To report the 2-year Phase IIIb CHORDS study (NCT02637856) results evaluating ocrelizumab in patients with relapsing-remitting multiple sclerosis (RRMS) and suboptimal response to previous disease-modifying therapy (DMT).

Ocrelizumab was superior to interferon β-1a in patients with relapsing MS (OPERA I and II). Evaluating ocrelizumab effectiveness in patients with suboptimal response to DMT is needed.

The CHORDS intention-to-treat (ITT) population (N=608) had suboptimal response (≥1 relapse, ≥1 T1 gadolinium-enhancing lesion(s) or ≥2 new/enlarging T2 lesions) to previous DMT after stable use (≥6 months). Patients received ocrelizumab 600 mg every 24 weeks for ≤96 weeks. The primary endpoint was the proportion of patients free of protocol-defined clinical or MRI activity (event), evaluated in a modified ITT population which imputed patients who terminated early for lack of efficacy or death as had an event and excluded patients who discontinued for other reasons without an event. Key secondary endpoints included annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) change from baseline. Safety was assessed in the ITT population.

A total of 555 patients completed treatment (baseline mean [SD] duration since first MS symptom and diagnosis, 5.4 [3.24] and 4.2 [3.03] years, respectively). At Week 96, 48.1% of patients were free of protocol-defined events. Most did not experience protocol-defined relapse (89.6%), any T1 gadolinium-enhancing lesions (95.5%) or new/enlarging T2 lesions (59.5%) or 24-week confirmed disability progression (89.6%). The ITT adjusted ARR was 0.046. Seventy-one relapses were observed (Year 1, 50; Year 2, 21). At Week 96, most patients had stable (<1-point change; 61.5%) or improved (≥1-point decrease; 22.7%) EDSS levels. Safety was consistent with the overall ocrelizumab safety profile.

This analysis demonstrates ocrelizumab treatment responses over 2 years in patients with RRMS who are relatively early in the disease course and experienced suboptimal response to another DMT.