Phase 3 Results for Olokizumab in RA Patients

ATLANTA—Olokizumab, a monoclonal antibody that targets interleukin (IL) 6, is currently in clinical trials for the treatment of moderate to severe active rheumatoid arthritis (RA) in adults for whom methotrexate is inadequate. During 2019 ACR/ARP Annual Meeting, results from a 24-week, randomized, placebo-controlled, phase 3 study (NCT02760368; CREDO1) evaluating the efficacy and safety of olokizumab were reported.¹

In the double-blind, multicenter study, patients were randomized to receive subcutaneous injections of 64 mg of olokizumab every two weeks, 64 mg of olokizumab once every four weeks or 24 weeks of placebo. Patients continued their background methotrexate therapy. At Week 14, non-responders were prescribed rescue medications, which included sulfasalazine and/or hydroxychloroquine, in addition to the study treatment. After Week 24, subjects entered either an ongoing, open-label study or the safety follow-up. The study’s primary endpoint was the ACR20 response at Week 12. Numerous secondary endpoints were evaluated at Weeks 12 and 24.

The Results
After 24 weeks of treatment with olokizumab, study patients showed significant improvements in the signs and symptoms of RA, as well as in their physical functioning. Additionally, most patients completed the study.

During the study, 428 patients were randomized to the various groups, with 143 patients receiving 64 mg of olokizumab every two weeks, 142 patients receiving 64 mg of olokizumab once every four weeks and 143 patients receiving placebo. At baseline, patient characteristics were comparable across treatment arms. Most patients were female (~81%), with a mean RA duration of 7.3– 8.7 years and a mean methotrexate dose of 16 mg. The study patients had a mean tender joint count of 22.2–24.4 and a mean swollen joint count of 14. The mean baseline DAS28-CRP was 6, with 41–52% of patients using glucocorticoids.

Patients in both olokizumab treatment regimens had significantly better responses for all primary and secondary endpoints than placebo-treated patients. At Week 12, 91% of patients treated with olokizumab every two weeks and 100% of patients treated with olokizumab every four weeks achieved an ACR20 response. Meanwhile, only 37% of placebo-treated patients achieved an ACR20 response. Also at Week 12, DAS28-CRP<3.2 responses were 48%, 55% and 5%, respectively. At Week 24, ACR50 response rates were 61%, 69% and 11%, respectively. These results were both clinically and statistically significant.

The overall incidence of treatment-emergent adverse events was 58% in the group receiving olokizumab once every two weeks, 57% in the group receiving olokizumab once every four weeks and 43.7% in the placebo group. During the study, one death due to septic shock occurred in the group receiving olokizumab once every two weeks. More treatment-emergent serious adverse events occurred in olokizumab-treated patients than in patients who received placebo.

No new safety signals identified during the study. Additionally, there were no noticeable efficacy or safety differences between the olokizumab doses.

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

Reference

1. Nasonov E, Fatenejad S, Korneva E, et al. Safety and efficacy of olokizumab in a phase 3 trial of patients with moderately to severely active rheumatoid arthritis inadequately controlled by methotrexate—CREDO1 study [abstract L12]. Arthritis Rheumatol. 2019 Oct; 71(suppl 10).