OBJECTIVES The great majority of adult patients with immune thrombocytopenia (ITP) who fail to respond to first-line medication or who relapse following response require additional treatment. Although broad guidelines currently exist for second-line and subsequent therapies, none to date have been prescriptive. The purpose of this systematic review and network meta-analysis was to establish a clinically relevant ranking of the
efficacy and safety of medications for adults (≥18 years old) with previously treated ITP. METHODS Relevant publications from Medline, Embase, and the Cochrane database were searched from their inceptions through July 31, 2018. The primary outcome was the overall response (OR, defined as a platelet count ≥50 x 10(9)/L at the end of treatment without rescue therapy), while the secondary endpoints included early response (ER; i.e. a platelet count ≥50 x 10(9)/L at week 2 after initiation of treatment) and therapy-related severe adverse events (AEs). RESULTS Thirteen randomized controlled trials (1,202 patients) were included in this study. According to pooled results, romiplostim appears to be the most suitable treatment in terms of OR, followed by avatrombopag, eltrombopag, fostamatinib, and rituximab. Avatrombopag produced more satisfactory outcomes than romiplostim, eltrombopag, and rituximab in terms of ER; severe AEs profiles were similar across all treatment arms. CONCLUSION Romiplostim appears to be the best option for patients who fail to respond to prior treatment or relapse thereafter, while avatrombopag and eltrombopag are reasonable alternatives. Rituximab monotherapy is not recommended, as it produces the lowest OR and ER rates.