(2025) Moderate-high efficacy disease-modifying therapies reduce relapse risk in late-onset multiple sclerosis. Journal of neurology, neurosurgery, and psychiatry. pp. 50-58. ISSN 1468-330X (Electronic) 0022-3050 (Linking)
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Abstract
INTRODUCTION: Late-onset multiple sclerosis (LOMS) now comprises over 10 of MS diagnoses in contemporary cohorts. The effectiveness of disease-modifying therapies (DMTs) in LOMS is unclear. We aimed to establish the comparative effectiveness of moderate-high-efficacy versus low-efficacy DMTs in LOMS. METHODS: Using data from the MSBase registry, this multicentre cohort study included people with MS with symptom onset after age 50. Covariates were balanced using inverse-probability-treatment-weighting (IPTW). Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP), confirmed disability improvement (CDI), relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA). RESULTS: Of 1032 participants, 472 received moderate-high-efficacy DMTs and 560 received low-efficacy DMTs. IPTW-weighted ARR was 0.06 for moderate-high-efficacy and 0.09 for low-efficacy DMTs, corresponding to an ARR ratio of 0.68 (95 CI 0.50 to 0.93, p=0.01). HR for time to first relapse was 0.66 (95 CI 0.47 to 0.91, p=0.01) in favour of moderate-high-efficacy DMTs.Among 856 participants with adequate follow-up, 37 experienced CDP over a median of 4.43 years, with most events (83.6) attributable to PIRA. The HR for time to CDP was 0.78 (p=0.08) and RAW was 0.69 (p=0.31) in favour of moderate-high-efficacy DMTs, though neither reached statistical significance. There was no difference in CDI or PIRA. CONCLUSION: Moderate-high-efficacy DMTs reduced relapse risk in LOMS. Relapse activity was low. CDP was common and driven by PIRA. Although the CDP and RAW results did not reach statistical significance, the overall findings support the initial use of moderate-high-efficacy DMTs in LOMS.
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| Keywords: | Humans Female Male Middle Aged Recurrence Disease Progression *Multiple Sclerosis/drug therapy Registries Treatment Outcome Cohort Studies Age of Onset Adult Multiple Sclerosis, Relapsing-Remitting/drug therapy Secondary Prevention Demyelinating diseases Geriatrics Multiple sclerosis STATISTICS honoraria from Biogen, and research funding from National Health and Medical Research Council, Multiple Sclerosis Research Australia and Australian and New Zealand Association of Neurologists. MG is currently working on observational studies funded by Biogen and Roche. DM has received honouraria from Novartis. KB has received honouraria for presentations and/or educational support from Biogen, Sanofi Genzyme, Merck, Roche, Alexion and Teva and serves on medical advisory boards for Merck and Biogen. DH was supported by the Charles University: Cooperatio Program in Neuroscience, by the project National Institute for Neurological Research (Programme EXCELES, ID Project Number LX22NPO5107)-Funded by the European Union-Next Generation EU, and by General University Hospital in Prague project MH CZ-DRO-VFN64165. She also received compensation for travel, speaker honouraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche and Teva, as well as support for research activities from Biogen Idec. IR served on scientific advisory boards, received conference travel support and/or speaker honouraria from Roche, Novartis, Merck and Biogen. IR is supported by a MS Australia and the Trish Multiple Sclerosis Research Foundation. TK served on scientific advisory boards or as a consultant for MS International Federation and World Health Organisation, Therapeutic Goods Administration, BMS, Roche, Janssen, Genzyme, Novartis, Merck and Biogen, received conference travel support and/or speaker honouraria from WebMD Global, Merck, Sandoz, Novartis, Biogen, Roche, Eisai, Genzyme, Teva and BioCSL and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck. SH has received consulting fees and speaker honouraria from Biogen, Novartis, Roche, Merck, and has received grants for her Institution from Biogen, Merck, Novartis and Roche. JL-S has received travel compensation from Novartis, Biogen, Roche and Merck. Her institution receives the honouraria for talks and advisory board commitment as well as research grants from Biogen, Merck, Roche and Novartis. AL has received personal compensation for consulting, serving on a scientific advisory board, speaking or other activities from Alexion, Amgen/Horizon, Biogen, Bristol Myers Squibb/Celgene, Janssen/Johnson has been a member of advisory boards for Actelion, Biogen, Celgene, Merck Serono, Novartis and Sanofi Genzyme received honoraria/research support from Biogen, Merck Serono, Novartis, Roche and Teva has been a member of advisory boards for Actelion, Biogen, Celgene, Merck Serono, Novartis and Sanofi Genzyme and has been supported by the Czech Ministry of Education - project Cooperatio LF1, research area Neuroscience, and the project National Institute for Neurological Research (Programme EXCELES, ID project No LX22NPO5107) - funded by the European Union-Next Generation EU. CB has received conference travel support from Biogen, Novartis, Bayer-Schering, Merck and Teva has participated in clinical trials by Sanofi Aventis, Roche and Novartis. SJK received compensation for serving on the IDMC for Biogen. BY received honouraria, consulting/speaker fees, and research grants from: Merck-Serono, Biogen, Bayer, Novartis and Sanofi. GL received travel and/or consultancy compensation from Sanofi-Genzyme, Roche, Teva, Merck, Novartis, Celgene, Biogen. YB received speaker honouraria/consulting fees from Merck, Biogen, Roche, Bristol, Novartis, Sanofi and Sandoz. OS received honouraria and consulting fees from Bayer Schering, Novartis, Merck, Biogen and Genzyme. JK received speaker fees, research support, travel support and/or served on advisory boards by Swiss MS Society, Swiss National Research Foundation (320030189140/1), University of Basel, Progressive MS Alliance, Alnylam, Bayer, Biogen, Bristol Myers Squibb, Celgene, Immunic, Merck, Neurogenesis, Novartis, Octave Bioscience, Quanterix, Roche, Sanofi, Stata DX. NJ is a PI on commercial MS studies sponsored by Novartis, Roche and Sanofi. He has received speaker's honouraria and consultancy fees from Merck. He has had conference travel and registration reimbursement, and consultancy fees from Novartis. RA received honouraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche and Sanofi-Genzyme. JP accepted travel compensation from Novartis, Biogen, Roche, EMD Serono and speaking honouraria from Biogen, Novartis, Roche and EMD Serono. VVP has received travel grants from Merck Healthcare KGaA (Darmstadt, Germany), Biogen, Sanofi, Bristol Myers Squibb, Almirall, Roche and Eisai. His institution has received research grants and consultancy fees from Roche, Biogen, Sanofi, Merck Healthcare KGaA (Darmstadt, Germany), Bristol Myers Squibb, Janssen, Almirall, Novartis Pharma, Alexion, Neuraxpharm and Eisai. VT has received consultation and speaker fees, travel grants and research support from: Biogen, Sanofi Genzyme, Merck, Novartis, Roche, Alexion, Viatris, Janssen, Bristol Myers Squibb, Almirall, Lundbeck. AP has no disclosures to declare. MT received travel grants from Novartis, Bayer-Schering, Merck and Teva has participated in clinical trials by Sanofi Aventis, Roche and Novartis. MG has no disclosures to declare. VS has no disclosures to declare. RA received conference travel support from Novartis, Teva, Biogen, Bayer and Merck and has participated in clinical trials by Biogen, Novartis, Teva and Actelion. OG received honouraria as consultant on scientific advisory boards for Genzyme, Biogen, Merck, Roche and Novartis has received travel grants from Biogen, Merck, Roche and Novartis has participated in clinical trials by Biogen and Merck. Her institution has received research grant support from Biogen. ME has no disclosures to declare. JG has no disclosures to declare. PAM received speakers' fees and travel grants from Novartis, Biogen, T'evalua and Sanofi. OG has no disclosures to declare. CS served on scientific advisory boards for Merck, Genzyme, Almirall and Biogen received honoraria and travel grants from Sanofi Aventis, Novartis, Biogen, Merck, Genzyme and Teva. CZ has no disclosures to declare. AvdW served on advisory boards and received lecture fees and travel support for Novartis, Biogen, Merck and Roche. She receives research grants from the National Health and Medical Research Council of Australia, The Trish Foundation and MS Research Australia. She receives personal compensation as the Chief Operating Officer of the MSBase Foundation. HB's Institution has received compensation for advisory boards or lecture fees from Novartis, Biogen, Merck, UCB Pharma and Roche and receives research funding from Novartis, Biogen, Merck, Roche, The National Health and Medical Research Council of Australia, The Medical Research Future Fund (Australia), Monash Partners, the Trish MS Foundation, The Pennycook Foundation and MS Australia he also receives personal compensation as the Managing Director of the MSBase Foundation and from the Oxford Health Policy Forum Brain Health Initiative. |
| Page Range: | pp. 50-58 |
| Journal or Publication Title: | Journal of neurology, neurosurgery, and psychiatry |
| Journal Index: | Pubmed |
| Volume: | 97 |
| Number: | 1 |
| Identification Number: | https://doi.org/10.1136/jnnp-2025-336513 |
| ISSN: | 1468-330X (Electronic) 0022-3050 (Linking) |
| Depositing User: | خانم ناهید ضیائی |
| URI: | http://eprints.mui.ac.ir/id/eprint/32967 |
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