Rituximab Inferior to Ocrelizumab for MS Relapse


Because MS patients who take rituximab have more relapses than those who take ocrelizumab, these two therapies may not be interchangeable in clinical practice.


Ocrelizumab was the first licensed B-cell therapy for the treatment of relapsing-remitting multiple sclerosis (RRMS), while rituximab, another monoclonal antibody, is often used as an off-label alternative at a lower cost.

Using data from two MS registries (MSBase and the Danish Multiple Sclerosis Registry), the study included 710 patients with RRMS who were treated with ocrelizumab and 186 matched patients who were treated with rituximab.

The primary endpoint was a noninferiority comparison of annualized relapse rate (ARR).

Relapses were defined as new symptoms or exacerbation of existing symptoms for at least 24 hours without concurrent illness or fever occurring 30 days or longer after the previous relapse.

The noninferiority margin for the relative ARR ratio of ocrelizumab vs rituximab was set as 1.63.


The mean ARR was higher among patients treated with rituximab than among those treated with ocrelizumab (0.20 vs 0.09; P < .001), which translates into a difference of one relapse every 9 patient-years.

The ARR ratio was higher among patients treated with rituximab than among those treated with ocrelizumab (1.8; 95% CI, 1.4 – 2.4), which met the predefined definition of noninferiority.

There was no difference in disability accumulation or disability improvement between therapies over a mean follow-up of 1.4 years.

Treatment discontinuation was more common among patients treated with rituximab.


Treatment selection is a highly personalized decision. Factors that are considered include availability, affordability, and adverse effects, write the authors. They note that efficacy between rituximab and ocrelizumab is being further explored in clinical trials.


The study was carried out by Izanne Roos, MBChB, PhD, Neuroimmunology Centre, Royal Melbourne Hospital, Melbourne, Australia, and colleagues. It was published online June 12 in JAMA Neurology.


Observational data are vulnerable to multiple forms of bias. The rituximab group included those taking the originator and those taking biosimilar products. As rituximab is used off label, there’s potential variability in dosing and administration schedules. The findings may not be generalizable to patients newly diagnosed with MS or those starting treatment ocrelizumab or rituximab as their first MS therapy. The study could not assess long-term outcomes such as disability.


The study was supported by the National Health and Medical Research Council, MS Australia, Biogen, Novartis, Merck, Roche, Teva, and Sanofi Genzyme. Individual authors’ conflicts of interest are listed in the original article.

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