Ocrelizumab (OCR) is a humanized monoclonal antibody that selectively targets CD20+B cells. In a randomized, double-blind, placebo-controlled Phase III study (ORATORIO), OCR significantly reduced disease activity in patients with primary progressive multiple sclerosis (PPMS).
Objectives were to evaluate the efficacy of OCR in the ORATORIO patient subgroups with and without T1 gadolinium-enhancing (Gd+) lesions at baseline.
A total of 732 patients were randomized (2:1) to receive OCR 600 mg or placebo (PBO) as two 300 mg intravenous infusions 14 days apart every 24 weeks for at least 120 weeks and until a prespecified number of 12-week confirmed disability progression (CDP) events occurred. Key eligibility criteria included age 18-55 years, diagnosis of PPMS (2005 revised McDonald criteria), Expanded Disability Status Scale (EDSS) score of 3.0-6.5, and documented history of elevated immunoglobulin index and/or presence of oligoclonal bands in the cerebrospinal fluid. Although not powered for comparisons, prespecified subgroups included age (≤ 45 vs > 45 years), sex, body mass index (< 25 vs ≥ 25), weight (< 75 vs ≥75 kg), region (US vs rest of world), treatment history, MS symptom duration, and disease activity (EDSS score ≤ 5.5 vs > 5 and presence/absence of T1 Gd+ lesions) at baseline. Efficacy of OCR on ≥ 12- and ≥ 24-week CDP, change in total T2 lesion volume at 120 weeks, and other secondary efficacy outcomes was evaluated in the subgroups with presence and absence of T1 Gd+lesions at baseline.
Compared with PBO, OCR significantly reduced the relative risk of 12-week CDP by 24% (hazard ratio [HR], 0.76; p= 0.0321) and 24-week CDP by 25% (HR, 0.75; p=0.0365). T1 Gd+ lesions were present at baseline in 27.5% of OCR-treated patients vs 24.7% of PBO-treated patients. In patients with and without T1 Gd+lesions at baseline, respectively, OCR reduced: the risk of 12-week CDP by 35% (HR, 0.65; 95% CI, 0.40-1.06; p=0.0826) and 16% (HR, 0.84; 95% CI, 0.62-1.13; p=0.2441); the risk of 24-week CDP by 33% (HR, 0.67; 95% CI, 0.40-1.14; p=0.1417) and 19% (HR, 0.81; 95% CI, 0.59-1.10; p=0.1783); and total T2 lesion volume by −3.8% (95% CI, −7.0 to −0.5) vs +12.0% with PBO (95% CI, 7.2-17.1; p<0.001) and by −3.1% (95% CI, −5.0 to −1.1) vs +6.1% with PBO (95% CI, 3.3-9.0; p<0.001).
In this subgroup analysis of patients with or without T1 Gd+ lesions at baseline, OCR reduced clinical and MRI disease activity compared with PBO.
Materials provided by Americas Committee for Treatment and Research in Multiple Sclerosis. Note: Content may be edited for style and length.
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