Costo-efficacia di rituximab nella terapia di mantenimento in soggetti affetti da linfoma non-Hodgkin follicolare refrattario

Objectives: Cost-effectiveness of rituximab in maintenance treatment of refractory or relapsing follicular non-Hodgkin lymphoma Scope of this analysis was to estimate the cost-effectiveness of rituximab maintenance (r-maintenance) therapy vs. observation, in relapsed/refractory follicular lymphoma patients following response to induction therapy with or without rituximab, based on data from a large multicenter study, in the Italian public payer's perspective. Methods: This study models the impact of r-maintenance vs. observation using a 15 years, health-state transition model. All patients entered the model following response to chemotherapy with or without rituximab as induction therapy (progression-free health state, PFHS). On the basis of probability estimates derived from the clinical trial, the model simulates transitions of patients from PFHS to either progressed health state (PHS) or death. Progression-free survival (PFS) and overall survival (OS) following r-maintenance are extrapolated from 2-year Kaplan-Meier curves from the study data (median trial follow-up 31 months) using a Weibull distribution (in the basecase PFS and OS clinical benefit is assumed to last 5 years). Quality of life utility values for the health states in the model were derived from a study of 165 patients using the EQ-5D questionnaire. Direct medical costs (including drug acquisition plus administration and management of adverse events) are reported in 2006 Euros and are derived from expert opinion and published sources. Costs and outcomes were discounted at a rate of 3.5%. In order to address uncertainty in point estimates, one-way and probabilistic sensitivity analyses were also performed. Results: The estimated lifetime incremental PFS is a 1.5 year increase for r-maintenance vs. observation (3.2 vs. 1.7 years). Overall survival analysis (based on 5 year extrapolation of the clinical benefit) yields an estimate of 5.9 life years (LY) for r-maintenance vs. 4.9 for observation (difference 0.99 LY gained). Total cost for r-maintenance is estimated as €26,027 vs. €16,146. R-maintenance results in a gain of 0.9 quality-adjusted life years (QALYs) [4.22 vs. 3.3] at an incremental cost of €9,881. The incremental cost-effectiveness ratio (ICER) of r-maintenance vs. observation is, therefore, estimated at €11,097/QALY gained. The ICER of r-maintenance is sensitive to the duration of treatment benefit and frequency of subsequent treatment; probabilistic sensitivity analysis shows that, over 2000 simulations, the cost/QALY never exceeds €14,000/QALY, a value well below commonly accepted cost-utility thresholds. Conclusions: In patients with partial or complete response to induction therapy, r-maintenance improves overall survival and progression-free survival and produces more QALYs compared with observation alone, at an acceptable cost/LY and cost/QALY ratio. Maintenance therapy with rituximab is a cost-effective approach for the management of patients with refractory/relapsed follicular lymphoma.