Psoriatic Arthritis

WASHINGTON – The approval last year of the interleukin (IL)-36 receptor antagonist spesolimab for treating generalized pustular psoriasis flares brightened the treatment landscape for this rare condition, and a recently published phase 2 study suggests a potential role of spesolimab for flare prevention. But when it comes to pustular disease localized to the hands and feet – palmoplantar pustulosis – treatment options have only modest efficacy, and spesolimab appears not to work, according to speakers at the annual research symposium of the National Psoriasis Foundation.

“The IL-36 receptor antagonists don’t seem to be quite the answer for [palmoplantar pustulosis] that they are for generalized pustular psoriasis [GPP],” Megan H. Noe, MD, MPH, assistant professor of dermatology at Harvard Medical School and a dermatologist at Brigham and Women’s Hospital, Boston, said at the meeting.

Psoriasis affecting the hands and feet – both pustular and nonpustular – has a higher impact on quality of life and higher functional disability than does non-acral psoriasis, is less responsive to treatment, and has a “very confusing nomenclature” that complicates research and thus management, said Jason Ezra Hawkes, MD, a dermatologist in Rocklin, Calif., and former faculty member of several departments of dermatology. Both he and Dr. Noe spoke during a tough-to-treat session at the NPF meeting.

IL-17 and IL-23 blockade, as well as tumor necrosis factor (TNF) inhibition, are effective overall for palmoplantar psoriasis (nonpustular), but in general, responses are lower than for plaque psoriasis. Apremilast (Otezla), a phosphodiesterase-4 inhibitor, has some efficacy for pustular variants, but for hyperkeratotic variants it “does not perform as well as more selective inhibition of IL-17 and IL-23 blockade,” he said.

Dr. Hawkes

Palmoplantar pustulosis, and a word on generalized disease

Dermatologists are using a variety of treatments for palmoplantar pustulosis, with no clear first-line choices, Dr. Noe said. In a case series of almost 200 patients with palmoplantar pustulosis across 20 dermatology practices, published in JAMA Dermatology, 35% of patients received a systemic therapy prescription at their initial encounter – most commonly acitretin, followed by methotrexate and phototherapy. “Biologics were used, but use was varied and not as often as with oral agents,” said Dr. Noe, a coauthor of the study.

TNF blockers led to improvements ranging from 57% to 84%, depending on the agent, in a 2020 retrospective study of patients with palmoplantar pustulosis or acrodermatitis continua of Hallopeau, Dr. Noe noted. However, rates of complete clearance were only 20%-29%.

Apremilast showed modest efficacy after 5 months of treatment, with 62% of patients achieving at least a 50% improvement in the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) in a 2021 open-label, phase 2 study involving 21 patients. “This may represent a potential treatment option,” Dr. Noe said. “It’s something, but not what we’re used to seeing in our plaque psoriasis patients.”

A 2021 phase 2a, double-blind, randomized, placebo-controlled study of spesolimab in patients with palmoplantar pustulosis, meanwhile, failed to meet its primary endpoint, with only 32% of patients achieving a 50% improvement at 16 weeks, compared with 24% of patients in the placebo arm. And a recently published network meta-analysis found that none of the five drugs studied in seven randomized controlled trials – biologic or oral – was more effective than placebo for clearance or improvement of palmoplantar pustulosis.

The spesolimab (Spevigo) results have been disappointing considering the biologic’s newfound efficacy and role as the first Food and Drug Administration–approved therapy for generalized pustular disease, according to Dr. Noe. The ability of a single 900-mg intravenous dose of the IL-36 receptor antagonist to completely clear pustules at 1 week in 54% of patients with generalized disease, compared with 6% of the placebo group, was “groundbreaking,” she said, referring to results of the pivotal trial published in the New England Journal of Medicine.

And given that “preventing GPP flares is ultimately what we want,” she said, more good news was reported this year in The Lancet: The finding from an international, randomized, placebo-controlled study that high-dose subcutaneous spesolimab significantly reduced the risk of a flare over 48 weeks. “There are lots of ongoing studies right now to understand the best way to dose spesolimab,” she said.

Moreover, another IL-36 receptor antagonist, imsidolimab, is being investigated in a phase 3 trial for generalized pustular disease, she noted. A phase 2, open-label study of patients with GPP found that “more than half of patients were very much improved at 4 weeks, and some patients started showing improvement at day 3,” Dr. Noe said.

An area of research she is interested in is the potential for Janus kinase (JAK) inhibitors as a treatment for palmoplantar pustulosis. For pustulosis on the hands and feet, recent case reports describing the efficacy of JAK inhibitors have caught her eye. “Right now, all we have is this case report data, mostly with tofacitinib, but I think it’s exciting,” she said, noting a recently published report in the British Journal of Dermatology.

Palmoplantar psoriasis

Pustular psoriatic disease can be localized to the hand and/or feet only, or can co-occur with generalized pustular disease, just as palmoplantar psoriasis can be localized to the hands and/or feet or, more commonly, can co-occur with widespread plaque psoriasis. Research has shown, Dr. Hawkes said, that with both types of acral disease, many patients have or have had plaque psoriasis outside of acral sites.

The nomenclature and acronyms for palmoplantar psoriatic disease have complicated patient education, communication, and research, Dr. Hawkes said. Does PPP refer to palmoplantar psoriasis, or palmoplantar pustulosis, for instance? What is the difference between palmoplantar pustulosis (coined PPP) and palmoplantar pustular psoriasis (referred to as PPPP)?

What if disease is only on the hands, only on the feet, or only on the backs of the hands? And at what point is disease not classified as palmoplantar psoriasis, but plaque psoriasis with involvement of the hands and feet? Inconsistencies and lack of clarification lead to “confusing” literature, he said.

Heterogeneity in populations across trials resulting from “inconsistent categorization and phenotype inclusion” may partly account for the recalcitrance to treatment reported in the literature, he said. Misdiagnosis as psoriasis in cases of localized disease (confusion with eczema, for instance), and the fact that hands and feet are subject to increased trauma and injury, compared with non-acral sites, are also at play.

Trials may also allow insufficient time for improvement, compared with non-acral sites. “What we’ve learned about the hands and feet is that it takes a much longer time for disease to improve,” Dr. Hawkes said, so primary endpoints must take this into account.

There is unique immunologic signaling in palmoplantar disease that differs from the predominant signaling in traditional plaque psoriasis, he emphasized, and “mixed immunophenotypes” that need to be unraveled.

Dr. Hawkes disclosed ties with AbbVie, Arcutis, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, LEO, Lilly, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB. Dr. Noe disclosed ties to Bristol-Myers Squibb and Boehringer Ingelheim.

WASHINGTON – The approval last year of the interleukin (IL)-36 receptor antagonist spesolimab for treating generalized pustular psoriasis flares brightened the treatment landscape for this rare condition, and a recently published phase 2 study suggests a potential role of spesolimab for flare prevention. But when it comes to pustular disease localized to the hands and feet – palmoplantar pustulosis – treatment options have only modest efficacy, and spesolimab appears not to work, according to speakers at the annual research symposium of the National Psoriasis Foundation.

“The IL-36 receptor antagonists don’t seem to be quite the answer for [palmoplantar pustulosis] that they are for generalized pustular psoriasis [GPP],” Megan H. Noe, MD, MPH, assistant professor of dermatology at Harvard Medical School and a dermatologist at Brigham and Women’s Hospital, Boston, said at the meeting.

Psoriasis affecting the hands and feet – both pustular and nonpustular – has a higher impact on quality of life and higher functional disability than does non-acral psoriasis, is less responsive to treatment, and has a “very confusing nomenclature” that complicates research and thus management, said Jason Ezra Hawkes, MD, a dermatologist in Rocklin, Calif., and former faculty member of several departments of dermatology. Both he and Dr. Noe spoke during a tough-to-treat session at the NPF meeting.

IL-17 and IL-23 blockade, as well as tumor necrosis factor (TNF) inhibition, are effective overall for palmoplantar psoriasis (nonpustular), but in general, responses are lower than for plaque psoriasis. Apremilast (Otezla), a phosphodiesterase-4 inhibitor, has some efficacy for pustular variants, but for hyperkeratotic variants it “does not perform as well as more selective inhibition of IL-17 and IL-23 blockade,” he said.

Dr. Hawkes

Palmoplantar pustulosis, and a word on generalized disease

Dermatologists are using a variety of treatments for palmoplantar pustulosis, with no clear first-line choices, Dr. Noe said. In a case series of almost 200 patients with palmoplantar pustulosis across 20 dermatology practices, published in JAMA Dermatology, 35% of patients received a systemic therapy prescription at their initial encounter – most commonly acitretin, followed by methotrexate and phototherapy. “Biologics were used, but use was varied and not as often as with oral agents,” said Dr. Noe, a coauthor of the study.

TNF blockers led to improvements ranging from 57% to 84%, depending on the agent, in a 2020 retrospective study of patients with palmoplantar pustulosis or acrodermatitis continua of Hallopeau, Dr. Noe noted. However, rates of complete clearance were only 20%-29%.

Apremilast showed modest efficacy after 5 months of treatment, with 62% of patients achieving at least a 50% improvement in the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) in a 2021 open-label, phase 2 study involving 21 patients. “This may represent a potential treatment option,” Dr. Noe said. “It’s something, but not what we’re used to seeing in our plaque psoriasis patients.”

A 2021 phase 2a, double-blind, randomized, placebo-controlled study of spesolimab in patients with palmoplantar pustulosis, meanwhile, failed to meet its primary endpoint, with only 32% of patients achieving a 50% improvement at 16 weeks, compared with 24% of patients in the placebo arm. And a recently published network meta-analysis found that none of the five drugs studied in seven randomized controlled trials – biologic or oral – was more effective than placebo for clearance or improvement of palmoplantar pustulosis.

The spesolimab (Spevigo) results have been disappointing considering the biologic’s newfound efficacy and role as the first Food and Drug Administration–approved therapy for generalized pustular disease, according to Dr. Noe. The ability of a single 900-mg intravenous dose of the IL-36 receptor antagonist to completely clear pustules at 1 week in 54% of patients with generalized disease, compared with 6% of the placebo group, was “groundbreaking,” she said, referring to results of the pivotal trial published in the New England Journal of Medicine.

And given that “preventing GPP flares is ultimately what we want,” she said, more good news was reported this year in The Lancet: The finding from an international, randomized, placebo-controlled study that high-dose subcutaneous spesolimab significantly reduced the risk of a flare over 48 weeks. “There are lots of ongoing studies right now to understand the best way to dose spesolimab,” she said.

Moreover, another IL-36 receptor antagonist, imsidolimab, is being investigated in a phase 3 trial for generalized pustular disease, she noted. A phase 2, open-label study of patients with GPP found that “more than half of patients were very much improved at 4 weeks, and some patients started showing improvement at day 3,” Dr. Noe said.

An area of research she is interested in is the potential for Janus kinase (JAK) inhibitors as a treatment for palmoplantar pustulosis. For pustulosis on the hands and feet, recent case reports describing the efficacy of JAK inhibitors have caught her eye. “Right now, all we have is this case report data, mostly with tofacitinib, but I think it’s exciting,” she said, noting a recently published report in the British Journal of Dermatology.

Palmoplantar psoriasis

Pustular psoriatic disease can be localized to the hand and/or feet only, or can co-occur with generalized pustular disease, just as palmoplantar psoriasis can be localized to the hands and/or feet or, more commonly, can co-occur with widespread plaque psoriasis. Research has shown, Dr. Hawkes said, that with both types of acral disease, many patients have or have had plaque psoriasis outside of acral sites.

The nomenclature and acronyms for palmoplantar psoriatic disease have complicated patient education, communication, and research, Dr. Hawkes said. Does PPP refer to palmoplantar psoriasis, or palmoplantar pustulosis, for instance? What is the difference between palmoplantar pustulosis (coined PPP) and palmoplantar pustular psoriasis (referred to as PPPP)?

What if disease is only on the hands, only on the feet, or only on the backs of the hands? And at what point is disease not classified as palmoplantar psoriasis, but plaque psoriasis with involvement of the hands and feet? Inconsistencies and lack of clarification lead to “confusing” literature, he said.

Heterogeneity in populations across trials resulting from “inconsistent categorization and phenotype inclusion” may partly account for the recalcitrance to treatment reported in the literature, he said. Misdiagnosis as psoriasis in cases of localized disease (confusion with eczema, for instance), and the fact that hands and feet are subject to increased trauma and injury, compared with non-acral sites, are also at play.

Trials may also allow insufficient time for improvement, compared with non-acral sites. “What we’ve learned about the hands and feet is that it takes a much longer time for disease to improve,” Dr. Hawkes said, so primary endpoints must take this into account.

There is unique immunologic signaling in palmoplantar disease that differs from the predominant signaling in traditional plaque psoriasis, he emphasized, and “mixed immunophenotypes” that need to be unraveled.

Dr. Hawkes disclosed ties with AbbVie, Arcutis, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, LEO, Lilly, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB. Dr. Noe disclosed ties to Bristol-Myers Squibb and Boehringer Ingelheim.

WASHINGTON – The approval last year of the interleukin (IL)-36 receptor antagonist spesolimab for treating generalized pustular psoriasis flares brightened the treatment landscape for this rare condition, and a recently published phase 2 study suggests a potential role of spesolimab for flare prevention. But when it comes to pustular disease localized to the hands and feet – palmoplantar pustulosis – treatment options have only modest efficacy, and spesolimab appears not to work, according to speakers at the annual research symposium of the National Psoriasis Foundation.

“The IL-36 receptor antagonists don’t seem to be quite the answer for [palmoplantar pustulosis] that they are for generalized pustular psoriasis [GPP],” Megan H. Noe, MD, MPH, assistant professor of dermatology at Harvard Medical School and a dermatologist at Brigham and Women’s Hospital, Boston, said at the meeting.

Psoriasis affecting the hands and feet – both pustular and nonpustular – has a higher impact on quality of life and higher functional disability than does non-acral psoriasis, is less responsive to treatment, and has a “very confusing nomenclature” that complicates research and thus management, said Jason Ezra Hawkes, MD, a dermatologist in Rocklin, Calif., and former faculty member of several departments of dermatology. Both he and Dr. Noe spoke during a tough-to-treat session at the NPF meeting.

IL-17 and IL-23 blockade, as well as tumor necrosis factor (TNF) inhibition, are effective overall for palmoplantar psoriasis (nonpustular), but in general, responses are lower than for plaque psoriasis. Apremilast (Otezla), a phosphodiesterase-4 inhibitor, has some efficacy for pustular variants, but for hyperkeratotic variants it “does not perform as well as more selective inhibition of IL-17 and IL-23 blockade,” he said.

Dr. Hawkes

Palmoplantar pustulosis, and a word on generalized disease

Dermatologists are using a variety of treatments for palmoplantar pustulosis, with no clear first-line choices, Dr. Noe said. In a case series of almost 200 patients with palmoplantar pustulosis across 20 dermatology practices, published in JAMA Dermatology, 35% of patients received a systemic therapy prescription at their initial encounter – most commonly acitretin, followed by methotrexate and phototherapy. “Biologics were used, but use was varied and not as often as with oral agents,” said Dr. Noe, a coauthor of the study.

TNF blockers led to improvements ranging from 57% to 84%, depending on the agent, in a 2020 retrospective study of patients with palmoplantar pustulosis or acrodermatitis continua of Hallopeau, Dr. Noe noted. However, rates of complete clearance were only 20%-29%.

Apremilast showed modest efficacy after 5 months of treatment, with 62% of patients achieving at least a 50% improvement in the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) in a 2021 open-label, phase 2 study involving 21 patients. “This may represent a potential treatment option,” Dr. Noe said. “It’s something, but not what we’re used to seeing in our plaque psoriasis patients.”

A 2021 phase 2a, double-blind, randomized, placebo-controlled study of spesolimab in patients with palmoplantar pustulosis, meanwhile, failed to meet its primary endpoint, with only 32% of patients achieving a 50% improvement at 16 weeks, compared with 24% of patients in the placebo arm. And a recently published network meta-analysis found that none of the five drugs studied in seven randomized controlled trials – biologic or oral – was more effective than placebo for clearance or improvement of palmoplantar pustulosis.

The spesolimab (Spevigo) results have been disappointing considering the biologic’s newfound efficacy and role as the first Food and Drug Administration–approved therapy for generalized pustular disease, according to Dr. Noe. The ability of a single 900-mg intravenous dose of the IL-36 receptor antagonist to completely clear pustules at 1 week in 54% of patients with generalized disease, compared with 6% of the placebo group, was “groundbreaking,” she said, referring to results of the pivotal trial published in the New England Journal of Medicine.

And given that “preventing GPP flares is ultimately what we want,” she said, more good news was reported this year in The Lancet: The finding from an international, randomized, placebo-controlled study that high-dose subcutaneous spesolimab significantly reduced the risk of a flare over 48 weeks. “There are lots of ongoing studies right now to understand the best way to dose spesolimab,” she said.

Moreover, another IL-36 receptor antagonist, imsidolimab, is being investigated in a phase 3 trial for generalized pustular disease, she noted. A phase 2, open-label study of patients with GPP found that “more than half of patients were very much improved at 4 weeks, and some patients started showing improvement at day 3,” Dr. Noe said.

An area of research she is interested in is the potential for Janus kinase (JAK) inhibitors as a treatment for palmoplantar pustulosis. For pustulosis on the hands and feet, recent case reports describing the efficacy of JAK inhibitors have caught her eye. “Right now, all we have is this case report data, mostly with tofacitinib, but I think it’s exciting,” she said, noting a recently published report in the British Journal of Dermatology.

Palmoplantar psoriasis

Pustular psoriatic disease can be localized to the hand and/or feet only, or can co-occur with generalized pustular disease, just as palmoplantar psoriasis can be localized to the hands and/or feet or, more commonly, can co-occur with widespread plaque psoriasis. Research has shown, Dr. Hawkes said, that with both types of acral disease, many patients have or have had plaque psoriasis outside of acral sites.

The nomenclature and acronyms for palmoplantar psoriatic disease have complicated patient education, communication, and research, Dr. Hawkes said. Does PPP refer to palmoplantar psoriasis, or palmoplantar pustulosis, for instance? What is the difference between palmoplantar pustulosis (coined PPP) and palmoplantar pustular psoriasis (referred to as PPPP)?

What if disease is only on the hands, only on the feet, or only on the backs of the hands? And at what point is disease not classified as palmoplantar psoriasis, but plaque psoriasis with involvement of the hands and feet? Inconsistencies and lack of clarification lead to “confusing” literature, he said.

Heterogeneity in populations across trials resulting from “inconsistent categorization and phenotype inclusion” may partly account for the recalcitrance to treatment reported in the literature, he said. Misdiagnosis as psoriasis in cases of localized disease (confusion with eczema, for instance), and the fact that hands and feet are subject to increased trauma and injury, compared with non-acral sites, are also at play.

Trials may also allow insufficient time for improvement, compared with non-acral sites. “What we’ve learned about the hands and feet is that it takes a much longer time for disease to improve,” Dr. Hawkes said, so primary endpoints must take this into account.

There is unique immunologic signaling in palmoplantar disease that differs from the predominant signaling in traditional plaque psoriasis, he emphasized, and “mixed immunophenotypes” that need to be unraveled.

Dr. Hawkes disclosed ties with AbbVie, Arcutis, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, LEO, Lilly, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB. Dr. Noe disclosed ties to Bristol-Myers Squibb and Boehringer Ingelheim.

TOPLINE:

Use of Janus kinase (JAK) inhibitors is associated with a nearly fourfold increase in risk of acne compared with placebo, according to an analysis of 25 JAK inhibitor studies.

METHODOLOGY:

• Acne has been reported to be an adverse effect of JAK inhibitors, but not much is known about how common acne is overall and how incidence differs between different JAK inhibitors and the disease being treated.
• For the systematic review and meta-analysis, researchers identified 25 phase 2 or 3 randomized, controlled trials that reported acne as an adverse event associated with the use of JAK inhibitors.
• The study population included 10,839 participants (54% male, 46% female).
• The primary outcome was the incidence of acne following a period of JAK inhibitor use.

TAKEAWAY:

• Overall, the risk of acne was significantly higher among those treated with JAK inhibitors in comparison with patients given placebo in a pooled analysis (odds ratio [OR], 3.83).
• The risk of acne was highest with abrocitinib (OR, 13.47), followed by baricitinib (OR, 4.96), upadacitinib (OR, 4.79), deuruxolitinib (OR, 3.30), and deucravacitinib (OR, 2.64). By JAK inhibitor class, results were as follows: JAK1-specific inhibitors (OR, 4.69), combined JAK1 and JAK2 inhibitors (OR, 3.43), and tyrosine kinase 2 inhibitors (OR, 2.64).
• In a subgroup analysis, risk of acne was higher among patients using JAK inhibitors for dermatologic conditions in comparison with those using JAK inhibitors for nondermatologic conditions (OR, 4.67 vs 1.18).
• Age and gender had no apparent impact on the effect of JAK inhibitor use on acne risk.

IN PRACTICE:

“The occurrence of acne following treatment with certain classes of JAK inhibitors is of potential concern, as this adverse effect may jeopardize treatment adherence among some patients,” the researchers wrote. More studies are needed “to characterize the underlying mechanism of acne with JAK inhibitor use and to identify best practices for treatment,” they added.

SOURCE:

The lead author was Jeremy Martinez, MPH, of Harvard Medical School, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The review was limited by the variable classification and reporting of acne across studies, the potential exclusion of relevant studies, and the small number of studies for certain drugs.

DISCLOSURES:

The studies were mainly funded by the pharmaceutical industry. Mr. Martinez disclosed no relevant financial relationships. Several coauthors have ties with Dexcel Pharma Technologies, AbbVie, Concert, Pfizer, 3Derm Systems, Incyte, Aclaris, Eli Lilly, Concert, Equillium, ASLAN, ACOM, and Boehringer Ingelheim.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Use of Janus kinase (JAK) inhibitors is associated with a nearly fourfold increase in risk of acne compared with placebo, according to an analysis of 25 JAK inhibitor studies.

METHODOLOGY:

• Acne has been reported to be an adverse effect of JAK inhibitors, but not much is known about how common acne is overall and how incidence differs between different JAK inhibitors and the disease being treated.
• For the systematic review and meta-analysis, researchers identified 25 phase 2 or 3 randomized, controlled trials that reported acne as an adverse event associated with the use of JAK inhibitors.
• The study population included 10,839 participants (54% male, 46% female).
• The primary outcome was the incidence of acne following a period of JAK inhibitor use.

TAKEAWAY:

• Overall, the risk of acne was significantly higher among those treated with JAK inhibitors in comparison with patients given placebo in a pooled analysis (odds ratio [OR], 3.83).
• The risk of acne was highest with abrocitinib (OR, 13.47), followed by baricitinib (OR, 4.96), upadacitinib (OR, 4.79), deuruxolitinib (OR, 3.30), and deucravacitinib (OR, 2.64). By JAK inhibitor class, results were as follows: JAK1-specific inhibitors (OR, 4.69), combined JAK1 and JAK2 inhibitors (OR, 3.43), and tyrosine kinase 2 inhibitors (OR, 2.64).
• In a subgroup analysis, risk of acne was higher among patients using JAK inhibitors for dermatologic conditions in comparison with those using JAK inhibitors for nondermatologic conditions (OR, 4.67 vs 1.18).
• Age and gender had no apparent impact on the effect of JAK inhibitor use on acne risk.

IN PRACTICE:

“The occurrence of acne following treatment with certain classes of JAK inhibitors is of potential concern, as this adverse effect may jeopardize treatment adherence among some patients,” the researchers wrote. More studies are needed “to characterize the underlying mechanism of acne with JAK inhibitor use and to identify best practices for treatment,” they added.

SOURCE:

The lead author was Jeremy Martinez, MPH, of Harvard Medical School, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The review was limited by the variable classification and reporting of acne across studies, the potential exclusion of relevant studies, and the small number of studies for certain drugs.

DISCLOSURES:

The studies were mainly funded by the pharmaceutical industry. Mr. Martinez disclosed no relevant financial relationships. Several coauthors have ties with Dexcel Pharma Technologies, AbbVie, Concert, Pfizer, 3Derm Systems, Incyte, Aclaris, Eli Lilly, Concert, Equillium, ASLAN, ACOM, and Boehringer Ingelheim.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Use of Janus kinase (JAK) inhibitors is associated with a nearly fourfold increase in risk of acne compared with placebo, according to an analysis of 25 JAK inhibitor studies.

METHODOLOGY:

• Acne has been reported to be an adverse effect of JAK inhibitors, but not much is known about how common acne is overall and how incidence differs between different JAK inhibitors and the disease being treated.
• For the systematic review and meta-analysis, researchers identified 25 phase 2 or 3 randomized, controlled trials that reported acne as an adverse event associated with the use of JAK inhibitors.
• The study population included 10,839 participants (54% male, 46% female).
• The primary outcome was the incidence of acne following a period of JAK inhibitor use.

TAKEAWAY:

• Overall, the risk of acne was significantly higher among those treated with JAK inhibitors in comparison with patients given placebo in a pooled analysis (odds ratio [OR], 3.83).
• The risk of acne was highest with abrocitinib (OR, 13.47), followed by baricitinib (OR, 4.96), upadacitinib (OR, 4.79), deuruxolitinib (OR, 3.30), and deucravacitinib (OR, 2.64). By JAK inhibitor class, results were as follows: JAK1-specific inhibitors (OR, 4.69), combined JAK1 and JAK2 inhibitors (OR, 3.43), and tyrosine kinase 2 inhibitors (OR, 2.64).
• In a subgroup analysis, risk of acne was higher among patients using JAK inhibitors for dermatologic conditions in comparison with those using JAK inhibitors for nondermatologic conditions (OR, 4.67 vs 1.18).
• Age and gender had no apparent impact on the effect of JAK inhibitor use on acne risk.

IN PRACTICE:

“The occurrence of acne following treatment with certain classes of JAK inhibitors is of potential concern, as this adverse effect may jeopardize treatment adherence among some patients,” the researchers wrote. More studies are needed “to characterize the underlying mechanism of acne with JAK inhibitor use and to identify best practices for treatment,” they added.

SOURCE:

The lead author was Jeremy Martinez, MPH, of Harvard Medical School, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The review was limited by the variable classification and reporting of acne across studies, the potential exclusion of relevant studies, and the small number of studies for certain drugs.

DISCLOSURES:

The studies were mainly funded by the pharmaceutical industry. Mr. Martinez disclosed no relevant financial relationships. Several coauthors have ties with Dexcel Pharma Technologies, AbbVie, Concert, Pfizer, 3Derm Systems, Incyte, Aclaris, Eli Lilly, Concert, Equillium, ASLAN, ACOM, and Boehringer Ingelheim.
 

A version of this article appeared on Medscape.com.

WASHINGTON – Multiple biologic failure in a minority of patients with psoriasis may have several causes, from genetic endotypes and immunologic factors to lower serum drug levels, the presence of anti-drug antibody levels, female sex, and certain comorbidities, Wilson Liao, MD, said at the annual research symposium of the National Psoriasis Foundation.

“Tough-to-treat psoriasis remains a challenge despite newer therapies ... Why do we still have this sub-population of patients who seem to be refractory?” said Dr. Liao, professor and associate vice chair of research in the department of dermatology at the University of California, San Francisco, who coauthored a 2015-2022 prospective cohort analysis that documented about 6% of patients failing two or more biologic agents of different mechanistic classes.

“These patients are really suffering,” he said. “We need to have better guidelines and treatment algorithms for these patients.”

A significant number of patients with psoriatic arthritis (PsA), meanwhile, are inadequate responders to tumor necrosis factor (TNF) inhibition, Christopher T. Ritchlin, MD, PhD, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), said during another session at the meeting.

The long-term “persistence,” or usage, of first-line biologics in patients with PsA – and of second-line biologics in patients who failed one TNF-inhibitor – is low, but the literature offers little information on the reasons for TNF-inhibitor discontinuation, said Dr. Ritchlin, who coauthored a perspective piece in Arthritis & Rheumatology on managing the patient with PsA who fails one TNF inhibitor.

Dr. Ritchlin and his coauthors were asked to provide evidence-informed advice and algorithms, but the task was difficult. “It’s hard to know what to recommend for the next step if we don’t know why patients failed the first,” he said. “The point is, we need more data. [Clinical trials] are not recording the kind of information we need.”
 

Anti-drug antibodies, genetics, other factors in psoriasis

Research shows that in large cohorts, “all the biologics do seem to lose efficacy over time,” said Dr. Liao, who directs the UCSF Psoriasis and Skin Treatment Center. “Some are better than others, but we do see a loss of effectiveness over time.”

A cohort study published in 2022 in JAMA Dermatology, for instance, documented declining “drug survival” associated with ineffectiveness during 2 years of treatment for each of five biologics studied (adalimumab [Humira], ustekinumab [Stelara], secukinumab [Cosentyx], guselkumab [Tremfya], and ixekizumab [Taltz]).

“There have been a number of theories put forward” as to why that’s the case, including lower serum drug levels, “which of course can be related to anti-drug antibody production,” he said.

He pointed to two studies of ustekinumab: One prospective observational cohort study that reported an association of lower early drug levels of the IL-12/23 receptor antagonist with lower Psoriasis Area and Severity Index (PASI) scores, and another observational study that documented an association between anti-drug antibody positivity with lower ustekinumab levels and impaired clinical response.

“We also now know ... that there are genetic endotypes in psoriasis, and that patients who are [HLA-C*06:02]-positive tend to respond a little better to drugs like ustekinumab, and those who are [HLA-C*06:02]-negative tend to do a little better with the TNF inhibitors,” Dr. Liao said. The human leukocyte antigen (HLA) allele HLA-C*06:02 is associated with susceptibility to psoriasis.

In a study using a national psoriasis registry, HLA-C*06:02-negative patients were 3 times more likely to achieve PASI90 status in response to adalimumab, a TNF-alpha inhibitor, than with ustekinumab treatment. And in a meta-analysis covering eight studies with more than 1,000 patients with psoriasis, the median PASI75 response rate after 6 months of ustekinumab therapy was 92% in the HLA-C*06:02-positive group and 67% in HLA-C*06:02-negative patients.

The recently published cohort study showing a 6% rate of multiple biologic failure evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for 2 or more years. Investigators looked for sociodemographic and clinical differences between the patients who continued use of their first biologic for at least 2 years (“good response”), and those who discontinued two or more biologics of different classes, each used for at least 90 days, because of inadequate efficacy.

Of 1,039 evaluated patients, 490 (47.2%) had good clinical response to their first biologic and 65 (6.3%) had multiple biologic failure. All biologic classes were represented among those who failed multiple biologics. The first and second biologic classes used were attempted for a mean duration of 10 months – “an adequate trial” of each, Dr. Liao said.

In multivariable regression analysis, six variables were significantly associated with multiple biologic failure: female sex at birth, shorter disease duration, earlier year of biologic initiation, prior nonbiologic systemic therapy, having Medicaid insurance, and a history of hyperlipidemia. The latter is “interesting because other studies have shown that metabolic syndrome, of which hyperlipidemia is a component, can also relate to poor response to biologics,” Dr. Liao said.

The most common sequences of first-to-second biologics among those with multiple biologic failure were TNF inhibitor to IL-17 inhibitor (30.8%); IL-12/23 inhibitor to IL-17 inhibitor (21.5%); TNF inhibitor to IL-12/23 inhibitor (12.3%); and IL-17 inhibitor to IL-23 inhibitor (10.8%).

The vast majority of patients failed more than two biologics, however, and “more than 20% had five or more biologics tried over a relatively short period,” Dr. Liao said.
 

Comorbidities and biologic failure in psoriasis, PsA

In practice, it was said during a discussion period, biologic failures in psoriasis can be of two types: a primary inadequate response or initial failure, or a secondary failure with initial improvement followed by declining or no response. “I agree 100% that these probably represent two different endotypes,” Dr. Liao said. “There’s research emerging that psoriasis isn’t necessarily a clean phenotype.”

The option of focusing on comorbidities in the face of biologic failure was another point of discussion. “Maybe the next biologic is not the answer,” a meeting participant said. “Maybe we should focus on metabolic syndrome.”

“I agree,” Dr. Liao said. “In clinic, there are people who may not respond to therapies but have other comorbidities and factors that make it difficult to manage [their psoriasis] ... that may be causative for psoriasis. Maybe if we treat the comorbidities, it will make it easier to treat the psoriasis.”

Addressing comorbidities and “extra-articular traits” such as poorly controlled diabetes, centralized pain, anxiety and depression, and obesity is something Dr. Ritchlin advocates for PsA. “Centralized pain, I believe, is a major driver of nonresponse,” he said at the meeting. “We have to be careful about blaming nonresponse and lack of efficacy of biologics when it could be a wholly different mechanism the biologic won’t treat ... for example, centralized pain.”

As with psoriasis, the emergence of antidrug antibodies may be one reason for the secondary failure of biologic agents for PsA, Dr. Ritchlin and his coauthors wrote in their paper on management of PsA after failure of one TNF inhibitor. Other areas to consider in evaluating failure, they wrote, are compliance and time of dosing, and financial barriers.

Low long-term persistence of second-line biologics for patients with PsA was demonstrated in a national cohort study utilizing the French health insurance database, Dr. Ritchlin noted at the research meeting. 

The French study covered almost 3,000 patients who started a second biologic after discontinuing a TNF inhibitor during 2015-2020. Overall, 1-year and 3-year persistence rates were 42% and 17%, respectively.

Dr. Liao disclosed research grant funding from AbbVie, Amgen, Janssen, Leo, Novartis, Pfizer, Regeneron, and Trex Bio. Dr. Ritchlin reported no disclosures.

WASHINGTON – Multiple biologic failure in a minority of patients with psoriasis may have several causes, from genetic endotypes and immunologic factors to lower serum drug levels, the presence of anti-drug antibody levels, female sex, and certain comorbidities, Wilson Liao, MD, said at the annual research symposium of the National Psoriasis Foundation.

“Tough-to-treat psoriasis remains a challenge despite newer therapies ... Why do we still have this sub-population of patients who seem to be refractory?” said Dr. Liao, professor and associate vice chair of research in the department of dermatology at the University of California, San Francisco, who coauthored a 2015-2022 prospective cohort analysis that documented about 6% of patients failing two or more biologic agents of different mechanistic classes.

“These patients are really suffering,” he said. “We need to have better guidelines and treatment algorithms for these patients.”

A significant number of patients with psoriatic arthritis (PsA), meanwhile, are inadequate responders to tumor necrosis factor (TNF) inhibition, Christopher T. Ritchlin, MD, PhD, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), said during another session at the meeting.

The long-term “persistence,” or usage, of first-line biologics in patients with PsA – and of second-line biologics in patients who failed one TNF-inhibitor – is low, but the literature offers little information on the reasons for TNF-inhibitor discontinuation, said Dr. Ritchlin, who coauthored a perspective piece in Arthritis & Rheumatology on managing the patient with PsA who fails one TNF inhibitor.

Dr. Ritchlin and his coauthors were asked to provide evidence-informed advice and algorithms, but the task was difficult. “It’s hard to know what to recommend for the next step if we don’t know why patients failed the first,” he said. “The point is, we need more data. [Clinical trials] are not recording the kind of information we need.”
 

Anti-drug antibodies, genetics, other factors in psoriasis

Research shows that in large cohorts, “all the biologics do seem to lose efficacy over time,” said Dr. Liao, who directs the UCSF Psoriasis and Skin Treatment Center. “Some are better than others, but we do see a loss of effectiveness over time.”

A cohort study published in 2022 in JAMA Dermatology, for instance, documented declining “drug survival” associated with ineffectiveness during 2 years of treatment for each of five biologics studied (adalimumab [Humira], ustekinumab [Stelara], secukinumab [Cosentyx], guselkumab [Tremfya], and ixekizumab [Taltz]).

“There have been a number of theories put forward” as to why that’s the case, including lower serum drug levels, “which of course can be related to anti-drug antibody production,” he said.

He pointed to two studies of ustekinumab: One prospective observational cohort study that reported an association of lower early drug levels of the IL-12/23 receptor antagonist with lower Psoriasis Area and Severity Index (PASI) scores, and another observational study that documented an association between anti-drug antibody positivity with lower ustekinumab levels and impaired clinical response.

“We also now know ... that there are genetic endotypes in psoriasis, and that patients who are [HLA-C*06:02]-positive tend to respond a little better to drugs like ustekinumab, and those who are [HLA-C*06:02]-negative tend to do a little better with the TNF inhibitors,” Dr. Liao said. The human leukocyte antigen (HLA) allele HLA-C*06:02 is associated with susceptibility to psoriasis.

In a study using a national psoriasis registry, HLA-C*06:02-negative patients were 3 times more likely to achieve PASI90 status in response to adalimumab, a TNF-alpha inhibitor, than with ustekinumab treatment. And in a meta-analysis covering eight studies with more than 1,000 patients with psoriasis, the median PASI75 response rate after 6 months of ustekinumab therapy was 92% in the HLA-C*06:02-positive group and 67% in HLA-C*06:02-negative patients.

The recently published cohort study showing a 6% rate of multiple biologic failure evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for 2 or more years. Investigators looked for sociodemographic and clinical differences between the patients who continued use of their first biologic for at least 2 years (“good response”), and those who discontinued two or more biologics of different classes, each used for at least 90 days, because of inadequate efficacy.

Of 1,039 evaluated patients, 490 (47.2%) had good clinical response to their first biologic and 65 (6.3%) had multiple biologic failure. All biologic classes were represented among those who failed multiple biologics. The first and second biologic classes used were attempted for a mean duration of 10 months – “an adequate trial” of each, Dr. Liao said.

In multivariable regression analysis, six variables were significantly associated with multiple biologic failure: female sex at birth, shorter disease duration, earlier year of biologic initiation, prior nonbiologic systemic therapy, having Medicaid insurance, and a history of hyperlipidemia. The latter is “interesting because other studies have shown that metabolic syndrome, of which hyperlipidemia is a component, can also relate to poor response to biologics,” Dr. Liao said.

The most common sequences of first-to-second biologics among those with multiple biologic failure were TNF inhibitor to IL-17 inhibitor (30.8%); IL-12/23 inhibitor to IL-17 inhibitor (21.5%); TNF inhibitor to IL-12/23 inhibitor (12.3%); and IL-17 inhibitor to IL-23 inhibitor (10.8%).

The vast majority of patients failed more than two biologics, however, and “more than 20% had five or more biologics tried over a relatively short period,” Dr. Liao said.
 

Comorbidities and biologic failure in psoriasis, PsA

In practice, it was said during a discussion period, biologic failures in psoriasis can be of two types: a primary inadequate response or initial failure, or a secondary failure with initial improvement followed by declining or no response. “I agree 100% that these probably represent two different endotypes,” Dr. Liao said. “There’s research emerging that psoriasis isn’t necessarily a clean phenotype.”

The option of focusing on comorbidities in the face of biologic failure was another point of discussion. “Maybe the next biologic is not the answer,” a meeting participant said. “Maybe we should focus on metabolic syndrome.”

“I agree,” Dr. Liao said. “In clinic, there are people who may not respond to therapies but have other comorbidities and factors that make it difficult to manage [their psoriasis] ... that may be causative for psoriasis. Maybe if we treat the comorbidities, it will make it easier to treat the psoriasis.”

Addressing comorbidities and “extra-articular traits” such as poorly controlled diabetes, centralized pain, anxiety and depression, and obesity is something Dr. Ritchlin advocates for PsA. “Centralized pain, I believe, is a major driver of nonresponse,” he said at the meeting. “We have to be careful about blaming nonresponse and lack of efficacy of biologics when it could be a wholly different mechanism the biologic won’t treat ... for example, centralized pain.”

As with psoriasis, the emergence of antidrug antibodies may be one reason for the secondary failure of biologic agents for PsA, Dr. Ritchlin and his coauthors wrote in their paper on management of PsA after failure of one TNF inhibitor. Other areas to consider in evaluating failure, they wrote, are compliance and time of dosing, and financial barriers.

Low long-term persistence of second-line biologics for patients with PsA was demonstrated in a national cohort study utilizing the French health insurance database, Dr. Ritchlin noted at the research meeting. 

The French study covered almost 3,000 patients who started a second biologic after discontinuing a TNF inhibitor during 2015-2020. Overall, 1-year and 3-year persistence rates were 42% and 17%, respectively.

Dr. Liao disclosed research grant funding from AbbVie, Amgen, Janssen, Leo, Novartis, Pfizer, Regeneron, and Trex Bio. Dr. Ritchlin reported no disclosures.

WASHINGTON – Multiple biologic failure in a minority of patients with psoriasis may have several causes, from genetic endotypes and immunologic factors to lower serum drug levels, the presence of anti-drug antibody levels, female sex, and certain comorbidities, Wilson Liao, MD, said at the annual research symposium of the National Psoriasis Foundation.

“Tough-to-treat psoriasis remains a challenge despite newer therapies ... Why do we still have this sub-population of patients who seem to be refractory?” said Dr. Liao, professor and associate vice chair of research in the department of dermatology at the University of California, San Francisco, who coauthored a 2015-2022 prospective cohort analysis that documented about 6% of patients failing two or more biologic agents of different mechanistic classes.

“These patients are really suffering,” he said. “We need to have better guidelines and treatment algorithms for these patients.”

A significant number of patients with psoriatic arthritis (PsA), meanwhile, are inadequate responders to tumor necrosis factor (TNF) inhibition, Christopher T. Ritchlin, MD, PhD, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), said during another session at the meeting.

The long-term “persistence,” or usage, of first-line biologics in patients with PsA – and of second-line biologics in patients who failed one TNF-inhibitor – is low, but the literature offers little information on the reasons for TNF-inhibitor discontinuation, said Dr. Ritchlin, who coauthored a perspective piece in Arthritis & Rheumatology on managing the patient with PsA who fails one TNF inhibitor.

Dr. Ritchlin and his coauthors were asked to provide evidence-informed advice and algorithms, but the task was difficult. “It’s hard to know what to recommend for the next step if we don’t know why patients failed the first,” he said. “The point is, we need more data. [Clinical trials] are not recording the kind of information we need.”
 

Anti-drug antibodies, genetics, other factors in psoriasis

Research shows that in large cohorts, “all the biologics do seem to lose efficacy over time,” said Dr. Liao, who directs the UCSF Psoriasis and Skin Treatment Center. “Some are better than others, but we do see a loss of effectiveness over time.”

A cohort study published in 2022 in JAMA Dermatology, for instance, documented declining “drug survival” associated with ineffectiveness during 2 years of treatment for each of five biologics studied (adalimumab [Humira], ustekinumab [Stelara], secukinumab [Cosentyx], guselkumab [Tremfya], and ixekizumab [Taltz]).

“There have been a number of theories put forward” as to why that’s the case, including lower serum drug levels, “which of course can be related to anti-drug antibody production,” he said.

He pointed to two studies of ustekinumab: One prospective observational cohort study that reported an association of lower early drug levels of the IL-12/23 receptor antagonist with lower Psoriasis Area and Severity Index (PASI) scores, and another observational study that documented an association between anti-drug antibody positivity with lower ustekinumab levels and impaired clinical response.

“We also now know ... that there are genetic endotypes in psoriasis, and that patients who are [HLA-C*06:02]-positive tend to respond a little better to drugs like ustekinumab, and those who are [HLA-C*06:02]-negative tend to do a little better with the TNF inhibitors,” Dr. Liao said. The human leukocyte antigen (HLA) allele HLA-C*06:02 is associated with susceptibility to psoriasis.

In a study using a national psoriasis registry, HLA-C*06:02-negative patients were 3 times more likely to achieve PASI90 status in response to adalimumab, a TNF-alpha inhibitor, than with ustekinumab treatment. And in a meta-analysis covering eight studies with more than 1,000 patients with psoriasis, the median PASI75 response rate after 6 months of ustekinumab therapy was 92% in the HLA-C*06:02-positive group and 67% in HLA-C*06:02-negative patients.

The recently published cohort study showing a 6% rate of multiple biologic failure evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for 2 or more years. Investigators looked for sociodemographic and clinical differences between the patients who continued use of their first biologic for at least 2 years (“good response”), and those who discontinued two or more biologics of different classes, each used for at least 90 days, because of inadequate efficacy.

Of 1,039 evaluated patients, 490 (47.2%) had good clinical response to their first biologic and 65 (6.3%) had multiple biologic failure. All biologic classes were represented among those who failed multiple biologics. The first and second biologic classes used were attempted for a mean duration of 10 months – “an adequate trial” of each, Dr. Liao said.

In multivariable regression analysis, six variables were significantly associated with multiple biologic failure: female sex at birth, shorter disease duration, earlier year of biologic initiation, prior nonbiologic systemic therapy, having Medicaid insurance, and a history of hyperlipidemia. The latter is “interesting because other studies have shown that metabolic syndrome, of which hyperlipidemia is a component, can also relate to poor response to biologics,” Dr. Liao said.

The most common sequences of first-to-second biologics among those with multiple biologic failure were TNF inhibitor to IL-17 inhibitor (30.8%); IL-12/23 inhibitor to IL-17 inhibitor (21.5%); TNF inhibitor to IL-12/23 inhibitor (12.3%); and IL-17 inhibitor to IL-23 inhibitor (10.8%).

The vast majority of patients failed more than two biologics, however, and “more than 20% had five or more biologics tried over a relatively short period,” Dr. Liao said.
 

Comorbidities and biologic failure in psoriasis, PsA

In practice, it was said during a discussion period, biologic failures in psoriasis can be of two types: a primary inadequate response or initial failure, or a secondary failure with initial improvement followed by declining or no response. “I agree 100% that these probably represent two different endotypes,” Dr. Liao said. “There’s research emerging that psoriasis isn’t necessarily a clean phenotype.”

The option of focusing on comorbidities in the face of biologic failure was another point of discussion. “Maybe the next biologic is not the answer,” a meeting participant said. “Maybe we should focus on metabolic syndrome.”

“I agree,” Dr. Liao said. “In clinic, there are people who may not respond to therapies but have other comorbidities and factors that make it difficult to manage [their psoriasis] ... that may be causative for psoriasis. Maybe if we treat the comorbidities, it will make it easier to treat the psoriasis.”

Addressing comorbidities and “extra-articular traits” such as poorly controlled diabetes, centralized pain, anxiety and depression, and obesity is something Dr. Ritchlin advocates for PsA. “Centralized pain, I believe, is a major driver of nonresponse,” he said at the meeting. “We have to be careful about blaming nonresponse and lack of efficacy of biologics when it could be a wholly different mechanism the biologic won’t treat ... for example, centralized pain.”

As with psoriasis, the emergence of antidrug antibodies may be one reason for the secondary failure of biologic agents for PsA, Dr. Ritchlin and his coauthors wrote in their paper on management of PsA after failure of one TNF inhibitor. Other areas to consider in evaluating failure, they wrote, are compliance and time of dosing, and financial barriers.

Low long-term persistence of second-line biologics for patients with PsA was demonstrated in a national cohort study utilizing the French health insurance database, Dr. Ritchlin noted at the research meeting. 

The French study covered almost 3,000 patients who started a second biologic after discontinuing a TNF inhibitor during 2015-2020. Overall, 1-year and 3-year persistence rates were 42% and 17%, respectively.

Dr. Liao disclosed research grant funding from AbbVie, Amgen, Janssen, Leo, Novartis, Pfizer, Regeneron, and Trex Bio. Dr. Ritchlin reported no disclosures.

TOPLINE:

Most patients with psoriasis are not participating in highly shared decision-making (SDM) with clinicians about their care.

METHODOLOGY:

• Researchers drew from the 2014-2017 and 2019 Medical Expenditure Panel Survey (MEPS) to identify 3,715,027 patients with psoriasis, to evaluate the association between SDM (a patient-centered approach to selecting treatment on the basis of a discussion between the clinician and patient) and satisfaction with care.
• SDM was determined by patient responses on a 4-point Likert scale to seven MEPS variables, including the question, “How often did doctors or other health providers listen carefully to you?”
• Patient satisfaction with care was measured with a MEPS variable that asked respondents to rate their health care providers on a scale of 1-10.
• Researchers used multiple logistic regression to assess the association between SDM and demographic and clinical characteristics in patients with psoriasis, and multiple linear regression analysis to assess the association between SDM and patient satisfaction with care.

TAKEAWAY:

• The average SDM score was 3.6 out of 4, and the average satisfaction with care score was 8.6 out of 10.
• However, only about 42% of the cohort reported a high SDM, defined as a score of 3.9 or greater.
• After adjusting for covariates, the researchers found that patients who had high SDM had, on average, 85% higher satisfaction with care (P < .001).
• Compared with men, women had about 27% higher satisfaction with care (P = .023), whereas non-Hispanic patients had lower satisfaction with care compared with Hispanic patients (P = .037).

IN PRACTICE:

“It is important to construct a framework for carrying out SDM with patients with psoriasis to enhance clinician-patient communication and improve patient outcomes,” the authors concluded.

SOURCE:

April W. Armstrong, MD, MPH, chief of dermatology at the University of California, Los Angeles, led the research. The study was published online  in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The ability to measure SDM in patients with psoriasis was limited by the seven items from MEPS. The diagnosis of psoriasis was based on self-report.

DISCLOSURES:

The study was funded by the National Psoriasis Foundation. Dr. Armstrong disclosed that she has served as a research investigator and/or scientific adviser to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, EPI, Incyte, Leo, UCB, Janssen, Lilly, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, Pfizer, and Modmed.

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

TOPLINE:

Most patients with psoriasis are not participating in highly shared decision-making (SDM) with clinicians about their care.

METHODOLOGY:

• Researchers drew from the 2014-2017 and 2019 Medical Expenditure Panel Survey (MEPS) to identify 3,715,027 patients with psoriasis, to evaluate the association between SDM (a patient-centered approach to selecting treatment on the basis of a discussion between the clinician and patient) and satisfaction with care.
• SDM was determined by patient responses on a 4-point Likert scale to seven MEPS variables, including the question, “How often did doctors or other health providers listen carefully to you?”
• Patient satisfaction with care was measured with a MEPS variable that asked respondents to rate their health care providers on a scale of 1-10.
• Researchers used multiple logistic regression to assess the association between SDM and demographic and clinical characteristics in patients with psoriasis, and multiple linear regression analysis to assess the association between SDM and patient satisfaction with care.

TAKEAWAY:

• The average SDM score was 3.6 out of 4, and the average satisfaction with care score was 8.6 out of 10.
• However, only about 42% of the cohort reported a high SDM, defined as a score of 3.9 or greater.
• After adjusting for covariates, the researchers found that patients who had high SDM had, on average, 85% higher satisfaction with care (P < .001).
• Compared with men, women had about 27% higher satisfaction with care (P = .023), whereas non-Hispanic patients had lower satisfaction with care compared with Hispanic patients (P = .037).

IN PRACTICE:

“It is important to construct a framework for carrying out SDM with patients with psoriasis to enhance clinician-patient communication and improve patient outcomes,” the authors concluded.

SOURCE:

April W. Armstrong, MD, MPH, chief of dermatology at the University of California, Los Angeles, led the research. The study was published online  in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The ability to measure SDM in patients with psoriasis was limited by the seven items from MEPS. The diagnosis of psoriasis was based on self-report.

DISCLOSURES:

The study was funded by the National Psoriasis Foundation. Dr. Armstrong disclosed that she has served as a research investigator and/or scientific adviser to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, EPI, Incyte, Leo, UCB, Janssen, Lilly, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, Pfizer, and Modmed.

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

TOPLINE:

Most patients with psoriasis are not participating in highly shared decision-making (SDM) with clinicians about their care.

METHODOLOGY:

• Researchers drew from the 2014-2017 and 2019 Medical Expenditure Panel Survey (MEPS) to identify 3,715,027 patients with psoriasis, to evaluate the association between SDM (a patient-centered approach to selecting treatment on the basis of a discussion between the clinician and patient) and satisfaction with care.
• SDM was determined by patient responses on a 4-point Likert scale to seven MEPS variables, including the question, “How often did doctors or other health providers listen carefully to you?”
• Patient satisfaction with care was measured with a MEPS variable that asked respondents to rate their health care providers on a scale of 1-10.
• Researchers used multiple logistic regression to assess the association between SDM and demographic and clinical characteristics in patients with psoriasis, and multiple linear regression analysis to assess the association between SDM and patient satisfaction with care.

TAKEAWAY:

• The average SDM score was 3.6 out of 4, and the average satisfaction with care score was 8.6 out of 10.
• However, only about 42% of the cohort reported a high SDM, defined as a score of 3.9 or greater.
• After adjusting for covariates, the researchers found that patients who had high SDM had, on average, 85% higher satisfaction with care (P < .001).
• Compared with men, women had about 27% higher satisfaction with care (P = .023), whereas non-Hispanic patients had lower satisfaction with care compared with Hispanic patients (P = .037).

IN PRACTICE:

“It is important to construct a framework for carrying out SDM with patients with psoriasis to enhance clinician-patient communication and improve patient outcomes,” the authors concluded.

SOURCE:

April W. Armstrong, MD, MPH, chief of dermatology at the University of California, Los Angeles, led the research. The study was published online  in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The ability to measure SDM in patients with psoriasis was limited by the seven items from MEPS. The diagnosis of psoriasis was based on self-report.

DISCLOSURES:

The study was funded by the National Psoriasis Foundation. Dr. Armstrong disclosed that she has served as a research investigator and/or scientific adviser to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, EPI, Incyte, Leo, UCB, Janssen, Lilly, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, Pfizer, and Modmed.

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

The U.S. Food and Drug Administration has approved ustekinumab-auub (Wezlana) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions. This is the first approval for a ustekinumab biosimilar in the United States.

Ustekinumab-auub was also granted an interchangeability designation, meaning that, depending on state law, a pharmacist may substitute the biosimilar for the reference product without consulting the prescribing provider.

“Today’s approval exemplifies the FDA’s longstanding commitment to support a competitive marketplace for biological products,” Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars in the FDA’s Center for Drug Evaluation and Research, said in a statement. “This approval can empower patients by helping to increase access to safe, effective, and high-quality medications at potentially lower cost.”

Ustekinumab, manufactured by Johnson & Johnson, targets interleukin-12 and IL-23 and was first approved in 2009. Ustekinumab-auub was developed by Amgen.

Ustekinumab-auub is approved for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, active psoriatic arthritis, moderate to severely active Crohn’s disease, and moderate to severely active ulcerative colitis. It is also approved for pediatric patients aged 6 years and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy and active psoriatic arthritis.

The approval was based on “comprehensive review of scientific evidence,” including “comparisons of the products on an analytical level using an extensive battery of chemical and biological tests and biological assays that confirmed similarity in the structural and functional features of Wezlana and Stelara (including those known to impact safety and efficacy), and comparative human pharmacokinetic data, clinical immunogenicity data, and other clinical safety and effectiveness data,” the FDA said.

Some common side effects of ustekinumab-auub include nasopharyngitis, upper respiratory tract infection, headache, fatigue, and nausea. The most severe side effect of the biosimilar, as with the reference drug ustekinumab, is infection.

The product launch of ustekinumab-auub will be delayed as a part of a settlement of Johnson & Johnson’s lawsuit against Amgen, according to Reuters. The details of the settlement are confidential, but it was stated that the biosimilar would be available by Jan. 1, 2025.

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

The U.S. Food and Drug Administration has approved ustekinumab-auub (Wezlana) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions. This is the first approval for a ustekinumab biosimilar in the United States.

Ustekinumab-auub was also granted an interchangeability designation, meaning that, depending on state law, a pharmacist may substitute the biosimilar for the reference product without consulting the prescribing provider.

“Today’s approval exemplifies the FDA’s longstanding commitment to support a competitive marketplace for biological products,” Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars in the FDA’s Center for Drug Evaluation and Research, said in a statement. “This approval can empower patients by helping to increase access to safe, effective, and high-quality medications at potentially lower cost.”

Ustekinumab, manufactured by Johnson & Johnson, targets interleukin-12 and IL-23 and was first approved in 2009. Ustekinumab-auub was developed by Amgen.

Ustekinumab-auub is approved for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, active psoriatic arthritis, moderate to severely active Crohn’s disease, and moderate to severely active ulcerative colitis. It is also approved for pediatric patients aged 6 years and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy and active psoriatic arthritis.

The approval was based on “comprehensive review of scientific evidence,” including “comparisons of the products on an analytical level using an extensive battery of chemical and biological tests and biological assays that confirmed similarity in the structural and functional features of Wezlana and Stelara (including those known to impact safety and efficacy), and comparative human pharmacokinetic data, clinical immunogenicity data, and other clinical safety and effectiveness data,” the FDA said.

Some common side effects of ustekinumab-auub include nasopharyngitis, upper respiratory tract infection, headache, fatigue, and nausea. The most severe side effect of the biosimilar, as with the reference drug ustekinumab, is infection.

The product launch of ustekinumab-auub will be delayed as a part of a settlement of Johnson & Johnson’s lawsuit against Amgen, according to Reuters. The details of the settlement are confidential, but it was stated that the biosimilar would be available by Jan. 1, 2025.

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

The U.S. Food and Drug Administration has approved ustekinumab-auub (Wezlana) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions. This is the first approval for a ustekinumab biosimilar in the United States.

Ustekinumab-auub was also granted an interchangeability designation, meaning that, depending on state law, a pharmacist may substitute the biosimilar for the reference product without consulting the prescribing provider.

“Today’s approval exemplifies the FDA’s longstanding commitment to support a competitive marketplace for biological products,” Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars in the FDA’s Center for Drug Evaluation and Research, said in a statement. “This approval can empower patients by helping to increase access to safe, effective, and high-quality medications at potentially lower cost.”

Ustekinumab, manufactured by Johnson & Johnson, targets interleukin-12 and IL-23 and was first approved in 2009. Ustekinumab-auub was developed by Amgen.

Ustekinumab-auub is approved for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, active psoriatic arthritis, moderate to severely active Crohn’s disease, and moderate to severely active ulcerative colitis. It is also approved for pediatric patients aged 6 years and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy and active psoriatic arthritis.

The approval was based on “comprehensive review of scientific evidence,” including “comparisons of the products on an analytical level using an extensive battery of chemical and biological tests and biological assays that confirmed similarity in the structural and functional features of Wezlana and Stelara (including those known to impact safety and efficacy), and comparative human pharmacokinetic data, clinical immunogenicity data, and other clinical safety and effectiveness data,” the FDA said.

Some common side effects of ustekinumab-auub include nasopharyngitis, upper respiratory tract infection, headache, fatigue, and nausea. The most severe side effect of the biosimilar, as with the reference drug ustekinumab, is infection.

The product launch of ustekinumab-auub will be delayed as a part of a settlement of Johnson & Johnson’s lawsuit against Amgen, according to Reuters. The details of the settlement are confidential, but it was stated that the biosimilar would be available by Jan. 1, 2025.

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

The Food and Drug Administration has approved an expanded indication for abatacept (Orencia) for treatment of psoriatic arthritis (PsA) in pediatric patients aged 2 years and older.

Juvenile psoriatic arthritis (JPsA) is a form of juvenile idiopathic arthritis (JIA). It is a rare condition, and it is estimated that as many as 5% of children with JIA have JPsA.

Olivier Le Moal/Getty Images

“The FDA’s approval of expanding Orencia’s indication adds a much-needed treatment option for children with JPsA, a rare, potentially serious condition characterized by chronic inflammation and joint damage,” said Carlos Dortrait, senior vice president of U.S. immunology at Bristol-Myers Squibb in a statement. BMS is the manufacturer of abatacept.

Abatacept was first approved in 2005 for the treatment of moderate to severe rheumatoid arthritis and was approved for treating active PsA in adults in 2017. In 2008, the drug was the first intravenous biologic approved for patients 6 years old and older to treat moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA). In 2017, a subcutaneous administration option was approved for children 2 years old and older with pJIA, according to a BMS press release.

This expanded approval was based on controlled studies of abatacept in adults with PsA; pharmacokinetic data from adults with RA, adults with PsA, and children with pJIA; and safety data from clinical studies in patients aged 2-17 years with pJIA.

“Children living with psoriatic arthritis can experience a number of challenging symptoms including swollen and painful joints,” Steven Taylor, president and CEO of the Arthritis Foundation, said in a BMS statement. “The FDA’s approval of Orencia for JPsA in patients 2 years of age and older means another treatment option is available to manage this rare chronic disease, which is exciting news for the arthritis community of young patients, their caregivers, and health care professionals.”

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

The Food and Drug Administration has approved an expanded indication for abatacept (Orencia) for treatment of psoriatic arthritis (PsA) in pediatric patients aged 2 years and older.

Juvenile psoriatic arthritis (JPsA) is a form of juvenile idiopathic arthritis (JIA). It is a rare condition, and it is estimated that as many as 5% of children with JIA have JPsA.

Olivier Le Moal/Getty Images

“The FDA’s approval of expanding Orencia’s indication adds a much-needed treatment option for children with JPsA, a rare, potentially serious condition characterized by chronic inflammation and joint damage,” said Carlos Dortrait, senior vice president of U.S. immunology at Bristol-Myers Squibb in a statement. BMS is the manufacturer of abatacept.

Abatacept was first approved in 2005 for the treatment of moderate to severe rheumatoid arthritis and was approved for treating active PsA in adults in 2017. In 2008, the drug was the first intravenous biologic approved for patients 6 years old and older to treat moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA). In 2017, a subcutaneous administration option was approved for children 2 years old and older with pJIA, according to a BMS press release.

This expanded approval was based on controlled studies of abatacept in adults with PsA; pharmacokinetic data from adults with RA, adults with PsA, and children with pJIA; and safety data from clinical studies in patients aged 2-17 years with pJIA.

“Children living with psoriatic arthritis can experience a number of challenging symptoms including swollen and painful joints,” Steven Taylor, president and CEO of the Arthritis Foundation, said in a BMS statement. “The FDA’s approval of Orencia for JPsA in patients 2 years of age and older means another treatment option is available to manage this rare chronic disease, which is exciting news for the arthritis community of young patients, their caregivers, and health care professionals.”

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

The Food and Drug Administration has approved an expanded indication for abatacept (Orencia) for treatment of psoriatic arthritis (PsA) in pediatric patients aged 2 years and older.

Juvenile psoriatic arthritis (JPsA) is a form of juvenile idiopathic arthritis (JIA). It is a rare condition, and it is estimated that as many as 5% of children with JIA have JPsA.

Olivier Le Moal/Getty Images

“The FDA’s approval of expanding Orencia’s indication adds a much-needed treatment option for children with JPsA, a rare, potentially serious condition characterized by chronic inflammation and joint damage,” said Carlos Dortrait, senior vice president of U.S. immunology at Bristol-Myers Squibb in a statement. BMS is the manufacturer of abatacept.

Abatacept was first approved in 2005 for the treatment of moderate to severe rheumatoid arthritis and was approved for treating active PsA in adults in 2017. In 2008, the drug was the first intravenous biologic approved for patients 6 years old and older to treat moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA). In 2017, a subcutaneous administration option was approved for children 2 years old and older with pJIA, according to a BMS press release.

This expanded approval was based on controlled studies of abatacept in adults with PsA; pharmacokinetic data from adults with RA, adults with PsA, and children with pJIA; and safety data from clinical studies in patients aged 2-17 years with pJIA.

“Children living with psoriatic arthritis can experience a number of challenging symptoms including swollen and painful joints,” Steven Taylor, president and CEO of the Arthritis Foundation, said in a BMS statement. “The FDA’s approval of Orencia for JPsA in patients 2 years of age and older means another treatment option is available to manage this rare chronic disease, which is exciting news for the arthritis community of young patients, their caregivers, and health care professionals.”

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

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

There is steady advance in the treatment of PsA. Bimekizumab is a novel monoclonal antibody that, by binding to similar sites on interleukin (IL)-17A and IL-17F, inhibits these cytokines. Ritchlin and colleagues recently reported the 52-week results from the phase 3 BE OPTIMAL study including 852 biological disease-modifying antirheumatic drug (bDMARD)-naive patients with active PsA who were randomly assigned to receive bimekizumab, adalimumab, or placebo. At week 16, 43.9% of patients receiving bimekizumab achieved ≥ 50% improvement in the American College of Rheumatology scores (ACR50), with the response being maintained up to week 52 (54.5%). Among patients who switched from placebo to bimekizumab at week 16, a similar proportion (53.0%) achieved ACR50 at week 52. No new safety signals were observed. Thus, bimekizumab led to sustained improvements in clinical response up to week 52 and probably will soon be available to patients with PsA.

The optimal management of axial PsA continues to be investigated. One major question is whether IL-23 inhibitors, which are not efficacious in axial spondyloarthritis, have efficacy in axial PsA. A post hoc analysis of the DISCOVER-2 study included 246 biologic-naive patients with active PsA and sacroiliitis who were randomly assigned to guselkumab every 4 weeks (Q4W; n = 82), guselkumab every 8 weeks (Q8W; n = 68), or placebo with crossover to guselkumab Q4W at week 24 (n = 96), Mease and colleagues report that at week 24, guselkumab Q4W and Q8W vs placebo showed significantly greater scores in the total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as well as Ankylosing Spondylitis Disease Activity Score (ASDAS), with further improvements noted at week 100. Thus, in patients with active PsA and imaging-confirmed sacroiliitis, 100 mg guselkumab Q4W and Q8W yielded clinically meaningful and sustained improvements in axial symptoms through 2 years.

Finally, attention is currently being paid to patients with refractory or difficult-to-treat (D2T) PsA. These patients are generally characterized as having active disease despite treatment with two or more targeted DMARD (tDMARD). Philippoteaux and colleagues have reported results from their retrospective cohort study that included 150 patients with PsA who initiated treatment with tDMARD and were followed for at least 2 years, of whom 49 patients had D2T PsA. They found that peripheral structural damage, axial involvement, and the discontinuation of bDMARD due to poor skin psoriasis control were more prevalent in patients with D2T PsA compared with in non-D2T PsA. Thus, patients with D2T PsA are more likely to have more structural damage. Early diagnosis and treatment to reduce structural damage might reduce the prevalence of D2T PsA.

There is steady advance in the treatment of PsA. Bimekizumab is a novel monoclonal antibody that, by binding to similar sites on interleukin (IL)-17A and IL-17F, inhibits these cytokines. Ritchlin and colleagues recently reported the 52-week results from the phase 3 BE OPTIMAL study including 852 biological disease-modifying antirheumatic drug (bDMARD)-naive patients with active PsA who were randomly assigned to receive bimekizumab, adalimumab, or placebo. At week 16, 43.9% of patients receiving bimekizumab achieved ≥ 50% improvement in the American College of Rheumatology scores (ACR50), with the response being maintained up to week 52 (54.5%). Among patients who switched from placebo to bimekizumab at week 16, a similar proportion (53.0%) achieved ACR50 at week 52. No new safety signals were observed. Thus, bimekizumab led to sustained improvements in clinical response up to week 52 and probably will soon be available to patients with PsA.

The optimal management of axial PsA continues to be investigated. One major question is whether IL-23 inhibitors, which are not efficacious in axial spondyloarthritis, have efficacy in axial PsA. A post hoc analysis of the DISCOVER-2 study included 246 biologic-naive patients with active PsA and sacroiliitis who were randomly assigned to guselkumab every 4 weeks (Q4W; n = 82), guselkumab every 8 weeks (Q8W; n = 68), or placebo with crossover to guselkumab Q4W at week 24 (n = 96), Mease and colleagues report that at week 24, guselkumab Q4W and Q8W vs placebo showed significantly greater scores in the total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as well as Ankylosing Spondylitis Disease Activity Score (ASDAS), with further improvements noted at week 100. Thus, in patients with active PsA and imaging-confirmed sacroiliitis, 100 mg guselkumab Q4W and Q8W yielded clinically meaningful and sustained improvements in axial symptoms through 2 years.

Finally, attention is currently being paid to patients with refractory or difficult-to-treat (D2T) PsA. These patients are generally characterized as having active disease despite treatment with two or more targeted DMARD (tDMARD). Philippoteaux and colleagues have reported results from their retrospective cohort study that included 150 patients with PsA who initiated treatment with tDMARD and were followed for at least 2 years, of whom 49 patients had D2T PsA. They found that peripheral structural damage, axial involvement, and the discontinuation of bDMARD due to poor skin psoriasis control were more prevalent in patients with D2T PsA compared with in non-D2T PsA. Thus, patients with D2T PsA are more likely to have more structural damage. Early diagnosis and treatment to reduce structural damage might reduce the prevalence of D2T PsA.

There is steady advance in the treatment of PsA. Bimekizumab is a novel monoclonal antibody that, by binding to similar sites on interleukin (IL)-17A and IL-17F, inhibits these cytokines. Ritchlin and colleagues recently reported the 52-week results from the phase 3 BE OPTIMAL study including 852 biological disease-modifying antirheumatic drug (bDMARD)-naive patients with active PsA who were randomly assigned to receive bimekizumab, adalimumab, or placebo. At week 16, 43.9% of patients receiving bimekizumab achieved ≥ 50% improvement in the American College of Rheumatology scores (ACR50), with the response being maintained up to week 52 (54.5%). Among patients who switched from placebo to bimekizumab at week 16, a similar proportion (53.0%) achieved ACR50 at week 52. No new safety signals were observed. Thus, bimekizumab led to sustained improvements in clinical response up to week 52 and probably will soon be available to patients with PsA.

The optimal management of axial PsA continues to be investigated. One major question is whether IL-23 inhibitors, which are not efficacious in axial spondyloarthritis, have efficacy in axial PsA. A post hoc analysis of the DISCOVER-2 study included 246 biologic-naive patients with active PsA and sacroiliitis who were randomly assigned to guselkumab every 4 weeks (Q4W; n = 82), guselkumab every 8 weeks (Q8W; n = 68), or placebo with crossover to guselkumab Q4W at week 24 (n = 96), Mease and colleagues report that at week 24, guselkumab Q4W and Q8W vs placebo showed significantly greater scores in the total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as well as Ankylosing Spondylitis Disease Activity Score (ASDAS), with further improvements noted at week 100. Thus, in patients with active PsA and imaging-confirmed sacroiliitis, 100 mg guselkumab Q4W and Q8W yielded clinically meaningful and sustained improvements in axial symptoms through 2 years.

Finally, attention is currently being paid to patients with refractory or difficult-to-treat (D2T) PsA. These patients are generally characterized as having active disease despite treatment with two or more targeted DMARD (tDMARD). Philippoteaux and colleagues have reported results from their retrospective cohort study that included 150 patients with PsA who initiated treatment with tDMARD and were followed for at least 2 years, of whom 49 patients had D2T PsA. They found that peripheral structural damage, axial involvement, and the discontinuation of bDMARD due to poor skin psoriasis control were more prevalent in patients with D2T PsA compared with in non-D2T PsA. Thus, patients with D2T PsA are more likely to have more structural damage. Early diagnosis and treatment to reduce structural damage might reduce the prevalence of D2T PsA.

WASHINGTON – In psoriatic disease, psoriatic arthritis (PsA) remains one of the greatest unmet needs, with the transition from cutaneous psoriasis poorly understood, diagnosis challenging, and therapeutic accomplishments trailing far behind advances for skin disease. However, leading researchers in rheumatology and dermatology believe that they’re turning the corner toward a day when therapies are phenotype-targeted and diagnosis can be made early and treatment begun well before inflammation worsens and pain and joint damage ensue.

“The challenge right now is that we don’t understand the discrete and overlapping endotypes that underlie the phenotypes or domains” of PsA, said Christopher Ritchlin, MD, MPH, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), who spoke about PsA at the annual research symposium of the National Psoriasis Foundation.

A deep dive into the tissue

Dr. Ritchlin is among those rheumatology clinician-researchers who advocated early on for a “domain” approach to the diagnosis and management of PsA – that is, consideration of the key domains of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.

The approach is an especially important part of treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. But while interventions can be tailored to some extent to these domains, or phenotypes, there are limitations without an understanding of the different pathophysiology and mechanisms driving the heterogeneity in tissue involvement.

Dr. Ritchlin draws inspiration from pulmonology, which subtyped asthma into various phenotypes (for example, eosinophilic, allergic, intrinsic, exercise-induced) and “drilled down” on understanding underlying mechanisms to guide more specific treatment. Similar phenotype-endotype research has been done for chronic obstructive pulmonary disease, he said at the meeting, pointing to a phase 3 randomized controlled trial, published in the New England Journal of Medicine, that found dupilimab (Dupixent) was effective for patients with COPD who had type 2 inflammation as indicated by elevated eosinophil counts.

“It’s a beautiful example of how to define an endotype from a phenotypic biomarker and then use a specific intervention to improve outcomes,” Dr. Ritchlin said. “We need to do this for psoriasis and PsA.”

The ELLIPSS project will utilize the host of -omics tools and technologies (for proteomics, metabolomics, and genomics, for instance) that are making it increasingly possible to dissect the heterogeneity of single diseases and achieve more precision with treatments.

Researchers will collect blood samples and skin and/or synovial tissue biopsies from cohorts of patients with psoriasis and PsA who are treatment naïve as well as patients who are treated with a biologic or DMARD (looking at responders and non-responders). They’ll also study a cohort of psoriasis patients who may be “on a transition pathway” for PsA based on risk factors such as family history, nail psoriasis, scalp psoriasis, and body surface area greater than 5%.

Patients in all cohorts will represent distinct synovio-entheseal domains of PsA and the heterogeneity of psoriasis (for example, plaque, general, pustular, palmoplantar) and will be followed longitudinally.

With regards to PsA, one goal is to “find new pathways in the joint, then find surrogate markers in the blood that we can use to help mark particular subphenotypes [that will be identified through deep phenotyping],” Dr. Ritchlin said in an interview after the meeting. “This will lead us hopefully to a more precision-based approach.”

The ELLIPSS team joins other researchers who have been studying rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in an earlier iteration of the AIM program, and that will continue this work. Research on RA has thus far elucidated T-cell subsets in the rheumatoid synovium, as well as interactions of mesenchymal cells with the endothelium, for instance, and led to the identification of key molecules such as granzyme A that weren’t previously known to be involved in RA pathogenesis, Dr. Ritchin said in the interview. The current AIM work also includes Sjögren’s disease.
 

Finding biomarkers, diagnostic signatures

The psoriasis-PsA team has the advantage today of being able to utilize a new technology called spatial transcriptomics, which takes transcriptomics (RNA) from the single-cell level to the tissue level, enabling a look at how disease is affecting cellular organization/tissue architecture, gene activity, and cellular signaling within tissues. “It’s a huge advance in technology,” said Dr. Ritchlin. “We can actually see how the cells are interacting in the synovium [and other tissues].”

A paper published in Science Immunology and discussed at the NPF meeting demonstrates the power of special transcriptomics for learning about the skin. Dr. Scher, Dr. Ritchlin, first authors Rochelle L. Castillo, MD, and Ikjot Sidhu, MS, and other co-investigators reported a “dynamic re-organization of the immune milieu and fibroblasts in PsO lesional and non-lesional skin,” the presence of B cells in lesioned skin, and cellular organization/ecosystems that vary occurring according to clinical severity, among other findings.

Dr. Scher is using the tool for his NPF-funded diagnostic test research and as part of his work at NYU Langone for the ELLIPPS project. Among his goals: To “discover new cell populations in the microenvironment and study how they interact with each other, then compare those cells between psoriasis and PsA patients to first understand if they’re any different,” he explained after the meeting. Researchers can then investigate the synovial tissue, comparing cell populations and interactions in both compartments and looking for any shared markers/cytokines/proteins, he said.

Multiomics research, meanwhile, is showing that a test for early PsA detection could potentially combine clinical parameters with integrated multi-omic markers into a “diagnostic signature” of sorts.

At the meeting, Vinod Chandran, MD, PhD, a rheumatologist at the University of Toronto who also has an NPF PsA diagnostic test grant, said that his multi-omics analysis of blood samples from patients with psoriasis and PsA has identified signatures with a “high discriminatory value” and that certain metabolic pathways appear to play “a central role in the development and differentiation of PsA.” (Validation in other cohorts and economic analyses are ongoing, Dr. Chandran said. Low-cost alternatives that can be applied broadly in the clinic will need to be pursued, Dr. Scher said.)

Eyes on combination therapy

“The likelihood that all patients will respond to one biologic is very low in PsA, so we’ve been thinking about combination therapy for some time,” Dr. Ritchlin said at the meeting. “I think [dual inhibition] is coming.”

Safety has been the concern, but a phase 2 trial published this year compared a combination of IL-23 and TNF inhibition (guselkumab [Tremfya] plus golimumab [Simponi]) with monotherapy of both biologics in patients with ulcerative colitis and showed that the combination safely drove synergistic restoration of a normal epithelium and mucosal healing, he said.

A phase 2 trial in PsA, designed by Dr. Ritchlin and Dr. Scher and named AFFINITY, will study the safety and efficacy of the same combination of IL-23 and TNF blockade, compared with guselkumab (IL-23 inhibition) alone. The trial is currently completing enrollment of patients who have failed one or two anti-TNF agents.

In the meantime, combination therapy is being employed in clinics for “PsA patients who’ve been channeled through multiple biologics and are still not responding ... when [physicians] feel they’re forced to, not right away,” Dr. Ritchlin said in an interview after the meeting. “As we get a better understanding [through clinical trials], it might be something you’ll see earlier in the treatment process.”

It is wise, Dr. Ritchlin said, to devote more time to addressing “extra-articular traits” (for example, obesity, diabetes, uveitis, colitis, centralized pain) and treatable lifestyle/behavioral risk factors (for example, smoking, exercise, nutrition, adherence to therapy, social support) that can contribute to PsA and treatment nonresponse. He calls this the “treatable traits” strategy.

In practice, “there’s a big focus on inflammation and immune dysfunction, but the problem is, there are other factors involved in nonresponse, and I think ‘treatable traits’ gets to those,” Dr. Ritchlin said after the meeting. Rheumatologists and dermatologists lack time and alliances to address these issues, but “if we can find ways to do it, I think we’ll have improved outcomes.”

Dr. Ritchlin, Dr. Chandran, and Dr. Liao reported no relevant disclosures. Dr. Scher reported ties to Janssen, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb.

WASHINGTON – In psoriatic disease, psoriatic arthritis (PsA) remains one of the greatest unmet needs, with the transition from cutaneous psoriasis poorly understood, diagnosis challenging, and therapeutic accomplishments trailing far behind advances for skin disease. However, leading researchers in rheumatology and dermatology believe that they’re turning the corner toward a day when therapies are phenotype-targeted and diagnosis can be made early and treatment begun well before inflammation worsens and pain and joint damage ensue.

“The challenge right now is that we don’t understand the discrete and overlapping endotypes that underlie the phenotypes or domains” of PsA, said Christopher Ritchlin, MD, MPH, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), who spoke about PsA at the annual research symposium of the National Psoriasis Foundation.

A deep dive into the tissue

Dr. Ritchlin is among those rheumatology clinician-researchers who advocated early on for a “domain” approach to the diagnosis and management of PsA – that is, consideration of the key domains of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.

The approach is an especially important part of treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. But while interventions can be tailored to some extent to these domains, or phenotypes, there are limitations without an understanding of the different pathophysiology and mechanisms driving the heterogeneity in tissue involvement.

Dr. Ritchlin draws inspiration from pulmonology, which subtyped asthma into various phenotypes (for example, eosinophilic, allergic, intrinsic, exercise-induced) and “drilled down” on understanding underlying mechanisms to guide more specific treatment. Similar phenotype-endotype research has been done for chronic obstructive pulmonary disease, he said at the meeting, pointing to a phase 3 randomized controlled trial, published in the New England Journal of Medicine, that found dupilimab (Dupixent) was effective for patients with COPD who had type 2 inflammation as indicated by elevated eosinophil counts.

“It’s a beautiful example of how to define an endotype from a phenotypic biomarker and then use a specific intervention to improve outcomes,” Dr. Ritchlin said. “We need to do this for psoriasis and PsA.”

The ELLIPSS project will utilize the host of -omics tools and technologies (for proteomics, metabolomics, and genomics, for instance) that are making it increasingly possible to dissect the heterogeneity of single diseases and achieve more precision with treatments.

Researchers will collect blood samples and skin and/or synovial tissue biopsies from cohorts of patients with psoriasis and PsA who are treatment naïve as well as patients who are treated with a biologic or DMARD (looking at responders and non-responders). They’ll also study a cohort of psoriasis patients who may be “on a transition pathway” for PsA based on risk factors such as family history, nail psoriasis, scalp psoriasis, and body surface area greater than 5%.

Patients in all cohorts will represent distinct synovio-entheseal domains of PsA and the heterogeneity of psoriasis (for example, plaque, general, pustular, palmoplantar) and will be followed longitudinally.

With regards to PsA, one goal is to “find new pathways in the joint, then find surrogate markers in the blood that we can use to help mark particular subphenotypes [that will be identified through deep phenotyping],” Dr. Ritchlin said in an interview after the meeting. “This will lead us hopefully to a more precision-based approach.”

The ELLIPSS team joins other researchers who have been studying rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in an earlier iteration of the AIM program, and that will continue this work. Research on RA has thus far elucidated T-cell subsets in the rheumatoid synovium, as well as interactions of mesenchymal cells with the endothelium, for instance, and led to the identification of key molecules such as granzyme A that weren’t previously known to be involved in RA pathogenesis, Dr. Ritchin said in the interview. The current AIM work also includes Sjögren’s disease.
 

Finding biomarkers, diagnostic signatures

The psoriasis-PsA team has the advantage today of being able to utilize a new technology called spatial transcriptomics, which takes transcriptomics (RNA) from the single-cell level to the tissue level, enabling a look at how disease is affecting cellular organization/tissue architecture, gene activity, and cellular signaling within tissues. “It’s a huge advance in technology,” said Dr. Ritchlin. “We can actually see how the cells are interacting in the synovium [and other tissues].”

A paper published in Science Immunology and discussed at the NPF meeting demonstrates the power of special transcriptomics for learning about the skin. Dr. Scher, Dr. Ritchlin, first authors Rochelle L. Castillo, MD, and Ikjot Sidhu, MS, and other co-investigators reported a “dynamic re-organization of the immune milieu and fibroblasts in PsO lesional and non-lesional skin,” the presence of B cells in lesioned skin, and cellular organization/ecosystems that vary occurring according to clinical severity, among other findings.

Dr. Scher is using the tool for his NPF-funded diagnostic test research and as part of his work at NYU Langone for the ELLIPPS project. Among his goals: To “discover new cell populations in the microenvironment and study how they interact with each other, then compare those cells between psoriasis and PsA patients to first understand if they’re any different,” he explained after the meeting. Researchers can then investigate the synovial tissue, comparing cell populations and interactions in both compartments and looking for any shared markers/cytokines/proteins, he said.

Multiomics research, meanwhile, is showing that a test for early PsA detection could potentially combine clinical parameters with integrated multi-omic markers into a “diagnostic signature” of sorts.

At the meeting, Vinod Chandran, MD, PhD, a rheumatologist at the University of Toronto who also has an NPF PsA diagnostic test grant, said that his multi-omics analysis of blood samples from patients with psoriasis and PsA has identified signatures with a “high discriminatory value” and that certain metabolic pathways appear to play “a central role in the development and differentiation of PsA.” (Validation in other cohorts and economic analyses are ongoing, Dr. Chandran said. Low-cost alternatives that can be applied broadly in the clinic will need to be pursued, Dr. Scher said.)

Eyes on combination therapy

“The likelihood that all patients will respond to one biologic is very low in PsA, so we’ve been thinking about combination therapy for some time,” Dr. Ritchlin said at the meeting. “I think [dual inhibition] is coming.”

Safety has been the concern, but a phase 2 trial published this year compared a combination of IL-23 and TNF inhibition (guselkumab [Tremfya] plus golimumab [Simponi]) with monotherapy of both biologics in patients with ulcerative colitis and showed that the combination safely drove synergistic restoration of a normal epithelium and mucosal healing, he said.

A phase 2 trial in PsA, designed by Dr. Ritchlin and Dr. Scher and named AFFINITY, will study the safety and efficacy of the same combination of IL-23 and TNF blockade, compared with guselkumab (IL-23 inhibition) alone. The trial is currently completing enrollment of patients who have failed one or two anti-TNF agents.

In the meantime, combination therapy is being employed in clinics for “PsA patients who’ve been channeled through multiple biologics and are still not responding ... when [physicians] feel they’re forced to, not right away,” Dr. Ritchlin said in an interview after the meeting. “As we get a better understanding [through clinical trials], it might be something you’ll see earlier in the treatment process.”

It is wise, Dr. Ritchlin said, to devote more time to addressing “extra-articular traits” (for example, obesity, diabetes, uveitis, colitis, centralized pain) and treatable lifestyle/behavioral risk factors (for example, smoking, exercise, nutrition, adherence to therapy, social support) that can contribute to PsA and treatment nonresponse. He calls this the “treatable traits” strategy.

In practice, “there’s a big focus on inflammation and immune dysfunction, but the problem is, there are other factors involved in nonresponse, and I think ‘treatable traits’ gets to those,” Dr. Ritchlin said after the meeting. Rheumatologists and dermatologists lack time and alliances to address these issues, but “if we can find ways to do it, I think we’ll have improved outcomes.”

Dr. Ritchlin, Dr. Chandran, and Dr. Liao reported no relevant disclosures. Dr. Scher reported ties to Janssen, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb.

WASHINGTON – In psoriatic disease, psoriatic arthritis (PsA) remains one of the greatest unmet needs, with the transition from cutaneous psoriasis poorly understood, diagnosis challenging, and therapeutic accomplishments trailing far behind advances for skin disease. However, leading researchers in rheumatology and dermatology believe that they’re turning the corner toward a day when therapies are phenotype-targeted and diagnosis can be made early and treatment begun well before inflammation worsens and pain and joint damage ensue.

“The challenge right now is that we don’t understand the discrete and overlapping endotypes that underlie the phenotypes or domains” of PsA, said Christopher Ritchlin, MD, MPH, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), who spoke about PsA at the annual research symposium of the National Psoriasis Foundation.

A deep dive into the tissue

Dr. Ritchlin is among those rheumatology clinician-researchers who advocated early on for a “domain” approach to the diagnosis and management of PsA – that is, consideration of the key domains of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis.

The approach is an especially important part of treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. But while interventions can be tailored to some extent to these domains, or phenotypes, there are limitations without an understanding of the different pathophysiology and mechanisms driving the heterogeneity in tissue involvement.

Dr. Ritchlin draws inspiration from pulmonology, which subtyped asthma into various phenotypes (for example, eosinophilic, allergic, intrinsic, exercise-induced) and “drilled down” on understanding underlying mechanisms to guide more specific treatment. Similar phenotype-endotype research has been done for chronic obstructive pulmonary disease, he said at the meeting, pointing to a phase 3 randomized controlled trial, published in the New England Journal of Medicine, that found dupilimab (Dupixent) was effective for patients with COPD who had type 2 inflammation as indicated by elevated eosinophil counts.

“It’s a beautiful example of how to define an endotype from a phenotypic biomarker and then use a specific intervention to improve outcomes,” Dr. Ritchlin said. “We need to do this for psoriasis and PsA.”

The ELLIPSS project will utilize the host of -omics tools and technologies (for proteomics, metabolomics, and genomics, for instance) that are making it increasingly possible to dissect the heterogeneity of single diseases and achieve more precision with treatments.

Researchers will collect blood samples and skin and/or synovial tissue biopsies from cohorts of patients with psoriasis and PsA who are treatment naïve as well as patients who are treated with a biologic or DMARD (looking at responders and non-responders). They’ll also study a cohort of psoriasis patients who may be “on a transition pathway” for PsA based on risk factors such as family history, nail psoriasis, scalp psoriasis, and body surface area greater than 5%.

Patients in all cohorts will represent distinct synovio-entheseal domains of PsA and the heterogeneity of psoriasis (for example, plaque, general, pustular, palmoplantar) and will be followed longitudinally.

With regards to PsA, one goal is to “find new pathways in the joint, then find surrogate markers in the blood that we can use to help mark particular subphenotypes [that will be identified through deep phenotyping],” Dr. Ritchlin said in an interview after the meeting. “This will lead us hopefully to a more precision-based approach.”

The ELLIPSS team joins other researchers who have been studying rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in an earlier iteration of the AIM program, and that will continue this work. Research on RA has thus far elucidated T-cell subsets in the rheumatoid synovium, as well as interactions of mesenchymal cells with the endothelium, for instance, and led to the identification of key molecules such as granzyme A that weren’t previously known to be involved in RA pathogenesis, Dr. Ritchin said in the interview. The current AIM work also includes Sjögren’s disease.
 

Finding biomarkers, diagnostic signatures

The psoriasis-PsA team has the advantage today of being able to utilize a new technology called spatial transcriptomics, which takes transcriptomics (RNA) from the single-cell level to the tissue level, enabling a look at how disease is affecting cellular organization/tissue architecture, gene activity, and cellular signaling within tissues. “It’s a huge advance in technology,” said Dr. Ritchlin. “We can actually see how the cells are interacting in the synovium [and other tissues].”

A paper published in Science Immunology and discussed at the NPF meeting demonstrates the power of special transcriptomics for learning about the skin. Dr. Scher, Dr. Ritchlin, first authors Rochelle L. Castillo, MD, and Ikjot Sidhu, MS, and other co-investigators reported a “dynamic re-organization of the immune milieu and fibroblasts in PsO lesional and non-lesional skin,” the presence of B cells in lesioned skin, and cellular organization/ecosystems that vary occurring according to clinical severity, among other findings.

Dr. Scher is using the tool for his NPF-funded diagnostic test research and as part of his work at NYU Langone for the ELLIPPS project. Among his goals: To “discover new cell populations in the microenvironment and study how they interact with each other, then compare those cells between psoriasis and PsA patients to first understand if they’re any different,” he explained after the meeting. Researchers can then investigate the synovial tissue, comparing cell populations and interactions in both compartments and looking for any shared markers/cytokines/proteins, he said.

Multiomics research, meanwhile, is showing that a test for early PsA detection could potentially combine clinical parameters with integrated multi-omic markers into a “diagnostic signature” of sorts.

At the meeting, Vinod Chandran, MD, PhD, a rheumatologist at the University of Toronto who also has an NPF PsA diagnostic test grant, said that his multi-omics analysis of blood samples from patients with psoriasis and PsA has identified signatures with a “high discriminatory value” and that certain metabolic pathways appear to play “a central role in the development and differentiation of PsA.” (Validation in other cohorts and economic analyses are ongoing, Dr. Chandran said. Low-cost alternatives that can be applied broadly in the clinic will need to be pursued, Dr. Scher said.)

Eyes on combination therapy

“The likelihood that all patients will respond to one biologic is very low in PsA, so we’ve been thinking about combination therapy for some time,” Dr. Ritchlin said at the meeting. “I think [dual inhibition] is coming.”

Safety has been the concern, but a phase 2 trial published this year compared a combination of IL-23 and TNF inhibition (guselkumab [Tremfya] plus golimumab [Simponi]) with monotherapy of both biologics in patients with ulcerative colitis and showed that the combination safely drove synergistic restoration of a normal epithelium and mucosal healing, he said.

A phase 2 trial in PsA, designed by Dr. Ritchlin and Dr. Scher and named AFFINITY, will study the safety and efficacy of the same combination of IL-23 and TNF blockade, compared with guselkumab (IL-23 inhibition) alone. The trial is currently completing enrollment of patients who have failed one or two anti-TNF agents.

In the meantime, combination therapy is being employed in clinics for “PsA patients who’ve been channeled through multiple biologics and are still not responding ... when [physicians] feel they’re forced to, not right away,” Dr. Ritchlin said in an interview after the meeting. “As we get a better understanding [through clinical trials], it might be something you’ll see earlier in the treatment process.”

It is wise, Dr. Ritchlin said, to devote more time to addressing “extra-articular traits” (for example, obesity, diabetes, uveitis, colitis, centralized pain) and treatable lifestyle/behavioral risk factors (for example, smoking, exercise, nutrition, adherence to therapy, social support) that can contribute to PsA and treatment nonresponse. He calls this the “treatable traits” strategy.

In practice, “there’s a big focus on inflammation and immune dysfunction, but the problem is, there are other factors involved in nonresponse, and I think ‘treatable traits’ gets to those,” Dr. Ritchlin said after the meeting. Rheumatologists and dermatologists lack time and alliances to address these issues, but “if we can find ways to do it, I think we’ll have improved outcomes.”

Dr. Ritchlin, Dr. Chandran, and Dr. Liao reported no relevant disclosures. Dr. Scher reported ties to Janssen, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb.

Key clinical point: Ultrasound assessment of individuals with painful ankles revealed that abnormalities of the flexor retinacula (FR) were more common in patients with psoriatic arthritis (PsA) vs rheumatoid arthritis (RA).

Major finding: The FR were thicker in patients with PsA vs patients with RA and control individuals (0.96 vs 0.64 and 0.56, respectively; both P < .001), with abnormalities, such as retinaculitis (39.0% vs 2.7%), hypoechogenicity (46.0% vs 6.8%), power Doppler positivity (43.0% vs 8.1%), and periostosis (43.0% vs 8.1%), being significantly more prevalent in patients with PsA vs RA (all P < .001).

Study details: Findings are from a cross-sectional observational study including patients with PsA (n = 23) and RA (n = 37) who reported painful ankles and control individuals (n = 20) without rheumatic disease or ankle pain.

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

Source: Forien M et al. Ankle retinacula abnormalities as features of psoriatic arthritis: An ultrasound study. Joint Bone Spine. 2023 (Oct 4). doi: 10.1016/j.jbspin.2023.105649

Key clinical point: Ultrasound assessment of individuals with painful ankles revealed that abnormalities of the flexor retinacula (FR) were more common in patients with psoriatic arthritis (PsA) vs rheumatoid arthritis (RA).

Major finding: The FR were thicker in patients with PsA vs patients with RA and control individuals (0.96 vs 0.64 and 0.56, respectively; both P < .001), with abnormalities, such as retinaculitis (39.0% vs 2.7%), hypoechogenicity (46.0% vs 6.8%), power Doppler positivity (43.0% vs 8.1%), and periostosis (43.0% vs 8.1%), being significantly more prevalent in patients with PsA vs RA (all P < .001).

Study details: Findings are from a cross-sectional observational study including patients with PsA (n = 23) and RA (n = 37) who reported painful ankles and control individuals (n = 20) without rheumatic disease or ankle pain.

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

Source: Forien M et al. Ankle retinacula abnormalities as features of psoriatic arthritis: An ultrasound study. Joint Bone Spine. 2023 (Oct 4). doi: 10.1016/j.jbspin.2023.105649

Key clinical point: Ultrasound assessment of individuals with painful ankles revealed that abnormalities of the flexor retinacula (FR) were more common in patients with psoriatic arthritis (PsA) vs rheumatoid arthritis (RA).

Major finding: The FR were thicker in patients with PsA vs patients with RA and control individuals (0.96 vs 0.64 and 0.56, respectively; both P < .001), with abnormalities, such as retinaculitis (39.0% vs 2.7%), hypoechogenicity (46.0% vs 6.8%), power Doppler positivity (43.0% vs 8.1%), and periostosis (43.0% vs 8.1%), being significantly more prevalent in patients with PsA vs RA (all P < .001).

Study details: Findings are from a cross-sectional observational study including patients with PsA (n = 23) and RA (n = 37) who reported painful ankles and control individuals (n = 20) without rheumatic disease or ankle pain.

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

Source: Forien M et al. Ankle retinacula abnormalities as features of psoriatic arthritis: An ultrasound study. Joint Bone Spine. 2023 (Oct 4). doi: 10.1016/j.jbspin.2023.105649