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The monoclonal antibody risankizumab (Skyrizi) showed significant efficacy for psoriatic arthritis (PsA) in two phase III randomized trials, a researcher reported.

In the KEEPSAKE 1 and 2 trials, 1,407 patients with active PsA were randomly assigned to receive subcutaneous risankizumab, 150 mg, or placebo at baseline and then at weeks 4 and 16. On the primary endpoint of a 20% improvement in the American College of Rheumatology (ACR) response criteria (ACR20) at week 24, 55.5% of those given risankizumab met that endpoint compared with 31.3% of those receiving placebo (P<0.001), according to Andrew Ostor, MD, of Monash University in Melbourne, Australia.

"As we all know, psoriatic arthritis is a chronic systemic inflammatory disease that reduces patients' quality of life and contributes to individual and societal healthcare burdens," he said at a plenary session at the ACR virtual meeting.

Risankizumab is a humanized immunoglobulin G1 monoclonal antibody that targets interleukin 23 by binding to the cytokine's p19 subunit. It has previously been approved for use in psoriasis.

Participants in the two trials had active skin or nail disease and at least five swollen and tender joints. In both trials, patients had previously had an inadequate response or intolerance to one or more conventional disease-modifying antirheumatic drug, and in KEEPSAKE 2, patients also could have failed one or more biologic agent.

Half of patients were women with a mean age of 51, and a mean BMI 31. Duration of PsA at baseline averaged 7.5 years, swollen and tender joint counts were high, at 12 and 21, respectively, and patient global assessment was 61.9. Enthesitis was present in 63% of patients and dactylitis in 27%.

"There also was a high burden of disability and fatigue," Ostor said.

Most patients were on background methotrexate, and 15% to 20% were on prednisone.

A total of 1,354 patients completed the randomized 24-week phase of the study; an open-label phase with all patients receiving the active treatment is ongoing.

Treatment with risankizumab also showed significantly superior results on multiple secondary endpoints at week 24 (P<0.001 for all):

• ACR50: 31.2% vs 10.6%, for a difference of 20.6 (95% CI 16.5-24.7)
• ACR70: 14.1% vs 5%, for a difference of 9 (95% CI 6-12.1)
• Resolution of enthesitis: 48.4% vs 34.8%, for a difference of 13.9 (95% CI 7.6-20.2)
• Resolution of dactylitis: 68.1% vs 51%, for a difference of 16.9 (95% CI 7.5-26.4)
• Minimal disease activity: 25.2% vs 10.6, for a difference of 14.6 (95% CI 10.6-18.5)
• Psoriasis Area and Severity Index 90% improvement: 53.2% vs 10%, for a difference of 43.1 (95% CI 37.3-48.8)

Significantly greater improvements also were seen on scores for disability, physical well being, and fatigue.

No new safety signals were observed. Overall, risankizumab was well tolerated, with serious adverse events being reported in 3% of risankizumab-treated patients and in 4.4% of those on placebo, and serious infections being seen in 1% and 1.6%, respectively. One patient in the risankizumab group died; the patient was age 81 with dementia and urosepsis.

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