Safety profile of ocrelizumab for the treatment of multiple sclerosis: a systematic review.

Ng, Huah Shin; Rosenbult, Constanza Luzon; Tremlett, Helen

INTRODUCTION We systematically collated and reviewed reported adverse events (AEs) for ocrelizumab for multiple sclerosis (MS). Areas covered: We searched Medline, Embase, Web of Science and Toxicology Data Network-TOXLINE from inception to 08-July-2020, and clinical trial registries, and product monographs for any clinical trials, observational studies or case reports examining AEs to ocrelizumab in person(s) with MS. Studies with/without a comparator drug or placebo were eligible. Expert opinion: Overall, 78 records were included (4 randomized controlled trials (RCTs), 4 open-label trials, 29 observational studies and 27 case reports). AEs affected 2756/4498 (61.3%) of ocrelizumab-exposed patients. The most common AEs were infections (n=1342, 39.2% of ocrelizumab-exposed patients) and infusion-related reactions (n=1391, 26.2%). Compared to beta-interferon, ocrelizumab-exposed patients were more likely to experience an infection (Risk Ratio (RR)=1.10; 95% confidence interval (CI):1.01-1.19), including: herpes virus-related (RR=1.75;95%CI:1.11-2.76), upper and lower respiratory tract infections (RR=1.42;95%CI:1.10-1.84 and RR=1.61;95%CI:1.10-2.35), nasopharyngitis (RR=1.47;95%CI:1.13-1.90) and rhinitis (RR=4.00;95%CI:1.13-14.14). Infusion-related reactions (RR range: 1.57 to 4.42) were also more common for ocrelizumab versus either placebo or beta-interferon. From pooled analyses of 3 RCTs, the risk of 'any' serious AE did not differ significantly between the ocrelizumab and comparator groups. However, insufficient data were available to assess longer-term AEs, such as malignancy.