Researchers in a phase 2b study of clazakizumab suggest that this drug may become a new option for treatment of the musculoskeletal effects—but not necessarily skin lesions—associated with psoriatic arthritis (PsA). Treatment for patients with predominant musculoskeletal effects represents an unmet need.
“This is the first clinical trial of an interleukin (IL)-6-targeted therapy in PsA, and the first controlled study to demonstrate a beneficial effect of targeting the IL-6 cytokine in PsA,” Philip Mease, MD, Swedish Medical Center and University of Washington, Seattle, and colleagues stated. Clazakizumab’s efficacy on musculoskeletal measures was of greater magnitude than that observed on measures of skin disease. This suggests nonoverlapping mechanisms of inflammation in the skin and joints of patients with PsA, according to the researchers.
“Thus, clazakizumab may be particularly well suited for patients with PsA in whom skin disease is well controlled with topical agents, ultraviolet therapy, and/or oral systemic therapy such as methotrexate, but whose musculoskeletal manifestations, such as joint signs and symptoms, enthesitis, and dactylitis, require more potent systemic therapy,” the researchers explained. “Furthermore, some PsA patients do not present with skin lesions at diagnosis, and those patients may benefit from clazakizumab treatment.”
Clazakizumab is a monoclonal antibody with high affinity and specificity for IL-6. It has been studied in intravenous and subcutaneous formulations as a treatment for rheumatoid arthritis, with encouraging results.
The double-blind, placebo-controlled, dose-ranging study was conducted at 44 sites in 13 countries. The study randomized 165 patients with active PsA and an inadequate response to nonsteroidal anti-inflammatory drugs in a 1:1:1:1 ratio to subcutaneous placebo or clazakizumab 25 mg, 100 mg, or 200 mg every 4 weeks—with or without methotrexate—for 24 weeks. This was followed by an open-label extension phase. The primary end point was ≥20% improvement, according to American College of Rheumatology (ACR) criteria (ACR20), at week 16; secondary efficacy end points assessed improvement at weeks 16 and 24.
At week 16, clazakizumab 100 mg achieved a significantly higher ACR20 response compared with placebo (52.4% vs 29.3%; P = .039). Other week 16 ACR20 responses for clazakizumab were 46.3% for the 25-mg group, and 39.0% for the 200-mg group.
ACR50/ACR70—representing 50% improvement and 70% improvement, respectively—at weeks 16 and 24 were numerically higher with clazakizumab versus placebo.
Musculoskeletal manifestations of PsA were significantly improved by clazakizumab versus placebo with only minimal improvements in skin.
There were no deaths reported in the study. Only 2 serious adverse events were reported in the clazakizumab 25-mg and 100-mg groups (and also 2 in the placebo arm); 4 patients in the 400-mg arm had a serious adverse event. The overall rate of any adverse event was numerically higher in all treatment groups, with the highest number in the clazakizumab 200-mg group. The number of treatment-related discontinuations was small, and comparable to that of placebo for the 25-mg and 100-mg groups.
- 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. 2016 Apr 5. Epub ahead of print.