In the first clinical trial evaluating interleukin (IL)-6 targeted therapy for psoriatic arthritis (PsA), treatment with clazakizumab was shown to improve enthesitis and dactylitis, but had minimal effects on the cutaneous manifestations of PsA. These phase 2b clinical trial findings were published in Arthritis & Rheumatology.
Philip Mease, MD, of the University of Washington in Seattle, and colleagues, conducted a randomized, double-blind, placebo-controlled, multi-national study of 165 patients with active PsA, who did not have a history of prior treatment with biologic drugs for PsA and previously had an inadequate response to nonsteroidal anti-inflammatory drugs. Study participants were permitted to remain on concomitant methotrexate and prednisone pharmacotherapy (at doses <10 mg per day) during the 24-week double-blind phase of the study.
Study participants (N=165) were randomized 1:1:1:1 to receive either placebo or clazakizumab 25mg, 100mg, or 200 mg subcutaneously administered every 4 weeks. The specified primary endpoint was American College of Rheumatology (ACR)-20 response rate 16 weeks after treatment initiation. Secondary endpoints were defined as ACR-20 response rates at weeks 16 and 24.
Researchers found that ACR20 response at week 16 was significantly higher in study participants treated with clazakizumab 100 mg versus placebo (52.4% vs 29.3%; P = .039). However, although ACR20 responses at week 16 in study participants treated with clazakizumab 25 mg or 200 mg were numerically higher (46.3% and 39%, respectively) versus placebo, they did not appear to be statistically significant.
The proportion of study participants who were in disease activity score 28 (DAS-28) remission at week 24 was 14.6% in the placebo treatment group, 41.5% in the clazakizumab 25mg treatment group, 40.5% in the clazakizumab 100mg treatment group, and 29.3%in the clazakizumab 200mg treatment group.
Cutaneous improvement with clazakizumab was noted by researchers to be minimal, with 75% improvement on the psoriasis area severity index score at week 24 occurring in 12.2%, 19.5%, 28.6%, and 12.2% of the placebo, clazakizumab 25 mg, clazakizumab 100 mg, and clazakizumab 200 mg groups, respectively.
Clazakizumab treatment was associated with elevations in serum transaminase and lipids, thrombocytopenia, and neutropenia. The researchers noted that these findings were consistent with other adverse effects associated with IL-6 blockade.
Clazakizumab was discontinued secondary to adverse effects in 3 study participants in the placebo treatment group, 1 study participant in the clazakizumab 25mg treatment group, 2 study participants in the clazakizumab 100 mg treatment group, and 7 patients in the clazakizumab 200 mg treatment group,
Summary and Clinical Applicability
“Compared with placebo, clazakizumab treatment [for PsA] significantly improved musculoskeletal manifestations (joint signs and symptoms, enthesitis, and dactylitis), with minimal improvements in skin, without clear evidence of a dose response,” the authors concluded.
Limitations and Disclosures
Lack of dose response to clazakizumab in this study indicates that additional research is needed to determine efficacious optimal dosing. The concomitant use of methotrexate in study participants could have a confounding effect. Additionally, clinicians should note the lack of improvement of cutaneous manifestations of PsA with clazakizumab treatment.
The study was sponsored by Bristol-Myers Squibb. Study co-authors disclosed financial relationships with Bristol-Myers Squibb, AbbVie, Amgen, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Novo Nordisk, GlaxoSmithKline, and Vertex.
Mease P, Gottlieb AB, Berman A, et al. The Efficacy and Safety of Clazakizumab, an Anti-Interleukin-6 Monoclonal Antibody, in a Phase 2b Study of Adults with Active Psoriatic Arthritis. Arthritis Rheumatol. [Epub ahead of print] April 5, 2016. doi: 10.1002/art.39700.