Background/Purpose: Ofatumumab is a unique anti-CD20 monoclonal antibody with its epitope more proximal and distinct from the epitope recognized by rituximab or by other anti-CD20 monoclonal antibodies. The proximity of this epitope probably accounts for the high efficiency of B-cell killing. The significant role of B-cells in RA and the uniqueness of ofatumumab’s epitope resulting in more efficient killing than other B-cell deleting antibodies makes it ideal for use in RA. Our objective was to assess the benefits and harms of ofatumumab in reducing disease activity, pain, and improving function in people with RA.

Methods: We searched multiple databases for eligible studies as well as the websites of the regulatory agencies for reported adverse events using the search strategy developed by a Cochrane librarian. We included randomized controlled trials comparing ofatumumab alone, or in combination with disease-modifying anti-rheumatic drugs (DMARDs) or biologics, to placebo or DMARDs or biologics alone or in combination with DMARDs, with no restrictions with regard to the dosage.Two authors independently assessed search results, trial quality and risk of bias, and extracted data.

Results: Our search identified three trials with low risk of bias, including 654 patients (383 in ofatumumab group and 271 in control group), for analysis. A stable methotrexate dose was allowed in all patients. Compared with placebo, patients in the ofatumumab group were 3.1 times more likely to achieve an ACR50 (RR 3.12, 95% CI 1.98 to 4.91). The efficacy was noted in patients with (RR, 95% CI: 3.76 (1.47 to 9.59) and without prior TNF-failure (RR, 95% CI: 2.78 (1.6 to 4.84), when given a dose of 700 mg, but not for the 300mg or the 1000 mg dose. The number needed to treat to achieve an ACR 50 response was 6 (95% CI 4 to 7). Patients in the ofatumumab group were 2.3 times more likely to achieve an ACR20 response (RR 2.3, 95% confidence interval (CI) 1.76 to 3.01). Only one trial found improvement in ACR70 response. A significant reduction in disease activity was found in ofatumumab-treated patients compared to placebo. The quality of life was also significantly improved with the ofatumumab treatment , as measured by SF-36 summary score (Mean Difference, 2.48, 95% CI 2.23, 2.73). Total withdrawals and withdrawals due to adverse effects were not statistically different between ofatumumab and placebo. However, withdrawal due to lack of efficacy were significantly lower in the ofatumumab treated patients compared to the placebo group (RR 0.24, 95% CI 0.10 to 0.60). The risk of adverse events was higher in ofatumumab group compared to placebo (RR 1.5, 95% CI 1.37 to 1.72). The incidence of serious adverse events was however not significantly different between ofatumumab and placebo (RR 1.72, 95% CI 0.91 to 3.26). The heterogeneity of the included trials was low (I²=0%), for all the outcomes.

Conclusion: This systematic review and meta-analysis suggests that ofatumumab is efficacious and safe for the treatment of rheumatoid arthritis compared to placebo. The adverse events profile appears to be acceptable at the present but long-term trials and post-marketing surveillance are required to further assess efficacy and harms.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/ofatumumab-for-rheumatoid-arthritis-a-cochrane-systematic-review-and-meta-analysis/