SAN FRANCISCO, CA—Ofatumumab is safe and effective against rheumatoid arthritis (RA), a systematic review and meta-analysis of data from three trials presented at the 2015 ACR/ARHP Annual Meeting has confirmed.
“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,” noted Vidhu Anand, MD, of the University of Minnesota, Minneapolis, MN, and coauthors.
Ofatumumab, an anti-CD20 monoclonal antibody (mAb), has its epitope more proximal and distinct from that recognized by rituximab or by other anti-CD20 mAbs, Dr. Anand explained. “The proximity of this epitope probably accounts for the high efficiency of B-cell killing.” That fact, as well as the significant role B-cells play in RA, makes ofatumumab “ideal for use in RA.”
To assess ofatumumab’s effects on disease activity, RA patient function and pain, and adverse events, the researchers interrogated research and regulatory databases using Cochrane systematic review methods.
Included were “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,” the investigators reported in their poster presentation. “Two authors independently assessed search results, trial quality, and risk of bias, and extracted data.”
They identified three clinical trials with a low risk of bias for analysis representing 654 patients, 383 administered ofatumumab, and 271 in control groups. Stable methotrexate dose was allowed in all patients, they noted.
Patients treated with ofatumumab group (vs. placebo) were 3.1 times more likely to achieve an ACR50 (RR 3.12; 95% CI: 1.98–4.91). This efficacy was noted in those both with (RR 3.76; 95% CI: 1.47–9.59) and without prior TNF-failure (RR 2.7; 95% CI: 1.6–4.84) at the 700mg dose, but not the 300mg or 1000mg doses.
“The number needed to treat to achieve an ACR50 response was 6 (95% CI: 4–7),” they reported. “Patients in the ofatumumab group were 2.3 times more likely to achieve an ACR20 response (RR 2.3; 95% CI: 1.76–3.01).”
Only one of the studies included in the analysis found improvement in ACR70 response, the coauthors reported.
“A significant reduction in disease activity was found in ofatumumab-treated patients compared to placebo,” they noted. “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).”
The risk of adverse events was higher for patients administered ofatumumab than placebo (all grades; RR 1.54, 95% CI 1.37-1.72), but the incidence of serious adverse events was not significantly different (RR 1.72; 95% CI:0.91 to 3.26). Discontinuations (both total number of withdrawals and withdrawals due to adverse effects) were not statistically different between ofatumumab and placebo, the coauthors reported.
“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: 0.10–0.60),” they noted.