Ocrelizumab Shows Benefit in Relapsing-Remitting MS With Prior Poor DMT Response

syringe and vials
Syringe and Vials
Using MRI rebaselining, researchers sought to assess the efficacy of ocrelizumab in patients with relapsing-remitting multiple sclerosis with a prior poor response to disease-modifying therapies.

Treatment with ocrelizumab, a recombinant humanized monoclonal antibody, led to increased rates of “no evidence of disease activity” (NEDA) in patients with relapsing-remitting multiple sclerosis (RRMS) who had previously discontinued a disease-modifying therapy (DMT) due to suboptimal disease control, according to study findings published in the European Journal of Neurology.

In RRMS, patients tend to experience disease activity despite receiving a DMT. Previous research has shown ocrelizumab has had a benefit on clinical and magnetic resonance imaging (MRI) measures of disease activity and disability progression in patients with RMS or primary progressive MS in crucial phase 3 studies. However, the data are limited on the efficacy and safety of ocrelizumab in patients with a poor response to prior DMTs.

The objective of the current study was evaluate the efficacy and safety of ocrelizumab in patients with RRMS with a poor response to prior DMTs.

A European-based single-arm, open-label phase 3b trial (CASTING; ClinicalTrials.gov Identifier: NCT02861014) included 680 patients with RRMS and an Expanded Disability Status Scale (EDSS) score ≤4.0. All patients had discontinued their prior DMT of ≥6 months’ duration because of suboptimal control of disease. Patients were treated with intravenous 600 mg ocrelizumab every 24 weeks for a total treatment period of 96 weeks.

Over the treatment period, researchers evaluated the rate of NEDA as defined by absence of relapses, 24-week confirmed disability progression, and inflammatory MRI measures.

According to the researchers, NEDA at week 96 was observed in 74.8% (95% CI, 71.3–78.0) of patients. The primary outcome was highest in the 167 patients who were enrolled due to MRI activity alone versus for relapse or relapse with MRI (80.6% vs 75.1% and 70.5%, respectively). Additionally, NEDA was highest in patients who had an EDSS score <2.5 at baseline (77.2%; 95% CI, 72.8–81.2) and those who had received 1 previous DMT vs 2 prior DMTs (77.6% vs 70.3%, respectively).

Gender was the only potential prognostic factor of the primary outcome and disability or other efficacy variables (female vs male; odds ratio, 0.65; 95% CI, 0.43-0.97; P =.037). The researchers found no new safety signals with ocrelizumab in the study.

A limitation of the study included its single-arm design, which the researchers noted limits the ability to evaluate whether rates of NEDA were higher due to ocrelizumab vs the natural history of the patients.

Despite this limitation, the researchers wrote that the findings highlight “the importance of recognising breakthrough disease and the value of reacting with a treatment switch to ocrelizumab in order to maintain disease control and optimise short- and long-term patient outcomes.”

Disclosure: This clinical trial was supported by F. Hoffmann-La Roche. Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


Vermersch P, Oreja-Guevara C, Siva A, et al. Efficacy and safety of ocrelizumab in patients with relapsing-remitting multiple sclerosis with suboptimal response to prior disease-modifying therapies: A primary analysis from the phase 3b CASTING single-arm, open-label trial. Eur J Neurol. Published online November 8, 2021. doi:10.1111/ene.15171