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PsA: Rapid and sustained improvement in pain with upadacitinib

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Key clinical point: Upadacitinib led to early, clinically meaningful, and sustained improvements in pain in patients with psoriatic arthritis (PsA) and an inadequate response to prior biological or nonbiological disease-modifying antirheumatic drugs (b/nbDMARD).

Major finding: A significantly higher proportion of patients receiving 15 mg upadacitinib vs. placebo achieved ≥30%, ≥50%, and ≥70% reductions in pain as early as at 2 weeks (P < .05), with improvements sustained till week 56.

Study details: Findings are from an analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2 , including 1113 patients with active PsA and an inadequate response to ≥1 nb/bDMARD who were randomly assigned to receive 15 mg upadacitinib once daily, placebo, or adalimumab (only in the SELECT-PsA 1 study).

Disclosures: This study was sponsored by AbbVie. Eight authors declared serving as employees or owning stock/stock options in AbbVie and other authors reported ties with several sources, including AbbVie.

Source: McInnes IB et al. Effect of upadacitinib on reducing pain in patients with active psoriatic arthritis or ankylosing spondylitis: Post hoc analysis of three randomised clinical trials. RMD Open. 2022;8:e002049 (Mar 24). Doi: 10.1136/rmdopen-2021-002049

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Key clinical point: Upadacitinib led to early, clinically meaningful, and sustained improvements in pain in patients with psoriatic arthritis (PsA) and an inadequate response to prior biological or nonbiological disease-modifying antirheumatic drugs (b/nbDMARD).

Major finding: A significantly higher proportion of patients receiving 15 mg upadacitinib vs. placebo achieved ≥30%, ≥50%, and ≥70% reductions in pain as early as at 2 weeks (P < .05), with improvements sustained till week 56.

Study details: Findings are from an analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2 , including 1113 patients with active PsA and an inadequate response to ≥1 nb/bDMARD who were randomly assigned to receive 15 mg upadacitinib once daily, placebo, or adalimumab (only in the SELECT-PsA 1 study).

Disclosures: This study was sponsored by AbbVie. Eight authors declared serving as employees or owning stock/stock options in AbbVie and other authors reported ties with several sources, including AbbVie.

Source: McInnes IB et al. Effect of upadacitinib on reducing pain in patients with active psoriatic arthritis or ankylosing spondylitis: Post hoc analysis of three randomised clinical trials. RMD Open. 2022;8:e002049 (Mar 24). Doi: 10.1136/rmdopen-2021-002049

Key clinical point: Upadacitinib led to early, clinically meaningful, and sustained improvements in pain in patients with psoriatic arthritis (PsA) and an inadequate response to prior biological or nonbiological disease-modifying antirheumatic drugs (b/nbDMARD).

Major finding: A significantly higher proportion of patients receiving 15 mg upadacitinib vs. placebo achieved ≥30%, ≥50%, and ≥70% reductions in pain as early as at 2 weeks (P < .05), with improvements sustained till week 56.

Study details: Findings are from an analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2 , including 1113 patients with active PsA and an inadequate response to ≥1 nb/bDMARD who were randomly assigned to receive 15 mg upadacitinib once daily, placebo, or adalimumab (only in the SELECT-PsA 1 study).

Disclosures: This study was sponsored by AbbVie. Eight authors declared serving as employees or owning stock/stock options in AbbVie and other authors reported ties with several sources, including AbbVie.

Source: McInnes IB et al. Effect of upadacitinib on reducing pain in patients with active psoriatic arthritis or ankylosing spondylitis: Post hoc analysis of three randomised clinical trials. RMD Open. 2022;8:e002049 (Mar 24). Doi: 10.1136/rmdopen-2021-002049

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Robust and sustained improvement with guselkumab in a diverse population of patients with PsA

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Key clinical point: A dose of 100 mg guselkumab every 4 weeks (Q4W) or 8 weeks (Q8W) effectively improved the signs and symptoms of psoriatic arthritis (PsA) at week 24, with effects sustained till week 52, in subgroups of patients with diverse baseline characteristics.

Major finding: At week 24, a higher proportion of patients receiving guselkumab Q4W/Q8W (62%/60%) vs. placebo (29%) achieved ≥20% improvement in the American College of Rheumatology (ACR20) criteria, with guselkumab demonstrating superior efficacy over placebo regardless of baseline patient demographics, disease characteristics, or medication use, with effects sustained till week 52.

Study details: This post hoc analysis of two phase 3 trials, DISCOVER-1, and DISCOVER-2, and included 1120 patients with active PsA with an inadequate response to standard therapies who were randomly assigned to receive subcutaneous 100 mg guselkumab Q4W, 100 mg guselkumab Q8W, or placebo.

Disclosures: This study was funded by Janssen Research & Development, LLC. Six authors declared being employees of Janssen and owned stocks in Johnson & Johnson, the parent of Janssen. The other authors reported ties with several sources, including Janssen.

Source: Ritchlin CT et al. Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: Pooled results through week 52 of two phase III, randomised, placebo-controlled studies.  RMD Open. 2022;8:e002195 (Mar 16). Doi: 10.1136/rmdopen-2022-002195

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Key clinical point: A dose of 100 mg guselkumab every 4 weeks (Q4W) or 8 weeks (Q8W) effectively improved the signs and symptoms of psoriatic arthritis (PsA) at week 24, with effects sustained till week 52, in subgroups of patients with diverse baseline characteristics.

Major finding: At week 24, a higher proportion of patients receiving guselkumab Q4W/Q8W (62%/60%) vs. placebo (29%) achieved ≥20% improvement in the American College of Rheumatology (ACR20) criteria, with guselkumab demonstrating superior efficacy over placebo regardless of baseline patient demographics, disease characteristics, or medication use, with effects sustained till week 52.

Study details: This post hoc analysis of two phase 3 trials, DISCOVER-1, and DISCOVER-2, and included 1120 patients with active PsA with an inadequate response to standard therapies who were randomly assigned to receive subcutaneous 100 mg guselkumab Q4W, 100 mg guselkumab Q8W, or placebo.

Disclosures: This study was funded by Janssen Research & Development, LLC. Six authors declared being employees of Janssen and owned stocks in Johnson & Johnson, the parent of Janssen. The other authors reported ties with several sources, including Janssen.

Source: Ritchlin CT et al. Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: Pooled results through week 52 of two phase III, randomised, placebo-controlled studies.  RMD Open. 2022;8:e002195 (Mar 16). Doi: 10.1136/rmdopen-2022-002195

Key clinical point: A dose of 100 mg guselkumab every 4 weeks (Q4W) or 8 weeks (Q8W) effectively improved the signs and symptoms of psoriatic arthritis (PsA) at week 24, with effects sustained till week 52, in subgroups of patients with diverse baseline characteristics.

Major finding: At week 24, a higher proportion of patients receiving guselkumab Q4W/Q8W (62%/60%) vs. placebo (29%) achieved ≥20% improvement in the American College of Rheumatology (ACR20) criteria, with guselkumab demonstrating superior efficacy over placebo regardless of baseline patient demographics, disease characteristics, or medication use, with effects sustained till week 52.

Study details: This post hoc analysis of two phase 3 trials, DISCOVER-1, and DISCOVER-2, and included 1120 patients with active PsA with an inadequate response to standard therapies who were randomly assigned to receive subcutaneous 100 mg guselkumab Q4W, 100 mg guselkumab Q8W, or placebo.

Disclosures: This study was funded by Janssen Research & Development, LLC. Six authors declared being employees of Janssen and owned stocks in Johnson & Johnson, the parent of Janssen. The other authors reported ties with several sources, including Janssen.

Source: Ritchlin CT et al. Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: Pooled results through week 52 of two phase III, randomised, placebo-controlled studies.  RMD Open. 2022;8:e002195 (Mar 16). Doi: 10.1136/rmdopen-2022-002195

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IL-17 inhibitors associated with higher treatment persistence in PsA

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Key clinical point: Interleukin-17 (IL-17) inhibitors were associated with higher treatment persistence than tumor necrosis factor (TNF) inhibitors or IL-12/23 inhibitors in patients with psoriatic arthritis (PsA) who initiated treatment with biologics.

Major finding: Treatment persistence was higher with IL-17 inhibitors than TNF inhibitors (weighted hazard ratio [HR] 0.70; P < .001) or IL-12/23 inhibitor (weighted HR 0.69; P < .001); however, IL-12/23 and TNF inhibitors showed similar persistence (P = .70).

Study details: This nationwide cohort study included 16,892 adults with psoriasis and 6531 adults with PsA who initiated first-line treatment with TNF, IL-12/23, or IL-17 inhibitors.

Disclosures: The study did not report any source of funding. P Claudepierre reported receiving consulting fees and serving as an investigator for several pharmaceutical companies.

Source: Vegas LP et al. Long-term persistence of first-line biologics for patients with psoriasis and psoriatic arthritis in the french health insurance database. JAMA Dermatol. 2022 (Mar 23). Doi: 10.1001/jamadermatol.2022.0364

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Key clinical point: Interleukin-17 (IL-17) inhibitors were associated with higher treatment persistence than tumor necrosis factor (TNF) inhibitors or IL-12/23 inhibitors in patients with psoriatic arthritis (PsA) who initiated treatment with biologics.

Major finding: Treatment persistence was higher with IL-17 inhibitors than TNF inhibitors (weighted hazard ratio [HR] 0.70; P < .001) or IL-12/23 inhibitor (weighted HR 0.69; P < .001); however, IL-12/23 and TNF inhibitors showed similar persistence (P = .70).

Study details: This nationwide cohort study included 16,892 adults with psoriasis and 6531 adults with PsA who initiated first-line treatment with TNF, IL-12/23, or IL-17 inhibitors.

Disclosures: The study did not report any source of funding. P Claudepierre reported receiving consulting fees and serving as an investigator for several pharmaceutical companies.

Source: Vegas LP et al. Long-term persistence of first-line biologics for patients with psoriasis and psoriatic arthritis in the french health insurance database. JAMA Dermatol. 2022 (Mar 23). Doi: 10.1001/jamadermatol.2022.0364

Key clinical point: Interleukin-17 (IL-17) inhibitors were associated with higher treatment persistence than tumor necrosis factor (TNF) inhibitors or IL-12/23 inhibitors in patients with psoriatic arthritis (PsA) who initiated treatment with biologics.

Major finding: Treatment persistence was higher with IL-17 inhibitors than TNF inhibitors (weighted hazard ratio [HR] 0.70; P < .001) or IL-12/23 inhibitor (weighted HR 0.69; P < .001); however, IL-12/23 and TNF inhibitors showed similar persistence (P = .70).

Study details: This nationwide cohort study included 16,892 adults with psoriasis and 6531 adults with PsA who initiated first-line treatment with TNF, IL-12/23, or IL-17 inhibitors.

Disclosures: The study did not report any source of funding. P Claudepierre reported receiving consulting fees and serving as an investigator for several pharmaceutical companies.

Source: Vegas LP et al. Long-term persistence of first-line biologics for patients with psoriasis and psoriatic arthritis in the french health insurance database. JAMA Dermatol. 2022 (Mar 23). Doi: 10.1001/jamadermatol.2022.0364

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Hypocaloric diet controls joint activity in psoriatic arthritis – regardless of weight loss

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A 12-week hypocaloric diet provided suitable control of joint disease activity in patients with psoriatic arthritis (PsA), regardless of weight loss, Brazilian researchers found.

Earlier research has reported that weight loss improves the symptoms of PsA.

Improvement in the Brazilian DIETA study was linked to both better eating patterns and better quality of diet, and while omega-3 supplementation caused relevant body composition changes, it did not improve disease activity, according to Beatriz F. Leite of the division of rheumatology at the Federal University of São Paulo and colleagues.

“The DIETA trial, a nonpharmacologic approach, is an inexpensive, suitable, and efficient approach that could be combined with standardized drug therapy,” the investigators wrote online in Advances in Rheumatology.

Dietary counseling aimed at losing or controlling weight could therefore be part of the global protocol for PsA patients, the researchers added. They conceded, however, that nonpharmacologic interventions traditionally have a low rate of adherence.

This recommendation aligns with a systematic review by the National Psoriasis Foundation, which found evidence of benefit with dietary weight reduction via a hypocaloric diet in overweight and obese patients with psoriasis and/or PsA. 
 

The DIETA trial

The 12-week randomized, double-blind, placebo-controlled study, conducted at three hospitals in São Paulo from September 2012 to May 2014, assessed whether dietary changes, antioxidant supplementation, or weight loss of 5%-10% could improve skin and joint activity in 97 enrolled PsA patients.

Participants were randomized into the following supervised dietary groups:

  • Diet-placebo (hypocaloric diet plus placebo supplementation).
  • Diet-fish (hypocaloric diet plus 3 g/day of omega-3 supplementation).
  • Placebo (with habitual diet).

Diets were carefully tailored to each individual patient. The regimen for overweight and obese patients included a 500-kcal restriction, while for eutrophic patients, diets were calculated to maintain weight with no caloric restriction.

In the 91 patients evaluable by multiple measures at 12 weeks, Ms. Leite and colleagues observed the following:

  • The Disease Activity Score 28 (DAS28) for Rheumatoid Arthritis with C-Reactive Protein and the Bath Ankylosing Spondylitis Disease Activity Index improved, especially in the diet-placebo group (−0.6 ± 0.9, P = .004 and −1.39 ± 1.97, P = .001, respectively).
  • Minimal disease activity improved in all groups.
  • The diet-fish group showed significant weight loss (−1.79 ± 2.4 kg, P = .004), as well as reductions in waist circumference (−3.28 ± 3.5 cm, P < .001) and body fat (−1.2 ± 2.2 kg, P = .006).

Other findings from this study showed the following:

  • No significant correlation was seen between weight loss and disease activity improvement.
  • Each 1-unit increase in the Healthy Eating Index value reduced the likelihood of achieving remission by 4%.
  • Each 100-calorie increase per day caused a 3.4-fold impairment on the DAS28-Erythrocyte Sedimentation Rate score.

The fact that no changes in PsA, medications, or physical activity were made during the study period reinforces the role of diet in the context of immunometabolism, the authors said. Supervised exercise, however, could contribute to weight loss, lean muscle mass, and better disease activity control.

The authors stressed that the data suggest “increased energy intake and worse diet quality may negatively affect joint activity and reduce the likelihood of achieving disease remission, regardless of weight loss or body composition changes.”

“There are other studies that have looked at the effect of weight loss from a very low-calorie diet, and they’ve suggested that PsA symptoms can improve, said rheumatologist Eric. M. Ruderman, MD, a professor of medicine at Northwestern Medicine in Chicago, in an interview. “The unique piece here is that they found that the improvement was really independent of weight loss.”

Dr. Ruderman, who was not involved in DIETA, cautioned, however, that the study is small and saw improvement in the placebo group as well, which could suggest that some of the improvement was related to the extra attention and regular communication with the nutritionist that came with participation in the study.

“Also, the absolute improvement was small, and the dietary restriction was pretty aggressive, so I’m not sure how generalizable this really is. While there are lots of benefits to maintaining a healthy diet and exercising, I don’t think that the results of this small study would justify taking an aggressive [dietary] approach as part of the clinical playbook for all PsA patients.”

This study was supported by the São Paulo Research Foundation and the Coordination for Improvement in Higher Education Foundation of the Ministry of Education, Brazil.

The authors had no competing interests to declare.

Dr. Ruderman disclosed no relevant competing interests.
 

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A 12-week hypocaloric diet provided suitable control of joint disease activity in patients with psoriatic arthritis (PsA), regardless of weight loss, Brazilian researchers found.

Earlier research has reported that weight loss improves the symptoms of PsA.

Improvement in the Brazilian DIETA study was linked to both better eating patterns and better quality of diet, and while omega-3 supplementation caused relevant body composition changes, it did not improve disease activity, according to Beatriz F. Leite of the division of rheumatology at the Federal University of São Paulo and colleagues.

“The DIETA trial, a nonpharmacologic approach, is an inexpensive, suitable, and efficient approach that could be combined with standardized drug therapy,” the investigators wrote online in Advances in Rheumatology.

Dietary counseling aimed at losing or controlling weight could therefore be part of the global protocol for PsA patients, the researchers added. They conceded, however, that nonpharmacologic interventions traditionally have a low rate of adherence.

This recommendation aligns with a systematic review by the National Psoriasis Foundation, which found evidence of benefit with dietary weight reduction via a hypocaloric diet in overweight and obese patients with psoriasis and/or PsA. 
 

The DIETA trial

The 12-week randomized, double-blind, placebo-controlled study, conducted at three hospitals in São Paulo from September 2012 to May 2014, assessed whether dietary changes, antioxidant supplementation, or weight loss of 5%-10% could improve skin and joint activity in 97 enrolled PsA patients.

Participants were randomized into the following supervised dietary groups:

  • Diet-placebo (hypocaloric diet plus placebo supplementation).
  • Diet-fish (hypocaloric diet plus 3 g/day of omega-3 supplementation).
  • Placebo (with habitual diet).

Diets were carefully tailored to each individual patient. The regimen for overweight and obese patients included a 500-kcal restriction, while for eutrophic patients, diets were calculated to maintain weight with no caloric restriction.

In the 91 patients evaluable by multiple measures at 12 weeks, Ms. Leite and colleagues observed the following:

  • The Disease Activity Score 28 (DAS28) for Rheumatoid Arthritis with C-Reactive Protein and the Bath Ankylosing Spondylitis Disease Activity Index improved, especially in the diet-placebo group (−0.6 ± 0.9, P = .004 and −1.39 ± 1.97, P = .001, respectively).
  • Minimal disease activity improved in all groups.
  • The diet-fish group showed significant weight loss (−1.79 ± 2.4 kg, P = .004), as well as reductions in waist circumference (−3.28 ± 3.5 cm, P < .001) and body fat (−1.2 ± 2.2 kg, P = .006).

Other findings from this study showed the following:

  • No significant correlation was seen between weight loss and disease activity improvement.
  • Each 1-unit increase in the Healthy Eating Index value reduced the likelihood of achieving remission by 4%.
  • Each 100-calorie increase per day caused a 3.4-fold impairment on the DAS28-Erythrocyte Sedimentation Rate score.

The fact that no changes in PsA, medications, or physical activity were made during the study period reinforces the role of diet in the context of immunometabolism, the authors said. Supervised exercise, however, could contribute to weight loss, lean muscle mass, and better disease activity control.

The authors stressed that the data suggest “increased energy intake and worse diet quality may negatively affect joint activity and reduce the likelihood of achieving disease remission, regardless of weight loss or body composition changes.”

“There are other studies that have looked at the effect of weight loss from a very low-calorie diet, and they’ve suggested that PsA symptoms can improve, said rheumatologist Eric. M. Ruderman, MD, a professor of medicine at Northwestern Medicine in Chicago, in an interview. “The unique piece here is that they found that the improvement was really independent of weight loss.”

Dr. Ruderman, who was not involved in DIETA, cautioned, however, that the study is small and saw improvement in the placebo group as well, which could suggest that some of the improvement was related to the extra attention and regular communication with the nutritionist that came with participation in the study.

“Also, the absolute improvement was small, and the dietary restriction was pretty aggressive, so I’m not sure how generalizable this really is. While there are lots of benefits to maintaining a healthy diet and exercising, I don’t think that the results of this small study would justify taking an aggressive [dietary] approach as part of the clinical playbook for all PsA patients.”

This study was supported by the São Paulo Research Foundation and the Coordination for Improvement in Higher Education Foundation of the Ministry of Education, Brazil.

The authors had no competing interests to declare.

Dr. Ruderman disclosed no relevant competing interests.
 

A 12-week hypocaloric diet provided suitable control of joint disease activity in patients with psoriatic arthritis (PsA), regardless of weight loss, Brazilian researchers found.

Earlier research has reported that weight loss improves the symptoms of PsA.

Improvement in the Brazilian DIETA study was linked to both better eating patterns and better quality of diet, and while omega-3 supplementation caused relevant body composition changes, it did not improve disease activity, according to Beatriz F. Leite of the division of rheumatology at the Federal University of São Paulo and colleagues.

“The DIETA trial, a nonpharmacologic approach, is an inexpensive, suitable, and efficient approach that could be combined with standardized drug therapy,” the investigators wrote online in Advances in Rheumatology.

Dietary counseling aimed at losing or controlling weight could therefore be part of the global protocol for PsA patients, the researchers added. They conceded, however, that nonpharmacologic interventions traditionally have a low rate of adherence.

This recommendation aligns with a systematic review by the National Psoriasis Foundation, which found evidence of benefit with dietary weight reduction via a hypocaloric diet in overweight and obese patients with psoriasis and/or PsA. 
 

The DIETA trial

The 12-week randomized, double-blind, placebo-controlled study, conducted at three hospitals in São Paulo from September 2012 to May 2014, assessed whether dietary changes, antioxidant supplementation, or weight loss of 5%-10% could improve skin and joint activity in 97 enrolled PsA patients.

Participants were randomized into the following supervised dietary groups:

  • Diet-placebo (hypocaloric diet plus placebo supplementation).
  • Diet-fish (hypocaloric diet plus 3 g/day of omega-3 supplementation).
  • Placebo (with habitual diet).

Diets were carefully tailored to each individual patient. The regimen for overweight and obese patients included a 500-kcal restriction, while for eutrophic patients, diets were calculated to maintain weight with no caloric restriction.

In the 91 patients evaluable by multiple measures at 12 weeks, Ms. Leite and colleagues observed the following:

  • The Disease Activity Score 28 (DAS28) for Rheumatoid Arthritis with C-Reactive Protein and the Bath Ankylosing Spondylitis Disease Activity Index improved, especially in the diet-placebo group (−0.6 ± 0.9, P = .004 and −1.39 ± 1.97, P = .001, respectively).
  • Minimal disease activity improved in all groups.
  • The diet-fish group showed significant weight loss (−1.79 ± 2.4 kg, P = .004), as well as reductions in waist circumference (−3.28 ± 3.5 cm, P < .001) and body fat (−1.2 ± 2.2 kg, P = .006).

Other findings from this study showed the following:

  • No significant correlation was seen between weight loss and disease activity improvement.
  • Each 1-unit increase in the Healthy Eating Index value reduced the likelihood of achieving remission by 4%.
  • Each 100-calorie increase per day caused a 3.4-fold impairment on the DAS28-Erythrocyte Sedimentation Rate score.

The fact that no changes in PsA, medications, or physical activity were made during the study period reinforces the role of diet in the context of immunometabolism, the authors said. Supervised exercise, however, could contribute to weight loss, lean muscle mass, and better disease activity control.

The authors stressed that the data suggest “increased energy intake and worse diet quality may negatively affect joint activity and reduce the likelihood of achieving disease remission, regardless of weight loss or body composition changes.”

“There are other studies that have looked at the effect of weight loss from a very low-calorie diet, and they’ve suggested that PsA symptoms can improve, said rheumatologist Eric. M. Ruderman, MD, a professor of medicine at Northwestern Medicine in Chicago, in an interview. “The unique piece here is that they found that the improvement was really independent of weight loss.”

Dr. Ruderman, who was not involved in DIETA, cautioned, however, that the study is small and saw improvement in the placebo group as well, which could suggest that some of the improvement was related to the extra attention and regular communication with the nutritionist that came with participation in the study.

“Also, the absolute improvement was small, and the dietary restriction was pretty aggressive, so I’m not sure how generalizable this really is. While there are lots of benefits to maintaining a healthy diet and exercising, I don’t think that the results of this small study would justify taking an aggressive [dietary] approach as part of the clinical playbook for all PsA patients.”

This study was supported by the São Paulo Research Foundation and the Coordination for Improvement in Higher Education Foundation of the Ministry of Education, Brazil.

The authors had no competing interests to declare.

Dr. Ruderman disclosed no relevant competing interests.
 

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Psoriatic Arthritis Workup

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Apremilast has neutral effect on vascular inflammation in psoriasis study

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– Treatment with apremilast (Otezla) did not significantly affect vascular inflammation in patients with psoriasis but was associated with a generally beneficial effect on biomarkers associated with heart disease, lipid metabolism, and glucose metabolism, in a study presented at the 2022 American Academy of Dermatology annual meeting.

In the phase 4, open-label, single arm trial, participants also lost subcutaneous and visceral fat after 16 weeks on the oral medication, a phosphodiesterase 4 (PDE4) inhibitor, and maintained that loss at 52 weeks.

People with psoriasis have an increased risk of obesity, type 2 diabetes, and cardiovascular events. Patients with more significant psoriasis “tend to die about 5 years younger than they should, based on their risk factors for mortality,” Joel Gelfand, MD, MSCE, professor of dermatology and epidemiology and vice chair of clinical research in dermatology at the University of Pennsylvania Perelman School of Medicine, Philadelphia, told this news organization.

He led the research and presented the findings at the AAD meeting March 26. “As a result, there has been a keen interest in understanding how psoriasis therapies impact cardiovascular risk, the idea being that by controlling inflammation, you may lower the risk of these patients developing cardiovascular disease over time,” he said.

Previous trials looking at the effect of psoriasis therapies on vascular inflammation “have been, for the most part, inconclusive,” Michael Garshick, MD, a cardiologist at NYU Langone Health, told this news organization. Dr. Garshick was not involved with the research. A 2021 systematic review of psoriasis clinicals trials reported that the tumor necrosis factor (TNF) blocker adalimumab (Humira) and phototherapy had the greatest effect on cardiometabolic markers, while ustekinumab (Stelara), an interleukin (IL)-12 and IL-23 antagonist, was the only treatment that improved vascular inflammation. These variable findings make this area “ripe for study,” noted Dr. Garshick.

To observe how apremilast, which is approved by the FDA for treating psoriasis and psoriatic arthritis, affected vascular inflammation, adiposity, and blood-based cardiometabolic markers, Dr. Gelfand organized an open-label study in adults with moderate-to-severe psoriasis. All participants were 18 years or older, had psoriasis for at least 6 months, and were candidates for systemic therapy. All patients underwent FDG PET/CT scans to assess aortic vascular inflammation and had blood work at baseline. Of the 70 patients originally enrolled in the study, 60 remained in the study at week 16, including 57 who underwent imaging for the second time. Thirty-nine participants remained in the study until week 52, and all except one had another scan.

The average age of participants was 47 years, and their mean BMI was 30. More than 80% of participants were White (83%) and 77% were male. The study population had lived with psoriasis for an average of 16 years and 8 patients also had psoriatic arthritis. At baseline, on average, participants had a Psoriasis Area and Severity Index (PASI) score of 18.62, a dermatology life quality index (DLQI) score of 11.60, and 22% of participants’ BSA (body surface area) were affected. The mean TBRmax, the marker for vascular inflammation, was 1.61.



Treatment responses were as expected for apremilast, with 35% of patients achieving PASI 75 and 65% of participants reporting DLQI scores of 5 or less by 16 weeks. At 52 weeks, 31% of the cohort had achieved PASI 75, and 67% reported DLQI score of 5 or higher. All psoriasis endpoints had improved since baseline (P = .001).

Throughout the study period, there was no significant change in TBRmax. However, in a sensitivity analysis, the 16 patients with a baseline TBRmax  of 1.6 or higher had an absolute reduction of 0.21 in TBR by week 52. “That suggests that maybe a subset of people who have higher levels of aortic inflammation at baseline may experience some reduction that portend, potentially, some health benefits over time,” Dr. Gelfand said. “Ultimately, I wouldn’t hang my hat on the finding,” he said, noting that additional research comparing the treatment to placebo is necessary.

Both visceral and subcutaneous adipose tissue (VAT and SAT) decreased by week 16, and this reduction was maintained through week 52. In the first 16 weeks of the study, VAT decreased by 5.32% (P = .0009), and SAT decreased by 5.53% (P = .0005). From baseline to 52 weeks, VAT decreased by 5.52% (P = .0148), and SAT decreased by 5.50% (P = .0096). There were no significant differences between week 16 and week 52 in VAT or SAT.

Of the 68 blood biomarkers analyzed, there were significant decreases in the inflammatory markers ferritin (P = .015) and IL-beta (P = .006), the lipid metabolism biomarker HDL-cholesterol efflux (P = .008), and ketone bodies (P = .006). There were also increases in the inflammatory marker IL-8 (P = .003), the lipid metabolism marker ApoA (P = .05), and insulin (P = .05). Ferritin was the only biomarker that was reduced on both week 16 and week 52.

“If you want to be a purist, this was a negative trial,” said Dr. Garshick, because apremilast was not found to decrease vascular inflammation; however, he noted that the biomarker changes “were hopeful secondary endpoints.” It could be, he said, that another outcome measure may be better able to show changes in vascular inflammation compared with FDG. “It’s always hard to figure out what a good surrogate endpoint is in cardiovascular trials,” he noted, “so it may be that FDG/PET is too noisy or not reliable enough to see the outcome that we want to see.”

Dr. Gelfand reports consulting fees/grants from Amgen, AbbVie, BMS, Boehringer Ingelheim, Janssen Biologics, Novartis Corp, Pfizer, and UCB (DSMB). He serves as the Deputy Editor for the Journal of Investigative Dermatology and the Chief Medical Editor at Healio Psoriatic Disease and receives honoraria for both roles. Dr. Garshick has received consulting fees from AbbVie.

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

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– Treatment with apremilast (Otezla) did not significantly affect vascular inflammation in patients with psoriasis but was associated with a generally beneficial effect on biomarkers associated with heart disease, lipid metabolism, and glucose metabolism, in a study presented at the 2022 American Academy of Dermatology annual meeting.

In the phase 4, open-label, single arm trial, participants also lost subcutaneous and visceral fat after 16 weeks on the oral medication, a phosphodiesterase 4 (PDE4) inhibitor, and maintained that loss at 52 weeks.

People with psoriasis have an increased risk of obesity, type 2 diabetes, and cardiovascular events. Patients with more significant psoriasis “tend to die about 5 years younger than they should, based on their risk factors for mortality,” Joel Gelfand, MD, MSCE, professor of dermatology and epidemiology and vice chair of clinical research in dermatology at the University of Pennsylvania Perelman School of Medicine, Philadelphia, told this news organization.

He led the research and presented the findings at the AAD meeting March 26. “As a result, there has been a keen interest in understanding how psoriasis therapies impact cardiovascular risk, the idea being that by controlling inflammation, you may lower the risk of these patients developing cardiovascular disease over time,” he said.

Previous trials looking at the effect of psoriasis therapies on vascular inflammation “have been, for the most part, inconclusive,” Michael Garshick, MD, a cardiologist at NYU Langone Health, told this news organization. Dr. Garshick was not involved with the research. A 2021 systematic review of psoriasis clinicals trials reported that the tumor necrosis factor (TNF) blocker adalimumab (Humira) and phototherapy had the greatest effect on cardiometabolic markers, while ustekinumab (Stelara), an interleukin (IL)-12 and IL-23 antagonist, was the only treatment that improved vascular inflammation. These variable findings make this area “ripe for study,” noted Dr. Garshick.

To observe how apremilast, which is approved by the FDA for treating psoriasis and psoriatic arthritis, affected vascular inflammation, adiposity, and blood-based cardiometabolic markers, Dr. Gelfand organized an open-label study in adults with moderate-to-severe psoriasis. All participants were 18 years or older, had psoriasis for at least 6 months, and were candidates for systemic therapy. All patients underwent FDG PET/CT scans to assess aortic vascular inflammation and had blood work at baseline. Of the 70 patients originally enrolled in the study, 60 remained in the study at week 16, including 57 who underwent imaging for the second time. Thirty-nine participants remained in the study until week 52, and all except one had another scan.

The average age of participants was 47 years, and their mean BMI was 30. More than 80% of participants were White (83%) and 77% were male. The study population had lived with psoriasis for an average of 16 years and 8 patients also had psoriatic arthritis. At baseline, on average, participants had a Psoriasis Area and Severity Index (PASI) score of 18.62, a dermatology life quality index (DLQI) score of 11.60, and 22% of participants’ BSA (body surface area) were affected. The mean TBRmax, the marker for vascular inflammation, was 1.61.



Treatment responses were as expected for apremilast, with 35% of patients achieving PASI 75 and 65% of participants reporting DLQI scores of 5 or less by 16 weeks. At 52 weeks, 31% of the cohort had achieved PASI 75, and 67% reported DLQI score of 5 or higher. All psoriasis endpoints had improved since baseline (P = .001).

Throughout the study period, there was no significant change in TBRmax. However, in a sensitivity analysis, the 16 patients with a baseline TBRmax  of 1.6 or higher had an absolute reduction of 0.21 in TBR by week 52. “That suggests that maybe a subset of people who have higher levels of aortic inflammation at baseline may experience some reduction that portend, potentially, some health benefits over time,” Dr. Gelfand said. “Ultimately, I wouldn’t hang my hat on the finding,” he said, noting that additional research comparing the treatment to placebo is necessary.

Both visceral and subcutaneous adipose tissue (VAT and SAT) decreased by week 16, and this reduction was maintained through week 52. In the first 16 weeks of the study, VAT decreased by 5.32% (P = .0009), and SAT decreased by 5.53% (P = .0005). From baseline to 52 weeks, VAT decreased by 5.52% (P = .0148), and SAT decreased by 5.50% (P = .0096). There were no significant differences between week 16 and week 52 in VAT or SAT.

Of the 68 blood biomarkers analyzed, there were significant decreases in the inflammatory markers ferritin (P = .015) and IL-beta (P = .006), the lipid metabolism biomarker HDL-cholesterol efflux (P = .008), and ketone bodies (P = .006). There were also increases in the inflammatory marker IL-8 (P = .003), the lipid metabolism marker ApoA (P = .05), and insulin (P = .05). Ferritin was the only biomarker that was reduced on both week 16 and week 52.

“If you want to be a purist, this was a negative trial,” said Dr. Garshick, because apremilast was not found to decrease vascular inflammation; however, he noted that the biomarker changes “were hopeful secondary endpoints.” It could be, he said, that another outcome measure may be better able to show changes in vascular inflammation compared with FDG. “It’s always hard to figure out what a good surrogate endpoint is in cardiovascular trials,” he noted, “so it may be that FDG/PET is too noisy or not reliable enough to see the outcome that we want to see.”

Dr. Gelfand reports consulting fees/grants from Amgen, AbbVie, BMS, Boehringer Ingelheim, Janssen Biologics, Novartis Corp, Pfizer, and UCB (DSMB). He serves as the Deputy Editor for the Journal of Investigative Dermatology and the Chief Medical Editor at Healio Psoriatic Disease and receives honoraria for both roles. Dr. Garshick has received consulting fees from AbbVie.

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

– Treatment with apremilast (Otezla) did not significantly affect vascular inflammation in patients with psoriasis but was associated with a generally beneficial effect on biomarkers associated with heart disease, lipid metabolism, and glucose metabolism, in a study presented at the 2022 American Academy of Dermatology annual meeting.

In the phase 4, open-label, single arm trial, participants also lost subcutaneous and visceral fat after 16 weeks on the oral medication, a phosphodiesterase 4 (PDE4) inhibitor, and maintained that loss at 52 weeks.

People with psoriasis have an increased risk of obesity, type 2 diabetes, and cardiovascular events. Patients with more significant psoriasis “tend to die about 5 years younger than they should, based on their risk factors for mortality,” Joel Gelfand, MD, MSCE, professor of dermatology and epidemiology and vice chair of clinical research in dermatology at the University of Pennsylvania Perelman School of Medicine, Philadelphia, told this news organization.

He led the research and presented the findings at the AAD meeting March 26. “As a result, there has been a keen interest in understanding how psoriasis therapies impact cardiovascular risk, the idea being that by controlling inflammation, you may lower the risk of these patients developing cardiovascular disease over time,” he said.

Previous trials looking at the effect of psoriasis therapies on vascular inflammation “have been, for the most part, inconclusive,” Michael Garshick, MD, a cardiologist at NYU Langone Health, told this news organization. Dr. Garshick was not involved with the research. A 2021 systematic review of psoriasis clinicals trials reported that the tumor necrosis factor (TNF) blocker adalimumab (Humira) and phototherapy had the greatest effect on cardiometabolic markers, while ustekinumab (Stelara), an interleukin (IL)-12 and IL-23 antagonist, was the only treatment that improved vascular inflammation. These variable findings make this area “ripe for study,” noted Dr. Garshick.

To observe how apremilast, which is approved by the FDA for treating psoriasis and psoriatic arthritis, affected vascular inflammation, adiposity, and blood-based cardiometabolic markers, Dr. Gelfand organized an open-label study in adults with moderate-to-severe psoriasis. All participants were 18 years or older, had psoriasis for at least 6 months, and were candidates for systemic therapy. All patients underwent FDG PET/CT scans to assess aortic vascular inflammation and had blood work at baseline. Of the 70 patients originally enrolled in the study, 60 remained in the study at week 16, including 57 who underwent imaging for the second time. Thirty-nine participants remained in the study until week 52, and all except one had another scan.

The average age of participants was 47 years, and their mean BMI was 30. More than 80% of participants were White (83%) and 77% were male. The study population had lived with psoriasis for an average of 16 years and 8 patients also had psoriatic arthritis. At baseline, on average, participants had a Psoriasis Area and Severity Index (PASI) score of 18.62, a dermatology life quality index (DLQI) score of 11.60, and 22% of participants’ BSA (body surface area) were affected. The mean TBRmax, the marker for vascular inflammation, was 1.61.



Treatment responses were as expected for apremilast, with 35% of patients achieving PASI 75 and 65% of participants reporting DLQI scores of 5 or less by 16 weeks. At 52 weeks, 31% of the cohort had achieved PASI 75, and 67% reported DLQI score of 5 or higher. All psoriasis endpoints had improved since baseline (P = .001).

Throughout the study period, there was no significant change in TBRmax. However, in a sensitivity analysis, the 16 patients with a baseline TBRmax  of 1.6 or higher had an absolute reduction of 0.21 in TBR by week 52. “That suggests that maybe a subset of people who have higher levels of aortic inflammation at baseline may experience some reduction that portend, potentially, some health benefits over time,” Dr. Gelfand said. “Ultimately, I wouldn’t hang my hat on the finding,” he said, noting that additional research comparing the treatment to placebo is necessary.

Both visceral and subcutaneous adipose tissue (VAT and SAT) decreased by week 16, and this reduction was maintained through week 52. In the first 16 weeks of the study, VAT decreased by 5.32% (P = .0009), and SAT decreased by 5.53% (P = .0005). From baseline to 52 weeks, VAT decreased by 5.52% (P = .0148), and SAT decreased by 5.50% (P = .0096). There were no significant differences between week 16 and week 52 in VAT or SAT.

Of the 68 blood biomarkers analyzed, there were significant decreases in the inflammatory markers ferritin (P = .015) and IL-beta (P = .006), the lipid metabolism biomarker HDL-cholesterol efflux (P = .008), and ketone bodies (P = .006). There were also increases in the inflammatory marker IL-8 (P = .003), the lipid metabolism marker ApoA (P = .05), and insulin (P = .05). Ferritin was the only biomarker that was reduced on both week 16 and week 52.

“If you want to be a purist, this was a negative trial,” said Dr. Garshick, because apremilast was not found to decrease vascular inflammation; however, he noted that the biomarker changes “were hopeful secondary endpoints.” It could be, he said, that another outcome measure may be better able to show changes in vascular inflammation compared with FDG. “It’s always hard to figure out what a good surrogate endpoint is in cardiovascular trials,” he noted, “so it may be that FDG/PET is too noisy or not reliable enough to see the outcome that we want to see.”

Dr. Gelfand reports consulting fees/grants from Amgen, AbbVie, BMS, Boehringer Ingelheim, Janssen Biologics, Novartis Corp, Pfizer, and UCB (DSMB). He serves as the Deputy Editor for the Journal of Investigative Dermatology and the Chief Medical Editor at Healio Psoriatic Disease and receives honoraria for both roles. Dr. Garshick has received consulting fees from AbbVie.

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

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Clinical Edge Journal Scan Commentary: PsA April 2022

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Dr. Chandran scans the journals, so you don't have to!

Vinod Chandran, MBBS, MD, DM, PhD

Treatment of psoriatic arthritis (PsA) was the focus of clinical research papers published this month. Despite the advances made in treating PsA with targeted therapies, in most parts of the world, conventional disease-modifying antirheumatic drugs (DMARDs) are the first line of treatment. Methotrexate (MTX) and leflunomide (LEF) are commonly used, but there are limited data on the effectiveness of combination therapy. To address this issue, Mulder and colleagues enrolled 78 patients with active PsA who have two or more swollen joints and randomly allocated them to either 25 mg oral MTX weekly after 4 weeks of 15 mg weekly plus 20 mg LEF daily (n = 39) or MTX plus placebo (monotherapy; n = 39). At week 16, PsA disease activity score was improved significantly in the MTX + LEF vs. MTX monotherapy group (3.1 vs. 3.7; P = .025). Incidence of mild adverse events, such as nausea/vomiting (44% vs. 28%) and altered bowel habits (26% vs. 8%), was higher with MTX + LEF vs. MTX + placebo. So although less well tolerated, MTX + LEF therapy was superior to MTX monotherapy at improving disease activity in patients with PsA.

 

Biologics targeting tumor necrosis factor (TNF), interleukin (IL) -12/23, -23, and -17A are efficacious for the management of PsA, but questions remain about comparative effectiveness. Gossec and colleagues reported the results from their prospective observational PsABio study that evaluated real-world treatment persistence and effectiveness at 1 year after initiation of first-line to third-line IL-12/23 inhibitor ustekinumab or a TNF inhibitor (TNFi). Their study followed 893 patients. After 1 year of treatment, ustekinumab and the TNFi showed similar persistence (hazard ratio [HR] for stopping/switching treatment 0.82; 95% CI 0.60-1.13) and a similar proportion of patients achieving (on the Disease Activity Index for PsA) clinical low disease activity (odds ratio [OR] 0.80; 95% CI 0.57-1.10) and remission (OR 0.73; 95% CI 0.49-1.07), along with similar safety profiles. Thus in real-world studies, TNFi and ustekinumab seem to have similar effectiveness and safety.

 

Drug persistence between patients with psoriasis alone vs. those with PsA is also of interest. In a real-life study including 62 patients with psoriasis and 90 patients with PsA who initiated treatment with secukinumab and were followed up for 24 months or until discontinuation, Ortolan and colleagues demonstrated that the retention rate of secukinumab was higher in psoriasis vs. PsA at 12 (85% vs. 68%) and 24 (61% vs. 57%) months, with the risk for secukinumab discontinuation being higher among patients with PsA in the overall cohort (HR 2.43; P = .035) and in patients with obesity in the PsA cohort (P = .021). Thus, the presence of PsA and obesity lower the secukinumab retention rate.

 

  1. Despite the advent of many targeted therapies for PsA, there remain many unmet needs. Deucravacitinib is a novel oral selective inhibitor of tyrosine kinase 2 (TYK2) acting via binding to the TYK2 regulatory domain. In a phase 2 study including 203 patients with active PsA that was intolerant to at least one therapy who were randomly assigned to receive 6 mg deucravacitinib once daily, 12 mg deucravacitinib once daily, or placebo for 16 weeks, Mease and colleagues demonstrated that at week 16, American College of Rheumatology 20 (ACR20) response was significantly higher with 6 mg once-daily deucravacitinib (52.9%, adjusted OR [aOR] 2.4; P = .0134) and 12 mg (62.7%, aOR 3.6; P = .0004) vs. placebo (31.8%), with 12 mg deucravacitinib improving ACR20 response as early as at 8 weeks (P < .05). No serious adverse events were reported. Thus, TYK2 inhibition shows promise in the treatment of PsA and the results from phase 3 trials are awaited.
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Vinod Chandran, MBBS, MD, DM, PhD, Associate Professor, Department of Medicine, University of Toledo, Toronto, Ontario, Canada

Vinod Chandran, MBBS, MD, DM, PhD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Amgen; Bristol-Myers Squibb; Eli Lilly; Janssen; Novartis; Pfizer; UCB

Received research grant from: Amgen; AbbVie; Eli Lilly

Spousal employment: Eli Lilly; AstraZeneca

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Vinod Chandran, MBBS, MD, DM, PhD, Associate Professor, Department of Medicine, University of Toledo, Toronto, Ontario, Canada

Vinod Chandran, MBBS, MD, DM, PhD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Amgen; Bristol-Myers Squibb; Eli Lilly; Janssen; Novartis; Pfizer; UCB

Received research grant from: Amgen; AbbVie; Eli Lilly

Spousal employment: Eli Lilly; AstraZeneca

Author and Disclosure Information

Vinod Chandran, MBBS, MD, DM, PhD, Associate Professor, Department of Medicine, University of Toledo, Toronto, Ontario, Canada

Vinod Chandran, MBBS, MD, DM, PhD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Amgen; Bristol-Myers Squibb; Eli Lilly; Janssen; Novartis; Pfizer; UCB

Received research grant from: Amgen; AbbVie; Eli Lilly

Spousal employment: Eli Lilly; AstraZeneca

Dr. Chandran scans the journals, so you don't have to!
Dr. Chandran scans the journals, so you don't have to!

Vinod Chandran, MBBS, MD, DM, PhD

Treatment of psoriatic arthritis (PsA) was the focus of clinical research papers published this month. Despite the advances made in treating PsA with targeted therapies, in most parts of the world, conventional disease-modifying antirheumatic drugs (DMARDs) are the first line of treatment. Methotrexate (MTX) and leflunomide (LEF) are commonly used, but there are limited data on the effectiveness of combination therapy. To address this issue, Mulder and colleagues enrolled 78 patients with active PsA who have two or more swollen joints and randomly allocated them to either 25 mg oral MTX weekly after 4 weeks of 15 mg weekly plus 20 mg LEF daily (n = 39) or MTX plus placebo (monotherapy; n = 39). At week 16, PsA disease activity score was improved significantly in the MTX + LEF vs. MTX monotherapy group (3.1 vs. 3.7; P = .025). Incidence of mild adverse events, such as nausea/vomiting (44% vs. 28%) and altered bowel habits (26% vs. 8%), was higher with MTX + LEF vs. MTX + placebo. So although less well tolerated, MTX + LEF therapy was superior to MTX monotherapy at improving disease activity in patients with PsA.

 

Biologics targeting tumor necrosis factor (TNF), interleukin (IL) -12/23, -23, and -17A are efficacious for the management of PsA, but questions remain about comparative effectiveness. Gossec and colleagues reported the results from their prospective observational PsABio study that evaluated real-world treatment persistence and effectiveness at 1 year after initiation of first-line to third-line IL-12/23 inhibitor ustekinumab or a TNF inhibitor (TNFi). Their study followed 893 patients. After 1 year of treatment, ustekinumab and the TNFi showed similar persistence (hazard ratio [HR] for stopping/switching treatment 0.82; 95% CI 0.60-1.13) and a similar proportion of patients achieving (on the Disease Activity Index for PsA) clinical low disease activity (odds ratio [OR] 0.80; 95% CI 0.57-1.10) and remission (OR 0.73; 95% CI 0.49-1.07), along with similar safety profiles. Thus in real-world studies, TNFi and ustekinumab seem to have similar effectiveness and safety.

 

Drug persistence between patients with psoriasis alone vs. those with PsA is also of interest. In a real-life study including 62 patients with psoriasis and 90 patients with PsA who initiated treatment with secukinumab and were followed up for 24 months or until discontinuation, Ortolan and colleagues demonstrated that the retention rate of secukinumab was higher in psoriasis vs. PsA at 12 (85% vs. 68%) and 24 (61% vs. 57%) months, with the risk for secukinumab discontinuation being higher among patients with PsA in the overall cohort (HR 2.43; P = .035) and in patients with obesity in the PsA cohort (P = .021). Thus, the presence of PsA and obesity lower the secukinumab retention rate.

 

  1. Despite the advent of many targeted therapies for PsA, there remain many unmet needs. Deucravacitinib is a novel oral selective inhibitor of tyrosine kinase 2 (TYK2) acting via binding to the TYK2 regulatory domain. In a phase 2 study including 203 patients with active PsA that was intolerant to at least one therapy who were randomly assigned to receive 6 mg deucravacitinib once daily, 12 mg deucravacitinib once daily, or placebo for 16 weeks, Mease and colleagues demonstrated that at week 16, American College of Rheumatology 20 (ACR20) response was significantly higher with 6 mg once-daily deucravacitinib (52.9%, adjusted OR [aOR] 2.4; P = .0134) and 12 mg (62.7%, aOR 3.6; P = .0004) vs. placebo (31.8%), with 12 mg deucravacitinib improving ACR20 response as early as at 8 weeks (P < .05). No serious adverse events were reported. Thus, TYK2 inhibition shows promise in the treatment of PsA and the results from phase 3 trials are awaited.

Vinod Chandran, MBBS, MD, DM, PhD

Treatment of psoriatic arthritis (PsA) was the focus of clinical research papers published this month. Despite the advances made in treating PsA with targeted therapies, in most parts of the world, conventional disease-modifying antirheumatic drugs (DMARDs) are the first line of treatment. Methotrexate (MTX) and leflunomide (LEF) are commonly used, but there are limited data on the effectiveness of combination therapy. To address this issue, Mulder and colleagues enrolled 78 patients with active PsA who have two or more swollen joints and randomly allocated them to either 25 mg oral MTX weekly after 4 weeks of 15 mg weekly plus 20 mg LEF daily (n = 39) or MTX plus placebo (monotherapy; n = 39). At week 16, PsA disease activity score was improved significantly in the MTX + LEF vs. MTX monotherapy group (3.1 vs. 3.7; P = .025). Incidence of mild adverse events, such as nausea/vomiting (44% vs. 28%) and altered bowel habits (26% vs. 8%), was higher with MTX + LEF vs. MTX + placebo. So although less well tolerated, MTX + LEF therapy was superior to MTX monotherapy at improving disease activity in patients with PsA.

 

Biologics targeting tumor necrosis factor (TNF), interleukin (IL) -12/23, -23, and -17A are efficacious for the management of PsA, but questions remain about comparative effectiveness. Gossec and colleagues reported the results from their prospective observational PsABio study that evaluated real-world treatment persistence and effectiveness at 1 year after initiation of first-line to third-line IL-12/23 inhibitor ustekinumab or a TNF inhibitor (TNFi). Their study followed 893 patients. After 1 year of treatment, ustekinumab and the TNFi showed similar persistence (hazard ratio [HR] for stopping/switching treatment 0.82; 95% CI 0.60-1.13) and a similar proportion of patients achieving (on the Disease Activity Index for PsA) clinical low disease activity (odds ratio [OR] 0.80; 95% CI 0.57-1.10) and remission (OR 0.73; 95% CI 0.49-1.07), along with similar safety profiles. Thus in real-world studies, TNFi and ustekinumab seem to have similar effectiveness and safety.

 

Drug persistence between patients with psoriasis alone vs. those with PsA is also of interest. In a real-life study including 62 patients with psoriasis and 90 patients with PsA who initiated treatment with secukinumab and were followed up for 24 months or until discontinuation, Ortolan and colleagues demonstrated that the retention rate of secukinumab was higher in psoriasis vs. PsA at 12 (85% vs. 68%) and 24 (61% vs. 57%) months, with the risk for secukinumab discontinuation being higher among patients with PsA in the overall cohort (HR 2.43; P = .035) and in patients with obesity in the PsA cohort (P = .021). Thus, the presence of PsA and obesity lower the secukinumab retention rate.

 

  1. Despite the advent of many targeted therapies for PsA, there remain many unmet needs. Deucravacitinib is a novel oral selective inhibitor of tyrosine kinase 2 (TYK2) acting via binding to the TYK2 regulatory domain. In a phase 2 study including 203 patients with active PsA that was intolerant to at least one therapy who were randomly assigned to receive 6 mg deucravacitinib once daily, 12 mg deucravacitinib once daily, or placebo for 16 weeks, Mease and colleagues demonstrated that at week 16, American College of Rheumatology 20 (ACR20) response was significantly higher with 6 mg once-daily deucravacitinib (52.9%, adjusted OR [aOR] 2.4; P = .0134) and 12 mg (62.7%, aOR 3.6; P = .0004) vs. placebo (31.8%), with 12 mg deucravacitinib improving ACR20 response as early as at 8 weeks (P < .05). No serious adverse events were reported. Thus, TYK2 inhibition shows promise in the treatment of PsA and the results from phase 3 trials are awaited.
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Slight improvement in axial PsA with DMARD therapy irrespective of HLA-B27 status

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Key clinical point: Irrespective of human leukocyte antigen-B27 (HLA-B27) status, patients with axial psoriatic arthritis (PsA) experienced mild improvement in disease outcomes after 6 months of initiating targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) or biologic DMARDs (bDMARD).

Major finding: After 6 months, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score remained >4, indicating moderate-to-severe disease activity irrespective of HLA-B27 status, with a mean reduction in BASDAI score of 0.80 and 0.84 (both not clinically meaningful) in the HLA-B27-positive and HLA-B27-negative groups, respectively.

Study details: This prospective, observational study included 135 patients with moderate-to-severe axial PsA who initiated bDMARDs or tsDMARDs and were followed up for 6 months, of which 39 and 96 patients had HLA-B27-positive and HLA-B27-negative status, respectively.

Disclosures: This study was sponsored by CorEvitas, LLC. The authors declared receiving research support, consulting fees, or speaker bureau support from several sources. Two authors declared being employees and shareholders of Johnson and Johnson; three authors declared being present or former employees of CorEvitas, LLC.

Source: Mease PJ et al. treatment responses in patients with psoriatic arthritis axial disease according to human leukocyte antigen-B27 Status: An analysis from the CorEvitas Psoriatic Arthritis/Spondyloarthritis registry. ACR Open Rheumatol. 2022 (Feb 26). Doi: 10.1002/acr2.11416

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Key clinical point: Irrespective of human leukocyte antigen-B27 (HLA-B27) status, patients with axial psoriatic arthritis (PsA) experienced mild improvement in disease outcomes after 6 months of initiating targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) or biologic DMARDs (bDMARD).

Major finding: After 6 months, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score remained >4, indicating moderate-to-severe disease activity irrespective of HLA-B27 status, with a mean reduction in BASDAI score of 0.80 and 0.84 (both not clinically meaningful) in the HLA-B27-positive and HLA-B27-negative groups, respectively.

Study details: This prospective, observational study included 135 patients with moderate-to-severe axial PsA who initiated bDMARDs or tsDMARDs and were followed up for 6 months, of which 39 and 96 patients had HLA-B27-positive and HLA-B27-negative status, respectively.

Disclosures: This study was sponsored by CorEvitas, LLC. The authors declared receiving research support, consulting fees, or speaker bureau support from several sources. Two authors declared being employees and shareholders of Johnson and Johnson; three authors declared being present or former employees of CorEvitas, LLC.

Source: Mease PJ et al. treatment responses in patients with psoriatic arthritis axial disease according to human leukocyte antigen-B27 Status: An analysis from the CorEvitas Psoriatic Arthritis/Spondyloarthritis registry. ACR Open Rheumatol. 2022 (Feb 26). Doi: 10.1002/acr2.11416

Key clinical point: Irrespective of human leukocyte antigen-B27 (HLA-B27) status, patients with axial psoriatic arthritis (PsA) experienced mild improvement in disease outcomes after 6 months of initiating targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) or biologic DMARDs (bDMARD).

Major finding: After 6 months, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score remained >4, indicating moderate-to-severe disease activity irrespective of HLA-B27 status, with a mean reduction in BASDAI score of 0.80 and 0.84 (both not clinically meaningful) in the HLA-B27-positive and HLA-B27-negative groups, respectively.

Study details: This prospective, observational study included 135 patients with moderate-to-severe axial PsA who initiated bDMARDs or tsDMARDs and were followed up for 6 months, of which 39 and 96 patients had HLA-B27-positive and HLA-B27-negative status, respectively.

Disclosures: This study was sponsored by CorEvitas, LLC. The authors declared receiving research support, consulting fees, or speaker bureau support from several sources. Two authors declared being employees and shareholders of Johnson and Johnson; three authors declared being present or former employees of CorEvitas, LLC.

Source: Mease PJ et al. treatment responses in patients with psoriatic arthritis axial disease according to human leukocyte antigen-B27 Status: An analysis from the CorEvitas Psoriatic Arthritis/Spondyloarthritis registry. ACR Open Rheumatol. 2022 (Feb 26). Doi: 10.1002/acr2.11416

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Effect of burdensome symptoms on treatment preferences of patients with PsA

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Key clinical point: Patients with psoriatic arthritis (PsA) reported musculoskeletal pain as the most burdensome symptom and preferred a treatment regimen that improved their joint symptoms and did not include a methotrexate coprescription.

Major finding: Joint pain (98%), fatigue (94%), and morning stiffness (94%) were the most common symptoms of PsA; therefore, 74% of patients preferred therapies that improved joint-related vs. psoriasis-related symptoms, with once-daily oral medication being preferred by 38% of patients and 47% of patients with experience receiving methotrexate preferring a treatment regimen without methotrexate.

Study details: This cross-sectional, web-based survey included 332 adults from ArthritisPower who had a self-reported physician diagnosis of PsA.

Disclosures: This study was funded by AbbVie and RTI Health Solutions. Three authors declared being employees of RTI Health Solutions, two authors declared being employees or share/stockowners of AbbVie, and other authors declared financial/nonfinancial ties with various sources.

Source: Ogdie A et al. Experiences and treatment preferences in patients with psoriatic arthritis: A cross-sectional study in the ArthritisPower registry. Rheumatol Ther. 2022 (Mar 13). Doi: 10.1007/s40744-022-00436-x

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Key clinical point: Patients with psoriatic arthritis (PsA) reported musculoskeletal pain as the most burdensome symptom and preferred a treatment regimen that improved their joint symptoms and did not include a methotrexate coprescription.

Major finding: Joint pain (98%), fatigue (94%), and morning stiffness (94%) were the most common symptoms of PsA; therefore, 74% of patients preferred therapies that improved joint-related vs. psoriasis-related symptoms, with once-daily oral medication being preferred by 38% of patients and 47% of patients with experience receiving methotrexate preferring a treatment regimen without methotrexate.

Study details: This cross-sectional, web-based survey included 332 adults from ArthritisPower who had a self-reported physician diagnosis of PsA.

Disclosures: This study was funded by AbbVie and RTI Health Solutions. Three authors declared being employees of RTI Health Solutions, two authors declared being employees or share/stockowners of AbbVie, and other authors declared financial/nonfinancial ties with various sources.

Source: Ogdie A et al. Experiences and treatment preferences in patients with psoriatic arthritis: A cross-sectional study in the ArthritisPower registry. Rheumatol Ther. 2022 (Mar 13). Doi: 10.1007/s40744-022-00436-x

Key clinical point: Patients with psoriatic arthritis (PsA) reported musculoskeletal pain as the most burdensome symptom and preferred a treatment regimen that improved their joint symptoms and did not include a methotrexate coprescription.

Major finding: Joint pain (98%), fatigue (94%), and morning stiffness (94%) were the most common symptoms of PsA; therefore, 74% of patients preferred therapies that improved joint-related vs. psoriasis-related symptoms, with once-daily oral medication being preferred by 38% of patients and 47% of patients with experience receiving methotrexate preferring a treatment regimen without methotrexate.

Study details: This cross-sectional, web-based survey included 332 adults from ArthritisPower who had a self-reported physician diagnosis of PsA.

Disclosures: This study was funded by AbbVie and RTI Health Solutions. Three authors declared being employees of RTI Health Solutions, two authors declared being employees or share/stockowners of AbbVie, and other authors declared financial/nonfinancial ties with various sources.

Source: Ogdie A et al. Experiences and treatment preferences in patients with psoriatic arthritis: A cross-sectional study in the ArthritisPower registry. Rheumatol Ther. 2022 (Mar 13). Doi: 10.1007/s40744-022-00436-x

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Secukinumab shows a satisfactory retention rate in PsA in real-world setting

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Key clinical point: In the real-world setting, secukinumab has a satisfactory retention rate in psoriatic arthritis (PsA). However, retention rates are lower in PsA than in psoriasis, with arthritis and obesity being significant predictors of shorter drug survival.

Major finding: Retention rate of secukinumab was higher in psoriasis vs. PsA at 12 (85% vs. 68%) and 24 (61% vs. 57%) months, with the risk for secukinumab discontinuation being higher among patients with arthritis in the overall cohort (hazard ratio 2.43; P = .035) and in patients with obesity in the PsA cohort (P = .021).

Study details: Findings are from a real-life study including 62 patients with psoriasis and 90 patients with PsA who initiated treatment with secukinumab and were followed up for 24 months or until discontinuation.

Disclosures: This study did not receive any funding. R Ramonda and S Piaserico declared receiving honoraria and speaker fees form Novartis, Abbvie, Pfizer, MSD, and Janssen.

Source: Ortolan A et al. Secukinumab drug survival in psoriasis and psoriatic arthritis patients: A 24-month real-life study. Dermatology. 2022 (Mar 9). Doi: 10.1159/000522008

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Key clinical point: In the real-world setting, secukinumab has a satisfactory retention rate in psoriatic arthritis (PsA). However, retention rates are lower in PsA than in psoriasis, with arthritis and obesity being significant predictors of shorter drug survival.

Major finding: Retention rate of secukinumab was higher in psoriasis vs. PsA at 12 (85% vs. 68%) and 24 (61% vs. 57%) months, with the risk for secukinumab discontinuation being higher among patients with arthritis in the overall cohort (hazard ratio 2.43; P = .035) and in patients with obesity in the PsA cohort (P = .021).

Study details: Findings are from a real-life study including 62 patients with psoriasis and 90 patients with PsA who initiated treatment with secukinumab and were followed up for 24 months or until discontinuation.

Disclosures: This study did not receive any funding. R Ramonda and S Piaserico declared receiving honoraria and speaker fees form Novartis, Abbvie, Pfizer, MSD, and Janssen.

Source: Ortolan A et al. Secukinumab drug survival in psoriasis and psoriatic arthritis patients: A 24-month real-life study. Dermatology. 2022 (Mar 9). Doi: 10.1159/000522008

Key clinical point: In the real-world setting, secukinumab has a satisfactory retention rate in psoriatic arthritis (PsA). However, retention rates are lower in PsA than in psoriasis, with arthritis and obesity being significant predictors of shorter drug survival.

Major finding: Retention rate of secukinumab was higher in psoriasis vs. PsA at 12 (85% vs. 68%) and 24 (61% vs. 57%) months, with the risk for secukinumab discontinuation being higher among patients with arthritis in the overall cohort (hazard ratio 2.43; P = .035) and in patients with obesity in the PsA cohort (P = .021).

Study details: Findings are from a real-life study including 62 patients with psoriasis and 90 patients with PsA who initiated treatment with secukinumab and were followed up for 24 months or until discontinuation.

Disclosures: This study did not receive any funding. R Ramonda and S Piaserico declared receiving honoraria and speaker fees form Novartis, Abbvie, Pfizer, MSD, and Janssen.

Source: Ortolan A et al. Secukinumab drug survival in psoriasis and psoriatic arthritis patients: A 24-month real-life study. Dermatology. 2022 (Mar 9). Doi: 10.1159/000522008

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