Cost-Effectiveness of Rituximab for Maintenance in Patients with Follicular Non-Hodgkin’s Lymphoma in the Dutch Setting
Authors: Pompen Marjolein , Huijgens P.C. 
Published: April 2020

Abstract
&lt;&gt;Cost-Effectiveness of Rituximab For Maintenance in Patients With Follicular Non-Hodgkin’s Lymphoma in the Dutch setting &lt;&gt;Rituximab (MabThera®/Rituxan®), a chimeric anti-CD20 monoclonal antibody, has shown to be effective in the treatment of indolent and aggressive non Hodgkin’s lymphoma (NHL), including follicular lymphoma (FL). The purpose of the current economic evaluation was to estimate the cost-effectiveness of rituximab added in the maintenance setting for patients with relapsed/refractory FL. The cost-effectiveness of rituximab maintenance therapy in the Dutch healthcare system was assessed by economic modelling based on survival data from an EORTC/HOVON randomized clinical trial (EORTC20981/HOVON 39 NHL) in which patients with relapsed or refractory FL were randomized for maintenance rituximab vs no treatment after having responded to induction therapy. Utility values were obtained from a study in patients with FL using the EQ-5D York Tariff (unpublished). The primary endpoint was the incremental cost per quality adjusted life year (QALY) gained. A secondary endpoint was the incremental cost per life year gained (LYG). Only direct health care costs (drug acquisition, administration, adverse events, treatment at relapse, and routine surveillance) were included in the economic evaluation. Effects (QALYs and LYG) and costs accruing after the first year of the economic evaluation were discounted at the rate of 1.5% and 4% per annum, respectively. The economic evaluation was done by using a three state health state transition model. In this model, all patients start in the progression free (PFD) state with possible transitions to progressive disease (PD) or death (D). Progression free survival (PFS) and overall survival (OS) data were extrapolated over a period of 30 years with monthly cycles. Rituximab maintenance was more effective than observation in terms of both LYG and QALYs gained. The average discounted life expectancy in the rituximab group exceeded the observation group by 1.10 years (6.27 vs. 5.16); rituximab maintenance was associated with an additional 0.97 QALYs compared to observation. Total costs were €27,094 (euro 2006) higher in the rituximab group than the observation group and were largely due to the cost of the study drug and its administration. The incremental cost per QALY gained was €27,896 and the incremental cost per LYG was €24,564. The results from the EORTC20981/HOVON 39 NHL trial provide evidence of an incremental clinical benefit for rituximab maintenance therapy compared to ‘observation’ in patients with relapsed or refractory FL who have responded to CHOP or R-CHOP induction therapy. Subsequently, the results of the current economic modelling show that rituximab maintenance therapy has an incremental cost-effectiveness ratio of €27,896/QALY. The results were most sensitive to the duration of treatment benefit and the difference in treatment frequency and costs upon relapse between the two treatment groups. However, in all cases rituximab maintenance therapy remained a treatment that represents a cost-effective intervention. The economic analysis has shown to be adequately robust, hence it can be concluded that rituximab maintenance therapy in the Dutch setting is cost-effective.