Ocrelizumab Shows Superiority to or Comparability with Other Multiple Sclerosis Treatments

Efficacy of ocrelizumab, a humanized anti-CD20 monoclonal antibody, was found to be superior to or comparable with 14 other disease-modifying therapies (DMTs) currently approved by the European Medicines Agency (EMA) forrelapsing multiple sclerosis (RMS) in 7 network meta analyses (NMAs). Ocrelizumab also demonstrated a similar safety profile to each of the DMTs in the analysis.

A systematic literature review was conducted in MEDLINE, Embase, the Cochrane Library, trial registers, relevant conferences websites, and health technology assessment agency websites by researchers at York Health Economics Consortium and Quantics Biostatistics. A total of 33 randomized controlled trials (RCTs) met the eligibility criteria of a trial duration of at least 12 weeks and evaluation of suitable interventions for a subject base in which at least 75% of patients had RMS. Key efficacy outcome variables of interest were the 12-week confirmed disability progression (12-week confirmed disability progression [CDP]) and annualized relapse rate (ARR).

The key safety outcomes of interest were severe adverse events (SAEs) and discontinuation of treatment due to an adverse events (AEs). Outcomes were analyzed using standard Bayesian approaches, as described in the NICE Decision Support Unit Technical Support Document (DSU TSD) 2. Two sensitivity analyses were conducted to evaluate the assumptions of the base-case NMA for each outcome.

Heterogeneity and inconsistency assessments were also conducted for base-case NMAs. Surface under the cumulative ranking curve (SUCRA) values were used to demonstrate the efficacy and safety profile of each treatment for the 2 key efficacy outcomes (12-week CDP and ARR) and 2 key safety outcomes (SAEs and discontinuation due to AEs).

Investigators found that ocrelizumab was more effective in reducing the risk of 12-week CDP compared to 10 other treatments, including placebo, with no evidence to suggest that any other treatment was more effective than Ocrelizumab. Analysis of the second key efficacy outcome showed that ocrelizumab was also found to be more effective in reducing ARR than 12 other treatments. There were no differences in SAEs or discontinuation due to AEs between ocrelizumab and other DMTs studied.

Ocrelizumab demonstrated a consistently high probability of ranking the most effective or tolerable treatment across all 4 outcomes when probabilities of the 2 key efficacy outcomes were plotted with the 2 key safety outcomes.

Limitations of using NMAs included the lack of RCTs that were statistically powered to analyze safety, and that SAEs and AEs were only recorded during trial periods. Short-term (12 week) results obtained from the RCTs may not be relevant for long-term outcomes.

The researchers concluded that “in the absence of head-to-head trials against other DMTs for the treatment of patients with RMS, this NMA provides important evidence on the relative efficacy and safety of ocrelizumab compared with other approved treatments for RMS. This evidence suggests that ocrelizumab has an efficacy superior to or comparable with all other current approved DMTs across all endpoints analyzed as well as a similar safety profile, indicating that it offers a complete and valuable package for the treatment of patients with RMS.”

The study, titled, “Systematic review and network meta-analysis comparing ocrelizumab with other treatments for relapsing multiple sclerosis,” was published online in Multiple Sclerosis and Related Disorders.