Does initial high efficacy therapy in multiple sclerosis surpass escalation treatment strategy? A comparison of patients with relapsing-remitting multiple sclerosis in the Czech and Swedish national multiple sclerosis registries.

BACKGROUND

In relapsing-remitting multiple sclerosis (RRMS) the most common treatment strategy has been to start with low-moderate efficacy disease modifying therapy (LE-DMT) and to escalate to more efficacious treatments in cases of breakthrough disease activity. However, recent evidence suggests a better outcome in patients commencing with moderate-high efficacy DMT (HE-DMT) immediately after clinical onset.

OBJECTIVE

The aim of this study is to compare disease activity and disability outcomes in patients treated with the two alternative strategies using the Swedish and Czech national multiple sclerosis registries, taking advantage of the fact that the relative frequency of each strategy differs markedly between these two countries.

METHODS

Adult RRMS patients who initiated their first-ever DMT between 2013 and 2016 and were included in the Swedish MS register were compared with a similar cohort from the MS register of the Czech Republic using propensity score overlap weighting as a balancing method. The main outcomes of interest were time to confirmed disability worsening (CDW), time to achieve an expanded disability status scale (EDSS) value of 4, time to relapse, and time to confirmed disability improvement (CDI). To support the results, a sensitivity analysis focusing solely on patients from Sweden starting with HE-DMT and patients from the Czech Republic starting with LE-DMT was performed.

RESULTS

In the Swedish cohort, 42% of patients received HE-DMT as initial therapy compared to 3.8% of patients in the Czech cohort. The time to CDW was not significantly different between the Swedish and Czech cohorts (p-value 0.2764), with hazard ratio (HR) of 0.89 and a 95% confidence interval (CI) of 0.77-1.03. Patients from the Swedish cohort exhibited better outcomes for all remaining variables. The risk of reaching EDSS 4 was reduced by 26% (HR 0.74, 95%CI 0.6-0.91, p-value 0.0327), the risk of relapse was reduced by 66% (HR 0.34, 95%CI 0.3-0.39, p-value <0.001), and the probability of CDI was three times higher (HR 3.04, 95%CI 2.37-3.9, p-value <0.001).

CONCLUSION

The analysis of the Czech and the Swedish RRMS cohorts confirmed a better prognosis for patients in Sweden, where a significant proportion of patients received HE-DMT as initial treatment.

Informations de copyright

Copyright © 2023. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T. Hrnciarova has nothing to disclose. J. Drahota has nothing to disclose. T. Spelman received compensation from serving on scientific advisory boards and steering comittees from Biogen and consultancy fees from Hartmann and Abbvie. J. Hillert received honoraria for serving on advisory boards for Biogen, Bristol-Myers-Squibb/Celgene, Janssen, Merck KGaA, Sandoz and Sanofi-Genzyme and speaker...s fees from Biogen, Janssen, Novartis, Merck, Teva, Sandoz and Sanofi-Genzyme. He has served as P.I. for projects sponsored by, or received unrestricted research support from, Biogen, Bristol-MyersSquibb/Celgene, Janssen, Merck KGaA, Novartis, Roche, and Sanofi-Genzyme. His MS research is funded by the Swedish Research Council and the Swedish Brain foundation. J. Lycke has received travel support and/or lecture honoraria and has served on scientific advisory boards for Alexion, Almirall, Biogen, Bristol Myers Squibb, Celgene, Janssen, Merck, Novartis, Roche and Sanofi; and has received unconditional research grants from Biogen and Novartis, and financial support from Sanofi for an investigator-initiated study. E. Kubala Havrdova has received honoraria/research support from Biogen, Merck Serono, Novartis, Roche, and Teva; has served as a member of advisory boards for Actelion, Biogen, Celgene, Merck Serono, Novartis, and Sanofi Genzyme; has been supported by the Czech Ministry of Education project Cooperatio LF1, research area Neuroscience, and the project National Institute for Neurological Research (Programme EXCELES, ID project No LX22NPO5107) funded by the European Union-Next Generation EU. E. Recmanova has nothing to disclose. J. Adamkova has nothing to disclose. J. Mares has nothing to disclose. J. Libertinova reported receiving grants, personal fees and funding for travel from Merck, Roche, Novartis, Biogen Inc, Sanofi Genzyme. Z. Pavelek reports personal fees from Biogen, Eli Lilly, Genzyme, Merck Serono, Novartis, Pfizer, Roche, and Teva Pharma. P. Hradilek received speakers honoraria and travel compensations from Biogen, Merck, Teva, Sanofi, Roche, Novartis and Janssen Cilag. R. Ampapa received conference travel support from Roche, Sanofi, Biogen and Merck and has participated in clinical trials by Biogen, Novartis, Sanofi, Merck and Roche. I. Stetkarova received compensation for travel and speaker honoraria from Biogen Idec, Merck, and Roche. M. Peterka has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck, Novartis, Biogen, Sanofi-Genzyme, Jansse-Cilag, Teva, Roche. A. Martinkova has nothing to disclose. P. Stourac has nothing to disclose. M. Grunermelova has nothing to disclose. M. Vachova received compensation for travel, conference fees, consulting fees and speaker honoraria from Biogen, Lundbeck, Merck, Novartis, Roche, Sanofi, and Teva. M. Dufek has nothing to disclose. D. Horakova was supported by the Charles University: Cooperatio Program in Neuroscience, by the project National Institute for Neurological Research (Programme EXCELES, ID Project No. LX22NPO5107) - Funded by the European Union Next Generation EU, and by General University Hospital in Prague project MH CZ-DRO-VFN64165. She also received compensation for travel, speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche, and Teva, as well as support for research activities from Biogen Idec.