BACKGROUND: Patients with highly active relapsing-remitting multiple sclerosis inadequately responding to first-line therapies (interferon-based therapies, glatiramer acetate, dimethyl fumarate, and teriflunomide, known collectively as "BRACETD") often switch to natalizumab or fingolimod. OBJECTIVE: The aim was to estimate the comparative effectiveness of switching to natalizumab or fingolimod or within BRACETD using real-world data and to evaluate the cost-effectiveness of switching to natalizumab versus fingolimod using a United Kingdom (UK) third-party payer perspective. METHODS: Real-world data were obtained from MSBase for patients relapsing on BRACETD in the year before switching to natalizumab or fingolimod or within BRACETD. Three-way-multinomial-propensity-score-matched cohorts were identified, and comparisons between treatment groups were conducted for annualised relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M). Results were applied in a cost-effectiveness model over a lifetime horizon using a published Markov structure with health states based on the Expanded Disability Status Scale. Other model parameters were obtained from the UK MS Survey 2015, published literature, and publicly available UK sources. RESULTS: The MSBase analysis found a significant reduction in ARR (rate ratio [RR] = 0.64; 95% confidence interval [CI] 0.57-0.72; p < 0.001) and an increase in CDI6M (hazard ratio [HR] = 1.67; 95% CI 1.30-2.15; p < 0.001) for switching to natalizumab compared with BRACETD. For switching to fingolimod, the reduction in ARR (RR = 0.91; 95% CI 0.81-1.03; p = 0.133) and increase in CDI6M (HR = 1.30; 95% CI 0.99-1.72; p = 0.058) compared with BRACETD were not significant. Switching to natalizumab was associated with a significant reduction in ARR (RR = 0.70; 95% CI 0.62-0.79; p < 0.001) and an increase in CDI6M (HR = 1.28; 95% CI 1.01-1.62; p = 0.040) compared to switching to fingolimod. No evidence of difference in CDW6M was found between treatment groups. Natalizumab dominated (higher quality-adjusted life-years [QALYs] and lower costs) fingolimod in the base-case cost-effectiveness analysis (0.453 higher QALYs and £20,843 lower costs per patient). Results were consistent across sensitivity analyses. CONCLUSIONS: This novel real-world analysis suggests a clinical benefit for therapy escalation to natalizumab versus fingolimod based on comparative effectiveness results, translating to higher QALYs and lower costs for UK patients inadequately responding to BRACETD.

Amiri Hospital Kuwait City Kuwait

Azienda Ospedaliero Universitaria Policlinico OCB Neurology Unit Modena Italy

Centre de Réadaptation Déficience Physique Chaudière Appalache Lévis Canada

Cliniques Universitaires Saint Luc Brussels Belgium

CORe Department of Medicine University of Melbourne Melbourne Australia

Department of Basic Medical Sciences Neuroscience and Sense Organs University of Bari Bari Italy

Department of Biomedical Metabolic and Neurosciences University of Modena and Reggio Emilia Modena Italy

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

Department of Neuroscience Central Clinical School Alfred Hospital Monash University Melbourne VIC Australia

Dipartimento di Scienze Biomediche e Neuromotorie Università di Bologna Bologna Italy

Hôpital Notre Dame Montreal Canada

Hospital ClínicoSan Carlos Madrid Spain

Hospital Universitario Virgen Macarena Seville Spain

IRCCS Istituto delle Scienze Neurologiche di Bologna Bologna Italy

Jahn Ferenc Teaching Hospital Budapest Hungary

John Hunter Hospital Newcastle Australia

Karadeniz Technical University Trabzon Turkey

Market Access Biogen Maidenhead UK

Mayis University Samsun Turkey

Medical Biogen Baar Switzerland

MS Centre Royal Melbourne Hospital Melbourne Australia

Multiple Sclerosis Centre Neurology Unit SS Annunziata Hospital University G d'Annunzio Chieti Pescara Italy

Neuro Rive Sud Hôpital Charles LeMoyne Longueuil Canada

Neurology Unit ASUR Marche AV3 Macerata Italy

RTI Health Solutions Manchester UK

RTI Health Solutions Research Triangle Park NC USA

University of Parma Parma Italy

Value and Market Access Biogen International GmbH Neuhofstrasse 30 6340 Baar Switzerland

Zuyderland Medical Center Sittard The Netherlands

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Long-term clinical outcomes in patients with multiple sclerosis who are initiating disease-modifying therapy with natalizumab compared with BRACETD first-line therapies