Since 2000, phase III randomized controlled trials (RCT) investigated the efficacy of rabbit anti-thymocyte globulins (ATG) in patients following allogeneic stem cell transplantation (allo-SCT). However, comparisons of different ATG formulations are lacking. Our aim was to synthesize all efficacy evidence, enabling a comparison of all available formulations of rabbit ATG in the allo-SCT setting. We performed a systematic literature review to identify all available phase III RCT evidence. We searched the Cochrane Library, MEDLINE, MEDLINE In-Process and the website www.ClinicalTrials.gov. In addition, one trial presented at the Annual Meeting of the American Society of Hematology 2016 was added to include the most recent evidence. In total, six RCTs were identified, including two formulations: Anti-t-lymphocyte globulins (ATLG, Grafalon(®), Neovii Biotech) and polyclonal globulins immunized with human thymocytes (Thymo, Thymoglobulin(®), Genzyme-Sanofi). The evidence was synthesized using a conventional network meta-analysis (NMA). The best treatment option to prevent GVHD was ATLG with the most favorable hazard ratio compared to standard treatment regarding chronic graft-versus-host-disease (GVHD; 0.42, 95% CI 0.31 to 0.56), acute GVHD II- IV (0.54, 95% CI 0.39 to 0.73) and acute GVHD III+IV (0.50, 95% CI 0.29 to 0.86), whereas both ATLG and Thymo were at least similarly effective regarding transplant-related mortality (TRM; 0.90, 95% CI 0.61 to 1.32 and 0.90, 95% CI 0.56 to 1.44). Thymo tended to be the better treatment option regarding overall survival (OS; 0.86, 95% CI 0.59 to 1.26). Our NMA provides the first relative efficacy of all available rabbit ATG formulations in patients undergoing allo-SCT. Until additional data from randomized head to head comparisons are available, based on this analysis, ATLG seems to be the best option to prevent chronic and acute GVHD. Both formulations show similar efficacy in TRM while Thymo tends to be the better treatment option regarding survival.
