Real-world effectiveness of horizontal switching between disease-modifying therapies in multiple sclerosis: a retrospective analysis of the MSBase Registry

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

doi:10.1177/17562864251399595

Real-world effectiveness of horizontal switching between disease-modifying therapies in multiple sclerosis: a retrospective analysis of the MSBase Registry

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

Neurology

Infectious Diseases Department
IMSS Hospital Regional #1
Centro Medico Naval
Universidad Autonoma de Nuevo Leon
Harvard University
IMSS Hospital General de Zona #2
Instituto Nacional de Neurologia y Neurocirugia
Royal Melbourne Hospital
University of Melbourne
Box Hill Hospital
Monash University
American University of Beirut
University of Montreal
Ospedale S. Maria delle Croci
University of L'Aquila
Razi University Hospital
Université de Tunis El Manar
University of Newcastle
Hunter Medical Research Institute, Australia
Hunter New England Health
Alfred Health
Al-Amiri Hospital
University of Catania
Neurology Institute and MS Center
Neuro Rive-Sud
Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino
Post Office Royal Brisbane Hospital
University of Queensland
Galdakao-Usansolo University Hospital
Biocruces-Bizkaia Health Research Institute
Izmir Ekonomi University
Multiple Sclerosis Research Association
Sultan Qaboos University
School of Clinical Sciences at Monash Health
AST Macerata
Westmead Hospital
Centre Hospitalier Universitaire de Sherbrooke
Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases
University of Córdoba
Maimonides Biomedical Research Institute of Cordoba (IMIBIC)
Unidade Local de Saúde de São João
University of Porto
Universidad de Guadalajara

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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.

Original language	English
Journal	Therapeutic Advances in Neurological Disorders
Volume	18
DOIs	https://doi.org/10.1177/17562864251399595
State	Published - Jan 1 2025

Keywords

disease-modifying therapies
multiple sclerosis
real-world evidence
treatment outcomes
treatment switching

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10.1177/17562864251399595

Cite this

Gomez-Figueroa, E., Orozco-Puga, P., Corona-Vázquez, C. P., Moreno-Bernardino, C., Elizabeth De la Mora-Landín, G., Jiménez-Ruiz, A., García-Estrada, C., Zertuche-Ortuño, L., Saldívar-Dávila, S., Rodríguez-Rivas, R., Bazán-Rodríguez, L., Flores-Rivera, J., Kalincik, T., Buzzard, K., Khoury, S., Duquette, P., Foschi, M., Surcinelli, A., Weinstock-Guttman, B., ... Ruiz-Sandoval, J. L. (2025). Real-world effectiveness of horizontal switching between disease-modifying therapies in multiple sclerosis: a retrospective analysis of the MSBase Registry. Therapeutic Advances in Neurological Disorders, 18. https://doi.org/10.1177/17562864251399595

@article{f873ebe3dfa243a0b0c83c9f2678f811,

title = "Real-world effectiveness of horizontal switching between disease-modifying therapies in multiple sclerosis: a retrospective analysis of the MSBase Registry",

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{\textendash}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.",

keywords = "disease-modifying therapies, multiple sclerosis, real-world evidence, treatment outcomes, treatment switching",

author = "Enrique Gomez-Figueroa and Patricia Orozco-Puga and Corona-V{\'a}zquez, \{Cynthia Patricia\} and Carlos Moreno-Bernardino and \{Elizabeth De la Mora-Land{\'i}n\}, Graciela and Amado Jim{\'e}nez-Ruiz and Christian Garc{\'i}a-Estrada and Lizeth Zertuche-Ortu{\~n}o and Sergio Sald{\'i}var-D{\'a}vila and Roberto Rodr{\'i}guez-Rivas and Lisette Baz{\'a}n-Rodr{\'i}guez and Jos{\'e} Flores-Rivera and Tomas Kalincik and Katherine Buzzard and Samia Khoury and Pierre Duquette and Matteo Foschi and Andrea Surcinelli and Bianca Weinstock-Guttman and Riadh Gouider and Saloua Mrabet and Jeannette Lechner-Scott and Helmut Butzkueven and Raed Alroughani and Izanne Roos and Francesco Patti and Bassem Yamout and Fran{\c c}ois Grand{\textquoteright}Maison and Daniele Spitaleri and Pamela McCombe and \{Luis Sanchez-Menoyo\}, Jos{\'e} and Serkan Ozakbas and Abdullah Al-Asmi and Nevin John and Elisabetta Cartechini and \{Van der Walt\}, Anneke and Justin Garber and Emmanuelle Lapointe and Aysun Soysal and Eduardo Aguera-Morales and Joana Guimar{\~a}es and Ruiz-Sandoval, \{Jos{\'e} Luis\}",

note = "Publisher Copyright: {\textcopyright} The Author(s), 2025. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).",

year = "2025",

month = jan,

day = "1",

doi = "10.1177/17562864251399595",

language = "English",

volume = "18",

journal = "Therapeutic Advances in Neurological Disorders",

issn = "1756-2856",

publisher = "SAGE Publications Ltd",

}

Gomez-Figueroa, E, Orozco-Puga, P, Corona-Vázquez, CP, Moreno-Bernardino, C, Elizabeth De la Mora-Landín, G, Jiménez-Ruiz, A, García-Estrada, C, Zertuche-Ortuño, L, Saldívar-Dávila, S, Rodríguez-Rivas, R, Bazán-Rodríguez, L, Flores-Rivera, J, Kalincik, T, Buzzard, K, Khoury, S, Duquette, P, Foschi, M, Surcinelli, A, Weinstock-Guttman, B, Gouider, R, Mrabet, S, Lechner-Scott, J, Butzkueven, H, Alroughani, R, Roos, I, Patti, F, Yamout, B, Grand’Maison, F, Spitaleri, D, McCombe, P, Luis Sanchez-Menoyo, J, Ozakbas, S, Al-Asmi, A, John, N, Cartechini, E, Van der Walt, A, Garber, J, Lapointe, E, Soysal, A, Aguera-Morales, E, Guimarães, J & Ruiz-Sandoval, JL 2025, 'Real-world effectiveness of horizontal switching between disease-modifying therapies in multiple sclerosis: a retrospective analysis of the MSBase Registry', Therapeutic Advances in Neurological Disorders, vol. 18. https://doi.org/10.1177/17562864251399595

Real-world effectiveness of horizontal switching between disease-modifying therapies in multiple sclerosis: a retrospective analysis of the MSBase Registry. / Gomez-Figueroa, Enrique; Orozco-Puga, Patricia; Corona-Vázquez, Cynthia Patricia et al.
In: Therapeutic Advances in Neurological Disorders, Vol. 18, 01.01.2025.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Real-world effectiveness of horizontal switching between disease-modifying therapies in multiple sclerosis

T2 - a retrospective analysis of the MSBase Registry

AU - Gomez-Figueroa, Enrique

AU - Orozco-Puga, Patricia

AU - Corona-Vázquez, Cynthia Patricia

AU - Moreno-Bernardino, Carlos

AU - Elizabeth De la Mora-Landín, Graciela

AU - Jiménez-Ruiz, Amado

AU - García-Estrada, Christian

AU - Zertuche-Ortuño, Lizeth

AU - Saldívar-Dávila, Sergio

AU - Rodríguez-Rivas, Roberto

AU - Bazán-Rodríguez, Lisette

AU - Flores-Rivera, José

AU - Kalincik, Tomas

AU - Buzzard, Katherine

AU - Khoury, Samia

AU - Duquette, Pierre

AU - Foschi, Matteo

AU - Surcinelli, Andrea

AU - Weinstock-Guttman, Bianca

AU - Gouider, Riadh

AU - Mrabet, Saloua

AU - Lechner-Scott, Jeannette

AU - Butzkueven, Helmut

AU - Alroughani, Raed

AU - Roos, Izanne

AU - Patti, Francesco

AU - Yamout, Bassem

AU - Grand’Maison, François

AU - Spitaleri, Daniele

AU - McCombe, Pamela

AU - Luis Sanchez-Menoyo, José

AU - Ozakbas, Serkan

AU - Al-Asmi, Abdullah

AU - John, Nevin

AU - Cartechini, Elisabetta

AU - Van der Walt, Anneke

AU - Garber, Justin

AU - Lapointe, Emmanuelle

AU - Soysal, Aysun

AU - Aguera-Morales, Eduardo

AU - Guimarães, Joana

AU - Ruiz-Sandoval, José Luis

N1 - Publisher Copyright: © The Author(s), 2025. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

PY - 2025/1/1

Y1 - 2025/1/1

N2 - 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.

AB - 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.

KW - disease-modifying therapies

KW - multiple sclerosis

KW - real-world evidence

KW - treatment outcomes

KW - treatment switching

UR - https://www.scopus.com/pages/publications/105025579439

U2 - 10.1177/17562864251399595

DO - 10.1177/17562864251399595

M3 - Article

AN - SCOPUS:105025579439

SN - 1756-2856

VL - 18

JO - Therapeutic Advances in Neurological Disorders

JF - Therapeutic Advances in Neurological Disorders

ER -

Gomez-Figueroa E, Orozco-Puga P, Corona-Vázquez CP, Moreno-Bernardino C, Elizabeth De la Mora-Landín G, Jiménez-Ruiz A et al. Real-world effectiveness of horizontal switching between disease-modifying therapies in multiple sclerosis: a retrospective analysis of the MSBase Registry. Therapeutic Advances in Neurological Disorders. 2025 Jan 1;18. doi: 10.1177/17562864251399595

Real-world effectiveness of horizontal switching between disease-modifying therapies in multiple sclerosis: a retrospective analysis of the MSBase Registry

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