Targeted interleukin(IL)-6 inhibition with clazakizumab may meet the clinical need for new treatments in patients with psoriatic arthritis (PsA) who have joint, enthesitis, or dactylitis symptoms, according to research published in Arthritis & Rheumatology.
Philip J Mease, MD, from the Swedish Medical Center and the University of Washington, Seattle, and colleagues conducted a randomized, double-blind, placebo-controlled, dose-ranging study of patients with active PsA who had previously designated as inadequate responders to nonsteroidal anti-inflammatory drugs (ClinicalTrials.gov identifier: NCT01490450). All patients had been diagnosed with PsA according to the Classification of Psoriatic Arthritis (CASPAR) criteria, with active disease defined by swollen joint count of ≥3 (66 joints), a tender joint count of ≥3 (68 joints), and active psoriatic skin lesions involving ≥3% of body surface area.
The primary endpoint of the study was the proportion of patients adequately responding to therapy, according to the American College of Rheumatology 20% criteria for improvement (ACR20) at week 16. Secondary efficacy endpoints were recorded at weeks 16 and 24. With the exception of methotrexate (MTX), all disease-modifying antirheumatic drugs (DMARDs) were discontinued prior to randomization.
High Yield Data Summary
- At 24 weeks, ACR20 response rates in all 3 clazakizumab-treatment arms were numerically higher than in the placebo group, with improvements seen as early as week 1
One hundred sixty-five study participants—mean age 47.9 years, 52.1% women, 94.5% white, mean PsA disease duration 7.1 years—were randomized 1:1:1:1 to receive subcutaneous injection of either placebo or clazakizumab in 25, 100, or 200 mg, with or without methotrexate every 4 weeks.
All patients received at least 1 dose of study medication; a total of 140 patients (84.8%) completed all 24 weeks of the study. Within the clazakizumab 200 mg arm of the study, 14.6% of patients (n=6) discontinued due to adverse events.
During the second phase of the double-blind period, 20 of 38 patients (52.6%) within the placebo arm and 11 of 32 patients (24.4%) in the clazakizumab 25, 100, and 200 mg arms received rescue therapy (topical steroids, oral steroids, single intramuscular, intravenous, and/or intraarticular glucocorticoid injection, open-label clazakizumab 200 mg, or an increase in MTX).
At week 16, ACR20 response rate in the clazakizumab 100 mg group was significantly higher than in the placebo group (52.4% vs 29.3%, P =.039, adjustment for multiple comparisons). Response rate in the clazakizumab 25 and 200 mg groups were numerically higher vs placebo (46.3% [P =.101] and 39.09% [P =.178], respectively).
Summary and Clinical Applicability
In the first randomized controlled study evaluating the efficacy of targeted IL-6 inhibition in PsA, Dr Mease and colleagues found that clazakizumab 100 mg significantly reduced PsA disease severity as quantified by ACR20 scores at week 16 post-randomization compared with placebo.
Significant efficacy was demonstrated with clazakizumab 100 mg vs the placebo for the primary endpoint (P =.039, with adjustment for multiple comparisons). Clazakizumab was generally well-maintained in all 3 doses, and maintained efficacy through 24 weeks of treatment.
“The improved HAQ DI responses seen with clazakizumab treatment in this study demonstrate that…treatment produces a clinically meaningful change in physical function in patients with PsA,” concluded Dr Mease.
Limitations and Disclosures
- Variations in MTX dose and frequency of administration among the study participants were not controlled for in the study design; too few patients were free of MTX for the entire 24-week, double-blind period, making it difficult to measure impact of concomitant treatment with MTX
Drs Mease and Gottlieb have received consulting fees, speaking fees, and/or honoraria from Amgen, Bristol-Myers Squibb, Celgene, Genentech, Lilly, Novartis, Pfizer, and UCB. Dr Mease has received additional fees and/or honoraria from AbbVie, Biogen Idec, Crescendo, Janssen, and Merck; Dr Gottlieb has received additional fees and/or honoraria from Abbott/AbbVie, Actelion, Akros, Astellas, Beiersdof, Canfite, Catabasis, Cedntocor/Janssen, Coronado, CSL Behring Biotherapies for Life, DermiPsor, DUSA Pharmaceuticals, GlaxoSmithKline, Karyopharm Theraputics, Meiji Seika Pharma, Novo Nordisk, Sanofi-Aventis, Teva Pharmaceuticals, Vertex, and Xenoport. Dr Gottlieb received research grants (to Tufts Medical Center) from Abbot/AbbVie, Amgen, Celgene, Centocor/Janssen, Daavlin, Lilly, Merck, Novartis, Pfizer, and XenoPort. Dr Dr Berman has received research grants from Bristol-Myers Squibb, and Drs Xing, Wong, and Banerjee own stock or stock options in Bristol-Myers Squibb.
Mease PJ, Gottlieb AB, Berman A, et al. The efficacy and safety of calzakizumab, an anti-interleukin=6 monoclonal antibody, in a phase IIb study of adults with active psoriatic arthritis. Arthritis Rheumatol. 2016;68(9):2163-2173. doi: 10.1002/art.39700