Spelman T, Herring WL, Zhang Y, Tempest M, Pearson I, Freudensprung U, Acosta C, Dort T, Hyde R, Havrdova E, Horakova D, Trojano M, De Luca G, Lugaresi A, Izquierdo G, Grammond P, Duquette P, Alroughani R, Pucci E, Granella F, Lechner-Scott J, Sola P, Ferraro D, Grand’Maison F, Terzi M, Rozsa C, Boz C, Hupperts R, Van Pesch V, Oreja-Guevara C, van der Walt A, Jokubaitis VG, Kalincik T, Butzkueven H. Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in patients with inadequate response to disease-modifying therapies in relapsing-remitting multiple sclerosis in the United Kingdom. Pharmacoeconomics. 2022 Mar;40(3):323-39. doi: 10.1007/s40273-021-01106-6.

BACKGROUND: Patients with highly active relapsing-remitting multiple sclerosis (HA-RRMS) inadequately responding to first-line therapies (collectively BRACETD) often switch to natalizumab or fingolimod.

OBJECTIVE: Estimate the comparative effectiveness of switching to natalizumab, fingolimod, or within BRACETD using real-world data and 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, 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 (RR=0.64; 95%CI=0.57-0.72; p<0.001) and increase in CDI6M (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 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 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 data 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.