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. 2024 Nov;38(11):921-930.
doi: 10.1007/s40263-024-01115-x. Epub 2024 Sep 6.

Effectiveness of Disease-Modifying Treatment on Spinal Cord Lesion Formation in Relapse-Onset Multiple Sclerosis: An MSBase Registry Study

Daniel Kreiter  1   2 , Tomas Kalincik  3   4 , Raymond Hupperts  5   6 , Francesco Patti  7   8 , Daniele Spitaleri  9 , Matteo Foschi  10   11 , Andrea Surcinelli  10 , Davide Maimone  12 , Bassem Yamout  13   14 , Samia J Khoury  13 , Jeannette Lechner-Scott  15   16 , Serkan Ozakbas  17   18 , Oliver Gerlach  5   6 ; MSBase Study Group
Collaborators, Affiliations

Effectiveness of Disease-Modifying Treatment on Spinal Cord Lesion Formation in Relapse-Onset Multiple Sclerosis: An MSBase Registry Study

Daniel Kreiter et al. CNS Drugs. 2024 Nov.

Abstract

Background: Spinal cord lesions in multiple sclerosis (MS) have considerable impact on disability. High-efficacy disease-modifying treatments (hDMTs) are associated with greater reduction of relapses and new brain lesions compared to low-efficacy treatments (lDMTs). Knowledge on the impact of DMTs on cord lesion formation is limited as these outcome measures were not included in MS treatment trials. This study aims to investigate whether hDMTs reduce the formation of cord lesions more effectively than lDMTs.

Methods: Patients with relapse-onset MS, a cord magnetic resonance imaging (MRI) within 6 months before/after initiation of their first DMT and ≥1 cord MRI at follow-up (interval > 6 months) were extracted from the MSBase registry (ACTRN12605000455662). Patients treated with hDMTs ≥90% or lDMTs ≥90% of follow-up duration were considered the hDMT and lDMT groups, respectively. Matching was performed using propensity scores. Cox proportional hazards models were used to estimate the hazards of new cord lesions, brain lesions and relapses.

Results: Ninety-four and 783 satisfied hDMT and lDMT group criteria, respectively. Seventy-seven hDMT patients were matched to 184 lDMT patients. In the hDMT group there was no evidence of reduction of new cord lesions (hazard ratio [HR] 0.99 [95% CI 0.51, 1.92], p = 0.97), while there were fewer new brain lesions (HR 0.22 [95% CI 0.10, 0.49], p < 0.001) and fewer relapses (HR 0.45 [95% CI 0.28, 0.72], p = 0.004).

Conclusion: A potential discrepancy exists in the effect of hDMTs over lDMTs in preventing spinal cord lesions versus brain lesions and relapses. While hDMTs provided a significant reduction for the latter when compared to lDMTs, there was no significant reduction in new spinal cord lesions.

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Conflict of interest statement

Serkan Ozakbas has nothing to disclose. Daniel Kreiter and Oliver Gerlach received institutional research grants. Tomas Kalincik served on scientific advisory boards for MS International Federation and World Health Organization, BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi-Genzyme, Teva, BioCSL and Merck and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck. Tomas Kalincik is also an Editorial Board member of CNS Drugs. He was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Raymond Hupperts received institutional research grants and fees for lectures and advisory boards from Biogen, Merck and Genzyme-Sanofi. Francesco Patti received personal compensation for serving on advisory board for Almirall, Alexion, Biogen, Bristol, Berck, Novartis and Roche. He further received research grants by Biogen, Merck and Roche and by FISM, Reload Association (Onlus), Italian Health Minister, University of Catania. Daniele Spitaleri received honoraria as a consultant on scientific advisory boards by Bayer-Schering, Novartis and Sanofi-Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva and Merck. Matteo Foschi received travel and meeting attendance support from Novartis, Biogen, Roche, Sanofi-Genzyme and Merck. Davide Maimone received speaker honoraria for Advisory Board and travel grants from Almirall, Biogen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. Bassem Yamout received honoraria as a speaker and member of scientific advisory boards from Sanofi, Bayer, Biogen, Merck, Janssen, Novartis, Roche and Aspen. Samia J. Khoury received compensation for scientific advisory board activity from Merck and Roche and received compensation for serving on the IDMC for Biogen. Jeannette Lechner-Scott travel compensation from Novartis, Biogen, Roche and Merck. Her institution receives the honoraria for talks and advisory board commitment as well as research grants from Biogen, Merck, Roche, TEVA and Novartis.

Figures

Fig. 1
Fig. 1
Baseline and follow-up time window definitions [34].* Censor on last follow-up spinal cord MRI within timeframe where treatment group cut-offs remained satisfied DMT disease modifying treatment; EDSS Expanded Disability Status Scale
Fig. 2
Fig. 2
Flowchart of screening, inclusion and matching of study population. EDSS Expanded Disability Status Scale, hDMT high-efficacy disease-modifying treatment, lDMT low-efficacy disease-modifying treatment, SC spinal cord
Fig. 3
Fig. 3
Disease-modifying treatment usage during follow-up as proportion of follow-up time. ALE alemtuzumab, CLA cladribine, GLA glatiramer acetate, IFN interferons, IVIG immunoglobulins, MIT mitoxantrone, NAT natalizumab, OCR ocrelizumab, OFA ofatumumab, ONA ozanimod, SIP siponimod, TER teriflunomide. * Fingolimod (0.06%), glatiramer acetate (0.17%) for the hDMT group. In the control group: methotrexate (0.21%), dimethylfumarate (0.03%), natalizumab (0.13%), fingolimod (0.12%), siponimod (0.44%). In the subgroup with new cord lesions in the control group: methotrexate (0.67%), natalizumab (0.10%)
Fig. 4
Fig. 4
Cumulative hazard plots and risk tables for A new spinal cord lesions, B new brain lesions and C relapses in the hDMT versus lDMT group. CI confidence interval, hDMT high-efficacy disease-modifying treatment, HR hazard ratio, lDMT low-efficacy disease-modifying treatment
See this image and copyright information in PMC

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