Psoriatic Arthritis

The Food and Drug Administration’s approval of leflunomide in September 1998 as a treatment for rheumatoid arthritis was sandwiched between the debuts of infliximab (Remicade and biosimilars) and etanercept (Enbrel) in August and November of that year, the latter of which was so exciting that “within 2 months you couldn’t get [it],” recalled Eric M. Ruderman, MD. And “like every middle child, [leflunomide] was underloved, underappreciated, and largely dismissed.”

Yet should it have been? Is it worth another look today?

Courtesy Michael Pollard

At the 2024 Rheumatology Winter Clinical Symposium, Dr. Ruderman reflected on some of the clinical trial data published after leflunomide’s approval that “got lost in the shuffle” of the rightful embrace of biologics in United States practice, and urged reconsideration of the loading strategy still advised in the drug’s labeling.

“I’m not telling you that you should be using [leflunomide] in place of biologics, instead of biologics, or before biologics … but it should be in your toolkit,” said Dr. Ruderman, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago. The drug “still has a role in RA, including in combination with methotrexate, and a potential role in other rheumatic diseases.”

“In our PsA clinic,” he noted, “we’ve actually not infrequently added leflunomide to some of the other agents we’ve been using.”
 

Key Findings Over the Years in RA

Leflunomide showed efficacy similar to that of sulfasalazine in a randomized trial published in 1999 that used primary endpoints of tender/swollen joints and physician and patient global scores. Then, against methotrexate, it proved just as efficacious in achieving at least 20% improvement in American College of Rheumatology composite response criteria (ACR20) over 52 weeks, and in meeting endpoints similar to those of the sulfasalazine trial, in two trials, one published in 1999 and another in 2000.

“So here were two big trials [comparing it with methotrexate] that suggested the drug was just as good as what had become our standard of care by that point,” Dr. Ruderman said.

Each of these three trials used a loading dose of 100 mg leflunomide for 3 days, followed by 20 mg daily. Sulfasalazine was initiated at 2 g and escalated over 4 weeks. Methotrexate was initiated in one of the trials at a dose of 7.5 mg, then increased to 15 mg in almost two-thirds of patients; in the other methotrexate trial the initial dose was 15 mg escalated over 3 months.

Side effects of leflunomide — GI issues, rash, alopecia (reversible), and elevated liver function tests — were similar across the trials, and represented “about the same toxicities as methotrexate,” he said.

Researchers then tested leflunomide as an add-on to methotrexate in patients who had inadequate response, which “was a little bit daunting since we were still concerned about the toxicity of methotrexate at this point,” Dr. Ruderman said. “The idea that we’d take another drug with similar toxicities and add it on to the methotrexate was a little scary.”

But it worked. Patients on a mean background dose of 16.5 mg methotrexate were randomized to placebo or to a 2-day leflunomide loading dose followed by 10 mg/day that could be escalated at 8 weeks to 20 mg if needed. At 6 months, 19.5% and 46.2%, respectively, met ACR20 (P < .001), and “interestingly,” he said, “adverse events were pretty similar” between combination therapy and methotrexate monotherapy.

“This was very much like all the studies we’ve seen over the years with new biologics — they were all added to background methotrexate,” he said. “And the truth is, the [46%] response seen when adding leflunomide to background methotrexate wasn’t very different from the 50% [ACR20] response you tend to see when you add a biologic.”

However, despite the study’s conclusion that combination therapy provided significant benefit to patients with inadequate response to methotrexate alone, “the drug got lost, because everyone was prescribing the biologics,” Dr. Ruderman said.

He said he found only one study comparing leflunomide with a biologic. In a notably small but well-designed study from Sri Lanka published in 2017, 40 patients with an inadequate response to methotrexate were randomized to low-dose rituximab (500 mg x 2) or 20 mg/day leflunomide (no loading dose). At week 24, ACR20 was nearly identical (85% vs 84%), with a similar rate of adverse events.

The researchers pointed out “that there’s a potential cost benefit in developing countries where biologics aren’t as accessible,” he said, agreeing that “the big opportunity for a drug like leflunomide is outside the US, where you don’t have access to the drugs we take advantage of all the time.”

A meeting participant from Canada pointed out that rheumatologists there are “mandated to use it for PsA in combination with methotrexate before we can get a biologic, and for RA we can use it with Plaquenil [hydroxychloroquine] and methotrexate before we get a biologic, so we’re using it all the time.”

Asked about efficacy, the physician said the combination with methotrexate is “absolutely” efficacious. “It works really well” he said. “The problem is, you really have to watch the white cell count and liver function … and the half-life is long.”

Indeed, Dr. Ruderman said during his talk, the plasma half-life of teriflunomide, its active metabolite, is 15.5 days, which is challenging when adverse events occur. “And it’s a terrible drug in young women thinking about pregnancy because it’s teratogenic and stays around,” he said.

Leflunomide, which, notably, was “developed specifically for RA from the get-go” and not borrowed from another specialty, works by blocking de novo pyrimidine synthesis, Dr. Ruderman said. T-cell activation requires the upregulation of pyrimidine production (salvage pathways are insufficient); the “drug prevents that” by inhibiting an enzyme that catalyzes conversion of dihydroorotate to orotate, which, in turn, is converted to pyrimidine ribonucleotides, he explained.

Other potential mechanisms of action have been proposed — mainly, inhibition of tumor necrosis factor signaling and inhibition of kinase activity, including the JAK/STAT pathway — but “there’s not great data for any of them,” he said.
 

Loading vs Not Loading, and Its Role in PsA and Other Diseases

“We stopped loading years ago because at 100 mg for 3 days in a row, everyone has GI issues,” Dr. Ruderman said. “It may have made sense from a pharmacokinetic standpoint because [based on the long half-life] you could get to a higher drug level quicker, but not a practical standpoint, because patients would stop the drug — they couldn’t take it.” The first study to examine the necessity of loading leflunomide in a “prospective, careful way” was published in 2013. It randomized 120 patients to 100 mg or 20 mg for 3 days, followed by a 3-month open-label period of 20 mg, and found no clinical benefit with loading but more diarrhea and elevated liver enzymes.

“It tells us something about how we need to think about half-lives,” he said. “Maybe [loading is] not necessary because the biological effects are different than the drug levels.”

In the PsA space, in 2004, researchers reported a double-blind randomized trial in which 190 patients with active PsA and cutaneous psoriasis with at least 3% body surface area involvement were randomized to receive leflunomide (a loading dose followed by 20 mg/day) or placebo for 24 weeks. Almost 60% of leflunomide-treated patients, compared with 30% of placebo-treated patients, were classified as responders by the Psoriatic Arthritis Response criteria (P < .0001), “which is a soft endpoint” but was utilized at the time, Dr. Ruderman said. The researchers noted improvements in ACR20 and skin responses as well, and toxicity was similar to that reported in the RA studies.

However, approval was never sought, and the drug was infrequently prescribed, “because etanercept came out for this disease, and then adalimumab … and then the world changed,” he said.

More recently, a single-center, double-blind, randomized trial that included 78 Dutch patients with PsA tested leflunomide plus methotrexate vs methotrexate monotherapy and was published in The Lancet Rheumatology. After 16 weeks, mean Psoriatic Arthritis Disease Activity Score (PASDAS) had improved for patients in the combination therapy group in comparison with the monotherapy group (3.1 [standard deviation (SD), 1.4] vs 3.7 [SD, 1.3]; treatment difference, -0.6; 90% CI, -1.0 to -0.1; P = .025). The combination therapy group also achieved PASDAS low disease activity at a higher rate (59%) than that of the monotherapy group (34%; P = .019). Three patients in the combination therapy group experienced serious adverse events, two of which were deemed unrelated to leflunomide. The most frequently occurring adverse events were nausea or vomiting, tiredness, and elevated alanine aminotransferase. Mild adverse events were more common in the methotrexate plus leflunomide group.

In an interview after the meeting, Dr. Ruderman explained that in his practice, about 15 years ago, leflunomide was sometimes prescribed as an alternative to a biologic change for patients whose skin disease improved significantly with ustekinumab (Stelara) but who “suddenly had more joint symptoms that they didn’t have before.”

And “we’ve found ourselves a bit recently with the same sort of story, where patients are prescribed IL-23 inhibitors like Skyrizi [risankizumab] and Tremfya [guselkumab] and their skin does really well but now they’re having more joint symptoms than previously,” he said. “Our choices are to switch to a whole different biologic, or to think about adding something as an adjunct — and maybe leflunomide is a reasonable option.”

In the last 5 years, Dr. Ruderman noted, randomized trial data has been published on leflunomide in lupus nephritis induction, and in lupus nephritis maintenance, as well as in IgG4-related disease.

Dr. Ruderman disclosed consulting and/or drug safety monitoring board work for AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Lilly, Merck, Novartis, NS Pharma, and UCB.

The Food and Drug Administration’s approval of leflunomide in September 1998 as a treatment for rheumatoid arthritis was sandwiched between the debuts of infliximab (Remicade and biosimilars) and etanercept (Enbrel) in August and November of that year, the latter of which was so exciting that “within 2 months you couldn’t get [it],” recalled Eric M. Ruderman, MD. And “like every middle child, [leflunomide] was underloved, underappreciated, and largely dismissed.”

Yet should it have been? Is it worth another look today?

Courtesy Michael Pollard

At the 2024 Rheumatology Winter Clinical Symposium, Dr. Ruderman reflected on some of the clinical trial data published after leflunomide’s approval that “got lost in the shuffle” of the rightful embrace of biologics in United States practice, and urged reconsideration of the loading strategy still advised in the drug’s labeling.

“I’m not telling you that you should be using [leflunomide] in place of biologics, instead of biologics, or before biologics … but it should be in your toolkit,” said Dr. Ruderman, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago. The drug “still has a role in RA, including in combination with methotrexate, and a potential role in other rheumatic diseases.”

“In our PsA clinic,” he noted, “we’ve actually not infrequently added leflunomide to some of the other agents we’ve been using.”
 

Key Findings Over the Years in RA

Leflunomide showed efficacy similar to that of sulfasalazine in a randomized trial published in 1999 that used primary endpoints of tender/swollen joints and physician and patient global scores. Then, against methotrexate, it proved just as efficacious in achieving at least 20% improvement in American College of Rheumatology composite response criteria (ACR20) over 52 weeks, and in meeting endpoints similar to those of the sulfasalazine trial, in two trials, one published in 1999 and another in 2000.

“So here were two big trials [comparing it with methotrexate] that suggested the drug was just as good as what had become our standard of care by that point,” Dr. Ruderman said.

Each of these three trials used a loading dose of 100 mg leflunomide for 3 days, followed by 20 mg daily. Sulfasalazine was initiated at 2 g and escalated over 4 weeks. Methotrexate was initiated in one of the trials at a dose of 7.5 mg, then increased to 15 mg in almost two-thirds of patients; in the other methotrexate trial the initial dose was 15 mg escalated over 3 months.

Side effects of leflunomide — GI issues, rash, alopecia (reversible), and elevated liver function tests — were similar across the trials, and represented “about the same toxicities as methotrexate,” he said.

Researchers then tested leflunomide as an add-on to methotrexate in patients who had inadequate response, which “was a little bit daunting since we were still concerned about the toxicity of methotrexate at this point,” Dr. Ruderman said. “The idea that we’d take another drug with similar toxicities and add it on to the methotrexate was a little scary.”

But it worked. Patients on a mean background dose of 16.5 mg methotrexate were randomized to placebo or to a 2-day leflunomide loading dose followed by 10 mg/day that could be escalated at 8 weeks to 20 mg if needed. At 6 months, 19.5% and 46.2%, respectively, met ACR20 (P < .001), and “interestingly,” he said, “adverse events were pretty similar” between combination therapy and methotrexate monotherapy.

“This was very much like all the studies we’ve seen over the years with new biologics — they were all added to background methotrexate,” he said. “And the truth is, the [46%] response seen when adding leflunomide to background methotrexate wasn’t very different from the 50% [ACR20] response you tend to see when you add a biologic.”

However, despite the study’s conclusion that combination therapy provided significant benefit to patients with inadequate response to methotrexate alone, “the drug got lost, because everyone was prescribing the biologics,” Dr. Ruderman said.

He said he found only one study comparing leflunomide with a biologic. In a notably small but well-designed study from Sri Lanka published in 2017, 40 patients with an inadequate response to methotrexate were randomized to low-dose rituximab (500 mg x 2) or 20 mg/day leflunomide (no loading dose). At week 24, ACR20 was nearly identical (85% vs 84%), with a similar rate of adverse events.

The researchers pointed out “that there’s a potential cost benefit in developing countries where biologics aren’t as accessible,” he said, agreeing that “the big opportunity for a drug like leflunomide is outside the US, where you don’t have access to the drugs we take advantage of all the time.”

A meeting participant from Canada pointed out that rheumatologists there are “mandated to use it for PsA in combination with methotrexate before we can get a biologic, and for RA we can use it with Plaquenil [hydroxychloroquine] and methotrexate before we get a biologic, so we’re using it all the time.”

Asked about efficacy, the physician said the combination with methotrexate is “absolutely” efficacious. “It works really well” he said. “The problem is, you really have to watch the white cell count and liver function … and the half-life is long.”

Indeed, Dr. Ruderman said during his talk, the plasma half-life of teriflunomide, its active metabolite, is 15.5 days, which is challenging when adverse events occur. “And it’s a terrible drug in young women thinking about pregnancy because it’s teratogenic and stays around,” he said.

Leflunomide, which, notably, was “developed specifically for RA from the get-go” and not borrowed from another specialty, works by blocking de novo pyrimidine synthesis, Dr. Ruderman said. T-cell activation requires the upregulation of pyrimidine production (salvage pathways are insufficient); the “drug prevents that” by inhibiting an enzyme that catalyzes conversion of dihydroorotate to orotate, which, in turn, is converted to pyrimidine ribonucleotides, he explained.

Other potential mechanisms of action have been proposed — mainly, inhibition of tumor necrosis factor signaling and inhibition of kinase activity, including the JAK/STAT pathway — but “there’s not great data for any of them,” he said.
 

Loading vs Not Loading, and Its Role in PsA and Other Diseases

“We stopped loading years ago because at 100 mg for 3 days in a row, everyone has GI issues,” Dr. Ruderman said. “It may have made sense from a pharmacokinetic standpoint because [based on the long half-life] you could get to a higher drug level quicker, but not a practical standpoint, because patients would stop the drug — they couldn’t take it.” The first study to examine the necessity of loading leflunomide in a “prospective, careful way” was published in 2013. It randomized 120 patients to 100 mg or 20 mg for 3 days, followed by a 3-month open-label period of 20 mg, and found no clinical benefit with loading but more diarrhea and elevated liver enzymes.

“It tells us something about how we need to think about half-lives,” he said. “Maybe [loading is] not necessary because the biological effects are different than the drug levels.”

In the PsA space, in 2004, researchers reported a double-blind randomized trial in which 190 patients with active PsA and cutaneous psoriasis with at least 3% body surface area involvement were randomized to receive leflunomide (a loading dose followed by 20 mg/day) or placebo for 24 weeks. Almost 60% of leflunomide-treated patients, compared with 30% of placebo-treated patients, were classified as responders by the Psoriatic Arthritis Response criteria (P < .0001), “which is a soft endpoint” but was utilized at the time, Dr. Ruderman said. The researchers noted improvements in ACR20 and skin responses as well, and toxicity was similar to that reported in the RA studies.

However, approval was never sought, and the drug was infrequently prescribed, “because etanercept came out for this disease, and then adalimumab … and then the world changed,” he said.

More recently, a single-center, double-blind, randomized trial that included 78 Dutch patients with PsA tested leflunomide plus methotrexate vs methotrexate monotherapy and was published in The Lancet Rheumatology. After 16 weeks, mean Psoriatic Arthritis Disease Activity Score (PASDAS) had improved for patients in the combination therapy group in comparison with the monotherapy group (3.1 [standard deviation (SD), 1.4] vs 3.7 [SD, 1.3]; treatment difference, -0.6; 90% CI, -1.0 to -0.1; P = .025). The combination therapy group also achieved PASDAS low disease activity at a higher rate (59%) than that of the monotherapy group (34%; P = .019). Three patients in the combination therapy group experienced serious adverse events, two of which were deemed unrelated to leflunomide. The most frequently occurring adverse events were nausea or vomiting, tiredness, and elevated alanine aminotransferase. Mild adverse events were more common in the methotrexate plus leflunomide group.

In an interview after the meeting, Dr. Ruderman explained that in his practice, about 15 years ago, leflunomide was sometimes prescribed as an alternative to a biologic change for patients whose skin disease improved significantly with ustekinumab (Stelara) but who “suddenly had more joint symptoms that they didn’t have before.”

And “we’ve found ourselves a bit recently with the same sort of story, where patients are prescribed IL-23 inhibitors like Skyrizi [risankizumab] and Tremfya [guselkumab] and their skin does really well but now they’re having more joint symptoms than previously,” he said. “Our choices are to switch to a whole different biologic, or to think about adding something as an adjunct — and maybe leflunomide is a reasonable option.”

In the last 5 years, Dr. Ruderman noted, randomized trial data has been published on leflunomide in lupus nephritis induction, and in lupus nephritis maintenance, as well as in IgG4-related disease.

Dr. Ruderman disclosed consulting and/or drug safety monitoring board work for AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Lilly, Merck, Novartis, NS Pharma, and UCB.

The Food and Drug Administration’s approval of leflunomide in September 1998 as a treatment for rheumatoid arthritis was sandwiched between the debuts of infliximab (Remicade and biosimilars) and etanercept (Enbrel) in August and November of that year, the latter of which was so exciting that “within 2 months you couldn’t get [it],” recalled Eric M. Ruderman, MD. And “like every middle child, [leflunomide] was underloved, underappreciated, and largely dismissed.”

Yet should it have been? Is it worth another look today?

Courtesy Michael Pollard

At the 2024 Rheumatology Winter Clinical Symposium, Dr. Ruderman reflected on some of the clinical trial data published after leflunomide’s approval that “got lost in the shuffle” of the rightful embrace of biologics in United States practice, and urged reconsideration of the loading strategy still advised in the drug’s labeling.

“I’m not telling you that you should be using [leflunomide] in place of biologics, instead of biologics, or before biologics … but it should be in your toolkit,” said Dr. Ruderman, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago. The drug “still has a role in RA, including in combination with methotrexate, and a potential role in other rheumatic diseases.”

“In our PsA clinic,” he noted, “we’ve actually not infrequently added leflunomide to some of the other agents we’ve been using.”
 

Key Findings Over the Years in RA

Leflunomide showed efficacy similar to that of sulfasalazine in a randomized trial published in 1999 that used primary endpoints of tender/swollen joints and physician and patient global scores. Then, against methotrexate, it proved just as efficacious in achieving at least 20% improvement in American College of Rheumatology composite response criteria (ACR20) over 52 weeks, and in meeting endpoints similar to those of the sulfasalazine trial, in two trials, one published in 1999 and another in 2000.

“So here were two big trials [comparing it with methotrexate] that suggested the drug was just as good as what had become our standard of care by that point,” Dr. Ruderman said.

Each of these three trials used a loading dose of 100 mg leflunomide for 3 days, followed by 20 mg daily. Sulfasalazine was initiated at 2 g and escalated over 4 weeks. Methotrexate was initiated in one of the trials at a dose of 7.5 mg, then increased to 15 mg in almost two-thirds of patients; in the other methotrexate trial the initial dose was 15 mg escalated over 3 months.

Side effects of leflunomide — GI issues, rash, alopecia (reversible), and elevated liver function tests — were similar across the trials, and represented “about the same toxicities as methotrexate,” he said.

Researchers then tested leflunomide as an add-on to methotrexate in patients who had inadequate response, which “was a little bit daunting since we were still concerned about the toxicity of methotrexate at this point,” Dr. Ruderman said. “The idea that we’d take another drug with similar toxicities and add it on to the methotrexate was a little scary.”

But it worked. Patients on a mean background dose of 16.5 mg methotrexate were randomized to placebo or to a 2-day leflunomide loading dose followed by 10 mg/day that could be escalated at 8 weeks to 20 mg if needed. At 6 months, 19.5% and 46.2%, respectively, met ACR20 (P < .001), and “interestingly,” he said, “adverse events were pretty similar” between combination therapy and methotrexate monotherapy.

“This was very much like all the studies we’ve seen over the years with new biologics — they were all added to background methotrexate,” he said. “And the truth is, the [46%] response seen when adding leflunomide to background methotrexate wasn’t very different from the 50% [ACR20] response you tend to see when you add a biologic.”

However, despite the study’s conclusion that combination therapy provided significant benefit to patients with inadequate response to methotrexate alone, “the drug got lost, because everyone was prescribing the biologics,” Dr. Ruderman said.

He said he found only one study comparing leflunomide with a biologic. In a notably small but well-designed study from Sri Lanka published in 2017, 40 patients with an inadequate response to methotrexate were randomized to low-dose rituximab (500 mg x 2) or 20 mg/day leflunomide (no loading dose). At week 24, ACR20 was nearly identical (85% vs 84%), with a similar rate of adverse events.

The researchers pointed out “that there’s a potential cost benefit in developing countries where biologics aren’t as accessible,” he said, agreeing that “the big opportunity for a drug like leflunomide is outside the US, where you don’t have access to the drugs we take advantage of all the time.”

A meeting participant from Canada pointed out that rheumatologists there are “mandated to use it for PsA in combination with methotrexate before we can get a biologic, and for RA we can use it with Plaquenil [hydroxychloroquine] and methotrexate before we get a biologic, so we’re using it all the time.”

Asked about efficacy, the physician said the combination with methotrexate is “absolutely” efficacious. “It works really well” he said. “The problem is, you really have to watch the white cell count and liver function … and the half-life is long.”

Indeed, Dr. Ruderman said during his talk, the plasma half-life of teriflunomide, its active metabolite, is 15.5 days, which is challenging when adverse events occur. “And it’s a terrible drug in young women thinking about pregnancy because it’s teratogenic and stays around,” he said.

Leflunomide, which, notably, was “developed specifically for RA from the get-go” and not borrowed from another specialty, works by blocking de novo pyrimidine synthesis, Dr. Ruderman said. T-cell activation requires the upregulation of pyrimidine production (salvage pathways are insufficient); the “drug prevents that” by inhibiting an enzyme that catalyzes conversion of dihydroorotate to orotate, which, in turn, is converted to pyrimidine ribonucleotides, he explained.

Other potential mechanisms of action have been proposed — mainly, inhibition of tumor necrosis factor signaling and inhibition of kinase activity, including the JAK/STAT pathway — but “there’s not great data for any of them,” he said.
 

Loading vs Not Loading, and Its Role in PsA and Other Diseases

“We stopped loading years ago because at 100 mg for 3 days in a row, everyone has GI issues,” Dr. Ruderman said. “It may have made sense from a pharmacokinetic standpoint because [based on the long half-life] you could get to a higher drug level quicker, but not a practical standpoint, because patients would stop the drug — they couldn’t take it.” The first study to examine the necessity of loading leflunomide in a “prospective, careful way” was published in 2013. It randomized 120 patients to 100 mg or 20 mg for 3 days, followed by a 3-month open-label period of 20 mg, and found no clinical benefit with loading but more diarrhea and elevated liver enzymes.

“It tells us something about how we need to think about half-lives,” he said. “Maybe [loading is] not necessary because the biological effects are different than the drug levels.”

In the PsA space, in 2004, researchers reported a double-blind randomized trial in which 190 patients with active PsA and cutaneous psoriasis with at least 3% body surface area involvement were randomized to receive leflunomide (a loading dose followed by 20 mg/day) or placebo for 24 weeks. Almost 60% of leflunomide-treated patients, compared with 30% of placebo-treated patients, were classified as responders by the Psoriatic Arthritis Response criteria (P < .0001), “which is a soft endpoint” but was utilized at the time, Dr. Ruderman said. The researchers noted improvements in ACR20 and skin responses as well, and toxicity was similar to that reported in the RA studies.

However, approval was never sought, and the drug was infrequently prescribed, “because etanercept came out for this disease, and then adalimumab … and then the world changed,” he said.

More recently, a single-center, double-blind, randomized trial that included 78 Dutch patients with PsA tested leflunomide plus methotrexate vs methotrexate monotherapy and was published in The Lancet Rheumatology. After 16 weeks, mean Psoriatic Arthritis Disease Activity Score (PASDAS) had improved for patients in the combination therapy group in comparison with the monotherapy group (3.1 [standard deviation (SD), 1.4] vs 3.7 [SD, 1.3]; treatment difference, -0.6; 90% CI, -1.0 to -0.1; P = .025). The combination therapy group also achieved PASDAS low disease activity at a higher rate (59%) than that of the monotherapy group (34%; P = .019). Three patients in the combination therapy group experienced serious adverse events, two of which were deemed unrelated to leflunomide. The most frequently occurring adverse events were nausea or vomiting, tiredness, and elevated alanine aminotransferase. Mild adverse events were more common in the methotrexate plus leflunomide group.

In an interview after the meeting, Dr. Ruderman explained that in his practice, about 15 years ago, leflunomide was sometimes prescribed as an alternative to a biologic change for patients whose skin disease improved significantly with ustekinumab (Stelara) but who “suddenly had more joint symptoms that they didn’t have before.”

And “we’ve found ourselves a bit recently with the same sort of story, where patients are prescribed IL-23 inhibitors like Skyrizi [risankizumab] and Tremfya [guselkumab] and their skin does really well but now they’re having more joint symptoms than previously,” he said. “Our choices are to switch to a whole different biologic, or to think about adding something as an adjunct — and maybe leflunomide is a reasonable option.”

In the last 5 years, Dr. Ruderman noted, randomized trial data has been published on leflunomide in lupus nephritis induction, and in lupus nephritis maintenance, as well as in IgG4-related disease.

Dr. Ruderman disclosed consulting and/or drug safety monitoring board work for AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Lilly, Merck, Novartis, NS Pharma, and UCB.

Tools to screen for spondyloarthritis (SpA) among people with the extra-musculoskeletal conditions that commonly co-occur with SpA — psoriasis, uveitis, and inflammatory bowel disease (IBD) — show potential for their use in target populations but have limited generalizability for patients at risk for SpA, according to findings from a scoping review of 18 tools.

Prior to the review comparing available tools, first author Vartika Kesarwani, MBBS, of the University of Connecticut, Farmington, and colleagues wrote that the performance of SpA screening tools in dermatology, ophthalmology, and gastroenterology contexts had not been evaluated.

“Given the evolving landscape of therapeutics for spondyloarthritis, recognizing the full spectrum of disease manifestations in individual patients becomes increasingly important. This knowledge can inform treatment decisions, potentially altering the course of the disease,” corresponding author Joerg Ermann, MD, of Brigham and Women’s Hospital, Boston, said in an interview.

In the study, published on February 1 in Arthritis Care & Research, the investigators identified 13 SpA screening tools for psoriasis (screening specifically for psoriatic arthritis), two for uveitis, and three for IBD. All tools with the exception of one for uveitis were patient-oriented questionnaires with an average completion time of less than 5 minutes.

Overall, the researchers found significant variability in the nature of the questions used to identify clinical features of SpA; 15 tools included at least one question on back pain or stiffness; 16 tools had at least one question on joint pain, swelling, or inflammation; 10 included questions about heel or elbow pain; and 10 included questions about swelling of digits.

All 13 of the psoriasis tools were screened for peripheral arthritis, while 10 screened for axial involvement, eight screened for enthesitis, and eight screened for dactylitis.

All three of the IBD tools were screened for axial involvement and peripheral arthritis, and two were screened for enthesitis and dactylitis.

Both of the uveitis tools were screened for axial involvement, but neither was screened for peripheral arthritis, enthesitis, or dactylitis.

Sensitivities in the primary validation groups were similar for the 16 tools for which sensitivities were reported, ranging mainly from 82% to 92% for 11 psoriasis tools, 91% to 96% for uveitis tools, and 83% to 93% for IBD tools.

Specificities for psoriasis tools ranged from 69% to 83% for all but two of the tools, which was 46% for one and 35%-89% for another across three geographical cohorts. For uveitis tools, specificities were 91%-97% for uveitis tools, and for IBD tools, 77%-90%. Most of the secondary validations involved psoriasis tools, and these were generally lower and also more variable.
 

The Case for a Generic Tool

The relatively few SpA tools for patients with uveitis and IBD, compared with psoriasis, may be attributable to a lack of awareness of the association between these conditions on the part of ophthalmologists and gastroenterologists, the researchers wrote in their discussion. Therefore, a generic SpA screening tool that could apply to any extra-articular manifestation might increase screening across clinical settings and streamline rheumatology referrals, they noted.

The review’s findings were limited by several factors, including the inclusion of only articles in English and the relatively few tools for uveitis and IBD patients, the researchers noted.

The findings suggested that although the performances of the tools are similar, their degree of variability supports the value of a generic tool, they concluded.
 

Streamlining to Increase Screening

“Compared to the large amount of research in psoriasis and psoriatic arthritis, relatively little has been done with regard to screening for spondyloarthritis in patients with uveitis or IBD,” Dr. Ermann told this news organization. “Despite the numerous screening tools developed for psoriatic arthritis, no ideal screening tool has emerged, and the implementation of effective screening strategies in clinical practice is challenging,” he said. In the current study, the compartmentalization of research into individual conditions like psoriasis, uveitis, and IBD was notable despite the interconnected nature of these conditions with SpA, he added.

In practice, Dr. Ermann advised clinicians to maintain a high index of suspicion for SpA in patients presenting with psoriasis, uveitis, or IBD and proactively ask patients about symptoms outside their primary specialty.

“Future research should focus on developing a universal spondyloarthritis screening tool that is comprehensive, easily understandable, and can be used across various clinical settings,” he said.
 

Need for Early Identification and Closer Collaboration

A delay in SpA diagnosis of as little as 6 months can lead to worse outcomes, Rebecca Haberman, MD, a rheumatologist at NYU Langone Health, New York City, said in an interview. “Patients with these conditions may first present to dermatologists, gastroenterologists, and/or ophthalmologists before rheumatologic evaluation. If we can identify these patients early at this stage, we might be able to improve outcomes, but the question remains of how we get these patients to the proper care,” she said.

The review examined the currently available screening tools for use in patients with psoriasis, IBD, and uveitis and highlights the heterogeneity of these tools in terms of use and disease characteristics, as well as the lack of tools for use in gastroenterology and ophthalmology offices, Dr. Haberman said.

The review “proposes several important ideas, such as creating a unified screening tool that can be used across diseases and fields, to reduce confusion by providers and help provide standardization of the referral process to rheumatologists,” she said.

“Even though SpA is prevalent in many patients with psoriasis, IBD, and uveitis, it remains very underdiagnosed, and often referrals to rheumatologists are not made,” Dr. Haberman told this news organization. Diagnostic challenges likely include SpA’s heterogeneous presentation, the specialists’ lack of knowledge regarding the connection between these conditions and joint disease, and time pressures in clinical settings, she said.

“Other practitioners are not always trained to ask about joint pain and often have limited time in their exams to ask additional questions. To overcome this, more collaboration is needed between dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, as many of our diseases live in the same family,” Dr. Haberman said.

Improving clinician education and creating relationships can help facilitate questions and referrals, she said. Short, effective screening tools that can be filled out by the patient may also help overcome specialists’ discomfort about asking musculoskeletal-related questions and would save time in the clinical visit, she said.

More research is needed to identify the best screening tools and questions and which are the most highly sensitive and specific, Dr. Haberman said. “This will allow for rheumatologists to see patients who may have SpA earlier in their course without overwhelming the system with new referrals.” In addition, more work is needed on how and whether screening tools are being used in clinical practice, not just in research studies, she said.

The study was supported by a grant from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers and Dr. Haberman had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Tools to screen for spondyloarthritis (SpA) among people with the extra-musculoskeletal conditions that commonly co-occur with SpA — psoriasis, uveitis, and inflammatory bowel disease (IBD) — show potential for their use in target populations but have limited generalizability for patients at risk for SpA, according to findings from a scoping review of 18 tools.

Prior to the review comparing available tools, first author Vartika Kesarwani, MBBS, of the University of Connecticut, Farmington, and colleagues wrote that the performance of SpA screening tools in dermatology, ophthalmology, and gastroenterology contexts had not been evaluated.

“Given the evolving landscape of therapeutics for spondyloarthritis, recognizing the full spectrum of disease manifestations in individual patients becomes increasingly important. This knowledge can inform treatment decisions, potentially altering the course of the disease,” corresponding author Joerg Ermann, MD, of Brigham and Women’s Hospital, Boston, said in an interview.

In the study, published on February 1 in Arthritis Care & Research, the investigators identified 13 SpA screening tools for psoriasis (screening specifically for psoriatic arthritis), two for uveitis, and three for IBD. All tools with the exception of one for uveitis were patient-oriented questionnaires with an average completion time of less than 5 minutes.

Overall, the researchers found significant variability in the nature of the questions used to identify clinical features of SpA; 15 tools included at least one question on back pain or stiffness; 16 tools had at least one question on joint pain, swelling, or inflammation; 10 included questions about heel or elbow pain; and 10 included questions about swelling of digits.

All 13 of the psoriasis tools were screened for peripheral arthritis, while 10 screened for axial involvement, eight screened for enthesitis, and eight screened for dactylitis.

All three of the IBD tools were screened for axial involvement and peripheral arthritis, and two were screened for enthesitis and dactylitis.

Both of the uveitis tools were screened for axial involvement, but neither was screened for peripheral arthritis, enthesitis, or dactylitis.

Sensitivities in the primary validation groups were similar for the 16 tools for which sensitivities were reported, ranging mainly from 82% to 92% for 11 psoriasis tools, 91% to 96% for uveitis tools, and 83% to 93% for IBD tools.

Specificities for psoriasis tools ranged from 69% to 83% for all but two of the tools, which was 46% for one and 35%-89% for another across three geographical cohorts. For uveitis tools, specificities were 91%-97% for uveitis tools, and for IBD tools, 77%-90%. Most of the secondary validations involved psoriasis tools, and these were generally lower and also more variable.
 

The Case for a Generic Tool

The relatively few SpA tools for patients with uveitis and IBD, compared with psoriasis, may be attributable to a lack of awareness of the association between these conditions on the part of ophthalmologists and gastroenterologists, the researchers wrote in their discussion. Therefore, a generic SpA screening tool that could apply to any extra-articular manifestation might increase screening across clinical settings and streamline rheumatology referrals, they noted.

The review’s findings were limited by several factors, including the inclusion of only articles in English and the relatively few tools for uveitis and IBD patients, the researchers noted.

The findings suggested that although the performances of the tools are similar, their degree of variability supports the value of a generic tool, they concluded.
 

Streamlining to Increase Screening

“Compared to the large amount of research in psoriasis and psoriatic arthritis, relatively little has been done with regard to screening for spondyloarthritis in patients with uveitis or IBD,” Dr. Ermann told this news organization. “Despite the numerous screening tools developed for psoriatic arthritis, no ideal screening tool has emerged, and the implementation of effective screening strategies in clinical practice is challenging,” he said. In the current study, the compartmentalization of research into individual conditions like psoriasis, uveitis, and IBD was notable despite the interconnected nature of these conditions with SpA, he added.

In practice, Dr. Ermann advised clinicians to maintain a high index of suspicion for SpA in patients presenting with psoriasis, uveitis, or IBD and proactively ask patients about symptoms outside their primary specialty.

“Future research should focus on developing a universal spondyloarthritis screening tool that is comprehensive, easily understandable, and can be used across various clinical settings,” he said.
 

Need for Early Identification and Closer Collaboration

A delay in SpA diagnosis of as little as 6 months can lead to worse outcomes, Rebecca Haberman, MD, a rheumatologist at NYU Langone Health, New York City, said in an interview. “Patients with these conditions may first present to dermatologists, gastroenterologists, and/or ophthalmologists before rheumatologic evaluation. If we can identify these patients early at this stage, we might be able to improve outcomes, but the question remains of how we get these patients to the proper care,” she said.

The review examined the currently available screening tools for use in patients with psoriasis, IBD, and uveitis and highlights the heterogeneity of these tools in terms of use and disease characteristics, as well as the lack of tools for use in gastroenterology and ophthalmology offices, Dr. Haberman said.

The review “proposes several important ideas, such as creating a unified screening tool that can be used across diseases and fields, to reduce confusion by providers and help provide standardization of the referral process to rheumatologists,” she said.

“Even though SpA is prevalent in many patients with psoriasis, IBD, and uveitis, it remains very underdiagnosed, and often referrals to rheumatologists are not made,” Dr. Haberman told this news organization. Diagnostic challenges likely include SpA’s heterogeneous presentation, the specialists’ lack of knowledge regarding the connection between these conditions and joint disease, and time pressures in clinical settings, she said.

“Other practitioners are not always trained to ask about joint pain and often have limited time in their exams to ask additional questions. To overcome this, more collaboration is needed between dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, as many of our diseases live in the same family,” Dr. Haberman said.

Improving clinician education and creating relationships can help facilitate questions and referrals, she said. Short, effective screening tools that can be filled out by the patient may also help overcome specialists’ discomfort about asking musculoskeletal-related questions and would save time in the clinical visit, she said.

More research is needed to identify the best screening tools and questions and which are the most highly sensitive and specific, Dr. Haberman said. “This will allow for rheumatologists to see patients who may have SpA earlier in their course without overwhelming the system with new referrals.” In addition, more work is needed on how and whether screening tools are being used in clinical practice, not just in research studies, she said.

The study was supported by a grant from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers and Dr. Haberman had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Tools to screen for spondyloarthritis (SpA) among people with the extra-musculoskeletal conditions that commonly co-occur with SpA — psoriasis, uveitis, and inflammatory bowel disease (IBD) — show potential for their use in target populations but have limited generalizability for patients at risk for SpA, according to findings from a scoping review of 18 tools.

Prior to the review comparing available tools, first author Vartika Kesarwani, MBBS, of the University of Connecticut, Farmington, and colleagues wrote that the performance of SpA screening tools in dermatology, ophthalmology, and gastroenterology contexts had not been evaluated.

“Given the evolving landscape of therapeutics for spondyloarthritis, recognizing the full spectrum of disease manifestations in individual patients becomes increasingly important. This knowledge can inform treatment decisions, potentially altering the course of the disease,” corresponding author Joerg Ermann, MD, of Brigham and Women’s Hospital, Boston, said in an interview.

In the study, published on February 1 in Arthritis Care & Research, the investigators identified 13 SpA screening tools for psoriasis (screening specifically for psoriatic arthritis), two for uveitis, and three for IBD. All tools with the exception of one for uveitis were patient-oriented questionnaires with an average completion time of less than 5 minutes.

Overall, the researchers found significant variability in the nature of the questions used to identify clinical features of SpA; 15 tools included at least one question on back pain or stiffness; 16 tools had at least one question on joint pain, swelling, or inflammation; 10 included questions about heel or elbow pain; and 10 included questions about swelling of digits.

All 13 of the psoriasis tools were screened for peripheral arthritis, while 10 screened for axial involvement, eight screened for enthesitis, and eight screened for dactylitis.

All three of the IBD tools were screened for axial involvement and peripheral arthritis, and two were screened for enthesitis and dactylitis.

Both of the uveitis tools were screened for axial involvement, but neither was screened for peripheral arthritis, enthesitis, or dactylitis.

Sensitivities in the primary validation groups were similar for the 16 tools for which sensitivities were reported, ranging mainly from 82% to 92% for 11 psoriasis tools, 91% to 96% for uveitis tools, and 83% to 93% for IBD tools.

Specificities for psoriasis tools ranged from 69% to 83% for all but two of the tools, which was 46% for one and 35%-89% for another across three geographical cohorts. For uveitis tools, specificities were 91%-97% for uveitis tools, and for IBD tools, 77%-90%. Most of the secondary validations involved psoriasis tools, and these were generally lower and also more variable.
 

The Case for a Generic Tool

The relatively few SpA tools for patients with uveitis and IBD, compared with psoriasis, may be attributable to a lack of awareness of the association between these conditions on the part of ophthalmologists and gastroenterologists, the researchers wrote in their discussion. Therefore, a generic SpA screening tool that could apply to any extra-articular manifestation might increase screening across clinical settings and streamline rheumatology referrals, they noted.

The review’s findings were limited by several factors, including the inclusion of only articles in English and the relatively few tools for uveitis and IBD patients, the researchers noted.

The findings suggested that although the performances of the tools are similar, their degree of variability supports the value of a generic tool, they concluded.
 

Streamlining to Increase Screening

“Compared to the large amount of research in psoriasis and psoriatic arthritis, relatively little has been done with regard to screening for spondyloarthritis in patients with uveitis or IBD,” Dr. Ermann told this news organization. “Despite the numerous screening tools developed for psoriatic arthritis, no ideal screening tool has emerged, and the implementation of effective screening strategies in clinical practice is challenging,” he said. In the current study, the compartmentalization of research into individual conditions like psoriasis, uveitis, and IBD was notable despite the interconnected nature of these conditions with SpA, he added.

In practice, Dr. Ermann advised clinicians to maintain a high index of suspicion for SpA in patients presenting with psoriasis, uveitis, or IBD and proactively ask patients about symptoms outside their primary specialty.

“Future research should focus on developing a universal spondyloarthritis screening tool that is comprehensive, easily understandable, and can be used across various clinical settings,” he said.
 

Need for Early Identification and Closer Collaboration

A delay in SpA diagnosis of as little as 6 months can lead to worse outcomes, Rebecca Haberman, MD, a rheumatologist at NYU Langone Health, New York City, said in an interview. “Patients with these conditions may first present to dermatologists, gastroenterologists, and/or ophthalmologists before rheumatologic evaluation. If we can identify these patients early at this stage, we might be able to improve outcomes, but the question remains of how we get these patients to the proper care,” she said.

The review examined the currently available screening tools for use in patients with psoriasis, IBD, and uveitis and highlights the heterogeneity of these tools in terms of use and disease characteristics, as well as the lack of tools for use in gastroenterology and ophthalmology offices, Dr. Haberman said.

The review “proposes several important ideas, such as creating a unified screening tool that can be used across diseases and fields, to reduce confusion by providers and help provide standardization of the referral process to rheumatologists,” she said.

“Even though SpA is prevalent in many patients with psoriasis, IBD, and uveitis, it remains very underdiagnosed, and often referrals to rheumatologists are not made,” Dr. Haberman told this news organization. Diagnostic challenges likely include SpA’s heterogeneous presentation, the specialists’ lack of knowledge regarding the connection between these conditions and joint disease, and time pressures in clinical settings, she said.

“Other practitioners are not always trained to ask about joint pain and often have limited time in their exams to ask additional questions. To overcome this, more collaboration is needed between dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, as many of our diseases live in the same family,” Dr. Haberman said.

Improving clinician education and creating relationships can help facilitate questions and referrals, she said. Short, effective screening tools that can be filled out by the patient may also help overcome specialists’ discomfort about asking musculoskeletal-related questions and would save time in the clinical visit, she said.

More research is needed to identify the best screening tools and questions and which are the most highly sensitive and specific, Dr. Haberman said. “This will allow for rheumatologists to see patients who may have SpA earlier in their course without overwhelming the system with new referrals.” In addition, more work is needed on how and whether screening tools are being used in clinical practice, not just in research studies, she said.

The study was supported by a grant from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers and Dr. Haberman had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Many factors may influence fatigue in patients with psoriasis and psoriatic arthritis (PsA), researchers report.

METHODOLOGY:

• The individual components of fatigue in psoriasis and PsA have not been examined thoroughly.
• Researchers drew from the nationwide prospective Danish Skin Cohort to identify 2741 adults with dermatologist-diagnosed psoriasis (of which 593 also had PsA) and 3788 controls in the general population.
• All adults in the analysis completed the multidimensional fatigue inventory (MIF-20), a validated 20-item tool that measures five dimensions of fatigue: General fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. A higher score indicates more severe fatigue.
• All adults were also asked about their current intensity of joint pain over the previous 7 days, severity of pruritus and skin pain over the previous 24 hours, and sleep problems over the previous 72 hours on a numerical rating scale (NRS). The researchers applied linear regression models to continuous outcomes and adjusted for age, sex, socioeconomic status, psoriasis severity, and joint pain intensity, and beta coefficients (β) for the slopes were estimated with 95% CIs.

TAKEAWAY:

• Compared with the general population, higher total MFI-20 scores were observed for psoriasis and PsA, respectively. However, on the adjusted analysis, the impact on total fatigue was greatest for those with PsA (β = 5.23; 95% CI, 3.55-6.90), followed by psoriasis (β = 2.10; 95% CI, 0.96-3.25) compared with the general population (P trend < .0001).
• Increasing age was associated with a lower impact on total fatigue in psoriasis (β = −0.13; 95% CI, −0.18 to −0.08) and in PsA (β = −0.10; 95% CI, −0.19 to −0.01).
• Among patients with psoriasis with or without PsA, increasing joint pain intensity was associated with overall fatigue (β = 2.23; 95% CI, 2.03-2.44) for each one-point increase in joint pain on the NRS.
• In other findings, greater intensity of itch was associated with higher fatigue scores for both psoriasis and PsA, while skin pain was significantly associated with fatigue in PsA (β = 0.65; 95% CI, 0.08-1.22) but not in psoriasis without PsA (P = .2043).

IN PRACTICE:

“The observation that joint pain and itch, rather than psoriasis severity, appear to be major drivers of fatigue in psoriasis and PsA highlights the importance of a symptom-based approach when treating psoriasis, rather than focusing on objective severity measures alone,” the authors wrote.

SOURCE:

Corresponding author Alexander Egeberg, MD, of the Department of Dermatology at Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark, and colleagues conducted the research, which was published in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The researchers were unable to assess whether the pain was inflammatory or noninflammatory or the number of affected joints. They also lacked information about the use of methotrexate, which commonly causes fatigue.

DISCLOSURES:

Dr. Egeberg is now an employee at LEO Pharma. He has received research funding from Pfizer, Eli Lilly, the Danish National Psoriasis Foundation, and the Royal Hofbundtmager Aage Bang Foundation, and honoraria as a consultant and/or speaker from AbbVie, Almirall, Bristol-Myers Squibb, Leo Pharma, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly, Novartis, UCB, Union Therapeutics, Horizon Therapeutics, Galderma, and Janssen Pharmaceuticals. Three of the coauthors reported being a consultant to, an adviser for, and/or having received research support from many pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Many factors may influence fatigue in patients with psoriasis and psoriatic arthritis (PsA), researchers report.

METHODOLOGY:

• The individual components of fatigue in psoriasis and PsA have not been examined thoroughly.
• Researchers drew from the nationwide prospective Danish Skin Cohort to identify 2741 adults with dermatologist-diagnosed psoriasis (of which 593 also had PsA) and 3788 controls in the general population.
• All adults in the analysis completed the multidimensional fatigue inventory (MIF-20), a validated 20-item tool that measures five dimensions of fatigue: General fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. A higher score indicates more severe fatigue.
• All adults were also asked about their current intensity of joint pain over the previous 7 days, severity of pruritus and skin pain over the previous 24 hours, and sleep problems over the previous 72 hours on a numerical rating scale (NRS). The researchers applied linear regression models to continuous outcomes and adjusted for age, sex, socioeconomic status, psoriasis severity, and joint pain intensity, and beta coefficients (β) for the slopes were estimated with 95% CIs.

TAKEAWAY:

• Compared with the general population, higher total MFI-20 scores were observed for psoriasis and PsA, respectively. However, on the adjusted analysis, the impact on total fatigue was greatest for those with PsA (β = 5.23; 95% CI, 3.55-6.90), followed by psoriasis (β = 2.10; 95% CI, 0.96-3.25) compared with the general population (P trend < .0001).
• Increasing age was associated with a lower impact on total fatigue in psoriasis (β = −0.13; 95% CI, −0.18 to −0.08) and in PsA (β = −0.10; 95% CI, −0.19 to −0.01).
• Among patients with psoriasis with or without PsA, increasing joint pain intensity was associated with overall fatigue (β = 2.23; 95% CI, 2.03-2.44) for each one-point increase in joint pain on the NRS.
• In other findings, greater intensity of itch was associated with higher fatigue scores for both psoriasis and PsA, while skin pain was significantly associated with fatigue in PsA (β = 0.65; 95% CI, 0.08-1.22) but not in psoriasis without PsA (P = .2043).

IN PRACTICE:

“The observation that joint pain and itch, rather than psoriasis severity, appear to be major drivers of fatigue in psoriasis and PsA highlights the importance of a symptom-based approach when treating psoriasis, rather than focusing on objective severity measures alone,” the authors wrote.

SOURCE:

Corresponding author Alexander Egeberg, MD, of the Department of Dermatology at Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark, and colleagues conducted the research, which was published in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The researchers were unable to assess whether the pain was inflammatory or noninflammatory or the number of affected joints. They also lacked information about the use of methotrexate, which commonly causes fatigue.

DISCLOSURES:

Dr. Egeberg is now an employee at LEO Pharma. He has received research funding from Pfizer, Eli Lilly, the Danish National Psoriasis Foundation, and the Royal Hofbundtmager Aage Bang Foundation, and honoraria as a consultant and/or speaker from AbbVie, Almirall, Bristol-Myers Squibb, Leo Pharma, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly, Novartis, UCB, Union Therapeutics, Horizon Therapeutics, Galderma, and Janssen Pharmaceuticals. Three of the coauthors reported being a consultant to, an adviser for, and/or having received research support from many pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Many factors may influence fatigue in patients with psoriasis and psoriatic arthritis (PsA), researchers report.

METHODOLOGY:

• The individual components of fatigue in psoriasis and PsA have not been examined thoroughly.
• Researchers drew from the nationwide prospective Danish Skin Cohort to identify 2741 adults with dermatologist-diagnosed psoriasis (of which 593 also had PsA) and 3788 controls in the general population.
• All adults in the analysis completed the multidimensional fatigue inventory (MIF-20), a validated 20-item tool that measures five dimensions of fatigue: General fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. A higher score indicates more severe fatigue.
• All adults were also asked about their current intensity of joint pain over the previous 7 days, severity of pruritus and skin pain over the previous 24 hours, and sleep problems over the previous 72 hours on a numerical rating scale (NRS). The researchers applied linear regression models to continuous outcomes and adjusted for age, sex, socioeconomic status, psoriasis severity, and joint pain intensity, and beta coefficients (β) for the slopes were estimated with 95% CIs.

TAKEAWAY:

• Compared with the general population, higher total MFI-20 scores were observed for psoriasis and PsA, respectively. However, on the adjusted analysis, the impact on total fatigue was greatest for those with PsA (β = 5.23; 95% CI, 3.55-6.90), followed by psoriasis (β = 2.10; 95% CI, 0.96-3.25) compared with the general population (P trend < .0001).
• Increasing age was associated with a lower impact on total fatigue in psoriasis (β = −0.13; 95% CI, −0.18 to −0.08) and in PsA (β = −0.10; 95% CI, −0.19 to −0.01).
• Among patients with psoriasis with or without PsA, increasing joint pain intensity was associated with overall fatigue (β = 2.23; 95% CI, 2.03-2.44) for each one-point increase in joint pain on the NRS.
• In other findings, greater intensity of itch was associated with higher fatigue scores for both psoriasis and PsA, while skin pain was significantly associated with fatigue in PsA (β = 0.65; 95% CI, 0.08-1.22) but not in psoriasis without PsA (P = .2043).

IN PRACTICE:

“The observation that joint pain and itch, rather than psoriasis severity, appear to be major drivers of fatigue in psoriasis and PsA highlights the importance of a symptom-based approach when treating psoriasis, rather than focusing on objective severity measures alone,” the authors wrote.

SOURCE:

Corresponding author Alexander Egeberg, MD, of the Department of Dermatology at Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark, and colleagues conducted the research, which was published in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The researchers were unable to assess whether the pain was inflammatory or noninflammatory or the number of affected joints. They also lacked information about the use of methotrexate, which commonly causes fatigue.

DISCLOSURES:

Dr. Egeberg is now an employee at LEO Pharma. He has received research funding from Pfizer, Eli Lilly, the Danish National Psoriasis Foundation, and the Royal Hofbundtmager Aage Bang Foundation, and honoraria as a consultant and/or speaker from AbbVie, Almirall, Bristol-Myers Squibb, Leo Pharma, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly, Novartis, UCB, Union Therapeutics, Horizon Therapeutics, Galderma, and Janssen Pharmaceuticals. Three of the coauthors reported being a consultant to, an adviser for, and/or having received research support from many pharmaceutical companies.

A version of this article appeared on Medscape.com.

An important comorbidity of PsA is vascular inflammation leading to accelerated atherosclerosis, and higher risk for cardiovascular and cerebrovascular disease. Previously, vascular imaging modalities have demonstrated vascular inflammation in PsA. In a cross-sectional study that included 75 patients with active PsA and 40 control individuals without PsA, Kleinrensink and colleagues demonstrated that vascular inflammation of the whole aorta was significantly increased in patients with PsA vs control individuals. Of note, the association remained significant after adjusting for gender, age, body mass index, mean arterial pressure, and aortic calcification, but it was not associated with disease-related parameters. Further studies to determine the contributions of PsA per se and its comorbidities to vascular inflammation are required. Nevertheless, the management of PsA should include close monitoring and aggressive treatment of risk factors for atherosclerotic vascular disease.

Psychotic disorders are known to be associated with psoriasis, but their association with PsA is less well known. Using French health administrative data, Brenaut and colleagues showed that the prevalence of psychotic disorders was higher in individuals with psoriasis but surprisingly lower in individuals with PsA, compared with the general population. Moreover, a co-diagnosis of psoriasis/PsA and psychotic disorders was associated with an increased mortality rate and at a lower age.

Clinical trials have demonstrated that Janus kinase (JAK) inhibitors have a remarkable efficacy in the treatment of the musculoskeletal manifestations of PsA. Observational studies are important to evaluate effectiveness in real-world settings. In a study that included 123 patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry who were treated with tofacitinib, Mease and colleagues observed that a quarter of patients achieved a state of low disease activity, based on the Clinical Disease Activity Index for PsA at 6 ± 3 months of follow-up. A substantial proportion of patients also reported the resolution of dactylitis (29.4%) and enthesitis (42.9%). Although these results are remarkable compared with what was seen with older therapies, one must note that only a quarter of patients achieved remission; more effective regimens for improving outcomes in PsA are required.

The safety of newer therapies is always of concern. It is reassuring that a meta-analysis of six randomized controlled trials that included 5038 patients with PsA who received either risankizumab (an anti-interleukin-23 antibody) or placebo by Su and colleagues demonstrated that the incidences of serious adverse events and serious treatment-emergent adverse events were similar between the risankizumab and placebo groups. Given the excellent safety profile of some of the newer therapies for PsA, trials with combinations of newer targeted therapies in treatment-resistant PsA should be conducted.

An important comorbidity of PsA is vascular inflammation leading to accelerated atherosclerosis, and higher risk for cardiovascular and cerebrovascular disease. Previously, vascular imaging modalities have demonstrated vascular inflammation in PsA. In a cross-sectional study that included 75 patients with active PsA and 40 control individuals without PsA, Kleinrensink and colleagues demonstrated that vascular inflammation of the whole aorta was significantly increased in patients with PsA vs control individuals. Of note, the association remained significant after adjusting for gender, age, body mass index, mean arterial pressure, and aortic calcification, but it was not associated with disease-related parameters. Further studies to determine the contributions of PsA per se and its comorbidities to vascular inflammation are required. Nevertheless, the management of PsA should include close monitoring and aggressive treatment of risk factors for atherosclerotic vascular disease.

Psychotic disorders are known to be associated with psoriasis, but their association with PsA is less well known. Using French health administrative data, Brenaut and colleagues showed that the prevalence of psychotic disorders was higher in individuals with psoriasis but surprisingly lower in individuals with PsA, compared with the general population. Moreover, a co-diagnosis of psoriasis/PsA and psychotic disorders was associated with an increased mortality rate and at a lower age.

Clinical trials have demonstrated that Janus kinase (JAK) inhibitors have a remarkable efficacy in the treatment of the musculoskeletal manifestations of PsA. Observational studies are important to evaluate effectiveness in real-world settings. In a study that included 123 patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry who were treated with tofacitinib, Mease and colleagues observed that a quarter of patients achieved a state of low disease activity, based on the Clinical Disease Activity Index for PsA at 6 ± 3 months of follow-up. A substantial proportion of patients also reported the resolution of dactylitis (29.4%) and enthesitis (42.9%). Although these results are remarkable compared with what was seen with older therapies, one must note that only a quarter of patients achieved remission; more effective regimens for improving outcomes in PsA are required.

The safety of newer therapies is always of concern. It is reassuring that a meta-analysis of six randomized controlled trials that included 5038 patients with PsA who received either risankizumab (an anti-interleukin-23 antibody) or placebo by Su and colleagues demonstrated that the incidences of serious adverse events and serious treatment-emergent adverse events were similar between the risankizumab and placebo groups. Given the excellent safety profile of some of the newer therapies for PsA, trials with combinations of newer targeted therapies in treatment-resistant PsA should be conducted.

An important comorbidity of PsA is vascular inflammation leading to accelerated atherosclerosis, and higher risk for cardiovascular and cerebrovascular disease. Previously, vascular imaging modalities have demonstrated vascular inflammation in PsA. In a cross-sectional study that included 75 patients with active PsA and 40 control individuals without PsA, Kleinrensink and colleagues demonstrated that vascular inflammation of the whole aorta was significantly increased in patients with PsA vs control individuals. Of note, the association remained significant after adjusting for gender, age, body mass index, mean arterial pressure, and aortic calcification, but it was not associated with disease-related parameters. Further studies to determine the contributions of PsA per se and its comorbidities to vascular inflammation are required. Nevertheless, the management of PsA should include close monitoring and aggressive treatment of risk factors for atherosclerotic vascular disease.

Psychotic disorders are known to be associated with psoriasis, but their association with PsA is less well known. Using French health administrative data, Brenaut and colleagues showed that the prevalence of psychotic disorders was higher in individuals with psoriasis but surprisingly lower in individuals with PsA, compared with the general population. Moreover, a co-diagnosis of psoriasis/PsA and psychotic disorders was associated with an increased mortality rate and at a lower age.

Clinical trials have demonstrated that Janus kinase (JAK) inhibitors have a remarkable efficacy in the treatment of the musculoskeletal manifestations of PsA. Observational studies are important to evaluate effectiveness in real-world settings. In a study that included 123 patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry who were treated with tofacitinib, Mease and colleagues observed that a quarter of patients achieved a state of low disease activity, based on the Clinical Disease Activity Index for PsA at 6 ± 3 months of follow-up. A substantial proportion of patients also reported the resolution of dactylitis (29.4%) and enthesitis (42.9%). Although these results are remarkable compared with what was seen with older therapies, one must note that only a quarter of patients achieved remission; more effective regimens for improving outcomes in PsA are required.

The safety of newer therapies is always of concern. It is reassuring that a meta-analysis of six randomized controlled trials that included 5038 patients with PsA who received either risankizumab (an anti-interleukin-23 antibody) or placebo by Su and colleagues demonstrated that the incidences of serious adverse events and serious treatment-emergent adverse events were similar between the risankizumab and placebo groups. Given the excellent safety profile of some of the newer therapies for PsA, trials with combinations of newer targeted therapies in treatment-resistant PsA should be conducted.

The US Food and Drug Administration has approved the first interchangeable, high-concentration, citrate-free adalimumab biosimilar, adalimumab-ryvk (Simlandi).

This is the 10th adalimumab biosimilar approved by the regulatory agency and the first biosimilar approval in the US market for the Icelandic pharmaceutical company Alvotech in partnership with Teva Pharmaceuticals.

“An interchangeable citrate-free, high-concentration biosimilar adalimumab has the potential to change the market dynamics in a rapidly evolving environment for biosimilars in the U.S.,” said Robert Wessman, chairman and CEO of Alvotech, in a company press release on February 23.

Adalimumab-ryvk was approved in the European Union in 2021 and in Australia and Canada in 2022. 

Adalimumab-ryvk is indicated for adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease, plaque psoriasis, hidradenitis suppurativa, and noninfectious intermediate and posterior uveitis and panuveitis. In pediatric patients, it is indicated for polyarticular juvenile idiopathic arthritis in children 2 years of age and older and Crohn’s disease in children 6 years of age and older.

Adalimumab-ryvk is the third Humira biosimilar overall granted interchangeability status, which allows pharmacists (depending on state law) to substitute the biosimilar for the reference product without involving the prescribing clinician. Adalimumab-adbm (Cyltezo), manufactured by Boehringer Ingelheim, and adalimumab-afzb (Abrilada), manufactured by Pfizer, were previously granted interchangeability status; however, they both are interchangeable with the low-concentration formulation of Humira, which make up only an estimated 15% of Humira prescriptions, according to a report by Goodroot. 

Adalimumab-ryvk will be launched “imminently” in the United States, according to the press release, but no specific dates were provided. It is also not yet known how the biosimilar will be priced compared with Humira. Other adalimumab biosimilars have launched with discounts from 5% to 85% of Humira’s list price.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has approved the first interchangeable, high-concentration, citrate-free adalimumab biosimilar, adalimumab-ryvk (Simlandi).

This is the 10th adalimumab biosimilar approved by the regulatory agency and the first biosimilar approval in the US market for the Icelandic pharmaceutical company Alvotech in partnership with Teva Pharmaceuticals.

“An interchangeable citrate-free, high-concentration biosimilar adalimumab has the potential to change the market dynamics in a rapidly evolving environment for biosimilars in the U.S.,” said Robert Wessman, chairman and CEO of Alvotech, in a company press release on February 23.

Adalimumab-ryvk was approved in the European Union in 2021 and in Australia and Canada in 2022. 

Adalimumab-ryvk is indicated for adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease, plaque psoriasis, hidradenitis suppurativa, and noninfectious intermediate and posterior uveitis and panuveitis. In pediatric patients, it is indicated for polyarticular juvenile idiopathic arthritis in children 2 years of age and older and Crohn’s disease in children 6 years of age and older.

Adalimumab-ryvk is the third Humira biosimilar overall granted interchangeability status, which allows pharmacists (depending on state law) to substitute the biosimilar for the reference product without involving the prescribing clinician. Adalimumab-adbm (Cyltezo), manufactured by Boehringer Ingelheim, and adalimumab-afzb (Abrilada), manufactured by Pfizer, were previously granted interchangeability status; however, they both are interchangeable with the low-concentration formulation of Humira, which make up only an estimated 15% of Humira prescriptions, according to a report by Goodroot. 

Adalimumab-ryvk will be launched “imminently” in the United States, according to the press release, but no specific dates were provided. It is also not yet known how the biosimilar will be priced compared with Humira. Other adalimumab biosimilars have launched with discounts from 5% to 85% of Humira’s list price.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has approved the first interchangeable, high-concentration, citrate-free adalimumab biosimilar, adalimumab-ryvk (Simlandi).

This is the 10th adalimumab biosimilar approved by the regulatory agency and the first biosimilar approval in the US market for the Icelandic pharmaceutical company Alvotech in partnership with Teva Pharmaceuticals.

“An interchangeable citrate-free, high-concentration biosimilar adalimumab has the potential to change the market dynamics in a rapidly evolving environment for biosimilars in the U.S.,” said Robert Wessman, chairman and CEO of Alvotech, in a company press release on February 23.

Adalimumab-ryvk was approved in the European Union in 2021 and in Australia and Canada in 2022. 

Adalimumab-ryvk is indicated for adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease, plaque psoriasis, hidradenitis suppurativa, and noninfectious intermediate and posterior uveitis and panuveitis. In pediatric patients, it is indicated for polyarticular juvenile idiopathic arthritis in children 2 years of age and older and Crohn’s disease in children 6 years of age and older.

Adalimumab-ryvk is the third Humira biosimilar overall granted interchangeability status, which allows pharmacists (depending on state law) to substitute the biosimilar for the reference product without involving the prescribing clinician. Adalimumab-adbm (Cyltezo), manufactured by Boehringer Ingelheim, and adalimumab-afzb (Abrilada), manufactured by Pfizer, were previously granted interchangeability status; however, they both are interchangeable with the low-concentration formulation of Humira, which make up only an estimated 15% of Humira prescriptions, according to a report by Goodroot. 

Adalimumab-ryvk will be launched “imminently” in the United States, according to the press release, but no specific dates were provided. It is also not yet known how the biosimilar will be priced compared with Humira. Other adalimumab biosimilars have launched with discounts from 5% to 85% of Humira’s list price.

A version of this article appeared on Medscape.com.

TOPLINE:

Pooled data from 9225 adults with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) showed no new safety signals with extended exposure to ixekizumab (Taltz).

METHODOLOGY:

• Researchers combined patient data from 25 randomized, controlled trials of the safety and effectiveness of at least one dose of ixekizumab in adults with PsO (n = 6892), PsA (n = 1401), and axSpA (n = 932).
• The study population included patients with a mean age of approximately 43-49 years; at least 49% were male and at least 74% were White across the three conditions.
• Patients’ median duration of ixekizumab exposure was 1.3 years for PsO, 1.4 years for PsA, and 2.7 years for axSpA, with data up to 6 years for PsO and up to 3 years for PsA and axSpA.
• The primary outcomes were exposure-adjusted incidence rates per 100 patient-years overall and at successive year intervals for treatment-emergent adverse events, serious adverse events, and selected adverse events of interest.

TAKEAWAY:

• The incidence rate per 100 person-years for any treatment-emergent adverse event was 32.5 for PsO, 50.3 for PsA, and 38.0 for axSpA; these did not increase with lengthier exposure.
• The incidence rates for serious adverse events for patients with PsO, PsA, or axSpA were 5.4, 6.0, and 4.8 per 100 person-years, respectively.
• A total of 45 deaths were reported across the studies, including 36 in patients with PsO, six with PsA, and three with axSpA.
• Infections were the most common treatment-emergent adverse events across all patient groups, reported in patients at rates of 62.5% with PsO, 52.4% with PsA, and 57.9% with axSpA; incidence of infections did not increase over time.

IN PRACTICE:

“These final, end-of-study program results surrounding the long-term use of [ixekizumab] in patients with PsO, PsA, and axSpA should serve as an important point of reference for physicians considering [ixekizumab],” the researchers wrote.

SOURCE:

The lead author on the study was Atul Deodhar, MD, of Oregon Health & Science University, Portland. The study was published online on February 12 in Arthritis Research & Therapy.

LIMITATIONS:

Study limitations included the small sample sizes and short treatment durations in some studies, the primarily White study population, the inability to stratify risk, the lack of a long-term comparator, and potential survivor bias.

DISCLOSURES:

The studies in the review were supported by Eli Lilly. Lead author Dr. Deodhar disclosed an honorarium and serving on advisory boards at AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, as well as research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Pooled data from 9225 adults with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) showed no new safety signals with extended exposure to ixekizumab (Taltz).

METHODOLOGY:

• Researchers combined patient data from 25 randomized, controlled trials of the safety and effectiveness of at least one dose of ixekizumab in adults with PsO (n = 6892), PsA (n = 1401), and axSpA (n = 932).
• The study population included patients with a mean age of approximately 43-49 years; at least 49% were male and at least 74% were White across the three conditions.
• Patients’ median duration of ixekizumab exposure was 1.3 years for PsO, 1.4 years for PsA, and 2.7 years for axSpA, with data up to 6 years for PsO and up to 3 years for PsA and axSpA.
• The primary outcomes were exposure-adjusted incidence rates per 100 patient-years overall and at successive year intervals for treatment-emergent adverse events, serious adverse events, and selected adverse events of interest.

TAKEAWAY:

• The incidence rate per 100 person-years for any treatment-emergent adverse event was 32.5 for PsO, 50.3 for PsA, and 38.0 for axSpA; these did not increase with lengthier exposure.
• The incidence rates for serious adverse events for patients with PsO, PsA, or axSpA were 5.4, 6.0, and 4.8 per 100 person-years, respectively.
• A total of 45 deaths were reported across the studies, including 36 in patients with PsO, six with PsA, and three with axSpA.
• Infections were the most common treatment-emergent adverse events across all patient groups, reported in patients at rates of 62.5% with PsO, 52.4% with PsA, and 57.9% with axSpA; incidence of infections did not increase over time.

IN PRACTICE:

“These final, end-of-study program results surrounding the long-term use of [ixekizumab] in patients with PsO, PsA, and axSpA should serve as an important point of reference for physicians considering [ixekizumab],” the researchers wrote.

SOURCE:

The lead author on the study was Atul Deodhar, MD, of Oregon Health & Science University, Portland. The study was published online on February 12 in Arthritis Research & Therapy.

LIMITATIONS:

Study limitations included the small sample sizes and short treatment durations in some studies, the primarily White study population, the inability to stratify risk, the lack of a long-term comparator, and potential survivor bias.

DISCLOSURES:

The studies in the review were supported by Eli Lilly. Lead author Dr. Deodhar disclosed an honorarium and serving on advisory boards at AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, as well as research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Pooled data from 9225 adults with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) showed no new safety signals with extended exposure to ixekizumab (Taltz).

METHODOLOGY:

• Researchers combined patient data from 25 randomized, controlled trials of the safety and effectiveness of at least one dose of ixekizumab in adults with PsO (n = 6892), PsA (n = 1401), and axSpA (n = 932).
• The study population included patients with a mean age of approximately 43-49 years; at least 49% were male and at least 74% were White across the three conditions.
• Patients’ median duration of ixekizumab exposure was 1.3 years for PsO, 1.4 years for PsA, and 2.7 years for axSpA, with data up to 6 years for PsO and up to 3 years for PsA and axSpA.
• The primary outcomes were exposure-adjusted incidence rates per 100 patient-years overall and at successive year intervals for treatment-emergent adverse events, serious adverse events, and selected adverse events of interest.

TAKEAWAY:

• The incidence rate per 100 person-years for any treatment-emergent adverse event was 32.5 for PsO, 50.3 for PsA, and 38.0 for axSpA; these did not increase with lengthier exposure.
• The incidence rates for serious adverse events for patients with PsO, PsA, or axSpA were 5.4, 6.0, and 4.8 per 100 person-years, respectively.
• A total of 45 deaths were reported across the studies, including 36 in patients with PsO, six with PsA, and three with axSpA.
• Infections were the most common treatment-emergent adverse events across all patient groups, reported in patients at rates of 62.5% with PsO, 52.4% with PsA, and 57.9% with axSpA; incidence of infections did not increase over time.

IN PRACTICE:

“These final, end-of-study program results surrounding the long-term use of [ixekizumab] in patients with PsO, PsA, and axSpA should serve as an important point of reference for physicians considering [ixekizumab],” the researchers wrote.

SOURCE:

The lead author on the study was Atul Deodhar, MD, of Oregon Health & Science University, Portland. The study was published online on February 12 in Arthritis Research & Therapy.

LIMITATIONS:

Study limitations included the small sample sizes and short treatment durations in some studies, the primarily White study population, the inability to stratify risk, the lack of a long-term comparator, and potential survivor bias.

DISCLOSURES:

The studies in the review were supported by Eli Lilly. Lead author Dr. Deodhar disclosed an honorarium and serving on advisory boards at AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, as well as research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB.
 

A version of this article appeared on Medscape.com.

Among patients with psoriasis, the risk of mortality was strongly associated with hepatic injury, cardiovascular disease, and psychiatric affective disorders, but was reduced among those who received systemic therapy with biologics, researchers from Canada report.

Those are key findings from a large retrospective registry study of patients with psoriasis, published in The Journal of the American Academy of Dermatology.

“Psoriasis, a chronic inflammatory condition affecting approximately 3% of the western populations, bears a higher risk of mortality compared to healthy individuals, possibly by inducing systemic inflammation associated with numerous comorbidities, especially cardiovascular diseases, metabolic syndrome, and others,” wrote corresponding author Robert Gniadecki, MD, PhD, of the division of dermatology at the University of Alberta, Canada, and colleagues. “It has been argued that the use of systemic immunomodulatory agents quenches systemic inflammation and potentially improves patient survival. However, the evidence to support this hypothesis is limited.”

To investigate the impact of comorbidities and systemic therapies on all-cause mortality in psoriasis, the researchers used the Alberta Health Services Data Repository of Reporting database from January 1, 2012, to June 1, 2019, which represents a population base of 4.47 million individuals. They extracted data on 18,618 psoriasis cases and 55,854 controls, stratified cases according to the Charlson Comorbidity Index (CCI), a surrogate measure for comorbidity burden, and by the type of therapy received, and conducted statistical analyses including Cox proportional hazards regression to determine absolute hazard ratios representing relative effects of specific demographic and comorbidity factors on mortality within groups.

The median age in both cohorts was 48 years, and 51% were male. The researchers observed that mortality in the psoriasis cohort was significantly higher than in the controls (5.7% vs. 3.8%, respectively; P < .05), with a median age at the time of death of 72 vs. 74.4 years.

The CCI and comorbidities strongly predicted mortality, especially drug-induced liver injury (hazard ratio [HR], 1.78), bipolar disorder and suicidal ideation (HR, 1.24-1.58), and major cardiovascular diseases, which included myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular disease (CVA) (HR, 1.2-1.4).

Among patients in the psoriasis cohort, survival of those treated with biologic agents was higher than in controls, even after matching for CCI (3.2% vs. 4.4%, respectively, P < .05). “These patients also exhibit reduced overall mortality compared to those treated with methotrexate or topical agents,” Dr. Gniadecki and colleagues wrote. “There was no difference in mortality between methotrexate patients and the topical therapy patients, but any of those treatment groups had superior survival compared to the no-treatment cohort.”

They added that despite better survival among patients treated with biologic agents, no significant improvements were detected in their comorbidity profiles. “Notably, the frequency of major cardiovascular disease (MI, CHF, CVA) was the same as in the controls, and overall, the frequency of diseases coded as cardiovascular was slightly increased,” they wrote.

The fact that some factors could not be measured, including the type and severity of psoriasis, response to treatment, smoking history, and alcohol intake, was a study limitation, they noted.

Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, who was asked to comment on the analysis, said the study confirms prior work indicating that having psoriasis is a predictor of mortality. In addition, “there is a strong healthy user affect among patients who take and stay on biologics for psoriasis,” he told this news organization.

Courtesy Dr. Gelfand

Among patients with psoriasis, the risk of mortality was strongly associated with hepatic injury, cardiovascular disease, and psychiatric affective disorders, but was reduced among those who received systemic therapy with biologics, researchers from Canada report.

Those are key findings from a large retrospective registry study of patients with psoriasis, published in The Journal of the American Academy of Dermatology.

“Psoriasis, a chronic inflammatory condition affecting approximately 3% of the western populations, bears a higher risk of mortality compared to healthy individuals, possibly by inducing systemic inflammation associated with numerous comorbidities, especially cardiovascular diseases, metabolic syndrome, and others,” wrote corresponding author Robert Gniadecki, MD, PhD, of the division of dermatology at the University of Alberta, Canada, and colleagues. “It has been argued that the use of systemic immunomodulatory agents quenches systemic inflammation and potentially improves patient survival. However, the evidence to support this hypothesis is limited.”

To investigate the impact of comorbidities and systemic therapies on all-cause mortality in psoriasis, the researchers used the Alberta Health Services Data Repository of Reporting database from January 1, 2012, to June 1, 2019, which represents a population base of 4.47 million individuals. They extracted data on 18,618 psoriasis cases and 55,854 controls, stratified cases according to the Charlson Comorbidity Index (CCI), a surrogate measure for comorbidity burden, and by the type of therapy received, and conducted statistical analyses including Cox proportional hazards regression to determine absolute hazard ratios representing relative effects of specific demographic and comorbidity factors on mortality within groups.

The median age in both cohorts was 48 years, and 51% were male. The researchers observed that mortality in the psoriasis cohort was significantly higher than in the controls (5.7% vs. 3.8%, respectively; P < .05), with a median age at the time of death of 72 vs. 74.4 years.

The CCI and comorbidities strongly predicted mortality, especially drug-induced liver injury (hazard ratio [HR], 1.78), bipolar disorder and suicidal ideation (HR, 1.24-1.58), and major cardiovascular diseases, which included myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular disease (CVA) (HR, 1.2-1.4).

Among patients in the psoriasis cohort, survival of those treated with biologic agents was higher than in controls, even after matching for CCI (3.2% vs. 4.4%, respectively, P < .05). “These patients also exhibit reduced overall mortality compared to those treated with methotrexate or topical agents,” Dr. Gniadecki and colleagues wrote. “There was no difference in mortality between methotrexate patients and the topical therapy patients, but any of those treatment groups had superior survival compared to the no-treatment cohort.”

They added that despite better survival among patients treated with biologic agents, no significant improvements were detected in their comorbidity profiles. “Notably, the frequency of major cardiovascular disease (MI, CHF, CVA) was the same as in the controls, and overall, the frequency of diseases coded as cardiovascular was slightly increased,” they wrote.

The fact that some factors could not be measured, including the type and severity of psoriasis, response to treatment, smoking history, and alcohol intake, was a study limitation, they noted.

Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, who was asked to comment on the analysis, said the study confirms prior work indicating that having psoriasis is a predictor of mortality. In addition, “there is a strong healthy user affect among patients who take and stay on biologics for psoriasis,” he told this news organization.

Courtesy Dr. Gelfand

Among patients with psoriasis, the risk of mortality was strongly associated with hepatic injury, cardiovascular disease, and psychiatric affective disorders, but was reduced among those who received systemic therapy with biologics, researchers from Canada report.

Those are key findings from a large retrospective registry study of patients with psoriasis, published in The Journal of the American Academy of Dermatology.

“Psoriasis, a chronic inflammatory condition affecting approximately 3% of the western populations, bears a higher risk of mortality compared to healthy individuals, possibly by inducing systemic inflammation associated with numerous comorbidities, especially cardiovascular diseases, metabolic syndrome, and others,” wrote corresponding author Robert Gniadecki, MD, PhD, of the division of dermatology at the University of Alberta, Canada, and colleagues. “It has been argued that the use of systemic immunomodulatory agents quenches systemic inflammation and potentially improves patient survival. However, the evidence to support this hypothesis is limited.”

To investigate the impact of comorbidities and systemic therapies on all-cause mortality in psoriasis, the researchers used the Alberta Health Services Data Repository of Reporting database from January 1, 2012, to June 1, 2019, which represents a population base of 4.47 million individuals. They extracted data on 18,618 psoriasis cases and 55,854 controls, stratified cases according to the Charlson Comorbidity Index (CCI), a surrogate measure for comorbidity burden, and by the type of therapy received, and conducted statistical analyses including Cox proportional hazards regression to determine absolute hazard ratios representing relative effects of specific demographic and comorbidity factors on mortality within groups.

The median age in both cohorts was 48 years, and 51% were male. The researchers observed that mortality in the psoriasis cohort was significantly higher than in the controls (5.7% vs. 3.8%, respectively; P < .05), with a median age at the time of death of 72 vs. 74.4 years.

The CCI and comorbidities strongly predicted mortality, especially drug-induced liver injury (hazard ratio [HR], 1.78), bipolar disorder and suicidal ideation (HR, 1.24-1.58), and major cardiovascular diseases, which included myocardial infarction (MI), congestive heart failure (CHF), and cerebrovascular disease (CVA) (HR, 1.2-1.4).

Among patients in the psoriasis cohort, survival of those treated with biologic agents was higher than in controls, even after matching for CCI (3.2% vs. 4.4%, respectively, P < .05). “These patients also exhibit reduced overall mortality compared to those treated with methotrexate or topical agents,” Dr. Gniadecki and colleagues wrote. “There was no difference in mortality between methotrexate patients and the topical therapy patients, but any of those treatment groups had superior survival compared to the no-treatment cohort.”

They added that despite better survival among patients treated with biologic agents, no significant improvements were detected in their comorbidity profiles. “Notably, the frequency of major cardiovascular disease (MI, CHF, CVA) was the same as in the controls, and overall, the frequency of diseases coded as cardiovascular was slightly increased,” they wrote.

The fact that some factors could not be measured, including the type and severity of psoriasis, response to treatment, smoking history, and alcohol intake, was a study limitation, they noted.

Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, who was asked to comment on the analysis, said the study confirms prior work indicating that having psoriasis is a predictor of mortality. In addition, “there is a strong healthy user affect among patients who take and stay on biologics for psoriasis,” he told this news organization.

Courtesy Dr. Gelfand

Key clinical point: Compared with control individuals without psoriatic arthritis (PsA), the burden of headache and migraine without aura was significantly higher in patients with PsA.

Major finding: The prevalence of headache (39.81% vs 26.44%; P = .028) and migraine without aura (18.52% vs 9.2%; P = .044) was significantly higher in patients with PsA vs control individuals without PsA. Patients with PsA who did vs did not have headaches also presented with a higher burden of comorbidities and prevalence of enthesitis (P = .02 for both).

Study details: This cross-sectional, observational cohort study included 216 patients with PsA, 70 patients with axial spondyloarthritis, and 87 gender-matched control individuals.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Marino A, Currado D, Altamura C, et al. Increased prevalence of headaches and migraine in patients with psoriatic arthritis and axial spondyloarthritis: Insights from an Italian cohort study. Biomedicines. 2024;12(2):371. doi: 10.3390/biomedicines12020371 Source

Key clinical point: Compared with control individuals without psoriatic arthritis (PsA), the burden of headache and migraine without aura was significantly higher in patients with PsA.

Major finding: The prevalence of headache (39.81% vs 26.44%; P = .028) and migraine without aura (18.52% vs 9.2%; P = .044) was significantly higher in patients with PsA vs control individuals without PsA. Patients with PsA who did vs did not have headaches also presented with a higher burden of comorbidities and prevalence of enthesitis (P = .02 for both).

Study details: This cross-sectional, observational cohort study included 216 patients with PsA, 70 patients with axial spondyloarthritis, and 87 gender-matched control individuals.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Marino A, Currado D, Altamura C, et al. Increased prevalence of headaches and migraine in patients with psoriatic arthritis and axial spondyloarthritis: Insights from an Italian cohort study. Biomedicines. 2024;12(2):371. doi: 10.3390/biomedicines12020371 Source

Key clinical point: Compared with control individuals without psoriatic arthritis (PsA), the burden of headache and migraine without aura was significantly higher in patients with PsA.

Major finding: The prevalence of headache (39.81% vs 26.44%; P = .028) and migraine without aura (18.52% vs 9.2%; P = .044) was significantly higher in patients with PsA vs control individuals without PsA. Patients with PsA who did vs did not have headaches also presented with a higher burden of comorbidities and prevalence of enthesitis (P = .02 for both).

Study details: This cross-sectional, observational cohort study included 216 patients with PsA, 70 patients with axial spondyloarthritis, and 87 gender-matched control individuals.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interest.

Source: Marino A, Currado D, Altamura C, et al. Increased prevalence of headaches and migraine in patients with psoriatic arthritis and axial spondyloarthritis: Insights from an Italian cohort study. Biomedicines. 2024;12(2):371. doi: 10.3390/biomedicines12020371 Source

Key clinical point: In patients with psoriatic arthritis (PsA), etanercept improved disease remission in routine clinical practice without showing any new safety signals.

Major finding: At week 12, 38.3% of patients with PsA achieved disease remission, with the proportion of patients achieving remission increasing to 51% and 54% at weeks 24 and 52, respectively. Among patients who achieved remission at week 12, 52.2% maintained it up to week 52. The most common treatment-emergent serious adverse events were aggravated condition, injury, poisoning, procedural complications, cardiac disorders, gastrointestinal disorders, and neoplasms.

Study details: Findings are from the prospective, non-interventional ADEQUATE study including patients with PsA (n = 254), axial spondyloarthritis (n = 305), or psoriasis (n = 70) who received etanercept for up to 52 weeks.

Disclosures: This study was funded by Pfizer Pharma GmbH. Three authors declared being employees and shareholders of Pfizer. Other authors declared receiving consulting fees, speaker fees, honoraria, or grants from or having other ties with various sources, including Pfizer.

Source: Feist E, Baraliakos X, Behrens F, et al. Etanercept in axial spondyloarthritis, psoriatic arthritis, and plaque psoriasis: Real-world outcome data from German non-interventional study ADEQUATE. Rheumatol Ther. 2024 (Feb 3). doi: 10.1007/s40744-023-00633-2  Source

Key clinical point: In patients with psoriatic arthritis (PsA), etanercept improved disease remission in routine clinical practice without showing any new safety signals.

Major finding: At week 12, 38.3% of patients with PsA achieved disease remission, with the proportion of patients achieving remission increasing to 51% and 54% at weeks 24 and 52, respectively. Among patients who achieved remission at week 12, 52.2% maintained it up to week 52. The most common treatment-emergent serious adverse events were aggravated condition, injury, poisoning, procedural complications, cardiac disorders, gastrointestinal disorders, and neoplasms.

Study details: Findings are from the prospective, non-interventional ADEQUATE study including patients with PsA (n = 254), axial spondyloarthritis (n = 305), or psoriasis (n = 70) who received etanercept for up to 52 weeks.

Disclosures: This study was funded by Pfizer Pharma GmbH. Three authors declared being employees and shareholders of Pfizer. Other authors declared receiving consulting fees, speaker fees, honoraria, or grants from or having other ties with various sources, including Pfizer.

Source: Feist E, Baraliakos X, Behrens F, et al. Etanercept in axial spondyloarthritis, psoriatic arthritis, and plaque psoriasis: Real-world outcome data from German non-interventional study ADEQUATE. Rheumatol Ther. 2024 (Feb 3). doi: 10.1007/s40744-023-00633-2  Source

Key clinical point: In patients with psoriatic arthritis (PsA), etanercept improved disease remission in routine clinical practice without showing any new safety signals.

Major finding: At week 12, 38.3% of patients with PsA achieved disease remission, with the proportion of patients achieving remission increasing to 51% and 54% at weeks 24 and 52, respectively. Among patients who achieved remission at week 12, 52.2% maintained it up to week 52. The most common treatment-emergent serious adverse events were aggravated condition, injury, poisoning, procedural complications, cardiac disorders, gastrointestinal disorders, and neoplasms.

Study details: Findings are from the prospective, non-interventional ADEQUATE study including patients with PsA (n = 254), axial spondyloarthritis (n = 305), or psoriasis (n = 70) who received etanercept for up to 52 weeks.

Disclosures: This study was funded by Pfizer Pharma GmbH. Three authors declared being employees and shareholders of Pfizer. Other authors declared receiving consulting fees, speaker fees, honoraria, or grants from or having other ties with various sources, including Pfizer.

Source: Feist E, Baraliakos X, Behrens F, et al. Etanercept in axial spondyloarthritis, psoriatic arthritis, and plaque psoriasis: Real-world outcome data from German non-interventional study ADEQUATE. Rheumatol Ther. 2024 (Feb 3). doi: 10.1007/s40744-023-00633-2  Source

Key clinical point: Patients with multimorbid psoriasis should be monitored for the potential development of psoriatic arthritis (PsA) as the presence of ≥2 morbidities at psoriasis incidence has been associated with an increased risk for PsA.

Major finding: The cumulative incidence of PsA in patients with psoriasis was 1.7%, 2.5%, and 2.9% at 5, 10, and 15 years after psoriasis incidence, respectively, with the risk for PsA being higher in those with ≥2 morbidities (hazard ratio 2.46; 95% CI 1.01-6.01).

Study details: Findings are from a retrospective cohort study including 817 patients with incident psoriasis and 849 age- and sex-matched comparator individuals without psoriasis; of these, 23 patients with psoriasis developed PsA during a median follow-up of 13.3 years.

Disclosures: This study was sponsored by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and other sources. Two authors declared serving as consultants for or receiving research support and grants from various sources.

Source: Karmacharya P, Chakradhar R, Hulshizer CA, et al. Multimorbidity in psoriasis as a risk factor for psoriatic arthritis: A population-based study. Rheumatology (Oxford). 2024 (Jan 30). doi: 10.1093/rheumatology/keae040 Source

Key clinical point: Patients with multimorbid psoriasis should be monitored for the potential development of psoriatic arthritis (PsA) as the presence of ≥2 morbidities at psoriasis incidence has been associated with an increased risk for PsA.

Major finding: The cumulative incidence of PsA in patients with psoriasis was 1.7%, 2.5%, and 2.9% at 5, 10, and 15 years after psoriasis incidence, respectively, with the risk for PsA being higher in those with ≥2 morbidities (hazard ratio 2.46; 95% CI 1.01-6.01).

Study details: Findings are from a retrospective cohort study including 817 patients with incident psoriasis and 849 age- and sex-matched comparator individuals without psoriasis; of these, 23 patients with psoriasis developed PsA during a median follow-up of 13.3 years.

Disclosures: This study was sponsored by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and other sources. Two authors declared serving as consultants for or receiving research support and grants from various sources.

Source: Karmacharya P, Chakradhar R, Hulshizer CA, et al. Multimorbidity in psoriasis as a risk factor for psoriatic arthritis: A population-based study. Rheumatology (Oxford). 2024 (Jan 30). doi: 10.1093/rheumatology/keae040 Source

Key clinical point: Patients with multimorbid psoriasis should be monitored for the potential development of psoriatic arthritis (PsA) as the presence of ≥2 morbidities at psoriasis incidence has been associated with an increased risk for PsA.

Major finding: The cumulative incidence of PsA in patients with psoriasis was 1.7%, 2.5%, and 2.9% at 5, 10, and 15 years after psoriasis incidence, respectively, with the risk for PsA being higher in those with ≥2 morbidities (hazard ratio 2.46; 95% CI 1.01-6.01).

Study details: Findings are from a retrospective cohort study including 817 patients with incident psoriasis and 849 age- and sex-matched comparator individuals without psoriasis; of these, 23 patients with psoriasis developed PsA during a median follow-up of 13.3 years.

Disclosures: This study was sponsored by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and other sources. Two authors declared serving as consultants for or receiving research support and grants from various sources.

Source: Karmacharya P, Chakradhar R, Hulshizer CA, et al. Multimorbidity in psoriasis as a risk factor for psoriatic arthritis: A population-based study. Rheumatology (Oxford). 2024 (Jan 30). doi: 10.1093/rheumatology/keae040 Source