This is what they say
Is horizontal switching a valid strategy in the treatment of MS?
“For people living with multiple sclerosis (MS), treatment changes are often necessary due to inadequate response, safety concerns, or personal preferences. These treatment switches can follow different strategies. One option is a “vertical switch,” where patients move to a treatment considered more effective. Another option is a “horizontal switch,” where patients change to a treatment of similar effectiveness but with a different mechanism or formulation. This study analyzed nearly 4,000 patients with relapsing MS from the global MSBase registry who underwent treatment switches. We aimed to better understand the effectiveness of horizontal switching and to identify patient characteristics associated with favourable outcomes. Our findings show that approximately one-third of patients who switched laterally (horizontally) achieved no evidence of disease activity (NEDA-3), meaning they experienced no relapses, disability worsening, or new disease activity on MRI during follow-up. Patients more likely to benefit from a horizontal switch were younger, had lower disability levels, fewer previous relapses, and had been on their prior treatment for longer. When directly compared, vertical switching was associated with superior clinical outcomes, including lower relapse rates and a higher likelihood of achieving NEDA-3. However, horizontal switching still proved to be a reasonable strategy for selected patients with lower disease activity and stable prior treatment exposure. These results can help guide treatment discussions between neurologists and patients, particularly in situations where vertical switching is not possible, preferred, or indicated”.
Surely if you start off with a high efficacy agents then all you do is switch to a high efficacy. When you switch vertically the extra benefic is relativelty small. Switching to anti-CD20 is a common good choice but you may expect this as the drugs of high efficacy are all trageting B cells sso it has done half or all the job for anti-CD20 and it works very quickly in most people, so of other take time to work.
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.Ther Adv Neurol Disord. 2025 Dec 23;18:17562864251399595.
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.
Source: multiple-sclerosis-research.org