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

ABSTRACT

Introduction

We systematically reviewed adverse events (AEs) for ocrelizumab for multiple sclerosis (MS).

Areas covered

We searched Medline, Embase, Web of Science, and Toxicology Data Network-TOXLINE (inception to 8-July-2020), clinical trial registries, and product monographs for any clinical trials, observational studies or case reports examining AEs to ocrelizumab. Studies with/without a comparator drug or placebo were eligible.

Expert opinion

Seventy-eight 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, infections were more likely in ocrelizumab-exposed patients (Risk Ratio (RR)=1.10; 95% confidence interval (CI):1.01–1.19), including: herpes-related (RR=1.75; 95%CI:1.11–2.76), respiratory tract-related (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: 1.57–4.42) were more common for ocrelizumab versus placebo or beta-interferon. From pooled analyses (three 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, e.g., malignancy.

KEYWORDS:

• Adverse events
• multiple sclerosis
• ocrelizumab
• patient safety
• systematic review

Article highlights

• In this systematic review, we collated all reported adverse events for over 7000 patients treated with ocrelizumab for multiple sclerosis from a diverse range of sources, including completed and ongoing clinical trials, postmarketing surveillance, and case reports.

• Infections were the most commonly reported adverse events, affecting 4 in every 10 patients treated with ocrelizumab, followed by infusion-related reactions, affecting nearly 1 in 3.

• Compared to beta-interferon, infection risk was higher for patients exposed to ocrelizumab, with the risk ratios ranging from 1.42 to 1.61 for upper and lower respiratory tract infections through to 1.47, 1.75, and 4.0 for nasopharyngitis, herpes virus-related infections, and rhinitis, respectively.

• The longer-term safety of ocrelizumab, including malignancy and serious infections remain unknown.

This box summarizes key points contained in the article.

Supplementary material

Supplemental data for this article can be accessed here.

Declaration of interest

HS Ng receives funding from the MS Society of Canada’s end MS Postdoctoral Fellowship, the Canadian Institutes of Health Research Drug Safety and Effectiveness Cross-Disciplinary Training Program and the Michael Smith Foundation for Health Research Trainee Award. CL Rosenbult was a former employee of Merck and is a current employee of Xenon Pharmaceuticals, although was a full-time student at the University of British Columbia when this study was conducted. H Tremlett is the Canada Research Chair for Neuroepidemiology and Multiple Sclerosis. Their current research support was received from the National Multiple Sclerosis Society, the Canadian Institutes of Health Research, the Multiple Sclerosis Society of Canada and the Multiple Sclerosis Scientific Research Foundation. In addition, in the last five years, they have received research support from the UK MS Trust; travel expenses to present at CME conferences from the Consortium of MS Centres (2018), the National MS Society (2016, 2018), ECTRIMS/ACTRIMS (2015, 2016, 2017, 2018, 2019, 2020), American Academy of Neurology (2015, 2016, 2019). Speaker honoraria are either declined or donated to an MS charity or to an unrestricted grant for use by H Tremlett’s research group. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have received honoraria and lectures and grants from Roche. All other peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was not funded.