COPENHAGEN, Denmark — For patients with active psoriatic arthritis for whom tumor necrosis factor (TNF) inhibitors failed to produce an adequate response, use of the dual interleukin-17 (IL-17) inhibitor bimekizumab (Bimzelx) was associated with significant improvement in joint, skin, and health-related quality-of-life parameters, compared with placebo, reported investigators in the phase 3, double-blind, randomized BE COMPLETE trial.
The primary endpoint, which was the percentage of patients who had 50% improvement in American College of Rheumatology response criteria (ACR50) at 16 weeks, was achieved in 43.4% of patients assigned to receive bimekizumab 160 mg every 4 weeks, compared with 6.8% among patients who received placebo, reported Joseph F. Merola, MD, a dermatologist and rheumatologist at Brigham and Women's Hospital in Boston.
"The high-level and exciting take-home [message is] that BE COMPLETE did meet all primary and all ranked secondary endpoints at week 16," he said at the European Alliance of Associations for Rheumatology (EULAR) 2022 Annual Meeting.
Also at EULAR 2022, Iain McInnes, MD, PhD, from the Institute of infection, Immunity, and Inflammation at the University of Glasgow, Glasgow, Scotland, presented data from a second phase 3, double-blind, randomized trial called BE OPTIMAL that showed similar benefits for patients with psoriatic arthritis who had not previously received biologic disease-modifying antirheumatic drugs.
"This is a new mode of action, inhibiting two cytokines simultaneously," he said in a late-breaking oral abstract session.
As previously reported by Medscape Medical News, use of bimekizumab led to rapid reductions in signs and symptoms of radiographic axial spondyloarthritis in the phase 3 trial called BE MOBILE 2.
Bimekizumab is a monoclonal immunoglobulin G1 antibody that selectively inhibits IL-17A and IL-17F. It is approved in the European Union for treating adults with moderate to severe plaque psoriasis.
BE COMPLETE Efficacy
Inclusion criteria included the following: adult-onset psoriatic arthritis meeting Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 6 months; tender and swollen joint counts of ≥3/68; one or more active psoriatic lesions and/or a documented history of psoriasis characterized by intolerance to one or two TNF inhibitors or failure of TNF inhibitors. Patients were randomly assigned in a 2:1 ratio to receive either bimekizumab 160 mg every 4 weeks (n = 267) or placebo (n = 133) for 16 weeks.
Some participants are being followed in the extension BE VITAL study, which will evaluate response to treatment and long-term safety. Patients who do enroll in the extension study will be followed for safety for a period of 20 weeks after the last dose.
As noted before, the trial met its primary endpoint of a significant improvement over placebo in ACR50 (hazard ratio, 11.1; P < .001).
In addition, the trial met all ranked secondary endpoints, including the Health Assessment Questionnaire–Disability Index change from baseline, 90% improvement in the Psoriasis Area and Severity Index (PASI90), Short-Form 36–Item Health Survey, and minimal disease activity (P < .001 for all comparisons).
Improvement with bimekizumab was rapid; curves began to separate from placebo by week 4, Merola said.
BE OPTIMAL Efficacy
In this study, which had the same eligibility criteria as BE COMPLETE, patients were randomly assigned in a 2:3:1 ratio to receive 16 weeks of treatment with either placebo, bimekizumab 160 mg every 4 weeks, or adalimumab 40 mg every 2 weeks as a reference treatment.
This trial also met its primary and ranked secondary endpoints, which were similar to those of BE COMPLETE but also included measures of pooled resolution of enthesitis and dactylitis and change from baseline in van der Heijde modified total Sharp score (P < .001 for all comparisons).
In all, 43.9% of patients who received bimekizumab and 45.7% who received adalimumab achieved ACR50 at week 16, compared with 10% of patients who received placebo. The difference between the placebo and bimekizumab groups was significant (P < .001).
More patients who received the two active agents in this trial had treatment-emergent adverse events (TEAEs) in comparison with those in the placebo arm, but the incidence of serious TEAEs was less than 2% in each arm.
The most frequent events were nasopharyngitis, upper respiratory tract infection, headache, diarrhea, and hypertension.
Patients tolerated bimekizumab well, and there were no unexpected safety signals, McInnes said.
Clues to Efficacy
In the question-and-answer session following McInnes' presentation, Ronald Van Vollenhoven, MD, from the University of Amsterdam, Amsterdam, the Netherlands, said, "I have a question that is sort of generic in studies of psoriatic arthritis, so it does not only apply to this study, but the skin responses seem to be excellent ― PASI90 sounds wonderful ― but given that this is the case, is it reasonable to claim that the study is double-blinded in respect to the joints?"
McInnes replied that while he has considered this conundrum for many years in trials of drugs for psoriatic arthritis, "it doesn't seem to be a major determinant of the outcome."
The studies were supported by UCB Pharma. Merola and McInnes have consulted for UCB and other pharmaceutical companies that market drugs for psoriatic arthritis and psoriasis. Van Vollenhoven has received research support, has consulted for, and has spoken on behalf of UCB and other pharmaceutical companies.
Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape.
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Cite this: Neil Osterweil. Bimekizumab Calms Psoriatic Arthritis in Phase 3 'BE' Trials - Medscape - Jun 15, 2022.