Higher-dosed ocrelizumab associated with less disability accrual

Higher ocrelizumab exposure over a period of 10 years was associated with less risk of disability progression in MS patients. The risk of serious infections did not increase, which suggests that higher ocrelizumab doses have an improved benefit-risk profile. This is the first time the association of ocrelizumab exposure with long-term outcomes has been explored.

In the double-blind treatment period of the phase 3 trials OPERA I (NCT01247324) and OPERA II (NCT01412333), a consistent trend was apparent where higher ocrelizumab exposure led to deeper B-cell depletion and less disability progression. A post hoc analysis by Dr Robert Bermel (Cleveland Clinic, OH, USA) explored if higher ocrelizumab concentrations were associated with more favourable efficacy and safety after up to 10 years [1].

A total of 786 patients were treated with ocrelizumab. Participants randomised to ocrelizumab were grouped into quartiles (Qs) of exposure, from Q1 (lowest: min to <15.4 μg/m) to Q4 (highest: ≥22.2 μg/mL to max). The authors observed that continuous ocrelizumab treatment very effectively suppressed relapses across all exposure quartiles, with low relapse rates (0.02–0.05 per year) in patients at year 10. The highest exposure to ocrelizumab (Q4) was associated with a 40% reduction (95% CI 0.34–1.04; P=0.09) in the risk of 48-week confirmed disability progression (48W-CDP) compared with the lowest exposure (Q1), with 84.5% of patients in Q4 and 73.9% of patients in Q1 free of 48W-CDP. Rates of whole brain volume were similar across the exposure quartiles (mean change from week 24 to year 10: -2.81% to -3.10%), with atrophy rates comparable to normal ageing.

Importantly, adjusted rates of serious infections remained stable over time in all quartiles. Over 10 years, no increased risk of serious infections was observed in Q4 compared with Q1, with a rate ratio of 1.97 (95% CI 0.89–4.37; P=0.097).

1. Bermel R, et al. Exposure-response analyses of ocrelizumab in patients with relapsing multiple sclerosis in OPERA I and II over 10 years. P100, ACTRIMS 2025, 27 February–01 March 2025, West Palm Beach, FL, USA.

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Posted on 28 March 2025