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A randomized head-to-head trial in multiple sclerosis (MS) found that rituximab, an off-label therapy, had outcomes comparable to those of ocrelizumab, a branded therapy, on the study's primary MRI measure, according to results published in the New England Journal of Medicine. The OVERLORD-MS trial compared the two antibodies, both of which deplete CD20-positive B cells, in adults with newly diagnosed relapsing MS.
Conducted in Norway and Sweden, the phase 3, double-blind, noninferiority trial randomly assigned 218 participants to receive rituximab or ocrelizumab every six months for 24 months. The primary endpoint was the absence of new or enlarging lesions on T2-weighted MRI between months 6 and 24. The estimated probability of remaining free of such lesions was 92.2% with rituximab and 94.8% with ocrelizumab. The 2.6% difference was within the prespecified noninferiority margin.
Safety outcomes were similar between the groups. Serious adverse events occurred in 8 percent of rituximab recipients and 7 percent of ocrelizumab recipients. Serious infections were reported in four participants in each group. Rituximab is approved for other conditions, including certain blood cancers and autoimmune diseases, and has been used off-label in MS. Ocrelizumab is approved for relapsing and progressive forms of MS.
The approval status and pricing of the two therapies may affect coverage and access decisions. For payers and health systems, the trial provides randomized evidence comparing an off-label anti-CD20 therapy with an MS-approved anti-CD20 therapy in early relapsing MS. The investigators reported that rituximab met the trial's noninferiority criterion relative to ocrelizumab for the primary MRI endpoint.
