Ocrelizumab significantly reduces new/enlarging cortical lesions

Treatment with ocrelizumab significantly reduced the number and volume of new/enlarging cortical lesions over 2 years. The mean number of lesions was reduced by 75% and the mean volume by 86%. This was established by reprocessing published trial data using new approaches to quantify cortical lesions.

Modern therapies can almost completely prevent new white matter lesions in many patients with MS. However, grey matter involvement remains prevalent and is likely to be a key component of disease progression. Cortical lesions, in particular, occur throughout the disease course. Thus far, large randomised studies have not reported the impact of current therapies on cortical lesions, as they are hard to detect. New approaches, however, permit reprocessing of existing images and quantification of cortical lesions. These approaches include FLAIR² [a combination of FLAIR and T2 source images], T1/T2 ratio, and artificial intelligence double inversion recovery (AI-DIR).

With these approaches, MRI data from the placebo-controlled phase 3 ORATORIO trial (NCT01194570) was re-analysed [1,2]. This was a study of ocrelizumab in patients with primary progressive MS, over 120 weeks. Prof. Michael Dwyer (University at Buffalo, NY, USA) and colleagues conducted a post hoc, blinded analysis of all eligible scans from participants: 482 and 242 patients who received intravenous ocrelizumab (600 mg) or placebo, respectively.

“The final results are very straighforward and simple, but very pronounced”, said Prof. Dwyer. Treatment with ocrelizumab resulted in a 74.8% reduction in new/enlarging cortical lesions compared with placebo (adjusted RR 0.252; P<0.0001) over 120 weeks. Cortical lesion volume accrual was reduced from 100.1 mm³ in the placebo group to 13.4 mm³ in the ocrelizumab group (adjusted mean difference: 86.62 mm³; P<0.0001).

Prof. Dwyer said these results show that cortical lesion analysis on retrospective clinical trial data is feasible by synthesis of cortical lesion-sensitive methods, and that simultaneous use of different contrasts is important.

1. Dwyer M, et al. The impact of ocrelizumab on cortical lesion accrual in primary progressive MS in the double-blind, Phase 3 ORATORIO Study. CE2.2, ACTRIMS 2025, 27 February–01 March 2025, West Palm Beach, FL, USA.
2. Montalban X, et al. N Engl J Med 2017;376(3):209-220.

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Posted on 28 March 2025