Psoriatic Arthritis

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

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

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

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

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

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

The prevalence of metabolic syndrome varies according to how it is defined, but approximately 30% of psoriatic arthritis (PsA) patients met the criteria in a cohort study of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.

Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.

However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.

For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.

The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.

The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.

Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).

The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).

Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”

“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.

The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.

However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.

“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.

The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.

The prevalence of metabolic syndrome varies according to how it is defined, but approximately 30% of psoriatic arthritis (PsA) patients met the criteria in a cohort study of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.

Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.

However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.

For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.

The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.

The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.

Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).

The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).

Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”

“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.

The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.

However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.

“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.

The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.

The prevalence of metabolic syndrome varies according to how it is defined, but approximately 30% of psoriatic arthritis (PsA) patients met the criteria in a cohort study of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.

Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.

However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.

For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.

The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.

The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.

Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).

The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).

Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”

“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.

The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.

However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.

“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.

The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting 7% of adults and 13% of children in the United States.^1,2 Atopic dermatitis is characterized by pruritus, dry skin, and pain, all of which can negatively impact quality of life and put patients at higher risk for psychiatric comorbidities such as anxiety and depression.³ The pathogenesis of AD is multifactorial, involving genetics, epidermal barrier dysfunction, and immune dysregulation. Overactivation of helper T cell (T_H2) pathway cytokines, including IL-4, IL-13, and IL-31, is thought to propagate both inflammation and pruritus, which are central to AD. The JAK-STAT signaling pathway plays a pivotal role in the immune system dysregulation and exaggeration of T_H2 cell response, making JAK-STAT inhibitors (or JAK inhibitors) strong theoretical candidates for the treatment of AD.⁴ In humans, the Janus kinases are composed of 4 different members—JAK1, JAK2, JAK3, and tyrosine kinase 2—all of which can be targeted by JAK inhibitors.⁵

JAK inhibitors such as tofacitinib have already been approved by the US Food and Drug Administration (FDA) to treat various inflammatory conditions, including rheumatoid arthritis, ulcerative colitis, and psoriatic arthritis; other JAK inhibitors such as baricitinib are only approved for patients with rheumatoid arthritis.^6,7 The success of these small molecule inhibitors in these immune-mediated conditions make them attractive candidates for the treatment of AD. Several JAK inhibitors are in phase 2 and phase 3 clinical trials as oral therapies (moderate to severe AD) or as topical treatments (mild to moderate AD). Currently, ruxolitinib (RUX) is the only topical JAK inhibitor that is FDA approved for the treatment of AD in the United States.⁸ In this editorial, we focus on recent trials of JAK inhibitors tested in patients with AD, including topical RUX, as well as oral abrocitinib, upadacitinib, and baricitinib.

Topical RUX in AD

Ruxolitinib is a topical JAK1/2 small molecule inhibitor approved by the FDA for the treatment of AD in 2021. In a randomized trial by Kim et al⁹ in 2020, all tested regimens of RUX demonstrated significant improvement in eczema area and severity index (EASI) scores vs vehicle; notably, RUX cream 1.5% applied twice daily achieved the greatest mean percentage change in baseline EASI score vs vehicle at 4 weeks (76.1% vs 15.5%; P<.0001). Ruxolitinib cream was well tolerated through week 8 of the trial, and all adverse events (AEs) were mild to moderate in severity and comparable to those in the vehicle group.⁹

Topical JAK inhibitors appear to be effective for mild to moderate AD and have had an acceptable safety profile in clinical trials thus far. Although topical corticosteroids and calcineurin inhibitors can have great clinical benefit in AD, they are recommended for short-term use given side effects such as thinning of the skin, burning, or telangiectasia formation.^10,11 The hope is that topical JAK inhibitors may be an alternative to standard topical treatments for AD, as they can be used for longer periods due to a safer side-effect profile.

Oral JAK Inhibitors in AD

Several oral JAK inhibitors are undergoing investigation for the systemic treatment of moderate to severe AD. Abrocitinib is an oral JAK1 inhibitor that has demonstrated efficacy in several phase 3 trials in patients with moderate to severe AD. In a 2021 trial, patients were randomized in a 2:2:2:1 ratio to receive abrocitinib 200 mg daily, abrocitinib 100 mg daily, subcutaneous dupilumab 300 mg every other week, or placebo, respectively.¹² Patients in both abrocitinib groups showed significant improvement in AD vs placebo, and EASI-75 response was achieved in 70.3%, 58.7%, 58.1%, and 27.1% of patients, respectively (P<.001 for both abrocitinib doses vs placebo). Adverse events occurred more frequently in the abrocitinib 200-mg group vs placebo. Nausea, acne, nasopharyngitis, and headache were the most frequently reported AEs with abrocitinib.¹² Another phase 3 trial by Silverberg et al¹³ (N=391) had similar treatment results, with 38.1% of participants receiving abrocitinib 200 mg and 28.4% of participants receiving abrocitinib 100 mg achieving investigator global assessment scores of 0 (clear) or 1 (almost clear) vs 9.1% of participants receiving placebo (P<.001). Abrocitinib was well tolerated in this trial with few serious AEs (ie, herpangina [0.6%], pneumonia [0.6%]).¹³ In both trials, there were rare instances of laboratory values indicating thrombocytopenia with the 200-mg dose (0.9%¹² and 3.2%¹³) without any clinical manifestations. Although a decrease in platelets was observed, no thrombocytopenia occurred in the abrocitinib 100-mg group in the latter trial.¹³

Baricitinib is another oral inhibitor of JAK1 and JAK2 with potential for the treatment of AD. One randomized trial (N=329) demonstrated its efficacy in combination with a topical corticosteroid (TCS). At 16 weeks, a higher number of participants treated with baricitinib and TCS achieved investigator global assessment scores of 0 (clear) or 1 (almost clear) compared to those who received placebo and TCS (31% with baricitinib 4 mg + TCS, 24% with baricitinib 2 mg + TCS, and 15% with placebo + TCS).¹⁴ Similarly, in BREEZE-AD5,another phase 3 trial (N=440), baricitinib monotherapy demonstrated a higher rate of treatment success vs placebo.¹⁵ Specifically, 13% of patients treated with baricitinib 1 mg and 30% of those treated with baricitinib 2 mg achieved 75% or greater reduction in EASI scores compared to 8% in the placebo group. The most common AEs associated with baricitinib were nasopharyngitis and headache. Adverse events occurred with similar frequency across both experimental and control groups.¹⁵ Reich et al¹⁴ demonstrated a higher overall rate of AEs—most commonly nasopharyngitis, upper respiratory tract infections, and folliculitis—in baricitinib-treated patients; however, serious AEs occurred with similar frequency across all groups, including the control group.

The selective JAK1 inhibitor upadacitinib also is undergoing testing in treating moderate to severe AD. In one trial, 167 patients were randomized to once daily oral upadacitinib 7.5 mg, 15 mg, or 30 mg or placebo.¹⁶ All doses of upadacitinib demonstrated considerably higher percentage improvements from baseline in EASI scores compared to placebo at 16 weeks with a clear dose-response relationship (39%, 62%, and 74% vs 23%, respectively). In this trial, there were no dose-limiting safety events. Serious AEs were infrequent, occurring in 4.8%, 2.4%, and 0% of upadacitinib groups vs 2.5% for placebo. The serious AEs observed with upadacitinib were 1 case of appendicitis, lower jaw pericoronitis in a patient with a history of repeated tooth infections, and an exacerbation of AD.¹⁶

Tofacitinib, another JAK inhibitor, has been shown to increase the risk for blood clots and death in a large trial in the treatment of rheumatoid arthritis. Following this study, the FDA is requiring black box warnings for tofacitinib and also for the 2 JAK inhibitors baricitinib and upadacitinib regarding the risks for heart-related events, cancer, blood clots, and death. Given that these medications share a similar mechanism of action to tofacitinib, they may have similar risks, though they have not yet been fully evaluated in large safety trials.¹⁷

With more recent investigation into novel therapeutics for AD, oral JAK inhibitors may play an important role in the future to treat patients with moderate to severe AD with inadequate response or contraindications to other systemic therapies. In trials thus far, oral JAK inhibitors have exhibited acceptable safety profiles and have demonstrated treatment success in AD. More randomized, controlled, phase 3 studies with larger patient populations are required to confirm their potential as effective treatments and elucidate their long-term safety.

Deucravacitinib in Psoriasis

Deucravacitinib is a first-in-class, oral, selective TYK2 inhibitor currently undergoing testing for the treatment of psoriasis. A randomized phase 2 trial (N=267) found that deucravacitinib was more effective than placebo in treating chronic plaque psoriasis at doses of 3 to 12 mg daily.¹⁸ The percentage of participants with a 75% or greater reduction from baseline in the psoriasis area and severity index score was 7% with placebo, 9% with deucravacitinib 3 mg every other day (P=.49 vs placebo), 39% with 3 mg once daily (P<.001 vs placebo), 69% with 3 mg twice daily (P<.001 vs placebo), 67% with 6 mg twice daily (P<.001 vs placebo), and 75% with 12 mg once daily (P<.001 vs placebo). The most commonly reported AEs were nasopharyngitis, headache, diarrhea, nausea, and upper respiratory tract infection. Adverse events occurred in 51% of participants in the control group and in 55% to 80% of those in the experimental groups. Additionally, there was 1 reported case of melanoma (stage 0) 96 days after the start of treatment in a patient in the 3-mg once-daily group. Serious AEs occurred in only 0% to 2% of participants who received deucravacitinib.¹⁸

Two phase 3 trials—POETYK PSO-1 and POETYK PSO-2 (N=1686)—found deucravacitinib to be notably more effective than both placebo and apremilast in treating psoriasis.¹⁹ Among participants receiving deucravacitinib 6 mg daily, 58.7% and 53.6% in the 2 respective trials achieved psoriasis area and severity index 75 response vs 12.7% and 9.4% receiving placebo and 35.1% and 40.2% receiving apremilast. Overall, the treatment was well tolerated, with a low rate of discontinuation of deucravacitinib due to AEs (2.4% of patients on deucravacitinib compared to 3.8% on placebo and 5.2% on apremilast). The most frequently observed AEs with deucravacitinib were nasopharyngitis and upper respiratory tract infection. The full results of these trials are expected to be published soon.^19,20

Final Thoughts

Overall, JAK inhibitors are a novel class of therapeutics that may have further success in the treatment of other dermatologic conditions that negatively affect patients’ quality of life and productivity. We should look forward to additional successful trials with these promising medications.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting 7% of adults and 13% of children in the United States.^1,2 Atopic dermatitis is characterized by pruritus, dry skin, and pain, all of which can negatively impact quality of life and put patients at higher risk for psychiatric comorbidities such as anxiety and depression.³ The pathogenesis of AD is multifactorial, involving genetics, epidermal barrier dysfunction, and immune dysregulation. Overactivation of helper T cell (T_H2) pathway cytokines, including IL-4, IL-13, and IL-31, is thought to propagate both inflammation and pruritus, which are central to AD. The JAK-STAT signaling pathway plays a pivotal role in the immune system dysregulation and exaggeration of T_H2 cell response, making JAK-STAT inhibitors (or JAK inhibitors) strong theoretical candidates for the treatment of AD.⁴ In humans, the Janus kinases are composed of 4 different members—JAK1, JAK2, JAK3, and tyrosine kinase 2—all of which can be targeted by JAK inhibitors.⁵

JAK inhibitors such as tofacitinib have already been approved by the US Food and Drug Administration (FDA) to treat various inflammatory conditions, including rheumatoid arthritis, ulcerative colitis, and psoriatic arthritis; other JAK inhibitors such as baricitinib are only approved for patients with rheumatoid arthritis.^6,7 The success of these small molecule inhibitors in these immune-mediated conditions make them attractive candidates for the treatment of AD. Several JAK inhibitors are in phase 2 and phase 3 clinical trials as oral therapies (moderate to severe AD) or as topical treatments (mild to moderate AD). Currently, ruxolitinib (RUX) is the only topical JAK inhibitor that is FDA approved for the treatment of AD in the United States.⁸ In this editorial, we focus on recent trials of JAK inhibitors tested in patients with AD, including topical RUX, as well as oral abrocitinib, upadacitinib, and baricitinib.

Topical RUX in AD

Ruxolitinib is a topical JAK1/2 small molecule inhibitor approved by the FDA for the treatment of AD in 2021. In a randomized trial by Kim et al⁹ in 2020, all tested regimens of RUX demonstrated significant improvement in eczema area and severity index (EASI) scores vs vehicle; notably, RUX cream 1.5% applied twice daily achieved the greatest mean percentage change in baseline EASI score vs vehicle at 4 weeks (76.1% vs 15.5%; P<.0001). Ruxolitinib cream was well tolerated through week 8 of the trial, and all adverse events (AEs) were mild to moderate in severity and comparable to those in the vehicle group.⁹

Topical JAK inhibitors appear to be effective for mild to moderate AD and have had an acceptable safety profile in clinical trials thus far. Although topical corticosteroids and calcineurin inhibitors can have great clinical benefit in AD, they are recommended for short-term use given side effects such as thinning of the skin, burning, or telangiectasia formation.^10,11 The hope is that topical JAK inhibitors may be an alternative to standard topical treatments for AD, as they can be used for longer periods due to a safer side-effect profile.

Oral JAK Inhibitors in AD

Several oral JAK inhibitors are undergoing investigation for the systemic treatment of moderate to severe AD. Abrocitinib is an oral JAK1 inhibitor that has demonstrated efficacy in several phase 3 trials in patients with moderate to severe AD. In a 2021 trial, patients were randomized in a 2:2:2:1 ratio to receive abrocitinib 200 mg daily, abrocitinib 100 mg daily, subcutaneous dupilumab 300 mg every other week, or placebo, respectively.¹² Patients in both abrocitinib groups showed significant improvement in AD vs placebo, and EASI-75 response was achieved in 70.3%, 58.7%, 58.1%, and 27.1% of patients, respectively (P<.001 for both abrocitinib doses vs placebo). Adverse events occurred more frequently in the abrocitinib 200-mg group vs placebo. Nausea, acne, nasopharyngitis, and headache were the most frequently reported AEs with abrocitinib.¹² Another phase 3 trial by Silverberg et al¹³ (N=391) had similar treatment results, with 38.1% of participants receiving abrocitinib 200 mg and 28.4% of participants receiving abrocitinib 100 mg achieving investigator global assessment scores of 0 (clear) or 1 (almost clear) vs 9.1% of participants receiving placebo (P<.001). Abrocitinib was well tolerated in this trial with few serious AEs (ie, herpangina [0.6%], pneumonia [0.6%]).¹³ In both trials, there were rare instances of laboratory values indicating thrombocytopenia with the 200-mg dose (0.9%¹² and 3.2%¹³) without any clinical manifestations. Although a decrease in platelets was observed, no thrombocytopenia occurred in the abrocitinib 100-mg group in the latter trial.¹³

Baricitinib is another oral inhibitor of JAK1 and JAK2 with potential for the treatment of AD. One randomized trial (N=329) demonstrated its efficacy in combination with a topical corticosteroid (TCS). At 16 weeks, a higher number of participants treated with baricitinib and TCS achieved investigator global assessment scores of 0 (clear) or 1 (almost clear) compared to those who received placebo and TCS (31% with baricitinib 4 mg + TCS, 24% with baricitinib 2 mg + TCS, and 15% with placebo + TCS).¹⁴ Similarly, in BREEZE-AD5,another phase 3 trial (N=440), baricitinib monotherapy demonstrated a higher rate of treatment success vs placebo.¹⁵ Specifically, 13% of patients treated with baricitinib 1 mg and 30% of those treated with baricitinib 2 mg achieved 75% or greater reduction in EASI scores compared to 8% in the placebo group. The most common AEs associated with baricitinib were nasopharyngitis and headache. Adverse events occurred with similar frequency across both experimental and control groups.¹⁵ Reich et al¹⁴ demonstrated a higher overall rate of AEs—most commonly nasopharyngitis, upper respiratory tract infections, and folliculitis—in baricitinib-treated patients; however, serious AEs occurred with similar frequency across all groups, including the control group.

The selective JAK1 inhibitor upadacitinib also is undergoing testing in treating moderate to severe AD. In one trial, 167 patients were randomized to once daily oral upadacitinib 7.5 mg, 15 mg, or 30 mg or placebo.¹⁶ All doses of upadacitinib demonstrated considerably higher percentage improvements from baseline in EASI scores compared to placebo at 16 weeks with a clear dose-response relationship (39%, 62%, and 74% vs 23%, respectively). In this trial, there were no dose-limiting safety events. Serious AEs were infrequent, occurring in 4.8%, 2.4%, and 0% of upadacitinib groups vs 2.5% for placebo. The serious AEs observed with upadacitinib were 1 case of appendicitis, lower jaw pericoronitis in a patient with a history of repeated tooth infections, and an exacerbation of AD.¹⁶

Tofacitinib, another JAK inhibitor, has been shown to increase the risk for blood clots and death in a large trial in the treatment of rheumatoid arthritis. Following this study, the FDA is requiring black box warnings for tofacitinib and also for the 2 JAK inhibitors baricitinib and upadacitinib regarding the risks for heart-related events, cancer, blood clots, and death. Given that these medications share a similar mechanism of action to tofacitinib, they may have similar risks, though they have not yet been fully evaluated in large safety trials.¹⁷

With more recent investigation into novel therapeutics for AD, oral JAK inhibitors may play an important role in the future to treat patients with moderate to severe AD with inadequate response or contraindications to other systemic therapies. In trials thus far, oral JAK inhibitors have exhibited acceptable safety profiles and have demonstrated treatment success in AD. More randomized, controlled, phase 3 studies with larger patient populations are required to confirm their potential as effective treatments and elucidate their long-term safety.

Deucravacitinib in Psoriasis

Deucravacitinib is a first-in-class, oral, selective TYK2 inhibitor currently undergoing testing for the treatment of psoriasis. A randomized phase 2 trial (N=267) found that deucravacitinib was more effective than placebo in treating chronic plaque psoriasis at doses of 3 to 12 mg daily.¹⁸ The percentage of participants with a 75% or greater reduction from baseline in the psoriasis area and severity index score was 7% with placebo, 9% with deucravacitinib 3 mg every other day (P=.49 vs placebo), 39% with 3 mg once daily (P<.001 vs placebo), 69% with 3 mg twice daily (P<.001 vs placebo), 67% with 6 mg twice daily (P<.001 vs placebo), and 75% with 12 mg once daily (P<.001 vs placebo). The most commonly reported AEs were nasopharyngitis, headache, diarrhea, nausea, and upper respiratory tract infection. Adverse events occurred in 51% of participants in the control group and in 55% to 80% of those in the experimental groups. Additionally, there was 1 reported case of melanoma (stage 0) 96 days after the start of treatment in a patient in the 3-mg once-daily group. Serious AEs occurred in only 0% to 2% of participants who received deucravacitinib.¹⁸

Two phase 3 trials—POETYK PSO-1 and POETYK PSO-2 (N=1686)—found deucravacitinib to be notably more effective than both placebo and apremilast in treating psoriasis.¹⁹ Among participants receiving deucravacitinib 6 mg daily, 58.7% and 53.6% in the 2 respective trials achieved psoriasis area and severity index 75 response vs 12.7% and 9.4% receiving placebo and 35.1% and 40.2% receiving apremilast. Overall, the treatment was well tolerated, with a low rate of discontinuation of deucravacitinib due to AEs (2.4% of patients on deucravacitinib compared to 3.8% on placebo and 5.2% on apremilast). The most frequently observed AEs with deucravacitinib were nasopharyngitis and upper respiratory tract infection. The full results of these trials are expected to be published soon.^19,20

Final Thoughts

Overall, JAK inhibitors are a novel class of therapeutics that may have further success in the treatment of other dermatologic conditions that negatively affect patients’ quality of life and productivity. We should look forward to additional successful trials with these promising medications.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting 7% of adults and 13% of children in the United States.^1,2 Atopic dermatitis is characterized by pruritus, dry skin, and pain, all of which can negatively impact quality of life and put patients at higher risk for psychiatric comorbidities such as anxiety and depression.³ The pathogenesis of AD is multifactorial, involving genetics, epidermal barrier dysfunction, and immune dysregulation. Overactivation of helper T cell (T_H2) pathway cytokines, including IL-4, IL-13, and IL-31, is thought to propagate both inflammation and pruritus, which are central to AD. The JAK-STAT signaling pathway plays a pivotal role in the immune system dysregulation and exaggeration of T_H2 cell response, making JAK-STAT inhibitors (or JAK inhibitors) strong theoretical candidates for the treatment of AD.⁴ In humans, the Janus kinases are composed of 4 different members—JAK1, JAK2, JAK3, and tyrosine kinase 2—all of which can be targeted by JAK inhibitors.⁵

JAK inhibitors such as tofacitinib have already been approved by the US Food and Drug Administration (FDA) to treat various inflammatory conditions, including rheumatoid arthritis, ulcerative colitis, and psoriatic arthritis; other JAK inhibitors such as baricitinib are only approved for patients with rheumatoid arthritis.^6,7 The success of these small molecule inhibitors in these immune-mediated conditions make them attractive candidates for the treatment of AD. Several JAK inhibitors are in phase 2 and phase 3 clinical trials as oral therapies (moderate to severe AD) or as topical treatments (mild to moderate AD). Currently, ruxolitinib (RUX) is the only topical JAK inhibitor that is FDA approved for the treatment of AD in the United States.⁸ In this editorial, we focus on recent trials of JAK inhibitors tested in patients with AD, including topical RUX, as well as oral abrocitinib, upadacitinib, and baricitinib.

Topical RUX in AD

Ruxolitinib is a topical JAK1/2 small molecule inhibitor approved by the FDA for the treatment of AD in 2021. In a randomized trial by Kim et al⁹ in 2020, all tested regimens of RUX demonstrated significant improvement in eczema area and severity index (EASI) scores vs vehicle; notably, RUX cream 1.5% applied twice daily achieved the greatest mean percentage change in baseline EASI score vs vehicle at 4 weeks (76.1% vs 15.5%; P<.0001). Ruxolitinib cream was well tolerated through week 8 of the trial, and all adverse events (AEs) were mild to moderate in severity and comparable to those in the vehicle group.⁹

Topical JAK inhibitors appear to be effective for mild to moderate AD and have had an acceptable safety profile in clinical trials thus far. Although topical corticosteroids and calcineurin inhibitors can have great clinical benefit in AD, they are recommended for short-term use given side effects such as thinning of the skin, burning, or telangiectasia formation.^10,11 The hope is that topical JAK inhibitors may be an alternative to standard topical treatments for AD, as they can be used for longer periods due to a safer side-effect profile.

Oral JAK Inhibitors in AD

Several oral JAK inhibitors are undergoing investigation for the systemic treatment of moderate to severe AD. Abrocitinib is an oral JAK1 inhibitor that has demonstrated efficacy in several phase 3 trials in patients with moderate to severe AD. In a 2021 trial, patients were randomized in a 2:2:2:1 ratio to receive abrocitinib 200 mg daily, abrocitinib 100 mg daily, subcutaneous dupilumab 300 mg every other week, or placebo, respectively.¹² Patients in both abrocitinib groups showed significant improvement in AD vs placebo, and EASI-75 response was achieved in 70.3%, 58.7%, 58.1%, and 27.1% of patients, respectively (P<.001 for both abrocitinib doses vs placebo). Adverse events occurred more frequently in the abrocitinib 200-mg group vs placebo. Nausea, acne, nasopharyngitis, and headache were the most frequently reported AEs with abrocitinib.¹² Another phase 3 trial by Silverberg et al¹³ (N=391) had similar treatment results, with 38.1% of participants receiving abrocitinib 200 mg and 28.4% of participants receiving abrocitinib 100 mg achieving investigator global assessment scores of 0 (clear) or 1 (almost clear) vs 9.1% of participants receiving placebo (P<.001). Abrocitinib was well tolerated in this trial with few serious AEs (ie, herpangina [0.6%], pneumonia [0.6%]).¹³ In both trials, there were rare instances of laboratory values indicating thrombocytopenia with the 200-mg dose (0.9%¹² and 3.2%¹³) without any clinical manifestations. Although a decrease in platelets was observed, no thrombocytopenia occurred in the abrocitinib 100-mg group in the latter trial.¹³

Baricitinib is another oral inhibitor of JAK1 and JAK2 with potential for the treatment of AD. One randomized trial (N=329) demonstrated its efficacy in combination with a topical corticosteroid (TCS). At 16 weeks, a higher number of participants treated with baricitinib and TCS achieved investigator global assessment scores of 0 (clear) or 1 (almost clear) compared to those who received placebo and TCS (31% with baricitinib 4 mg + TCS, 24% with baricitinib 2 mg + TCS, and 15% with placebo + TCS).¹⁴ Similarly, in BREEZE-AD5,another phase 3 trial (N=440), baricitinib monotherapy demonstrated a higher rate of treatment success vs placebo.¹⁵ Specifically, 13% of patients treated with baricitinib 1 mg and 30% of those treated with baricitinib 2 mg achieved 75% or greater reduction in EASI scores compared to 8% in the placebo group. The most common AEs associated with baricitinib were nasopharyngitis and headache. Adverse events occurred with similar frequency across both experimental and control groups.¹⁵ Reich et al¹⁴ demonstrated a higher overall rate of AEs—most commonly nasopharyngitis, upper respiratory tract infections, and folliculitis—in baricitinib-treated patients; however, serious AEs occurred with similar frequency across all groups, including the control group.

The selective JAK1 inhibitor upadacitinib also is undergoing testing in treating moderate to severe AD. In one trial, 167 patients were randomized to once daily oral upadacitinib 7.5 mg, 15 mg, or 30 mg or placebo.¹⁶ All doses of upadacitinib demonstrated considerably higher percentage improvements from baseline in EASI scores compared to placebo at 16 weeks with a clear dose-response relationship (39%, 62%, and 74% vs 23%, respectively). In this trial, there were no dose-limiting safety events. Serious AEs were infrequent, occurring in 4.8%, 2.4%, and 0% of upadacitinib groups vs 2.5% for placebo. The serious AEs observed with upadacitinib were 1 case of appendicitis, lower jaw pericoronitis in a patient with a history of repeated tooth infections, and an exacerbation of AD.¹⁶

Tofacitinib, another JAK inhibitor, has been shown to increase the risk for blood clots and death in a large trial in the treatment of rheumatoid arthritis. Following this study, the FDA is requiring black box warnings for tofacitinib and also for the 2 JAK inhibitors baricitinib and upadacitinib regarding the risks for heart-related events, cancer, blood clots, and death. Given that these medications share a similar mechanism of action to tofacitinib, they may have similar risks, though they have not yet been fully evaluated in large safety trials.¹⁷

With more recent investigation into novel therapeutics for AD, oral JAK inhibitors may play an important role in the future to treat patients with moderate to severe AD with inadequate response or contraindications to other systemic therapies. In trials thus far, oral JAK inhibitors have exhibited acceptable safety profiles and have demonstrated treatment success in AD. More randomized, controlled, phase 3 studies with larger patient populations are required to confirm their potential as effective treatments and elucidate their long-term safety.

Deucravacitinib in Psoriasis

Deucravacitinib is a first-in-class, oral, selective TYK2 inhibitor currently undergoing testing for the treatment of psoriasis. A randomized phase 2 trial (N=267) found that deucravacitinib was more effective than placebo in treating chronic plaque psoriasis at doses of 3 to 12 mg daily.¹⁸ The percentage of participants with a 75% or greater reduction from baseline in the psoriasis area and severity index score was 7% with placebo, 9% with deucravacitinib 3 mg every other day (P=.49 vs placebo), 39% with 3 mg once daily (P<.001 vs placebo), 69% with 3 mg twice daily (P<.001 vs placebo), 67% with 6 mg twice daily (P<.001 vs placebo), and 75% with 12 mg once daily (P<.001 vs placebo). The most commonly reported AEs were nasopharyngitis, headache, diarrhea, nausea, and upper respiratory tract infection. Adverse events occurred in 51% of participants in the control group and in 55% to 80% of those in the experimental groups. Additionally, there was 1 reported case of melanoma (stage 0) 96 days after the start of treatment in a patient in the 3-mg once-daily group. Serious AEs occurred in only 0% to 2% of participants who received deucravacitinib.¹⁸

Two phase 3 trials—POETYK PSO-1 and POETYK PSO-2 (N=1686)—found deucravacitinib to be notably more effective than both placebo and apremilast in treating psoriasis.¹⁹ Among participants receiving deucravacitinib 6 mg daily, 58.7% and 53.6% in the 2 respective trials achieved psoriasis area and severity index 75 response vs 12.7% and 9.4% receiving placebo and 35.1% and 40.2% receiving apremilast. Overall, the treatment was well tolerated, with a low rate of discontinuation of deucravacitinib due to AEs (2.4% of patients on deucravacitinib compared to 3.8% on placebo and 5.2% on apremilast). The most frequently observed AEs with deucravacitinib were nasopharyngitis and upper respiratory tract infection. The full results of these trials are expected to be published soon.^19,20

Final Thoughts

Overall, JAK inhibitors are a novel class of therapeutics that may have further success in the treatment of other dermatologic conditions that negatively affect patients’ quality of life and productivity. We should look forward to additional successful trials with these promising medications.

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). 
5.    Walscheid K et al. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15).

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). 
5.    Walscheid K et al. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15).

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). 
5.    Walscheid K et al. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15).

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴ demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). doi: 10.1093/aje/kwac009. Epub ahead of print. PMID: 35029650.
5.    Walscheid K, Rothaus K, Niewerth M, Klotsche J, Minden K, Heiligenhaus A. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15). doi: 10.3899/jrheum.210755. Epub ahead of print. PMID: 35034000.
 

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴ demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). doi: 10.1093/aje/kwac009. Epub ahead of print. PMID: 35029650.
5.    Walscheid K, Rothaus K, Niewerth M, Klotsche J, Minden K, Heiligenhaus A. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15). doi: 10.3899/jrheum.210755. Epub ahead of print. PMID: 35034000.
 

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴ demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). doi: 10.1093/aje/kwac009. Epub ahead of print. PMID: 35029650.
5.    Walscheid K, Rothaus K, Niewerth M, Klotsche J, Minden K, Heiligenhaus A. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15). doi: 10.3899/jrheum.210755. Epub ahead of print. PMID: 35034000.
 

Key clinical point: Despite reducing cellular inflammation and improving clinical outcome for joint involvement, adalimumab, a tumor necrosis factor (TNF) inhibitor, did not affect the levels of interleukin (IL)-17 cytokines and its receptors in the skin and synovium of patients with psoriatic arthritis (PsA).

Major finding: At baseline, the skin of patients with PsA vs. healthy donors (HD) showed significantly lower levels of IL-17A (P = .017) and its receptor IL-17RA (P = .007), but higher levels of IL-17F (P = .0002) and its receptor IL-17RC (P = .024). After 4 weeks of treatment, patients recieving adalimumab and placebo showed similar levels of IL-17A, IL-17F, and IL-17RC.

Study details: Findings are from a double-blind, single-center study including 24 patients with PsA and mild psoriatic skin lesions who were randomly assigned to adalimumab or placebo.

Disclosures: This study was funded by the Innovative Medicines Initiatives European Union. The authors declared no conflicts of interest.

Source: Bolt JW et al. Biomedicines. 2022;10(2):324 (Jan 29). Doi: 10.3390/biomedicines10020324.

Key clinical point: Despite reducing cellular inflammation and improving clinical outcome for joint involvement, adalimumab, a tumor necrosis factor (TNF) inhibitor, did not affect the levels of interleukin (IL)-17 cytokines and its receptors in the skin and synovium of patients with psoriatic arthritis (PsA).

Major finding: At baseline, the skin of patients with PsA vs. healthy donors (HD) showed significantly lower levels of IL-17A (P = .017) and its receptor IL-17RA (P = .007), but higher levels of IL-17F (P = .0002) and its receptor IL-17RC (P = .024). After 4 weeks of treatment, patients recieving adalimumab and placebo showed similar levels of IL-17A, IL-17F, and IL-17RC.

Study details: Findings are from a double-blind, single-center study including 24 patients with PsA and mild psoriatic skin lesions who were randomly assigned to adalimumab or placebo.

Disclosures: This study was funded by the Innovative Medicines Initiatives European Union. The authors declared no conflicts of interest.

Source: Bolt JW et al. Biomedicines. 2022;10(2):324 (Jan 29). Doi: 10.3390/biomedicines10020324.

Key clinical point: Despite reducing cellular inflammation and improving clinical outcome for joint involvement, adalimumab, a tumor necrosis factor (TNF) inhibitor, did not affect the levels of interleukin (IL)-17 cytokines and its receptors in the skin and synovium of patients with psoriatic arthritis (PsA).

Major finding: At baseline, the skin of patients with PsA vs. healthy donors (HD) showed significantly lower levels of IL-17A (P = .017) and its receptor IL-17RA (P = .007), but higher levels of IL-17F (P = .0002) and its receptor IL-17RC (P = .024). After 4 weeks of treatment, patients recieving adalimumab and placebo showed similar levels of IL-17A, IL-17F, and IL-17RC.

Study details: Findings are from a double-blind, single-center study including 24 patients with PsA and mild psoriatic skin lesions who were randomly assigned to adalimumab or placebo.

Disclosures: This study was funded by the Innovative Medicines Initiatives European Union. The authors declared no conflicts of interest.

Source: Bolt JW et al. Biomedicines. 2022;10(2):324 (Jan 29). Doi: 10.3390/biomedicines10020324.

Key clinical point: The disease burden of psoriatic arthritis (PsA) was higher in women vs. men even after 1 year of standard-of-care treatment.

Major finding: Women vs. men reported a significantly longer duration of symptoms, higher tender joint count (both P < .05) and enthesitis at baseline (P < .05), and higher disease activity, higher levels of pain, and a lower functional capacity even after 1 year of follow-up (all P < .05). Minimal disease activity was predominantly present among men vs. women at baseline (18% vs. 10%; P < .05) and at 1 year of follow-up (59% vs. 37%, P < .00).

Study details: This prospective cohort study included 307 men and 313 women newly diagnosed with PsA from the Dutch south-west Early Psoriatic Arthritis Registry (DEPAR), who were followed up for 1 year.

Disclosures: No source of funding was reported for the study. The DEPAR cohort received funding from the Dutch Government, Pfizer, and other sources. The authors declared no conflicts of interest.

Source: Passia E et al. Arthritis Res Ther. 2022;24:22 (Jan 11). Doi: 10.1186/s13075-021-02680-y.

Key clinical point: The disease burden of psoriatic arthritis (PsA) was higher in women vs. men even after 1 year of standard-of-care treatment.

Major finding: Women vs. men reported a significantly longer duration of symptoms, higher tender joint count (both P < .05) and enthesitis at baseline (P < .05), and higher disease activity, higher levels of pain, and a lower functional capacity even after 1 year of follow-up (all P < .05). Minimal disease activity was predominantly present among men vs. women at baseline (18% vs. 10%; P < .05) and at 1 year of follow-up (59% vs. 37%, P < .00).

Study details: This prospective cohort study included 307 men and 313 women newly diagnosed with PsA from the Dutch south-west Early Psoriatic Arthritis Registry (DEPAR), who were followed up for 1 year.

Disclosures: No source of funding was reported for the study. The DEPAR cohort received funding from the Dutch Government, Pfizer, and other sources. The authors declared no conflicts of interest.

Source: Passia E et al. Arthritis Res Ther. 2022;24:22 (Jan 11). Doi: 10.1186/s13075-021-02680-y.

Key clinical point: The disease burden of psoriatic arthritis (PsA) was higher in women vs. men even after 1 year of standard-of-care treatment.

Major finding: Women vs. men reported a significantly longer duration of symptoms, higher tender joint count (both P < .05) and enthesitis at baseline (P < .05), and higher disease activity, higher levels of pain, and a lower functional capacity even after 1 year of follow-up (all P < .05). Minimal disease activity was predominantly present among men vs. women at baseline (18% vs. 10%; P < .05) and at 1 year of follow-up (59% vs. 37%, P < .00).

Study details: This prospective cohort study included 307 men and 313 women newly diagnosed with PsA from the Dutch south-west Early Psoriatic Arthritis Registry (DEPAR), who were followed up for 1 year.

Disclosures: No source of funding was reported for the study. The DEPAR cohort received funding from the Dutch Government, Pfizer, and other sources. The authors declared no conflicts of interest.

Source: Passia E et al. Arthritis Res Ther. 2022;24:22 (Jan 11). Doi: 10.1186/s13075-021-02680-y.

Key clinical point: Patients with psoriatic arthritis (PsA) have high anxiety levels before initiating biologics, which decreased within 6 months thereafter and was tied with better patient outcomes.

Major finding: Overall, 64% of patients had high anxiety levels before initiating biologics, with the proportion of patients with high anxiety levels and mean anxiety scores decreasing significantly within 6 months of initiating biologics (both P < .001). A change in anxiety score correlated positively with a change in pain score, patient global assessment score, Bath Ankylosing Spondylitis Disease Activity Index, Health Assessment Questionnaire-Disability Index score, Disease Activity Score-28, and PsA Impact of Disease score (all P < .05).

Study details: Findings are from an analysis of 147 patients with PsA who initiated  biologic agents and had an anxiety score assessed at both baseline and first visit within 6 months.

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

Source: Ayan G et al. Clin Rheumatol. 2022 (Jan 27). Doi: 10.1007/s10067-021-06012-y.

Key clinical point: Patients with psoriatic arthritis (PsA) have high anxiety levels before initiating biologics, which decreased within 6 months thereafter and was tied with better patient outcomes.

Major finding: Overall, 64% of patients had high anxiety levels before initiating biologics, with the proportion of patients with high anxiety levels and mean anxiety scores decreasing significantly within 6 months of initiating biologics (both P < .001). A change in anxiety score correlated positively with a change in pain score, patient global assessment score, Bath Ankylosing Spondylitis Disease Activity Index, Health Assessment Questionnaire-Disability Index score, Disease Activity Score-28, and PsA Impact of Disease score (all P < .05).

Study details: Findings are from an analysis of 147 patients with PsA who initiated  biologic agents and had an anxiety score assessed at both baseline and first visit within 6 months.

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

Source: Ayan G et al. Clin Rheumatol. 2022 (Jan 27). Doi: 10.1007/s10067-021-06012-y.

Key clinical point: Patients with psoriatic arthritis (PsA) have high anxiety levels before initiating biologics, which decreased within 6 months thereafter and was tied with better patient outcomes.

Major finding: Overall, 64% of patients had high anxiety levels before initiating biologics, with the proportion of patients with high anxiety levels and mean anxiety scores decreasing significantly within 6 months of initiating biologics (both P < .001). A change in anxiety score correlated positively with a change in pain score, patient global assessment score, Bath Ankylosing Spondylitis Disease Activity Index, Health Assessment Questionnaire-Disability Index score, Disease Activity Score-28, and PsA Impact of Disease score (all P < .05).

Study details: Findings are from an analysis of 147 patients with PsA who initiated  biologic agents and had an anxiety score assessed at both baseline and first visit within 6 months.

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

Source: Ayan G et al. Clin Rheumatol. 2022 (Jan 27). Doi: 10.1007/s10067-021-06012-y.