Long-Term Treatment With Ocrelizumab in Patients With Early-Stage Relapsing MS Nine-Year Data From the OPERA Studies Open-Label Extension

Background and Objectives Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stage relapsing MS (RMS). Methods Post hoc exploratory analyses of efficacy and safety were performed in a subgroup of treatment-naive patients with RMS who received ≥1 dose of OCR in the multicenter OPERA I/II (NCT01247324/NCT01412333) studies. Patients were randomized to OCR or interferon β-1a for 96 weeks (double-blind controlled treatment period [DBP]), before switching to OCR in the open-label extension (OLE). Efficacy assessments included no evidence of disease activity (NEDA-3), 24-week confirmed disability progression (CDP), MRI lesion activity, change in whole-brain volume; with safety outcomes assessed over a 9-year treatment period. Results Overall, 757 patients were included (interferon-treated n = 382, mean age 36.3 years, 65.7% female; OCR-treated n = 375, mean age 35.5 years, 64.0% female); 505 of 757 (66.7%) completed 9 years of follow-up. The difference in NEDA status between OCR-treated and interferon-treated patients achieved during the DBP (72.5% and 43.8%, respectively, odds ratio 3.48, 95% CI 2.52–4.81) was maintained throughout the 7-year OLE (48.2% vs 25.7%; odds ratio 2.72, 95% CI 1.94–3.82). No 24-week CDP was observed in 78.7% of OCR-treated patients over 9 years. Brain volume loss over the entire study period remained numerically higher among patients starting OCR later (p = 0.09 at OLE at week 336). During the DBP, safety profiles in both groups were similar; no new safety signals were observed during the OLE. Over >9 years of continuous OCR treatment, the rate of infections remained low and stable over time. Discussion A higher proportion of OCR-treated patients achieved NEDA status compared with interferon-treated patients during the DBP, which was maintained throughout the OLE. After switching to OCR, disability accrual and brain volume loss among interferon-treated patients became similar Glossary AE = adverse event; ARR = annualized relapse rate; cCDP = composite CDP; CDP = confirmed disability progression; COVID-19 = coronavirus disease 2019; CTCAE = Common Terminology Criteria for AEs; DBP = double-blind controlled treatment period; DMT = disease-modifying therapy; EDSS = Expanded Disability Status Scale; Gd = gadolinium; HR = hazard ratio; IFN = interferon; IgG = immunoglobulin G; LLN = lower limit of normal; MMRM = mixed-effects model of repeated measures; MS = multiple sclerosis; NEDA = no evidence of disease activity; NfL = neurofilament light chain; OCR = ocrelizumab; OLE = open-label extension; PY = patient-years; RMS = relapsing MS; SAE = serious AE; SI = serious infection.