In patients with rheumatoid arthritis (RA) who did not respond to methotrexate treatment, olokizumab demonstrated significant improvements in signs and symptoms of RA with expected safety and low immunogenicity, according to phase 3 study results published in the Annals of Rheumatic Diseases.

Olokizumab is an anti-interleukin 6 (IL-6) antibody that has been shown to be effective in phase 2 trials. This phase 3 randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT02760368) continued the investigation of olokizumab’s safety and efficacy.

Participants with active RA and prior inadequate response to methotrexate were assigned randomly 1:1:1 to 64 mg olokizumab every 2 weeks, 64 mg olokizumab every 4 weeks, or placebo. Previous methotrexate doses were continued for all participants. The primary endpoint was the proportion of participants achieving American College of Rheumatology 20% (ACR20) response at week 12. Secondary endpoints included the percentage of participants with a Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) lower than 3.2 at week 12, improvement in the Health Assessment Questionnaire Disability Index (HAQ-DI) at week 12, ACR50 response at week 24, and percentage of participants in remission at week 24 as indicated by a Clinical Disease Activity Index (CDAI) score of  2.8 or lower. Safety and immunogenicity were assessed continually.


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Among 427 participants randomly assigned to 3 groups (olokizumab every 2 weeks [n=143], olokizumab every 2 weeks [n=142], placebo [n=143]), ACR20 responses were 63.6%, 70.4%, and 25.9%, respectively (P <.0001 for both comparisons). Significant differences (P <.0001 or P <.001) were observed between the 2- and 4-week treatment groups compared with placebo for all secondary endpoints. Incidences of treatment-emergent serious adverse events (TESAEs) were 5.6%, 5.6%, and 2.8% in the olokizumab every 2 weeks, olokizumab every 4 weeks, and placebo groups, respectively. Infections were the most frequently reported TESAEs. Neutralizing antibodies were not detected in any of the participants, indicating low immunogenicity.

Limitations of the study included a lack of an active comparator to compare olokizumab with other agents, absence of radiographic assessments, and limited geographic and racial diversity.

“This study evaluated two effective doses with a frequency of injection of once per 2 weeks and once per month, and both regimens of [olokizumab] were superior to [placebo] in reducing signs and symptoms and improving disability and quality of life over a period of 24 weeks,” the researchers concluded. “As expected, there were more adverse events observed in the [olokizumab]-treated patients, but they were mostly mild to moderate with few serious adverse events and no unexpected safety findings and relatively low number of dropouts due to an adverse event.”

Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Nasonov E, Fatenejad S, Feist E, et al. Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. Published online August 3, 2021. doi: 10.1136/annrheumdis-2021-219876.