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(ACR2014) Direct interleukin 6 blocker controls arthritis, enthesitis, and dactylitis in psoriatic arthritis.
Mease P, Gottlieb AB, Berman A, et al., Phase 11b, Randomize, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study to Evaluate the Efficacy and Safety of Clazakizumab, an Anti-IL-6 Monoclonal Antibody, in Adults with Active Psoriatic Arthritis. ACR Abstract #952. Arthritis & Rheumatism. 2014;66(1)-Supplement.
Clazakizumab proves effective at controlling arthritis, enthesitis, and dactylitis in psoriatic arthritis (PsA) compared with placebo, according to a small pilot study.
However, the direct interleukin 6 (IL-6) blocker has only modest skin effects among active PsA patients, with or without methotrexate, says Philip J. Mease MD, director of rheumatology research at the Swedish Medical Center in Seattle and clinical professor of medicine at the University of Washington. Mease presented results of his team's research at the 2014 meeting of the American College of Rheumatology.
The 165 participants (more than 90% Caucasian; about equal numbers of men and women; mean age of 49) have an inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs) and biologic and non-biologic disease modifying anti-rheumatic drugs (DMARDS).
Their average PsA duration ranged from 5 to 9 years, and 70% of patients were using methotrexate at baseline.
The patients were randomized to one of three subcutaneous doses of clazakizumab (25 mg, 100 mg, or 200 mg once a month), with methotrexate for 24 weeks.
More than half (52.4%) achieved the primary endpoint, an American College of Rheumatology 20% response (ACR20) at 16 weeks compared with placebo. Almost 60% reached an ACR20 response with a 25-mg or 100-mg dose at 24 weeks, compared with placebo.
Interestingly, the 200-mg dose is considerably less effective than the 25-mg or 100-mg dose, Mease reports, with a response rate of less than 40% at both time points.
“Some of that is explained by adverse events for the higher dose in patients dropping out of the trials, but we don’t have a full explanation for this yet,” Mease told Rheumatology Network.
Approximately 35% of patients achieve ACR50 and ACR70 responses at a 25-mg or 100-mg dose of clazakizumab at both time points, compared with 24.4% and 12.2% at the 200-mg dose.
There are no significant differences in declines in disease activity in 28 joints with C-reactive protein (DAS28-CRP) among the clazakizumab patients. There are similar decreases in enthesitis scores by week 16 among the dose profiles, with the 25-mg dose being a little more effective.
However, decreases in the number of dactylitis digits are greater for the 25-mg and 200- mg dose of clazakizumab.
The clazakizumab PsA safety profile is similar to that of rheumatoid arthritis (RA) therapy, with the most common adverse event a non-clinically significant increase in liver enzymes, and acceptable safety signals consistent with IL-6 blockade.
“An IL-6 inhibitor may be effective in musculoskeletal domains but since the effects in skin were disappointing, clearly needs more work,” Mease says.
The study was funded by Bristol-Myers Squibb; Mease reports research grants and consulting fees from the company as do other authors.