Olokizumab Outperforms Placebo in RA patients on maintenance Methotrexate: NEJM

VIENNA: Patients with rheumatoid arthritis taking maintenance methotrexate respond better to olokizumab than to a placebo and non-inferior to adalimumab states a research study published in The New England Journal of Medicine.

About 5 out of every 1000 persons develop rheumatoid arthritis (RA), which can cause significant joint damage and disability. The pathophysiology of rheumatoid arthritis is influenced by the cytokine interleukin-6. Olokizumab is a humanized monoclonal antibody that is being studied for the treatment of rheumatoid arthritis. It specifically targets the interleukin-6 cytokine.

"Adalimumab monotherapy is not a recommended course of treatment for rheumatoid arthritis since studies have indicated that adalimumab plus methotrexate is more effective than adalimumab alone", asserted the authors.

The researchers aimed to compare subcutaneous olokizumab (UCB) to adalimumab and placebo in terms of the safety and effectiveness of treating RA patients who are already taking Methotrexate.

For this objective a phase 3, multicenter, double-blind, parallel-group, randomized, placebo- and active-comparator controlled trial was carried out by the authors which included a total of 1643 patients. From May 2016 to November 2019, the study was carried out at 209 locations across the United States, the United Kingdom, continental Europe, South Korea, Taiwan, and Latin America. Olokizumab 64 mg subcutaneous injections were given to 464 patients randomly assigned at 2:2:2:1 ratio, followed by olokizumab 64 mg subcutaneous injections every 4 weeks given to 479 patients, adalimumab 40 mg subcutaneous injections every 2 weeks administered to 462 individuals, or a placebo subcutaneous injection given to 243 subjects every 2 weeks.

Patients had to meet the American College of Rheumatology-EULAR 2010 updated classification criteria for active RA and be at least 18 years old to be included. By week 12, the ACR20 or greater improvement was the study's primary efficacy goal. Secondary endpoints included noninferiority of each olokizumab dose to adalimumab regarding the ACR20 response at week 12, the proportion of patients with a DAS28 based on C-reactive protein levels of less than 3.2 at week 12, decrease in the Health Assessment Questionnaire-Disability Index score from baseline to week 12, ACR50 responses at week 24, and a Clinical Disease Activity Index score of 2.8 or less at week 24.

Key findings of the study:

• At week 12, an ACR20 response was seen in 44.4% of patients who received placebo, 70.3% of patients who received olokizumab every two weeks, 71.4% of patients who received olokizumab every four weeks, and 66.9% of patients who received adalimumab (P<0.001 for the superiority of each olokizumab dose to placebo).
• In terms of the proportion of patients who had an ACR20 response at week 12, both olokizumab doses were noninferior to adalimumab.
• 70% of the patients who got olokizumab experienced adverse events, the most frequent of which were infections.
• 3.8% of patients taking olokizumab every two weeks and 5.1% of those receiving it every 4 weeks had antibodies against the medication.

"To ascertain the effectiveness and safety of olokizumab in patients with rheumatoid arthritis, larger and longer trials are necessary", writes the authors.

The researchers concluded that in terms of an ACR20 response at week 12, olokizumab with methotrexate surpassed placebo plus methotrexate and was comparable to the combination of adalimumab and methotrexate.

REFERENCE

Smolen JS, Feist E, Fatenejad S, Grishin SA, Korneva EV, Nasonov EL, Samsonov MY, Fleischmann RM; CREDO2 Group; CREDOZ Group. Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2022 Aug 25;387(8):715-726. doi: 10.1056/NEJMoa2201302. PMID: 36001712.