1. Olokizumab was superior to placebo in improving rheumatoid arthritis (RA) symptoms.

2. Olokizumab was also noninferior to adalimumab in improving rheumatoid arthritis symptoms.

Evidence Rating Level: 1 (Excellent)

Study Rundown: RA is an inflammatory autoimmune disease characterized by persistent synovitis and destructive changes in bone and cartilage of multiple joints, leading to joint damage and permanent disability. Prior studies have demonstrated that the combination of adalimumab and methotrexate is superior to monotherapy in the treatment of RA to achieve remission or lower disease activity. It has also been proposed that interleukin-6 receptor inhibitors, such as olokizumab, can potentially be used to treat RA. The IL-6 cytokine has multiple functions in cell growth, bone metabolism, and inflammation. However, there is a gap in knowledge as to understanding the efficacy and safety of subcutaneous olokizumab in the treatment of RA. Overall, this study found that treatment of olokizumab with methotrexate resulted in a higher percentage of patients with significant response to RA symptoms when compared to placebo plus methotrexate. It also found that it was noninferior to treatment with Adalimumab plus methotrexate. This study was limited by a relatively small number of patients over a short duration, especially for the assessment of rare events such as cancers. Additionally, a lack of imaging evaluation was performed on joint disease. Nevertheless, this study’s findings are significant, as they demonstrate that treatment with olokizumab plus methotrexate provides a clinical benefit for the management of RA symptoms when compared to placebo and treatment with adalimumab.

Click to read the study in NEJM

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In-Depth [randomized control trial]: This phase three, multicenter, double-blind, randomized controlled trial was conducted at 209 sites in the United States, Europe, Asia, and Latin America. Patients who were aged 18 years or older with active RA, had an inadequate response to methotrexate for at least 12 weeks, had at least six swollen joints, at least six tender joints, and an elevated CRP level were eligible for the study. Patients were randomized to receive either olokizumab, adalimumab, or placebo. All patients continued to receive methotrexate. The primary outcome measured was an improvement of at least 20% in the American College of Rheumatology (ACR) response criteria. An ACR20 response was defined as a decrease of 20% or more in both the tender-joint count and the swollen-joint count as well as an improvement of 20% or more in at least three of five measures. Measures included factors such as a patient’s assessment of pain, patient function, a physician’s assessment of disease activity, and the level of acute-phase reactants. Based on the primary analysis, an ACR20 response at week 12 occurred in 44.4% of the patients receiving placebo, in 70.3% receiving olokizumab every two weeks (difference vs. placebo, 25.9%; 97.5% Confidence Interval [CI], 17.1 to 34.1), in 71.4% receiving olokizumab every four weeks (difference vs. placebo, 27.0%; 97.5% CI, 18.3 to 35.2), and in 66.9% receiving adalimumab (difference vs. placebo, 22.5%; 95% CI, 14.8 to 29.8) (p<0.001 for the superiority of each olokizumab dose to placebo). Overall, this study demonstrates that treatment of RA with olokizumab was superior to placebo and noninferior to adalimumab in producing an ACR20 response at 12 weeks.

Image: PD

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