Supplementary Material for: Efficacy and incidence of treatment related adverse events of thrombopoietin receptor agonists in adults with immune thrombocytopenia: a systematic review and network meta-analysis of randomized controlled study

Introduction: To conduct a network meta-analysis to assess the efficacy and incidence of treatment related adverse events (TRAEs) of eltrombopag, romiplostim, avatrombopag, recombinant human thrombopoietin (rhTPO) and hetrombopag for adult immune thrombocytopenia (ITP). Methods: Randomized controlled trails (RCTs) of the five therapies from inception to June 1, 2022 were included. The efficacy outcome was the rate of platelet response, defined as the achievement of platelet counts above 50 x 109/L. Pairwise odds ratios (ORs) and 95% confidence intervals (CIs) were caculated. The surface under the cumulative ranking (SUCRA) was used to rank the included therapies for each outcome. Results: In total, 1,360 participants were analyzed in 14 eligible RCTs. All of the therapies showed a significantly better platelet response than the placebo, and avatrombopag (OR, 7.42; 95% CI, 1.74–31.69) and rhTPO (OR, 3.86; 95%CI, 1.62–9.18) were better than eltrombopag. Regarding TRAEs, no significant differences were found between patients receiving eltrombopag, romiplostim, and avatrombopag. Avatrombopag carried the highest platelet response rate with SUCRA value of 87.5, and carried the least TRAEs risk with SUCRA value of 37.0. Conclusions: These findings indicated that avatrombopag appeared to be the optimal choice as the second-line therapy of adult ITP.

引言：本研究拟开展网状meta分析，以评估艾曲波帕（eltrombopag）、罗米司亭（romiplostim）、阿伐曲泊帕（avatrombopag）、重组人血小板生成素（recombinant human thrombopoietin, rhTPO）以及海曲泊帕（hetrombopag）治疗成人原发免疫性血小板减少症（immune thrombocytopenia, ITP）的疗效与治疗相关不良事件（treatment related adverse events, TRAEs）的发生率。
方法：纳入建库至2022年6月1日发表的上述五种治疗方案的随机对照试验（randomized controlled trials, RCTs）。本研究的疗效结局指标为血小板应答率，定义为血小板计数升至50×10^9/L以上。计算两两比较的比值比（odds ratios, ORs）与95%置信区间（confidence intervals, CIs），采用累积排序曲线下面积（surface under the cumulative ranking, SUCRA）对纳入的各治疗方案的结局效应进行排序。
结果：最终共纳入14项符合标准的随机对照试验，涉及1360名受试者。所有受试治疗方案的血小板应答率均显著优于安慰剂；其中阿伐曲泊帕（OR=7.42，95%CI：1.74~31.69）与重组人血小板生成素（OR=3.86，95%CI：1.62~9.18）的疗效优于艾曲波帕。在治疗相关不良事件方面，艾曲波帕、罗米司亭与阿伐曲泊帕组患者的不良事件发生率无显著差异。阿伐曲泊帕的血小板应答率最高，SUCRA值为87.5；同时其治疗相关不良事件风险最低，SUCRA值为37.0。
结论：本研究结果表明，阿伐曲泊帕可作为成人原发免疫性血小板减少症二线治疗的最优选择。