ABSTRACT
BACKGROUND: The impact of early versus later high-efficacy disease-modifying therapy (DMT) in patients with multiple sclerosis (MS) is uncertain. This study reported the association of early versus later natalizumab treatment with real-world clinical outcomes in MS patients. METHODS: The study included 661 participants diagnosed with MS in 1994 or later from 7 US centers participating in the MS Partners Advancing Technology for Health Solutions (MS PATHS) network. Time to natalizumab treatment between diagnosis and first infusion (TTNT) was determined from the Tysabri Outreach: Unified Commitment to Health (TOUCH) registry. Clinical outcomes were defined using neuroperformance tests included in the Multiple Sclerosis Performance Test. Associations were tested using TTNT as a categorical and continuous variable. Linear mixed models addressed within-subject and within-site clustering. RESULTS: TTNT varied from 0.1 to 19.8 years (median [interquartile range] 4.2 [1.8, 9.0] years). A significant association between later natalizumab use and worse outcomes was demonstrated for walking speed (p < 0.001), processing speed (p < 0.001), manual dexterity (p < 0.001), brain atrophy (p = 0.001), and T2 lesion volume (p = 0.02). Covariate-adjusted modelling of a sensitivity population diagnosed with MS in 2006 or later (n = 424) demonstrated significant associations between longer TTNT and worse walking speed (p < 0.05), processing speed (p < 0.001), and manual dexterity (p < 0.001). CONCLUSION: Later initiation of natalizumab was associated with worse clinical and radiologic imaging outcomes. Thus, high-efficacy DMT may have greater benefit when started earlier in MS patients. These results provide a rationale for randomized controlled trials to further assess the impact of early highly-effective DMT use versus later escalation of therapy.
