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. 2025 Sep 4;272(9):609.
doi: 10.1007/s00415-025-13330-7.

Age-related differences in switching highly effective disease-modifying therapy in patients with multiple sclerosis

David Ellenberger #  1 , Niklas Frahm #  2 , Alexander Stahmann  1 , Clemens Warnke  3 , Kerstin Hellwig  4 , Christoph Kleinschnitz  5 , Peter Flachenecker  6 , Michaela Mai  7 , Matthias Grothe #  8 , Uwe K Zettl #  9
Affiliations

Age-related differences in switching highly effective disease-modifying therapy in patients with multiple sclerosis

David Ellenberger et al. J Neurol. .

Abstract

Background: High efficacy therapies (HET) play a crucial role in multiple sclerosis (MS) management. HET discontinuation/de-escalation is a critical decision, especially in different age groups, due to potential changes in relapse rates. We aimed at evaluating the impact of HET discontinuation on annualized relapse rates (ARRs) in people with MS (pwMS) aged ≥ 50 or < 50 years.

Methods: We retrospectively analyzed data of 1,091 pwMS (German MS Register). ARR before and 12 months after the HET washout period were compared between older and younger patients for switching from HET to HET (H-H), HET to mild/moderate efficacy therapies (H-M) or HET to discontinuation (H-D). Reasons for therapy switches were assessed for all subgroups.

Results: Most treatment switches continued with another HET (H-H n = 786), while de-escalation (H-M n = 86) or discontinuation (H-D n = 219) occurred less frequently. The minority within each switching group were ≥ 50 years of age (H-H 29%, H-M 22%, H-D 32%). ARR in H-H decreased after switching in both age groups (< 50: 0.19-0.12; ≥ 50: 0.17 to 0.09), increased in H-M < 50 (0.13-0.63) and remained stable in ≥ 50 (0.11-0.08), and increased in H-D < 50 (0.05-0.13) and remained stable in ≥ 50 (0.14-0.11). Main reason for therapy switch was lack of efficacy in H-H, adverse events in H-M regardless of age, patient's choice (23%) in H-D < 50, and lack of efficacy (26%) in H-D ≥ 50.

Conclusions: Discontinuation strategies should be individualized, considering age-related changes in disease activity, adverse events and patient's choice.

Keywords: Age; De-escalation; Disease-modifying therapy; Multiple sclerosis; Switch.

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Conflict of interest statement

Declarations. Conflict of interest: D.E. had no personal financial interests to disclose other than being an employee of the GMSR. N.F. is an employee of the GMSR. Moreover, he is an employee of Rostock’s University Medical Center and received travel funds for research meetings from Novartis. None resulted in a conflict of interest. A.S. has no personal pecuniary interests to disclose, other than being the lead of the German MS Registry, which receives (project) funding from a range of public and corporate sponsors, recently including The German Innovation Fund (G-BA), The German Retirement Insurance, The German MS Trust, The German MS Society, Bristol Myers Squibb, Merck Healthcare Germany GmbH, Novartis Pharma GmbH, Roche Pharma AG and TG Therapeutics/Neuraxpharm. None resulted in a conflict of interest. C.W. has received institutional support from Novartis, Alexion, Sanofi Genzyme, Biogen, Merck, and Roche. None resulted in a conflict of interest. K.H. has received speaking fees and/or institutional grant support from Bayer, Biogen, BMS, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva. None resulted in a conflict of interest. D.K. has nothing to disclose. C.K. has received speaker’s fees, honoraria for attending advisory boards, and financial support for conducting research projects from Merck Serono GmbH Germany, and Merck KgaA Germany. None resulted in a conflict of interest. P.F. has received speaker’s fees and honoraria for advisory boards from Almirall, Bayer, Biogen Idec, BMS-Celgene, Coloplast, Genzyme, GW Pharma, Hexal, Janssen-Cilag, Novartis, Merck, Roche, Sanofi, Stadapharm, and Teva. None resulted in a conflict of interest. M.M. is an employee of the German MS Society, federal association, which receives funding from a range of public and corporate sponsors, recently including BMG, G-BA, The German MS Trust, Biogen, BMS, Merck Serono, Novartis, Roche, Sanofi, and Viatris. None resulted in a conflict of interest. M.G. received honoraria and travel reimbursements for attending meetings from Biogen, Celgene, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Merck Serono, and Novartis. None resulted in a conflict of interest. U.K.Z. has received speaking fees, travel support and /or financial support for research activities from Alexion, Almirall, Bayer, Biogen, Bristol Myers Squibb, Janssen, Merck Serono, Novartis, Octapharma, Roche, Sanofi Genzyme, Teva as well as EU, BMBF, BMWi, and DFG. None resulted in a conflict of interest. Ethical approval and consent: The registration of the GMSR took place at the German Registry for Clinical Trials [Deutsches Register Klinischer Studien (DRKS); No. DRKS00011257]. The initial ethics vote was approved by University of Würzburg’s institutional review board (Permit No. 142/12). All participants provided written consent for the utilization of their anonymized data for research purposes.

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