PB2247 ADJUSTED INDIRECT COMPARISON OF ELTROMBOPAG RELATIVE TO RITUXIMAB OR SPLENECTOMY IN SECOND LINE TREATMENT FOR CHRONIC IMMUNE THROMBOCYTOPENIC PURPURA
Authors: J. Felix, V. Andreozzi, B. Vandewalle
Journal: HemaSphere (2019)

Background: Current guidelines recommend thrombopoietin receptor agonists (TPO‐RAs: eltrombopag and romiplostim), splenectomy and rituximab as second‐line treatment options for chronic immune thrombocytopenic purpura (ITP). To date no head‐to‐head randomized trial exists comparing these therapies. There is some sparse evidence for indirect comparison between eltrombopag and romiplostim, but no indirect comparison of TPO‐RAs with splenectomy or rituximab for ITP patients eligible to splenectomy. This is because evidence for the effect of rituximab and splenectomy in ITP comes from single arms trials and from observational studies or case series, respectively. Aims: To apply indirect adjusted comparison methods to assess the relative efficacy of eltrombopag in comparison to rituximab or splenectomy in second line treatment of ITP in patients eligible for splenectomy. Methods: A subset of 84 patients treated with eltrombopag but not subject to splenectomy in the randomised, phase 3 study RAISE (PMID: 20739054) were indirectly compared with the 60 adult splenectomy candidates with ITP treated with rituximab and included in the prospective multicentre phase 2 study by Godeau et al (PMID:18463354), and a large retrospective cohort of patients (n = 233) who underwent splenectomy for ITP in the study by Vianelli et al (PMID:23144195). After controlling for covariates, we estimate that the odds of response (platelet count &gt;50 000 per μL) to eltrombopag is significantly higher than rituximab (OR = 4.6; 95%CI: 1.9 to 10.0). An adjusted response rate (platelet count &gt;30 000 per μL) of 83.3% for eltrombopag treatment in ITP was estimate relative to 73.2% for splenectomy (OR = 2.8; 95%CI: 0.7 to 11.1). Results: A subset of 84 patients treated with eltrombopag but not subject to splenectomy in the randomised, phase 3 study RAISE (PMID: 20739054) were indirectly compared with the 60 adult splenectomy candidates with ITP included in the prospective multicentre phase 2 study by Godeau et al (PMID:18463354), and a large retrospective cohort of patients (n = 233) who underwent splenectomy for ITP in the study by Vianelli et al (PMID:23144195). After controlling for covariates, we estimate that the odds of response (platelet count &gt;50 000 per μL) to eltrombopag is significantly higher than rituximab (OR = 4.6; 95%CI: 1.9 to 10.0). An adjusted response rate (platelet count &gt;30 000 per μL) of 83.3% for eltrombopag treatment in ITP was estimate relative to 73.2% for splenectomy (OR = 2.8; 95%CI: 0.7 to 11.1). Summary/Conclusion: Adjusted indirect comparisons is a useful resource for evidence‐based decision‐making when no head‐to‐head data exists between alternative treatment options. Within the limits of the available data and of the methodology, eltrombopag is estimated to be the most effective second line treatment for the management of chronic immune thrombocytopenia patients candidates to splenectomy. Head‐to‐head clinical trials are needed to support these findings.