Real-life impact of early interferonβ therapy in relapsing multiple sclerosis

TypeofStudy:A prospective, multicenter study evaluating the impact of early versus (vs.) delayed interferon beta (IFNβ, including Extavia) treatment in patients with relapsing-remitting multiple sclerosis and assessing the optimal time to initiate IFNβ with regard to the greatest benefits on disability progression. DosageDuration:250 mcg sc every other day. Duration not stated. Results:Results are given for the whole group of patients without separate data for Extavia. The lowest hazard ratios (HRs) for the 3 PS quintiles-adjusted models were noted with a cutoff of ≤1 year. HRs for times from IFNβ treatment initiation and from date of birth to reaching an EDSS score of 4.0 were 0.63 and 0.56; to reaching an EDSS score of 6.0 were 0.58 and 0.49; and to reaching a 1-point EDSS score progression were 0.61 and 0.63, respectively. Early treatment remarkably reduced, by approximately 40%, the risk of reaching the EDSS 4.0 and 1-point EDSS progression compared with delayed treatment; there was a trend to reduce the risk of reaching EDSS 6.0 with early treatment vs. delayed treatment. HRs for times from IFNβ treatment initiation and from date of birth to reaching an EDSS score of 4.0 were 0.49 and 0.70; to reaching an EDSS score of 6.0 were 0.43 and 0.63; and to reaching a 1-point progression in EDSS score were 0.52 and 0.66. PS-adjusted estimated survival curves, which graphically translated risk reductions expressed by HRs, showed that early treatment slowed the time to reach an EDSS of 4.0 and a 1-point progression in EDSS progression. The estimated percentage of patients that would reach EDSS 4.0 after a median follow-up of 4.5 years was 33.5% for the delayed treatment group vs. 23.2% for early treatment. The 23.2% threshold was reached with a delay of 19.5 months (84 months for the early-treatment group and 64.5 months for the delayed-treatment group). About 60% of delayed treatment patients compared with 42.6% of the early treated group would reach a 1-point EDSS progression after 4.5 years. The 42.6% threshold was reached with a delay of 14 months (84 months for the early-treatment group and 70 months for the delayed treatment group). Sensitivity analysis showed the bound of significance for unmeasured confounders. AdverseEffects:No adverse events were mentioned. AuthorsConclusions:The results show that patients treated early respond better than those who initiated the treatment later. Early IFNβ treatment was associated with a significant reduction in the risk of reaching an EDSS milestone of 4.0 and the risk of a 1-point progression in EDSS score, and with a trend suggestive of reduction in risk of reaching an EDSS milestone of 6.0 (likely not statistically significant due to a low number of events during the follow-up) when compared with delayed treatment. More interestingly, we found that the greatest difference in treatment benefit was observed between patients who received IFNβ within the first year from disease onset in comparison with those who received the treatment after this time. Since patients had some clinical heterogeneity, it could be useful for clinical practice to further analyze the long-term benefit of early-stage IFNβ treatment in different patient subgroups. FreeText: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 IFNβ treatment on risk of reaching a 1-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 1 year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings. Concomitant drugs: mitoxanthone or corticosteroids in an unspecified number of patients. Patients:2570 outpatients, 1774 females and 796 males, age range 4.4-61.4 years (mean 33.5 years and median 32.8 years). Early treatment group: n=310, 237 females and 73 males, age range 6.3-59.2 years (mean 28.8 years and median 27.4 years), 22 received Extavia, and 288 IFNβ-1a. Delayed treatment group: n=2260, 1537 females and 723 males, age range 4.4-61.4 years (mean 34.2 years and median 33.4 years), 181 received Extavia, and 2080 IFNβ-1a. Follow-up: 7 years (median 4.5 years). Indications:203 patients with relapsing-remitting multiple sclerosis. Objective: Recent findings support greater efficacy of early vs. delayed interferon beta (IFNβ) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of early IFNβ treatment in definite relapsing-remitting MS (RRMS) and to assess the optimal time to initiate IFNβ treatment with regard to the greatest benefits on disability progression. Methods: A cohort of 2,570 IFNβ-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 IFNβ treatment on risk of reaching a 1-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 1 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 1-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 IFNβ treatment in RRMS