Abstract Details

The benefits and risks of highly effective therapy as first-line treatment early in RMS should inform evidence-based decisions, to improve patient outcomes compared with escalating from low efficacy treatments.

To assess the efficacy and safety of first-line ocrelizumab (OCR) in a subgroup of treatment-naive patients (N=757) with early relapsing multiple sclerosis (RMS) (diagnosis ≤2 years) from the OPERA I/II trials (NCT01247324/NCT01412333) over 9 years of follow-up.

Patients were randomized to OCR or interferon (IFN)-β-1a during the 96-week, double-blind period (DBP). In the open-label extension (OLE), patients continued with OCR (OCR–OCR) or switched to OCR (IFN–OCR). Efficacy endpoints included no evidence of disease activity (NEDA) with MRI rebaselining at Week 24 (defined as absence of: Protocol-defined relapses, 24-week confirmed disability progression [24W-CDP], contrast-enhancing T1-weighted and new/enlarging T2-weighted lesions) and annualized relapse rate. Safety measures included incidence/nature of adverse events (AEs) and the association between immunoglobulin (Ig)G below the lower limit of normal (LLN) and serious infections (SIs).

Of 757 analyzed patients (OCR, 375; IFN, 382), 67% remained on treatment for over 9 years (OCR, 69%; IFN, 65%). During DBP, a higher proportion of OCR-treated patients, compared with IFN, had NEDA (72% vs 44%; p<0.001) and no 24W-CDP (92% vs 88%; p=0.062). In DBP+OLE, OCR–OCR patients had higher rates of NEDA compared with IFN–OCR (48% vs 26%; p<0.001) and no 24W-CDP (79% vs 75%; p=0.2) or relapses (0.05 vs 0.09; p=0.004). Rates of AEs, serious AEs, SIs and malignancies remained low over 9 years of OCR treatment. In DBP+OLE, 1.8% (12/668) of patients reported SIs during periods of IgG <LLN, with comparable types, characteristics and treatment outcomes to the overall SI profile over 9 years.

In this treatment-naive, early RMS OPERA subgroup, long-term safety and efficacy data over 9 years support the use of ocrelizumab as first-line therapy.