INTRODUCTION: Prescribing guidance for disease-modifying treatment (DMT) in multiple sclerosis (MS) is centred on a clinical diagnosis of relapsing-remitting MS (RRMS). DMT prescription guidelines and monitoring vary across countries. Standardising the approach to diagnosis of disease course, for example, assigning RRMS or secondary progressive MS (SPMS) diagnoses, allows examination of the impact of health system characteristics on the stated clinical diagnosis and treatment access. METHODS: We analysed registry data from six cohorts in five countries (Czech Republic, Denmark, Germany, Sweden and United Kingdom) on patients with an initial diagnosis of RRMS. We standardised our approach utilising a pre-existing algorithm (DecisionTree, DT) to determine patient diagnoses of RRMS or secondary progressive MS (SPMS). We identified five global drivers of DMT prescribing: Provision, Availability, Funding, Monitoring and Audit, data were analysed against these concepts using meta-analysis and univariate meta-regression. RESULTS: In 64,235 patients, we found variations in DMT use between countries, with higher usage in RRMS and lower usage in SPMS, with correspondingly lower usage in the UK compared to other registers. Factors such as female gender (p = 0.041), increasing disability via Expanded Disability Status Scale (EDSS) score (p = 0.004), and the presence of monitoring (p = 0.029) in SPMS influenced the likelihood of receiving DMTs. Standardising the diagnosis revealed differences in reclassification rates from clinical RRMS to DT-SPMS, with Sweden having the lowest rate Sweden (Sweden 0.009, range: Denmark 0.103 - UK portal 0.311). Those with higher EDSS at index (p < 0.03) and female gender (p < 0.049) were more likely to be reclassified from RRMS to DT-SPMS. The study also explored the impact of diagnosis on DMT usage in clinical SPMS, finding that the prescribing environment and auditing practices affected access to treatment. DISCUSSION: This highlights the importance of a healthcare system's approach to verifying the clinical label of MS course in facilitating appropriate prescribing, with some flexibility allowed in uncertain cases to ensure continued access to treatment.

Czech National Multiple Sclerosis Patient Registry ReMuS IMPULS Endowment Fund Kateřinská CZ Prague

Danish Multiple Sclerosis Registry Department of Neurology University Hospital Copenhagen Rigshospitalet Denmark

Department of Cellular and Molecular Neuroscience Imperial College London London UK

Department of Clinical Neuroscience Karolinska Institute Stockholm Sweden

Department of Clinical Neuroscience Karolinska Institute Stockholm Sweden MS Register

Department of Clinical Neurosciences Centre for Molecular Medicine Karolinska Institute Stockholm Sweden

Department of Mathematics KTH Royal Institute of Technology Stockholm Sweden

Department of Medical Statistics University Medical Center Göttingen Göttingen Germany

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

Department of Neurology Danish Multiple Sclerosis Center University Hospital Copenhagen Rigshospitalet Denmark

Department of Neuroscience Central Clinical School Monash University Australia

Department of Visual Neuroscience UCL Institute of Ophthalmology London UK

Faculty of Medicine Health and Life Science Swansea University Medical School Singleton Campus Swansea SA2 8PP UK

Faculty of Medicine Health and Life Science Swansea University Medical School Swansea UK

German MS Registry MS Forschungs und Projektentwicklungs gGmbH Hannover Germany

Novartis Pharma AG Basel Switzerland

Swansea University Medical School Swansea UK

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