To determine whether high-efficacy early therapy (HEET) compared to low-efficacy early therapy (LEET) affects risk of PIRA and sustained disability.

Treatment initiation strategies for disease modifying therapy in multiple sclerosis are debated, with recent trends favoring early aggressive induction immunotherapy over escalation approaches. Whether this impacts risk of silent progressive disease and long-term accumulation of disability is unclear.

Risks of progression independent of relapse activity (PIRA), relapse associated worsening (RAW), and Expanded Disability Status Scale (EDSS) ≥5 were calculated for a real-world cohort of 750 multiple sclerosis patients aged 12-50 years in a longitudinal database  established at our institution. Patients were grouped by treatment initiated within 6 months of diagnosis into LEET (n = 583) and HEET (n = 112) groups.

HEET versus LEET groups had similar relative risk of PIRA (adjusted hazard ratio = 0.99, P-adjusted = 0.95) but significantly lower risk of RAW (adjusted hazard ratio = 0.48, P-adjusted = 0.015). Sub-stratification of the HEET group into high- and very high-efficacy early therapy groups did not affect risk of PIRA. Cox proportional hazards analysis adjusted for treatment group, age at diagnosis, race, gender, and EDSS at first visit revealed older age at diagnosis as a significant contributor to risk of progression independent of relapse activity. Nonetheless young patients still had substantial risk of PIRA, regardless of treatment efficacy group. Patients in HEET or LEET groups also had similar risk of achieving a sustained EDSS score ≥ 5.0, though patients receiving high-efficacy and very high-efficacy early therapy had a marginally but significantly lower mean change in EDSS score over time.