Cost-effectiveness analysis of escalating to natalizumab or switching among immunomodulators in relapsing-remitting multiple sclerosis in Italy

Background: Published literature suggests that early treatment with natalizumab ("escalation strategy") is more effective than switch within the same class of immunomodulators (interferons/glatiramer acetate, "switching strategy") in relapsing-remitting multiple sclerosis (RRMS) patients who failed first-line self-injectable disease-modifying treatment (DMT). The present analysis aims to evaluate the cost-effectiveness profile of escalation strategy vs. switching strategy, adopting the Italian societal perspective. Methods: A lifetime horizon Markov model was developed to compare early escalation to natalizumab vs. switching among immunomodulators, followed by subsequent escalation to natalizumab. The two compared treatment algorithms were: a) early escalation until progression to Expanded Disability Status Scale (EDSS) = 7.0 vs. b) switching until EDSS = 4.0, followed by escalation until EDSS = 7.0. The model analyzed social costs, quality-adjusted survival and effects of therapies in prolonging time without disability progression and burden of relapses. Clinical data were mainly extracted from a published observational study. Results: Lifetime costs of early escalation to natalizumab and switching among immunomodulators amounted to €699,700 and €718,600 per patient, respectively. Early escalation was associated with prolonged quality-adjusted survival (11.19 vs. 9.67 QALYs, + 15.8%). A slight overall survival increase was also observed (20.10 vs. 19.67 life years). Both deterministic and probabilistic sensitivity analyses confirmed the robustness of findings. Conclusions: Adopting the Italian social perspective, early escalation to natalizumab is dominant vs. switching among immunomodulators, in RRMS patients who do not respond adequately to conventional immunomodulators.