Early Versus Delayed Treatment with Ocrelizumab: A Multicenter, Real-World Observational Study in People with Multiple Sclerosis

INTRODUCTION: Growing evidence suggests that first-line (1L) treatment with high-efficacy disease-modifying therapies (HE-DMTs) may have greater clinical benefit in multiple sclerosis (MS) than delaying HE-DMTs to second- or subsequent-line (2L+) therapy. However, MS treatment is often initiated using an escalation approach, involving initial treatment with low- to moderate-efficacy DMTs followed by escalation to HE-DMTs in the presence of new disease activity or disability worsening. Ocrelizumab is a HE-DMT approved for the treatment of relapsing and primary progressive MS, but real-world outcomes of ocrelizumab as a 1L vs 2L+ therapy are not well characterized. METHODS: Real-world data from people with MS (pwMS) receiving treatment at four centers in the USA were analyzed. The effectiveness of ocrelizumab when administered as 1L or 2L+ treatment was compared for up to 60 months in follow-up. The primary outcome was time to confirmed disability worsening (based on Patient-Determined Disease Steps [PDDS]). Secondary outcomes were time to requiring a walking aid (PDDS ≥ 4), annualized patient-reported relapse rate, and magnetic resonance imaging measures (e.g., brain volume and number and volume of new T2 lesions). RESULTS: A total of 403 pwMS (1L n = 309, 2L+ n = 94) were identified. Overall, pwMS who received 1L ocrelizumab experienced less confirmed disease worsening (25.8% vs 42.6%; P = 0.03) and requirement for a walking aid (6.5% vs 27.4%; P < 0.01) compared with the 2L+ cohort. The 1L group also had a significantly lower change in T2 lesion volume (mean difference - 0.797 mL; P < 0.05) and a lower risk of developing new T2 lesions than the 2L+ group (incidence rate ratio 0.88 [95% CI 0.78-0.99]; P = 0.04). Relapse rate and brain volume outcomes were not significantly different between groups. CONCLUSION: This study contributes to the growing pool of evidence that 1L treatment with HE-DMTs such as ocrelizumab can improve clinical outcomes for pwMS compared with delaying HE-DMT to 2L+ .