Olokizumab effective in patients with rheumatoid arthritis unresponsive to TNF inhibitors
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In patients with rheumatoid arthritis who failed to respond to TNF inhibitors, olokizumab is effective and carries an acceptable safety risk, especially when paired with methotrexate, according to data published in Clinical Rheumatology.
“Despite the advancement in the DMARDs, less than 50% of patients with RA are in remission, and 10-20% are refractory to the available treatment options,” Mohamed Abuelazm, MD, of Tanta University, in Egypt, and co-authors wrote. “New treatments targeting different pathways in the disease’s pathophysiology are emerging to cover this unmet gap, including IL-6 inhibitors.
“To clarify, [olokizumab (OKZ)] is a new humanized monoclonal antibody targeting the IL-6 cytokine,” they added. “Unlike [tocilizumab (TCZ)], it does not target the IL-6 receptor. Instead, it targets specific sites on the IL-6 itself and blocks the formation of the extracellular signaling complex, consequently inhibiting the transmembrane signaling. Two phase II randomized controlled trials (RCTs) reported significant improvement in DAS28-CRP, ACR20, and ACR50 indices in OKZ group, compared to the placebo. In another phase III clinical trial, OKZ combined with [methotrexate (MTX)] was superior to MTX monotherapy and non-inferior to adalimumab combined with MTX.”
To investigate the effectiveness and safety of olokizumab (UCB) in patients with RA, Abuelazm and colleagues conducted a systematic literature review and meta-analysis of previously reported data. They searched several databases — including WOS, CENTRAL, SCOPUS, EMBASE and PubMed — for studies focusing on patients with RA being treated with olokizumab or placebo with a primary outcome of ACR20 repsonse. Publication cutoff was set at Aug. 31, 2022. Secondary endpoints included ACR50 and ACR70 responses, disease severity scores and safety outcomes.
Following study selection and the elimination of duplicates, Abuelazm and colleagues evaluated the papers for title and abstract relevance. They collected study characteristics, baseline data, rheumatoid factor positivity, tender and swollen joint counts and the use of various therapies. They additionally collected data on therapy effectiveness and safety outcomes.
The analysis included a total of five randomized controlled trials representing 2,277 patients. Overall, the researchers reported that olokizumab improved ACR20 (RR = 1.97; 95% CI, 1.49-2.58), ACR50 (RR = 3.83; 95% CI, 2.13-6.87) and ACR70 (RR = 3.83; 95% CI, 2.13-6.87) criteria after 12 weeks, compared with placebo. In addition, DAS28 based on C-reactive protein, clinical disease activity index and health assessment questionnaire disability index scores all improved in patients treated with olokizumab vs. those who received placebo.
Regarding safety, patients who received olokizumab demonstrated higher incidence rates of adverse events (RR = 1.15; 95% CI, 1.06-1.25), as well as adverse events leading to therapy discontinuation (RR = 1.86; 95% CI, 1.05-3.29), compared with the placebo groups.
“OKZ treatment with MTX was effective in improving RA indices with an improvement of the RA’s symptoms and signs along with the expected safety profile,” Abuelazm and colleagues wrote. ”However, more large-scale RCTs are still required to investigate the optimal dosing, long-term effects, and comparative efficacy versus established biological DMARDs.”
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