Journal Article Epublish
PubMed: 41466847 DOI: 10.1177/17562864251399595
Real-world effectiveness of horizontal switching between disease-modifying therapies in multiple sclerosis: a retrospective analysis of the MSBase Registry.
Ther Adv Neurol Disord 18:17562864251399595
Authors: Enrique Gomez-Figueroa, Patricia Orozco-Puga, Cynthia Patricia Corona-Vázquez, Carlos Moreno-Bernardino, Graciela Elizabeth De la Mora-Landín, Amado Jiménez-Ruiz, Christian García-Estrada, Lizeth Zertuche-Ortuño, Sergio Saldívar-Dávila, Roberto Rodríguez-Rivas, Lisette Bazán-Rodríguez, José Flores-Rivera, Tomas Kalincik, Katherine Buzzard, Samia Khoury, Pierre Duquette, Matteo Foschi, Andrea Surcinelli, Bianca Weinstock-Guttman, Riadh Gouider, Saloua Mrabet, Jeannette Lechner-Scott, Helmut Butzkueven, Raed Alroughani, Izanne Roos, Francesco Patti, Bassem Yamout, François Grand'Maison, Daniele Spitaleri, Pamela McCombe, José Luis Sanchez-Menoyo, Serkan Ozakbas, Abdullah Al-Asmi, Nevin John, Elisabetta Cartechini, Anneke Van der Walt, Justin Garber, Emmanuelle Lapointe, Aysun Soysal, Eduardo Aguera-Morales, Joana Guimarães, José Luis Ruiz-Sandoval
Affiliations
- Department of Neurology, Hospital Civil de Guadalajara "Fray Antonio Alcalde," Coronel Calderón 777, Col. El Retiro, ZC 44280 Guadalajara, Jalisco, Mexico.
- Department of Neurology, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Mexico.
- Department of Internal Medicine, IMSS Hospital Regional #1, Durango, Mexico.
- Centro Medico Naval, Mexico City, Mexico.
- Department of Neurology, Hospital Universitario Dr. José Eleuterio González, Monterrey, Mexico.
- Department Executive and Continuing Professional Education, Harvard University-T.H. Chan School of Public Health, Boston, MA, USA.
- Department of Internal Medicine, IMSS Hospital General de Zona #2, Hermosillo, Mexico.
- Neurology Division, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.
- Neuroimmunology Centre, Department of Neurology, The Royal Melbourne Hospital, Melbourne, VIC, Australia.
- CORe, Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia.
- Department of Neurosciences, Box Hill Hospital, Box Hill, VIC, Australia.
- Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia.
- Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon.
- CHUM and Universite de Montreal, Montreal, QC, Canada.
- Department of Neuroscience, MS Center-Neurology Unit, S. Maria delle Croci Hospital, AUSL Romagna, Ravenna, Italy.
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
- Jacobs MS Center for Treatment and Research, Buffalo, NY, USA.
- Department of Neurology, Clinical Investigation Centre Neurosciences and Mental Health, Razi University Hospital, Tunis, Tunisia.
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.
- Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW, Australia.
- Hunter Medical Research Institute, New Lambton Heights, NSW, Australia.
- Hunter New England Health, John Hunter Hospital, Newcastle, NSW Australia.
- Department of Neurology, The Alfred Hospital, Melbourne, VIC, Australia.
- Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, VIC, Australia.
- Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait.
- Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania, Italy.
- Multiple Sclerosis Unit, AOU Policlinico G Rodolico-San Marco, University of Catania, Catania, Italy.
- Harley Street Medical Centre, Neurology Institute and MS Center, Abu Dhabi, United Arab Emirates.
- Neuro Rive-Sud, Longueuil, QC, Canada.
- Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy.
- Department of Neurology, Royal Brisbane Hospital, Brisbane, QLD, Australia.
- Faculty of Health, Medicine and Behavioral Sciences, The University of Queensland, Brisbane, QLD, Australia.
- Department of Neurology, Osakidetza-Basque Health Service, Galdakao-Usansolo University Hospital, Galdakao, Spain.
- Biocruces-Bizkaia Health Research Institute, Barakaldo, Spain.
- Izmir University of Economics, Medical Point Hospital, Izmir, Turkey.
- Multiple Sclerosis Research Association, Izmir, Turkey.
- College of Medicine and Health Sciences, Sultan Qaboos University, Seeb, Oman.
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC, Australia.
- Department of Neurology, Monash Health, Clayton, VIC, Australia.
- Neurology Unit, AST Macerata, Macerata, Italy.
- Department of Neurology, Westmead Hospital, Sydney, NSW, Australia.
- Division of Neurology, Department of Medicine, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
- Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey.
- Department of Medicine and Surgery, University of Cordoba, Córdoba, Spain.
- Maimonides Biomedical Research Institute of Cordoba, Córdoba, Spain.
- Department of Neurology, Unidade Local de Saúde de São João, Porto, Portugal.
- Department of Clinical Neurosciences and Mental Health, Faculty of Medicine of University of Porto, Porto, Portugal.
- Department of Neurosciences, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico.
Abstract
BACKGROUND
Switching disease-modifying therapies (DMTs) is common in relapsing-remitting multiple sclerosis (RRMS). Vertical switching to higher-efficacy agents generally outperforms horizontal switching within the same efficacy tier, yet horizontal switches remain frequent where escalation is impractical.
OBJECTIVES
To compare real-world outcomes after horizontal versus vertical DMT switches and to identify predictors of successful horizontal switching.
DESIGN
Retrospective, registry-based observational study.
METHODS
Adults with RRMS who switched DMTs in the MSBase Registry (2010-2023) were analyzed. Horizontal switches were defined as transitions within efficacy tiers, and vertical switches as transitions to a higher tier. Propensity score matching (1:1) generated balanced cohorts. Multivariable mixed-effects models with a random intercept for patients were used to evaluate associations with outcomes. The primary outcome was no evidence of disease activity (NEDA-3) during the treatment period; secondary outcomes included annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) change, confirmed disability worsening (CDW), confirmed disability improvement (CDI), and progression independent of relapse activity (PIRA). Predictors of successful horizontal switching were explored using logistic regression.
RESULTS
A total of 4934 matched switches (2467 pairs) were analyzed. Vertical switching achieved higher NEDA-3 rates than horizontal switching (45.8% vs 33.7%) and was associated with lower ARR, reduced CDW risk, and more frequent CDI; differences in EDSS progression and PIRA were not significant. Among horizontal switchers, 33.7% achieved NEDA-3. Success was associated with lower baseline EDSS, fewer prior relapses, and later-line switching. Outcomes varied by destination therapy: anti-CD20 agents had the highest success (≈50%), followed by cladribine (≈43%) and natalizumab (≈41%), whereas interferon and glatiramer acetate performed the poorest. Switches toward anti-CD20 therapies generally yielded better outcomes than other within-tier changes.
CONCLUSION
Vertical switching should be preferred when treatment modification is required, particularly for patients with active disease. However, a subset of patients can achieve disease stability after horizontal switching, especially those with lower disability and fewer prior relapses. The dynamics of horizontal switching may further influence outcomes, warranting prospective validation.
MeSH
Registries, Sclerosis, Multiple Sclerosis, Treatment Switching, Therapeutics