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.

1st Department of Neurology Masaryk University St Anne's University Hospital Brno Czech Republic

Bata Regional Hospital Zlín Czech Republic

Department of Clinical Neuroscience Institute of Neuroscience and Physiology Sahlgrenska Academy University of Gothenburg Gothenburg Sweden

Department of Clinical Neuroscience Karolinska Institute Stockholm Sweden

Department of Clinical Neuroscience Medical Faculty Ostrava University and Department of Neurology University Hospital Ostrava Czech Republic

Department of Epidemiology and Biostatistics 3rd Faculty of Medicine Charles University Prague Prague Czech Republic

Department of Neurology 2nd Faculty of Medicine and Motol University Hospital Charles University Prague Prague Czech Republic

Department of Neurology 3rd Faculty of Medicine Charles University Prague and University Hospital Kralovske Vinohrady Prague Czech Republic

Department of Neurology and Centre of Clinical Neuroscience 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czech Republic

Department of Neurology and Centre of Clinical Neuroscience Faculty of Medicine and Dentistry Palacký University and University Hospital Olomouc Olomouc Czech Republic

Department of Neurology Faculty of Medicine and University Hospital Hradec Králové Charles University Prague Hradec Králové Czech Republic

Department of Neurology Faculty of Medicine in Pilsen and University Hospital Pilsen Charles University Prague Pilsen Czech Republic

Department of Neurology Hospital České Budějovice České Budějovice Czech Republic

Department of Neurology Hospital Jihlava Jihlava Czech Republic

Department of Neurology Hospital Pardubice Pardubice Czech Republic

Department of Neurology KZ a s Hospital Teplice Teplice Czech Republic

Department of Neurology Thomayer Hospital Prague Czech Republic

Department of Neurology University Hospital Brno Brno Czech Republic

IMPULS Endowment Fund Prague Czech Republic

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$a Hrnciarova, Tereza $u Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic; Department of Epidemiology and Biostatistics, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

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$a 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 / $c T. Hrnciarova, J. Drahota, T. Spelman, J. Hillert, J. Lycke, E. Kubala Havrdova, E. Recmanova, J. Adamkova, J. Mares, J. Libertinova, Z. Pavelek, P. Hradilek, R. Ampapa, I. Stetkarova, M. Peterka, A. Martinkova, P. Stourac, M. Grunermelova, M. Vachova, M. Dufek, D. Horakova

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$a 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.

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$a Drahota, Jiri $u Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic; IMPULS Endowment Fund, Prague, Czech Republic

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$a Spelman, Tim $u Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden

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$a Hillert, Jan $u Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden

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$a Lycke, Jan $u Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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$a Kubala Havrdova, Eva $u Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic

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$a Recmanova, Eva $u Bata Regional Hospital, Zlín, Czech Republic

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$a Adamkova, Jana $u Department of Neurology, Hospital České Budějovice, České Budějovice, Czech Republic

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$a Mares, Jan $u Department of Neurology and Centre of Clinical Neuroscience, Faculty of Medicine and Dentistry, Palacký University and University Hospital Olomouc, Olomouc, Czech Republic

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$a Libertinova, Jana $u Department of Neurology, Second Faculty of Medicine and Motol University Hospital, Charles University in Prague, Prague, Czech Republic

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$a Pavelek, Zbysek $u Department of Neurology, Faculty of Medicine and University Hospital Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic

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$a Hradilek, Pavel $u Department of Clinical Neuroscience, Medical Faculty, Ostrava University and Department of Neurology, University Hospital, Ostrava, Czech Republic

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$a Ampapa, Radek $u Department of Neurology, Hospital Jihlava, Jihlava, Czech Republic

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$a Stetkarova, Ivana $u Department of Neurology, Third Faculty of Medicine, Charles University in Prague and University Hospital Kralovske Vinohrady, Prague, Czech Republic

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$a Peterka, Marek $u Department of Neurology, Faculty of Medicine in Pilsen and University Hospital Pilsen, Charles University in Prague, Pilsen, Czech Republic

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$a Martinkova, Alena $u Department of Neurology, Hospital Pardubice, Pardubice, Czech Republic

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$a Stourac, Pavel $u Department of Neurology, University Hospital Brno, Brno, Czech Republic

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$a Grunermelova, Marketa $u Department of Neurology, Thomayer Hospital, Prague, Czech Republic

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$a Vachova, Marta $u Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic; Department of Neurology, KZ a.s., Hospital Teplice, Teplice, Czech Republic

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$a Dufek, Michal $u First Department of Neurology, Masaryk University, St. Anne's University Hospital, Brno, Czech Republic

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$a Horakova, Dana $u Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic. Electronic address: dana.horakova@vfn.cz

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