Eltrombopag versus romiplostim in treatment of adult patients with immune thrombocytopenia: A systematic review incorporating an indirect-comparison meta-analysis

Abstract

PurposeIn absence of direct comparison randomized controlled trials (RCTs), indirect comparison was conducted to evaluate the efficacy and safety of thrombopoietin-receptor agonists (TPO-RAs) in treatment of adult immune thrombocytopenia (ITP).MethodsWe searched PubMed, Embase and Cochrane Library, Clinical Trials.gov, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database from their earliest records to May 2017. RCTs comparing the TPO-RAs with placebo in adult ITP were included. Primary outcomes were the overall response rate. Secondary outcomes included safety, durable response, overall or clinically significant bleeding, and the proportion of patients receiving rescue medication.ResultsNine randomized placebo-controlled trials (786 participants) were included in this systematic review. Overall response [Risk Ratio(RR) = 0.59, 95%Confidence Interval(CI): 0.24–1.45], the incidence of adverse events (RR = 0.98, 95%CI: 0.79–1.21), durable response (RR = 0.47, 95%CI: 0.08–2.81), the incidence of overall bleeding (RR = 1.15, 95%CI: 0.52–2.57) and clinically significant bleeding (RR = 1.09, 95%CI: 0.37–3.24), and the proportion of patients receiving rescue treatment (RR = 0.95, 95%CI: 0.47–1.90) were similar between eltrombopag and romiplostim.ConclusionsEltrombopag and romiplostim might be equivalent in efficacy and safety for adult ITP, however, physicians should still take into account drug cost and comorbidities of the specific patient while making decisions on the treatment of ITP with TPO-RAs.RegistrationPROSPERO International Prospective Register of Systematic Review (PROSPERO 2017: CRD42017068661).

Second‐line treatments in children with immune thrombocytopenia: Effect on platelet count and patient‐centered outcomes

“…An earlier cost per response analysis slightly favors romiplostim over eltrombopag in adults with ITP . Eltrombopag and romiplostim appear to be equivalent in terms of safety in a systematic review, including nine randomized trials in 786 adults, using an indirect comparison design . The side effect profile and cost of rituximab and oral immunosuppressants have not been directly compared to the thrombopoietin‐receptor agonists in a meaningful way.…”

Treatment efficacy for adult persistent immune thrombocytopenia: a systematic review and network meta‐analysis

“…Eight meta‐analyses assessed second‐line medical therapy in paediatric and adult patients with newly diagnosed, relapsed and persistent ITP (Cooper et al , ; Chugh et al , ; Feng et al , ; Wang et al , ; Elgebaly et al , ; Arai et al , ; Zhang et al , ; Bylsma et al , ). Among them, 4 (Cooper et al , ; Wang et al , ; Elgebaly et al , ; Zhang et al , ), 2 (Chugh et al , ; Feng et al , ) and 2 (Arai et al , ; Bylsma et al , ) meta‐analyses assessed efficacy of TPO‐RAs, monoclonal antibody and both, respectively.…”

“…Eight meta‐analyses assessed second‐line medical therapy in paediatric and adult patients with newly diagnosed, relapsed and persistent ITP (Cooper et al , ; Chugh et al , ; Feng et al , ; Wang et al , ; Elgebaly et al , ; Arai et al , ; Zhang et al , ; Bylsma et al , ). Among them, 4 (Cooper et al , ; Wang et al , ; Elgebaly et al , ; Zhang et al , ), 2 (Chugh et al , ; Feng et al , ) and 2 (Arai et al , ; Bylsma et al , ) meta‐analyses assessed efficacy of TPO‐RAs, monoclonal antibody and both, respectively. For the TPO‐RAs, 2 meta‐analyses (Wang et al , ; Elgebaly et al , ) combined paediatric and adult ITP patients, 1 (Wang et al , ) combined randomised controlled trials (RCTs) with observational studies, and the rest (Cooper et al , ; Elgebaly et al , ; Arai et al , ; Zhang et al , ; Bylsma et al , ) considered only RCTs.…”

“…Among them, 4 (Cooper et al , ; Wang et al , ; Elgebaly et al , ; Zhang et al , ), 2 (Chugh et al , ; Feng et al , ) and 2 (Arai et al , ; Bylsma et al , ) meta‐analyses assessed efficacy of TPO‐RAs, monoclonal antibody and both, respectively. For the TPO‐RAs, 2 meta‐analyses (Wang et al , ; Elgebaly et al , ) combined paediatric and adult ITP patients, 1 (Wang et al , ) combined randomised controlled trials (RCTs) with observational studies, and the rest (Cooper et al , ; Elgebaly et al , ; Arai et al , ; Zhang et al , ; Bylsma et al , ) considered only RCTs. Three of them directly pooled the effects of eltrombopag and romiplostim individually or combined them as TPO‐RAs (Wang et al , ; Elgebaly et al , ; Bylsma et al , ), while 3 (Cooper et al , ; Arai et al , ; Zhang et al , ) indirectly pooled the effects of romiplostim relative to eltrombopag.…”

“…For the TPO‐RAs, 2 meta‐analyses (Wang et al , ; Elgebaly et al , ) combined paediatric and adult ITP patients, 1 (Wang et al , ) combined randomised controlled trials (RCTs) with observational studies, and the rest (Cooper et al , ; Elgebaly et al , ; Arai et al , ; Zhang et al , ; Bylsma et al , ) considered only RCTs. Three of them directly pooled the effects of eltrombopag and romiplostim individually or combined them as TPO‐RAs (Wang et al , ; Elgebaly et al , ; Bylsma et al , ), while 3 (Cooper et al , ; Arai et al , ; Zhang et al , ) indirectly pooled the effects of romiplostim relative to eltrombopag. For the 2 direct meta‐analyses on monoclonal antibody, 5 (Chugh et al , ) and 7 (Feng et al , ) RCTs comparing rituximab with placebo or standard treatments were pooled.…”