Olokizumab superior to placebo and noninferior to adalimumab in RA patients

The cytokine interleukin-6 is involved in the pathogenesis of rheumatoid arthritis. Olokizumab, a humanized monoclonal antibody targeting the interleukin-6 cytokine directly, is being tested for the treatment of rheumatoid arthritis.

In a 24-week, phase 3, multicenter, placebo- and active-controlled trial, we randomly assigned patients with rheumatoid arthritis and an inadequate response to methotrexate to receive subcutaneous olokizumab at a dose of 64 mg every 2 or 4 weeks, adalimumab, or placebo; all patients continued methotrexate therapy. The primary end point was an American College of Rheumatology 20 (ACR20) response at week 12, with each olokizumab dose tested for superiority to placebo. We also tested the noninferiority of each olokizumab dose to adalimumab with respect to the percentage of patients with an ACR20 response

The results:

• A total of 464 patients were assigned to receive olokizumab every 2 weeks, 479 to receive olokizumab every 4 weeks, 462 to receive adalimumab, and 243 to receive placebo.
• An ACR20 response at week 12 occurred in 44.4% of the patient's receiving placebo, in 70.3% receiving olokizumab every 2 weeks in 71.4% receiving olokizumab every 4 weeks, and in 66.9% receiving adalimumab
• Both olokizumab doses were noninferior to adalimumab with respect to the percentage of patients with an ACR20 response at week 12 with olokizumab every 2 weeks and 4.5 percentage points
• Adverse events, most commonly infections, occurred in approximately 70% of the patients who received olokizumab.
• Antibodies against olokizumab were detected in 3.8% of the patients receiving the drug every 2 weeks and in 5.1% of those receiving it every 4 weeks.

Thus, in patients with rheumatoid arthritis who were receiving maintenance methotrexate, olokizumab was superior to placebo and noninferior to adalimumab in producing an ACR20 response at 12 weeks. Larger and longer trials are required to determine the efficacy and safety of olokizumab in patients with rheumatoid arthritis.

Reference:

Josef S. Smolen, et al. Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med 2022; 387:715-726. DOI: 10.1056/NEJMoa2201302