Age-dependent response to initial highly effective treatment in relapsing multiple sclerosis
- PMID: 40534483
- DOI: 10.1177/13524585251345317
Age-dependent response to initial highly effective treatment in relapsing multiple sclerosis
Abstract
Objectives: To assess the impact of age on the superiority of highly effective (HE) disease-modifying treatments (DMTs) compared to platform DMTs in a real-world population of relapsing MS patients (pwMS).
Methods: A total of 20,984 pwMS were extracted from the Italian Multiple Sclerosis Register with a diagnosis of Clinically Isolated Syndrome or Relapsing-Remitting MS, at least four Expanded Disability Status Scale (EDSS) evaluations and 2 years follow-up, starting DMT. The baseline was the nearest visit to the first DMT starting date. The risk of first 24-week confirmed disability accumulation (CDA) on EDSS in HE versus platform DMTs after 2 years and the entire follow-up was assessed through Cox regression models.
Results: After 1:1 propensity score matching, we evaluated 1698 pwMS initiating HE-DMTs and 1698 initiating platforms. After 2 years follow-up, the proportion of CDA events was lower in patients on HE-DMTs (12.2%) than those on platform DMTs (15%), as confirmed by Cox regression analysis (hazard ratio (HR) = 0.22, 95% confidence interval (CI) = 0.10-0.47; p < 0.001). HE-DMTs were more effective in patients under 45 years of age (HR = 0.49, 95% CI = 0.39-0.63; p < 0.001), but not in patients over 45 (HR = 0.77, 95% CI = 0.54-1.08, p = 0.125). Notably, prolonged exposure to any DMT during follow-up reduced disability accumulation even in patients over 45 (HR = 0.13, 95% CI = 0.02-0.99; p = 0.050).
Conclusion: This real-world study of relapsing pwMS demonstrates that the benefit of initial HE treatment diminishes with age. However, even in older patients, DMT exposure, regardless of the efficacy level, appears to reduce disability accumulation, and so, on an individual level, initial HE treatment could still be more effective.
Keywords: Multiple sclerosis; aging; de-escalation; disease-modifying treatment; high efficacy; older age.
Conflict of interest statement
Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: E.P. reported receiving personal fees from Biogen, Celgene, Genzyme, Merck, Novartis, Sanofi, and Roche outside the submitted work. L.P. received research support from Novartis and Biogen and speaker honoraria from Teva outside the submitted work. L.R. reported receiving personal fees from Merck, Sanofi Genzyme, Novartis, Roche, Biogen, and Janssen outside the submitted work. F.P. received honoraria for speaking activities from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva; he also served as an advisory board member to the following companies: Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva; he was also funded by Pfizer and FISM for epidemiological studies and received grants for congress participation from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva outside the submitted work. V.B.M. received grants to attend scientific congresses or speaker honoraria from Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva. C.P. reported receiving grants from Roche and Novartis and personal fees from Bristol, Alexion, and Merck outside the submitted work. E.C. received research grants and honoraria as a speaker and member of advisory boards from Almirall, Bayer, Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, Teva, and Roche outside the submitted work. G.S. received grants to attend scientific congresses or speaker honoraria from Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva outside the submitted work. M.V. received compensation for travel grants or speaking activities from Biogen, Merck Serono, Roche, BMS Celgene, Janssen, and Novartis. A.L. has served as an Amgen/Horizon, Biogen, Bristol Myers Squibb/Celgene, Merck Serono, Novartis, Roche, and Sanofi Genzyme Advisory Board Member. She received congress and travel/accommodation expense compensations or speaker honoraria from Alexion, Biogen, Merck Serono, Novartis, Sanofi Genzyme, and Fondazione Italiana Sclerosi Multipla (FISM). Her institutions received research grants from Novartis and Sanofi Genzyme outside the submitted work. M.I. received grants from NIH, NMSS, and FISM and received fees for consultation from BMS, Janssen, Roche, Genzyme, Merck, Biogen, and Novartis. A.D.S. received personal compensation for speaking and consulting from Biogen, Novartis, Roche, Sanofi, Merck Serono, and Alexion and has been reimbursed by Merck, Biogen, Sanofi, and Roche for attending several conferences outside the submitted work. P.I. received grants to attend scientific congresses or speaker honoraria from Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva outside the submitted work. M.F. reported receiving personal fees from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi, Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, Teva, Alexion, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, and Sanofi Genzyme and grants from Biogen Idec, Merck Serono, Novartis, and Roche outside the submitted work. M.T. reported receiving personal fees from Biogen, Novartis, Roche, Merck, Bristol Meyer Squibb, and Genzyme and grants from Biogen, Novartis, and Roche outside the submitted work. M.P.A. reported receiving grants from Biogen, Merck, Novartis, Roche, and Sanofi Genzyme and personal fees from Biogen, Merck, Novartis, Roche, Sanofi Genzyme, Celgene BMS, Janssen, Horizon, Teva, and Bayer outside the submitted work. M.B., E.D.M., G.D.L., C.T., D.F., G.L., G.T., S.M., M.Z., and M.S. declared no potential conflicts of interest.
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