Getting ocrelizumab first line offers benefits over getting ocrelizumab second line, meaning you have failed treatment. In these scenarios they are both as effective at controlling relapse rate but when you get it first line you progress slower, telling us that progression is in part dependent on the immune system entering the CNS and creating damage, stop that and less damage occurs.
Alvarez E, Naismith RT, Hua LH, Pineda ED, Romdhani H, Guérin A, Lévesque-Leroux M, Marathe G, Nakamura K, Ontaneda D. Early Versus Delayed Treatment with Ocrelizumab: A Multicenter, Real-World Observational Study in People with Multiple Sclerosis. Neurol Ther. 2026 May 30. doi: 10.1007/s40120-026-00951-x. Epub ahead of print. PMID: 42217095.
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+ .
Source: multiple-sclerosis-research.org