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. 2023 Jun;270(6):3103-3111.
doi: 10.1007/s00415-023-11644-y. Epub 2023 Mar 2.

Effects of horizontal versus vertical switching of disease-modifying treatment after platform drugs on disease activity in patients with relapsing-remitting multiple sclerosis in Austria

Michael Guger  1   2 , Christian Enzinger  3 , Fritz Leutmezer  4   5 , Franziska Di Pauli  6 , Jörg Kraus  7   8 , Stefan Kalcher  9 , Erich Kvas  10 , Thomas Berger  4   5 ; Austrian MS Treatment Registry (AMSTR)
Affiliations

Effects of horizontal versus vertical switching of disease-modifying treatment after platform drugs on disease activity in patients with relapsing-remitting multiple sclerosis in Austria

Michael Guger et al. J Neurol. 2023 Jun.

Abstract

Objectives: To compare in a nationwide observational cohort the effectiveness, frequency and reasons for treatment interruption of dimethylfumarate (DMF) and teriflunomide (TERI) (horizontal switchers) versus alemtuzumab (AZM), cladribine (CLAD), fingolimod (FTY), natalizumab (NTZ), ocrelizumab (OCR) and ozanimod (OZA) (vertical switchers) in patients with relapsing-remitting multiple sclerosis (pwRRMS) and prior interferon beta (IFN-beta) or glatiramer-acetate (GLAT) treatment.

Materials and methods: The "horizontal switch cohort" included 669 and the "vertical switch cohort" 800 RRMS patients. We used propensity scores for inverse probability weighting in generalized linear (GLM) and Cox proportional hazards models to correct for bias in this non-randomized registry study.

Results: Estimated mean annualized relapse rates (ARR) were 0.39 for horizontal and 0.17 for vertical switchers. The incidence rate ratio (IRR) in the GLM model showed an increased relapse probability of 86% for horizontal versus vertical switchers (IRR = 1.86; 95% CI 1.38-2.50; p < 0.001). Analyzing the time to the first relapse after treatment switch by Cox regression, a hazard ratio of 1.58 (95% CI 1.24-2.02; p < 0.001) indicated an increased risk of 58% for horizontal switchers. The hazard ratios for treatment interruption comparing horizontal versus vertical switchers were 1.78 (95% CI 1.46-2.18; p < 0.001).

Conclusions: Horizontal switching after a platform therapy resulted in a higher relapse and interrupt probability and was associated with a trend towards less EDSS improvement comparing to vertical switching in Austrian RRMS patients.

Keywords: Escalation; Horizontal; Multiple sclerosis; Switch; Vertical.

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Conflict of interest statement

Michael Guger received support and honoraria for research, consultation, lectures and education from Alexion, Almirall, Bayer, Biogen, Bristol-Myers-Squibb, Celgene, Genzyme, Horizon, Janssen-Cilag, MedDay, Merck, Novartis, Roche, Sanofi Aventis and TEVA ratiopharm. Christian Enzinger received funding for travel and speaker honoraria from Bayer, Biogen, Genzyme, Merck, Novartis, Roche, Shire, and Teva Pharmaceutical Industries Ltd./sanofi-aventis, research support from Biogen, Merck, and Teva Pharmaceutical Industries Ltd./sanofi-aventis and serving on scientific advisory boards for Bayer, Biogen, Merck, Novartis, Roche and Teva Pharmaceutical Industries Ltd./sanofi- Aventis. Fritz Leutmezer has received funding for travel and speaker honoraria from Actelion, Almirall, Bayer, Biogen, Celgene, Genzyme, MedDay, Merck, Novartis, Pfizer, Octapharm, Roche, Sanofi-Genzyme and Teva. Franziska Di Pauli has participated in meetings sponsored by, received honoraria (lectures, advisory boards, consultations) or travel funding from Almirall, Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme, Teva, Celgene and Roche. Her institution received scientific grants from Roche. Jörg Kraus received consulting and/or research funding and/or educational support from Almirall, Bayer, Biogen, Celgene, MedDay, Medtronic, Merck, Novartis, Roche, Sanofi-Aventis, Shire, TEVA ratiopharm. Stefan Kalcher declares that there is no conflict of interest. Erich Kvas declares that there is no conflict of interest. Thomas Berger has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for multiple sclerosis: Almirall, Bayer, Biogen, Biologix, Bionorica, Bristol-Myers-Squibb, Eisai, GW Pharma, Horizon, Janssen-Cilag, MedDay, Merck, Novartis, Octapharma, Roche, Sandoz, Sanofi/Genzyme, TG Pharmaceuticals, TEVA-ratiopharm and UCB. His institution has received financial support in the last 12 months by unrestricted research grants (Biogen, Bayer, Bristol-Myers-Squibb, Merck, Novartis, Sanofi/Genzyme, and TEVA ratiopharm) and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, Bristol-Myers-Squibb, Merck, Novartis, Octapharma, Roche, Sanofi/Genzyme, and TEVA.

Figures

Fig. 1
Fig. 1
Cumulative probability for experiencing a relapse in RRMS patients comparing horizontal and vertical switchers
Fig. 2
Fig. 2
Cumulative probability for disability progression sustained for 12 (a) and 24 weeks (b) in RRMS patients comparing horizontal and vertical switchers
Fig. 3
Fig. 3
Cumulative probability for disability regression sustained for 12 (a) and 24 weeks (b) in RRMS patients comparing horizontal and vertical switchers
Fig. 4
Fig. 4
Cumulative probability for treatment interruption in RRMS patients comparing horizontal and vertical switchers
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