PSY9 - Comparative Effectiveness Study of Enzymatic Replacement Therapies In the Treatment of Gaucherxs Disease On Adults

Abstract

This study aims to perform a comparative effectiveness study of licensed Enzymatic Replacement Therapies (ERT´, taliglucerase, imiglucerase and velaglucerase) on the treatment of Gaucher´s disease on adult patients. A systematic review of published clinical trials was performed on three Medical databases. Inclusion criteria were randomized, double-blind and phase III clinical trials measuring the efficacy of ERT on adult patients. Using meta-analysis methodology, the difference in the clinical outputs due the use of a specific ERT in four endpoints was assessed: Hemoglobin concentration increase, platelet count increase, Spleen and Liver volume reduction. Since no placebo group is reported in clinical trials of orphan drugs, outcomes previous to ERT were considered as control. In this study we report the p-value of test for subgroup differences to compare among the three alternatives. For the higher dose (60U/kg for the three enzymes), the data reported allowed a taliglucerase, velaglucerase and Imiglucerase comparison in efficacy measures (except the analysis of imiglucerase in platelet count endpoint). Hemoglobin concentration increased a mean of 1.79 g/dL [95% CI 1.08,2. 51; p-value for therapy differences=0.82]. Spleen volume decreased a mean of -5.17 Multiples of Normal (MN) [-10.09, -0.25; p-value for therapy differences=0.90]. ERT showed a trend favouring liver volume reduction, -0.28 MN [-0.57,0. 01; p-value for therapy differences=0.80] and increased platelet count, 33.11x109/L [-1.67,67.89; p-value for therapy differences=0.74]. However, for data limitations, we were unable to perform the comparison for the lower dose (taliglucerase and imiglucerase 30U/kg, velaglucerase 45U/kg). Non significative differences implies overlapped confidence intervals for the three therapies in all the efficacy endpoints. This analysis suggests a comparable effect of the velaglucerase and taliglucerase on platelet count increase, as well as a comparable effect of the three enzymes approved for Gaucher disease on Hemoglobin concentration increase, Liver and Spleen volume reduction.