a great idea, and it probably works. It’s just a matter of what is the readout of long-term remission, because the big challenge in the clinical world is when do we stop these expensive biological treatments? When can we feel secure that patients are in deep remission?” she asked.

TRM cells are also far from the only immune cells involved in psoriasis. Others include keratinocytes, Langerhans cells, and fibroblasts. Dr. Eidsmo referenced a recent spatial analysis that used single-cell and spatial RNA sequencing to identify the localization of specific cell populations and inflammatory pathways within psoriasis lesions and epidermal compartments as well as also suggested crosstalk links between cell types. Epigenetic changes in stem cells may also maintain a lower threshold for tissue inflammation.

Dr. Eidsmo advised caution in eliminating TRM T cells, which play a key role in protecting against melanoma and other cancers, especially later in life. “We don’t want to get rid of them. We want to have the right balance.”

She noted a study in her own lab that mapped TRM T cells in healthy epidermis and found that they could be renewed from both circulating precursors and cells within the epidermis. “So getting rid of the mature TRM T cells will most likely just lead to a new generation of the same subset.”

Other data show that there are a wide range of subsets of TRM T cells, and she recommended focusing on the functionality of TRM T cells rather than sheer numbers. “This is something we’re working on now: Can we change the functionality [of TRM T cells], rather than eradicate them and hope for the best in the next generation? Can we change the functionality of the T cells we already have in the skin?”

There is also epigenetic data in TRM T cells, keratinocytes, stem cells, and other cells thus suggesting complexity and plasticity in the system that remains poorly understood. 

Taken together, the research is at too early of a stage to be clinically useful, said Dr. Eidsmo. “We need to go back to the drawing board and just realize what we need to measure, and with the new techniques coming out, maybe spatial [measurement] at a high resolution, we can find biomarkers that better dictate the future of this. Be a little bit wary when you read the outcomes from the clinical trials that are ongoing, because right now, it’s a bit of a race between different biologics. These cells are used as a readout of efficacy of the treatments, and we’re not quite there yet.”

During the Q&A session after the presentation, one audience member asked about the heterogeneity of cells found within the skin of patients with psoriasis and pointed out that many proinflammatory cells likely play a role in tumor control. Dr. Eidsmo responded that her group’s analysis of a large database of patients with metastatic melanoma found that a factor that is important to the development of TRM T cells was strongly correlated to survival in patients with metastatic melanoma receiving immune checkpoint blockade. “So we really don’t want to eradicate them,” she said.

Also during the Q&A, Iain McInnes, MD, PhD, commented about the need to understand the previous events that drove the creation of memory T cells. “For me, the question is about the hierarchy, the primacy of what really drives the memory. In the infectious world, we’re trained to think [that memory responses] are T cell driven memory, but I wonder whether you have an idea of whether the T cell is responding to other memories, particularly in the stroma. Because certainly in the arthropathies, we have really good evidence now of epigenetic change in the synovial stroma and subsets,” said Dr. McInnes, who is director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Glasgow, Scotland.

Dr. Eidsmo responded that she believes responses are different among different individuals. “We know too little about how these two systems interact with one another. I think the TRM T cells are very good at amplifying the stroma to recruit cells in. I think we need to think of two-step therapies. You need to normalize this [stromal] environment. How you can do that, I don’t know.”

Dr. McInnes agreed. “As a myeloid doctor, I strongly believe that perpetuators are innate and the adaptive is following on. But how do we test that? That’s really hard,” he said. 

Dr. Eidsmo did not list any disclosures. Dr. McInnes has financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer, Compugen, Cabaletta, Causeway, Dextera, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, Versus Arthritis, MRC, and UCB. 

Many patients struggle with healthcare costs and basic expenses, according to new research.

People with rheumatologic diseases often experience a hidden symptom: financial toxicity or significant economic strain from out-of-pocket costs. A new study of 41,502 patients published in JCR: Journal of Clinical Rheumatology showed that 20% of those with rheumatologic diseases faced financial hardship from medical expenses, with 55% of those unable to pay their bills. 

Compared with patients who do not have rheumatologic diseases, and after clinical and sociodemographic factors were controlled for, patients with rheumatologic diseases were:

• 29% more likely to have high levels of financial hardship — difficulty paying; needing to pay over time; or inability to pay bills for doctors, dentists, hospitals, therapists, medication, equipment, nursing homes, or home care.
• 53% more likely to have high levels of financial distress — significant worry about having enough money for retirement, paying medical costs in the event of a serious illness or accident, maintaining their standard of living, paying their usual healthcare costs, and affording their normal monthly bills and housing costs.
• 29% more likely to experience food insecurity, defined as limited or uncertain access to adequate food.
• 58% more likely to report cost-related medication nonadherence — skipping doses, taking less medication, or delaying filling a prescription to save money.

People who were younger than 64 years, male, Black, or uninsured had higher odds of experiencing financial hardship, financial distress, food insecurity, and cost-related medication nonadherence. 

This study highlights “just how costly everyday rheumatologic conditions can be for your average American,” said lead study author Troy Amen, MD, MBA, an orthopedic surgery resident at the Hospital for Special Surgery in New York City. These diseases can be disabling, limiting a patient’s ability to work at the very time when expensive medications are needed. 

“It’s critical for clinicians to recognize how common the financial burden from healthcare costs can be, and only then can they take steps to better support patients,” said G. Caleb Alexander, MD, MS, professor of epidemiology at Johns Hopkins University in Baltimore, who was not involved in the study. 

Here’s how healthcare providers can help. 

Consider skipped medication a red flag. It’s often the first sign of a financial concern. “Sometimes with these problems, it looks like simple medication noncompliance, but it’s really a more complex form of nonadherence,” said Susan M. Goodman, MD, professor of clinical medicine at Weill Cornell Medicine in New York City and a coauthor of the study. “And I think if someone’s not taking the medication that had been very helpful, it does behoove the physician to try and figure out why that is.”

Normalize the issue to help patients open up. “I will often say, ‘You know, many, many patients don’t take their medicines exactly as prescribed. About how many days a week do you take this medicine?’” said Dr. Alexander. “If you ask in a nonconfrontational, supportive manner, I’ve found that patients are quite candid.” 

Don’t assume insurance has it covered. If patients are uninsured, help them enroll in (or renew) insurance coverage. But don’t assume insurance will solve the whole problem. “There are many people who, although they do have coverage, still can’t afford their medications,” said Dr. Goodman.

For products on high formulary tiers, the patient’s monthly cost can be hundreds to thousands of dollars. “Over the past 10-20 years, we’ve seen remarkable technological innovation in the types of medicines being brought to market, and here, I’m referring primarily to biologics and medicines made from living cells,” said Dr. Alexander, “but many of these have a price tag that is simply astronomical, and insurers aren’t going to bear the brunt of these costs alone.” 

Biosimilars can be a bit more affordable, but “the dirty little secret of biosimilars is that they’re not really very much less expensive,” said Dr. Goodman. “If your patient is doing well on a drug that gets dropped from their insurance plan’s formulary, or if they switch to a plan that doesn’t cover it, try calling and advocating for an exception. It’s an uphill battle, but it sometimes works,” she said.

If not? Help your patients apply for a patient assistance program. Many drug manufacturers offer copay assistance through their websites, and nonprofit patient assistance organizations such as the PAN Foundation, the Patient Advocate Foundation’s Co-Pay Relief Program, or The Assistance Fund can also help fill the gaps. One study published in the Journal of Managed Care and Specialty Pharmacy showed that in patients with rheumatoid arthritis, copay assistance was associated with 79% lower odds of prescription abandonment (failure to fill within 30 days of health plan approval).

Beware of “shiny penny syndrome.” It’s easy to get excited about new, innovative medications, especially when sales reps provide plenty of free samples. “There is a tendency to treat every new medicine as if it’s a bright shiny object in the streambed, and you know that’s not always the case,” said Dr. Alexander. “So, I think we have to be careful, especially in settings when we’re talking about ultra–high-cost medicines, that we’re aware of the burden these medicines may place on patients and that we’re navigating that with patients together, and not simply leaving that as a conversation that never happens in the exam room.”

Maybe there’s an older, time-tested drug that works just as well as the newer, more expensive one. Perhaps there is a slightly less effective medicine that costs a lot less. “These are cost–quality trade-offs that clinicians and patients should be navigating together,” said Dr. Alexander. For example, in a patient with rheumatoid arthritis, a tumor necrosis factor alpha inhibitor might work similarly to or almost as well as an interleukin inhibitor, the newer and typically more expensive choice. 

“Some clinicians may find it quite unpalatable to be potentially compromising on safety or efficacy in the interest of reducing the cost of therapies, but as former Surgeon General C. Everett Koop said, ‘Drugs don’t work in patients who don’t take them,’ ” said Dr. Alexander. “So, if the choice is for someone not to be taking a treatment, or to be taking one that may be a little bit less good, I’ll take the latter.”

Consider the patient’s broader care team. Encourage patients to discuss costs with their other healthcare providers. For patients taking multiple medications, a few adjustments could make a big impact on their wallets. Primary care providers or other specialists might recommend some older and less expensive, but still effective, drugs, such as thiazides for hypertension or metformin for type 2 diabetes. Another option might be to simplify the patient’s regimen or include some fixed-dose combination pills in place of two others.

And if no one has referred the patient to a medical social worker, make the connection. A social worker can put patients in touch with local agencies that can help them with food, housing, and other nonmedical costs. 

Talk about this problem with anyone who will listen. One of the best ways to help patients with rheumatologic diseases is to ensure that decision-makers don’t overlook them. Professional societies such as the American College of Rheumatology can be great resources for advocacy in Washington, DC. Political movements can make drugs more affordable — for example, insulin prices have dropped in recent years because of political pressure, said Dr. Goodman.

“A lot of our national policy now focuses on aiding patients with single high-cost events, but we hope studies like these can really get policymakers to think through how to better support patients with chronic conditions that may have been historically ignored, such as patients with rheumatologic disease,” said Dr. Amen. 

The first step is raising awareness and telling your story. “As providers, we are often [at the] forefront in witnessing how chronic conditions and their associated costs can negatively affect patients’ lives and even alter clinical outcomes,” Dr. Amen added. “By publishing data and sharing meaningful patient stories and clinical vignettes, we can begin to advocate and humanize these patients to policymakers.” 

Information on study funding was not available. All authors reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Many patients struggle with healthcare costs and basic expenses, according to new research.

People with rheumatologic diseases often experience a hidden symptom: financial toxicity or significant economic strain from out-of-pocket costs. A new study of 41,502 patients published in JCR: Journal of Clinical Rheumatology showed that 20% of those with rheumatologic diseases faced financial hardship from medical expenses, with 55% of those unable to pay their bills. 

Compared with patients who do not have rheumatologic diseases, and after clinical and sociodemographic factors were controlled for, patients with rheumatologic diseases were:

• 29% more likely to have high levels of financial hardship — difficulty paying; needing to pay over time; or inability to pay bills for doctors, dentists, hospitals, therapists, medication, equipment, nursing homes, or home care.
• 53% more likely to have high levels of financial distress — significant worry about having enough money for retirement, paying medical costs in the event of a serious illness or accident, maintaining their standard of living, paying their usual healthcare costs, and affording their normal monthly bills and housing costs.
• 29% more likely to experience food insecurity, defined as limited or uncertain access to adequate food.
• 58% more likely to report cost-related medication nonadherence — skipping doses, taking less medication, or delaying filling a prescription to save money.

People who were younger than 64 years, male, Black, or uninsured had higher odds of experiencing financial hardship, financial distress, food insecurity, and cost-related medication nonadherence. 

This study highlights “just how costly everyday rheumatologic conditions can be for your average American,” said lead study author Troy Amen, MD, MBA, an orthopedic surgery resident at the Hospital for Special Surgery in New York City. These diseases can be disabling, limiting a patient’s ability to work at the very time when expensive medications are needed. 

“It’s critical for clinicians to recognize how common the financial burden from healthcare costs can be, and only then can they take steps to better support patients,” said G. Caleb Alexander, MD, MS, professor of epidemiology at Johns Hopkins University in Baltimore, who was not involved in the study. 

Here’s how healthcare providers can help. 

Consider skipped medication a red flag. It’s often the first sign of a financial concern. “Sometimes with these problems, it looks like simple medication noncompliance, but it’s really a more complex form of nonadherence,” said Susan M. Goodman, MD, professor of clinical medicine at Weill Cornell Medicine in New York City and a coauthor of the study. “And I think if someone’s not taking the medication that had been very helpful, it does behoove the physician to try and figure out why that is.”

Normalize the issue to help patients open up. “I will often say, ‘You know, many, many patients don’t take their medicines exactly as prescribed. About how many days a week do you take this medicine?’” said Dr. Alexander. “If you ask in a nonconfrontational, supportive manner, I’ve found that patients are quite candid.” 

Don’t assume insurance has it covered. If patients are uninsured, help them enroll in (or renew) insurance coverage. But don’t assume insurance will solve the whole problem. “There are many people who, although they do have coverage, still can’t afford their medications,” said Dr. Goodman.

For products on high formulary tiers, the patient’s monthly cost can be hundreds to thousands of dollars. “Over the past 10-20 years, we’ve seen remarkable technological innovation in the types of medicines being brought to market, and here, I’m referring primarily to biologics and medicines made from living cells,” said Dr. Alexander, “but many of these have a price tag that is simply astronomical, and insurers aren’t going to bear the brunt of these costs alone.” 

Biosimilars can be a bit more affordable, but “the dirty little secret of biosimilars is that they’re not really very much less expensive,” said Dr. Goodman. “If your patient is doing well on a drug that gets dropped from their insurance plan’s formulary, or if they switch to a plan that doesn’t cover it, try calling and advocating for an exception. It’s an uphill battle, but it sometimes works,” she said.

If not? Help your patients apply for a patient assistance program. Many drug manufacturers offer copay assistance through their websites, and nonprofit patient assistance organizations such as the PAN Foundation, the Patient Advocate Foundation’s Co-Pay Relief Program, or The Assistance Fund can also help fill the gaps. One study published in the Journal of Managed Care and Specialty Pharmacy showed that in patients with rheumatoid arthritis, copay assistance was associated with 79% lower odds of prescription abandonment (failure to fill within 30 days of health plan approval).

Beware of “shiny penny syndrome.” It’s easy to get excited about new, innovative medications, especially when sales reps provide plenty of free samples. “There is a tendency to treat every new medicine as if it’s a bright shiny object in the streambed, and you know that’s not always the case,” said Dr. Alexander. “So, I think we have to be careful, especially in settings when we’re talking about ultra–high-cost medicines, that we’re aware of the burden these medicines may place on patients and that we’re navigating that with patients together, and not simply leaving that as a conversation that never happens in the exam room.”

Maybe there’s an older, time-tested drug that works just as well as the newer, more expensive one. Perhaps there is a slightly less effective medicine that costs a lot less. “These are cost–quality trade-offs that clinicians and patients should be navigating together,” said Dr. Alexander. For example, in a patient with rheumatoid arthritis, a tumor necrosis factor alpha inhibitor might work similarly to or almost as well as an interleukin inhibitor, the newer and typically more expensive choice. 

“Some clinicians may find it quite unpalatable to be potentially compromising on safety or efficacy in the interest of reducing the cost of therapies, but as former Surgeon General C. Everett Koop said, ‘Drugs don’t work in patients who don’t take them,’ ” said Dr. Alexander. “So, if the choice is for someone not to be taking a treatment, or to be taking one that may be a little bit less good, I’ll take the latter.”

Consider the patient’s broader care team. Encourage patients to discuss costs with their other healthcare providers. For patients taking multiple medications, a few adjustments could make a big impact on their wallets. Primary care providers or other specialists might recommend some older and less expensive, but still effective, drugs, such as thiazides for hypertension or metformin for type 2 diabetes. Another option might be to simplify the patient’s regimen or include some fixed-dose combination pills in place of two others.

And if no one has referred the patient to a medical social worker, make the connection. A social worker can put patients in touch with local agencies that can help them with food, housing, and other nonmedical costs. 

Talk about this problem with anyone who will listen. One of the best ways to help patients with rheumatologic diseases is to ensure that decision-makers don’t overlook them. Professional societies such as the American College of Rheumatology can be great resources for advocacy in Washington, DC. Political movements can make drugs more affordable — for example, insulin prices have dropped in recent years because of political pressure, said Dr. Goodman.

“A lot of our national policy now focuses on aiding patients with single high-cost events, but we hope studies like these can really get policymakers to think through how to better support patients with chronic conditions that may have been historically ignored, such as patients with rheumatologic disease,” said Dr. Amen. 

The first step is raising awareness and telling your story. “As providers, we are often [at the] forefront in witnessing how chronic conditions and their associated costs can negatively affect patients’ lives and even alter clinical outcomes,” Dr. Amen added. “By publishing data and sharing meaningful patient stories and clinical vignettes, we can begin to advocate and humanize these patients to policymakers.” 

Information on study funding was not available. All authors reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Many patients struggle with healthcare costs and basic expenses, according to new research.

People with rheumatologic diseases often experience a hidden symptom: financial toxicity or significant economic strain from out-of-pocket costs. A new study of 41,502 patients published in JCR: Journal of Clinical Rheumatology showed that 20% of those with rheumatologic diseases faced financial hardship from medical expenses, with 55% of those unable to pay their bills. 

Compared with patients who do not have rheumatologic diseases, and after clinical and sociodemographic factors were controlled for, patients with rheumatologic diseases were:

• 29% more likely to have high levels of financial hardship — difficulty paying; needing to pay over time; or inability to pay bills for doctors, dentists, hospitals, therapists, medication, equipment, nursing homes, or home care.
• 53% more likely to have high levels of financial distress — significant worry about having enough money for retirement, paying medical costs in the event of a serious illness or accident, maintaining their standard of living, paying their usual healthcare costs, and affording their normal monthly bills and housing costs.
• 29% more likely to experience food insecurity, defined as limited or uncertain access to adequate food.
• 58% more likely to report cost-related medication nonadherence — skipping doses, taking less medication, or delaying filling a prescription to save money.

People who were younger than 64 years, male, Black, or uninsured had higher odds of experiencing financial hardship, financial distress, food insecurity, and cost-related medication nonadherence. 

This study highlights “just how costly everyday rheumatologic conditions can be for your average American,” said lead study author Troy Amen, MD, MBA, an orthopedic surgery resident at the Hospital for Special Surgery in New York City. These diseases can be disabling, limiting a patient’s ability to work at the very time when expensive medications are needed. 

“It’s critical for clinicians to recognize how common the financial burden from healthcare costs can be, and only then can they take steps to better support patients,” said G. Caleb Alexander, MD, MS, professor of epidemiology at Johns Hopkins University in Baltimore, who was not involved in the study. 

Here’s how healthcare providers can help. 

Consider skipped medication a red flag. It’s often the first sign of a financial concern. “Sometimes with these problems, it looks like simple medication noncompliance, but it’s really a more complex form of nonadherence,” said Susan M. Goodman, MD, professor of clinical medicine at Weill Cornell Medicine in New York City and a coauthor of the study. “And I think if someone’s not taking the medication that had been very helpful, it does behoove the physician to try and figure out why that is.”

Normalize the issue to help patients open up. “I will often say, ‘You know, many, many patients don’t take their medicines exactly as prescribed. About how many days a week do you take this medicine?’” said Dr. Alexander. “If you ask in a nonconfrontational, supportive manner, I’ve found that patients are quite candid.” 

Don’t assume insurance has it covered. If patients are uninsured, help them enroll in (or renew) insurance coverage. But don’t assume insurance will solve the whole problem. “There are many people who, although they do have coverage, still can’t afford their medications,” said Dr. Goodman.

For products on high formulary tiers, the patient’s monthly cost can be hundreds to thousands of dollars. “Over the past 10-20 years, we’ve seen remarkable technological innovation in the types of medicines being brought to market, and here, I’m referring primarily to biologics and medicines made from living cells,” said Dr. Alexander, “but many of these have a price tag that is simply astronomical, and insurers aren’t going to bear the brunt of these costs alone.” 

Biosimilars can be a bit more affordable, but “the dirty little secret of biosimilars is that they’re not really very much less expensive,” said Dr. Goodman. “If your patient is doing well on a drug that gets dropped from their insurance plan’s formulary, or if they switch to a plan that doesn’t cover it, try calling and advocating for an exception. It’s an uphill battle, but it sometimes works,” she said.

If not? Help your patients apply for a patient assistance program. Many drug manufacturers offer copay assistance through their websites, and nonprofit patient assistance organizations such as the PAN Foundation, the Patient Advocate Foundation’s Co-Pay Relief Program, or The Assistance Fund can also help fill the gaps. One study published in the Journal of Managed Care and Specialty Pharmacy showed that in patients with rheumatoid arthritis, copay assistance was associated with 79% lower odds of prescription abandonment (failure to fill within 30 days of health plan approval).

Beware of “shiny penny syndrome.” It’s easy to get excited about new, innovative medications, especially when sales reps provide plenty of free samples. “There is a tendency to treat every new medicine as if it’s a bright shiny object in the streambed, and you know that’s not always the case,” said Dr. Alexander. “So, I think we have to be careful, especially in settings when we’re talking about ultra–high-cost medicines, that we’re aware of the burden these medicines may place on patients and that we’re navigating that with patients together, and not simply leaving that as a conversation that never happens in the exam room.”

Maybe there’s an older, time-tested drug that works just as well as the newer, more expensive one. Perhaps there is a slightly less effective medicine that costs a lot less. “These are cost–quality trade-offs that clinicians and patients should be navigating together,” said Dr. Alexander. For example, in a patient with rheumatoid arthritis, a tumor necrosis factor alpha inhibitor might work similarly to or almost as well as an interleukin inhibitor, the newer and typically more expensive choice. 

“Some clinicians may find it quite unpalatable to be potentially compromising on safety or efficacy in the interest of reducing the cost of therapies, but as former Surgeon General C. Everett Koop said, ‘Drugs don’t work in patients who don’t take them,’ ” said Dr. Alexander. “So, if the choice is for someone not to be taking a treatment, or to be taking one that may be a little bit less good, I’ll take the latter.”

Consider the patient’s broader care team. Encourage patients to discuss costs with their other healthcare providers. For patients taking multiple medications, a few adjustments could make a big impact on their wallets. Primary care providers or other specialists might recommend some older and less expensive, but still effective, drugs, such as thiazides for hypertension or metformin for type 2 diabetes. Another option might be to simplify the patient’s regimen or include some fixed-dose combination pills in place of two others.

And if no one has referred the patient to a medical social worker, make the connection. A social worker can put patients in touch with local agencies that can help them with food, housing, and other nonmedical costs. 

Talk about this problem with anyone who will listen. One of the best ways to help patients with rheumatologic diseases is to ensure that decision-makers don’t overlook them. Professional societies such as the American College of Rheumatology can be great resources for advocacy in Washington, DC. Political movements can make drugs more affordable — for example, insulin prices have dropped in recent years because of political pressure, said Dr. Goodman.

“A lot of our national policy now focuses on aiding patients with single high-cost events, but we hope studies like these can really get policymakers to think through how to better support patients with chronic conditions that may have been historically ignored, such as patients with rheumatologic disease,” said Dr. Amen. 

The first step is raising awareness and telling your story. “As providers, we are often [at the] forefront in witnessing how chronic conditions and their associated costs can negatively affect patients’ lives and even alter clinical outcomes,” Dr. Amen added. “By publishing data and sharing meaningful patient stories and clinical vignettes, we can begin to advocate and humanize these patients to policymakers.” 

Information on study funding was not available. All authors reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Early detection and treatment of rheumatoid arthritis (RA; within 12 weeks of symptom onset) results in lower treatment-related costs over 5 years compared with later diagnosis.

METHODOLOGY:

• The study enrolled 431 patients in the Leiden Early Arthritis Clinic at Leiden University Medical Center, Leiden, the Netherlands.
• Symptom duration was defined as time between symptom onset and first clinic visit.
• Early treatment was defined as a symptom duration of under 12 weeks, and later treatment defined as symptom duration over 12 weeks.
• Prescription data from patient records and 2022 disease-modifying antirheumatic drug prices (including biologics) was used to determine overall costs over 5 years.
• Autoantibody-negative and autoantibody-positive RA were studied separately because of possible differences in disease severity.

TAKEAWAY:

• For the 165 patients with autoantibody-negative RA, late treatment was associated with 316% higher costs over 5 years than early treatment (€4856/$5292 vs €1159/$1263)
• For antibody-positive RA, costs were 19% higher in the late-treatment group.
• In the 43 patients with antibody-positive RA only prescribed biologics, costs were 46% higher for those with delayed treatment.

IN PRACTICE:

“This is the first study showing the effect of early diagnosis and treatment on treatment-related costs,” wrote the authors. “When RA is detected within 12 weeks after symptom onset, treatment-related costs seem to be lower.”

SOURCE:

The study was led by Elise van Mulligen, PhD, Department of Rheumatology, Leiden University Medical Center. It was published online in Annals of the Rheumatic Diseases. 

LIMITATIONS:

The division of symptom duration by 12 weeks was “arbitrary.” Baseline characteristics, though similar, showed differences for inflammatory markers in autoantibody-positive and autoantibody-negative RA. Thirty seven patients were lost to follow-up, which could induce attrition bias, though the percentage of these patients in the early- and late-treatment groups was similar.

DISCLOSURES:

This study was funded by ZonMw, a Dutch organization for healthcare research. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Early detection and treatment of rheumatoid arthritis (RA; within 12 weeks of symptom onset) results in lower treatment-related costs over 5 years compared with later diagnosis.

METHODOLOGY:

• The study enrolled 431 patients in the Leiden Early Arthritis Clinic at Leiden University Medical Center, Leiden, the Netherlands.
• Symptom duration was defined as time between symptom onset and first clinic visit.
• Early treatment was defined as a symptom duration of under 12 weeks, and later treatment defined as symptom duration over 12 weeks.
• Prescription data from patient records and 2022 disease-modifying antirheumatic drug prices (including biologics) was used to determine overall costs over 5 years.
• Autoantibody-negative and autoantibody-positive RA were studied separately because of possible differences in disease severity.

TAKEAWAY:

• For the 165 patients with autoantibody-negative RA, late treatment was associated with 316% higher costs over 5 years than early treatment (€4856/$5292 vs €1159/$1263)
• For antibody-positive RA, costs were 19% higher in the late-treatment group.
• In the 43 patients with antibody-positive RA only prescribed biologics, costs were 46% higher for those with delayed treatment.

IN PRACTICE:

“This is the first study showing the effect of early diagnosis and treatment on treatment-related costs,” wrote the authors. “When RA is detected within 12 weeks after symptom onset, treatment-related costs seem to be lower.”

SOURCE:

The study was led by Elise van Mulligen, PhD, Department of Rheumatology, Leiden University Medical Center. It was published online in Annals of the Rheumatic Diseases. 

LIMITATIONS:

The division of symptom duration by 12 weeks was “arbitrary.” Baseline characteristics, though similar, showed differences for inflammatory markers in autoantibody-positive and autoantibody-negative RA. Thirty seven patients were lost to follow-up, which could induce attrition bias, though the percentage of these patients in the early- and late-treatment groups was similar.

DISCLOSURES:

This study was funded by ZonMw, a Dutch organization for healthcare research. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Early detection and treatment of rheumatoid arthritis (RA; within 12 weeks of symptom onset) results in lower treatment-related costs over 5 years compared with later diagnosis.

METHODOLOGY:

• The study enrolled 431 patients in the Leiden Early Arthritis Clinic at Leiden University Medical Center, Leiden, the Netherlands.
• Symptom duration was defined as time between symptom onset and first clinic visit.
• Early treatment was defined as a symptom duration of under 12 weeks, and later treatment defined as symptom duration over 12 weeks.
• Prescription data from patient records and 2022 disease-modifying antirheumatic drug prices (including biologics) was used to determine overall costs over 5 years.
• Autoantibody-negative and autoantibody-positive RA were studied separately because of possible differences in disease severity.

TAKEAWAY:

• For the 165 patients with autoantibody-negative RA, late treatment was associated with 316% higher costs over 5 years than early treatment (€4856/$5292 vs €1159/$1263)
• For antibody-positive RA, costs were 19% higher in the late-treatment group.
• In the 43 patients with antibody-positive RA only prescribed biologics, costs were 46% higher for those with delayed treatment.

IN PRACTICE:

“This is the first study showing the effect of early diagnosis and treatment on treatment-related costs,” wrote the authors. “When RA is detected within 12 weeks after symptom onset, treatment-related costs seem to be lower.”

SOURCE:

The study was led by Elise van Mulligen, PhD, Department of Rheumatology, Leiden University Medical Center. It was published online in Annals of the Rheumatic Diseases. 

LIMITATIONS:

The division of symptom duration by 12 weeks was “arbitrary.” Baseline characteristics, though similar, showed differences for inflammatory markers in autoantibody-positive and autoantibody-negative RA. Thirty seven patients were lost to follow-up, which could induce attrition bias, though the percentage of these patients in the early- and late-treatment groups was similar.

DISCLOSURES:

This study was funded by ZonMw, a Dutch organization for healthcare research. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.