Olokizumab, a humanized monoclonal antibody specific for the interleukin-6 cytokine, showed promise for patients with rheumatoid arthritis who had an inadequate response to antitumor necrosis factor therapies in a 12-week, phase II trial.
Olokizumab showed comparable efficacy to tocilizumab in this patient population and at doses in line with this class of drug. Treatment-related adverse events and laboratory profiles in the trial also were consistent with the use of an IL-6 targeted therapy in patients with moderate to severe rheumatoid arthritis.
The randomized, double-blind, placebo- and active-controlled multicenter trial of 221 patients measured changes in 28-joint and C-reactive protein Disease Activity Score (DAS28-CRP) at week 12 as its primary endpoint. Secondary endpoints included the American College of Rheumatology (ACR) 20, ACR50, and ACR70 response rates at week 12. The patients were randomly assigned to one of nine treatment arms, receiving either an intravenous subcutaneous injection of the trial drug or placebo every 2 weeks or every 4 weeks in dosages of 60 mg, 120 mg, or 240 mg, or an 8 mg/kg infusion of tocilizumab (Actemra) every 4 weeks. Patients who were not randomized to tocilizumab also received a placebo infusion every 4 weeks (Ann. Rheum. Dis. 2014 March 18 [doi:10.1136/annrheumdis-2013-204760]).
First author Dr. Mark C. Genovese of Stanford (Calif.) University and his associates found that at week 12, olokizumab produced greater reductions in baseline DAS28-CRP scores than did placebo (P less than .001), regardless of the dose tested. ACR20 and ACR50 responses were numerically higher in the test group than in placebo, but the trial was not powered to detect between-group differences in ACR endpoints. The investigators recorded ACR20 responses in 32.5%-60.7% of olokizumab-treated patients and in 17.1%-29.9% of placebo-treated patients. ACR50 responses occurred in 11.5%-33.2% of patients who received olokizumab, compared with 1.3%-4.9% of placebo patients. Few patients in any treatment arm were ACR70 responders.
Regardless of dose, olokizumab demonstrated comparable efficacy to tocilizumab across multiple endpoints. Most adverse events, such as upper respiratory infection or gastrointestinal disorders, were mild to moderate, and did not vary significantly between the two drug treatment groups.
Funding for the study was provided by UCB Pharma. Dr. Genovese disclosed he receives funding from UCB beyond the scope of this study. The other researchers involved in this study disclosed an extensive list of industry relationships.