Real-Life Impact of Early Interferonβ Therapy in Relapsing Multiple Sclerosis

Objective: Recent findings support greater efficacy of early vs. delayed interferon beta (IFN beta) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of early IFN beta treatment in definite relapsing-remitting MS (RRMS) and to assess the optimal time to initiate IFN beta treatment with regard to the greatest benefits on disability progression. Methods: A cohort of 2,570 IFN beta-treated RRMS patients was prospectively followed for up to 7 years in 15 Italian MS Centers. A Cox proportional hazards regression model adjusted for propensity score (PS) quintiles was used to assess differences between groups of patients with early vs. delayed IFN beta treatment on risk of reaching a I-point progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS 4.0 and 6.0 milestones. A set of PS-adjusted Cox hazards regression models were calculated according to different times of treatment initiation (within I year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings. Results: The lowest hazard ratios (HRs) for the three PS quintiles-adjusted models were obtained by a cutoff of treatment initiation within 1 year from disease onset. Early treatment significantly reduced the risk of reaching a I-point progression in EDSS score (HR = 0.63; 95% CI = 0.48-0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36-0.90; P = 0.015). Sensitivity analysis showed the bound of significance for unmeasured confounders. Interpretation: Greater benefits on disability progression may be obtained by an early IFN beta treatment in RRMS.