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

ABSTRACT: Persistent immune thrombocytopenia (ITP) patients require second-line treatments, for which information on clinical outcomes are lacking. A systematic review and network meta-analysis (NMA) were conducted. Only randomised controlled trials (RCT) of second-line drugs in adult persistent ITP patients with platelet response, platelet count, any bleeding or serious adverse events (SAE) outcome were eligible. Twelve RCTs (n = 1313) were included in NMA. For platelet response outcome, eltrombopag and romiplostin were the best relative to placebo; the former had a non-significant advantage [risk ratio (RR) = 1·10 (95% confidence interval: 0·46, 2·67)]. Both treatments were superior to rituximab and recombinant human thrombopoietin (rhTPO)+rituximab, with corresponding RRs of 4·56 (1·89, 10·96) and 4·18 (1·21, 14·49) for eltrombopag; 4·13 (1·56, 10·94) and 3·79 (1·02, 14·09) for romiplostim. For platelet count, romiplostim ranked highest, followed by eltrombopag, rhTPO+rituximab, and rituximab. For bleeding, rituximab had lowest risk, followed by eltrombopag and romiplostim. For SAEs, rhTPO+rituximab had highest risk, followed by rituximab, eltrombopag and romiplostim. From clustered ranking, romiplostim had the best balance between short-term efficacy and SAEs, followed by eltrombopag. In conclusion, romiplostim and eltrombopag may yield high efficacy and safety. Rituximab may not be beneficial due to lower efficacy and higher complications compared with the thrombopoietin receptor agonists. RCTs with long-term clinical outcomes are required.

SUBMITTER: Puavilai T

PROVIDER: S-EPMC7003949 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Puavilai Teeraya T Thadanipon Kunlawat K Rattanasiri Sasivimol S Ingsathit Atiporn A McEvoy Mark M Attia John J Thakkinstian Ammarin A

British journal of haematology 20190818 3

Persistent immune thrombocytopenia (ITP) patients require second-line treatments, for which information on clinical outcomes are lacking. A systematic review and network meta-analysis (NMA) were conducted. Only randomised controlled trials (RCT) of second-line drugs in adult persistent ITP patients with platelet response, platelet count, any bleeding or serious adverse events (SAE) outcome were eligible. Twelve RCTs (n = 1313) were included in NMA. For platelet response outcome, eltrombopag and ...[more]

PMID: 31423574

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Project description:BackgroundImmune thrombocytopenia is an autoimmune disease characterised by decreased platelet count. In recent years, novel therapeutic regimens have been investigated in randomised controlled trials (RCTs). We aimed to compare the efficacy and safety of different treatments in newly diagnosed adult primary immune thrombocytopenia.MethodsWe did a systematic review and network meta-analysis of RCTs involving treatments for newly diagnosed primary immune thrombocytopenia. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched up to April 31, 2022. The primary outcomes were 6-month sustained response and early response. Secondary outcome was grade 3 or higher adverse events. This study is registered with PROSPERO (CRD42022296179).FindingsEighteen RCTs (n = 1944) were included in this study. Pairwise meta-analysis showed that the percentage of patients achieving early response was higher in the dexamethasone-containing doublet group than in the dexamethasone group (79.7% vs 68.7%, odds ratio [OR] 1.82, 95% CI 1.10-3.02). The difference was more profound for sustained response (60.5% vs 37.4%, OR 2.57, 95% CI 1.95-3.40). Network meta-analysis showed that dexamethasone plus recombinant human thrombopoietin ranked first for early response, followed by dexamethasone plus oseltamivir or tacrolimus. Rituximab plus prednisolone achieved highest sustained response, followed by dexamethasone plus all-trans retinoic acid or rituximab. Rituximab plus dexamethasone showed 15.3% of grade 3 or higher adverse events, followed by prednis(ol)one (4.8%) and all-trans retinoic acid plus dexamethasone (4.7%).InterpretationOur findings suggested that compared with monotherapy dexamethasone or prednis(ol)one, the combined regimens had better early and sustained responses. rhTPO plus dexamethasone ranked top in early response, while rituximab plus corticosteroids obtained the best sustained response, but with more adverse events. Adding oseltamivir, all-trans retinoic acid or tacrolimus to dexamethasone reached equally encouraging sustained response, without compromising safety profile. Although this network meta-analysis compared all the therapeutic regimens up to date, more head-to-head RCTs with larger sample size are warranted to make direct comparison among these strategies.FundingNational Natural Science Foundation of China, Major Research Plan of National Natural Science Foundation of China, Shandong Provincial Natural Science Foundation and Young Taishan Scholar Foundation of Shandong Province.

Project description:IntroductionA network meta-analysis (NMA) was performed to assess the efficacy and safety of avatrombopag, relative to eltrombopag, romiplostim, and fostamatinib, for patients with chronic immune thrombocytopenia (ITP) not responding adequately to corticosteroids.MethodsA systematic search of publication and clinical trial databases was conducted to identify relevant randomized controlled trials (RCTs) and observational studies. Data from eligible studies were extracted and analyzed in a Bayesian framework using relative effect sizes vs placebo. Outcomes included durable platelet response; need for rescue therapy; reduction in use of concomitant ITP medication; incidence of any or World Health Organization (WHO) grade 2-4 bleeding events, and any adverse events. Results were reported as odds ratios or incidence rate ratios (IRR) with 95% credible intervals (CrIs).ResultsThe NMA included seven phase 3 RCTs. Compared with placebo, avatrombopag was associated with statistically significant improvements in durable platelet response, reduction in use of concomitant ITP medication, and incidence of any bleeding events. Statistically significant differences vs placebo were also observed for durable platelet response and need for rescue therapy (eltrombopag, romiplostim, and fostamatinib); reduction in use of concomitant ITP medication (eltrombopag and romiplostim); incidence of any bleeding events (fostamatinib); and incidence of WHO grade 2-4 bleeding events (romiplostim and fostamatinib). No statistically significant differences were observed for any adverse events. Avatrombopag was associated with a statistically significant lower incidence of any bleeding events vs eltrombopag (IRR 0.38 [95% CrI 0.19, 0.75]) and romiplostim (IRR 0.38 [95% Crl 0.17, 0.86]); no other between-treatment differences were observed.ConclusionIn this NMA, avatrombopag significantly increased the chance of achieving durable platelet response and reducing the use of concomitant ITP medication vs placebo, and significantly reduced the incidence of any bleeding events compared with placebo, eltrombopag, and romiplostim. The study aims to help guide clinicians managing patients with chronic ITP and insufficient response to previous treatment.

Project description:Corticosteroids such as prednisolone and dexamethasone have been established as up-front therapy for the treatment of newly diagnosed immune thrombocytopenia. Recent studies have indicated that other treatments such as rituximab or thrombopoietin receptor agonist can also be effective choices. We performed a systematic review and network meta-analysis to establish a clinically meaningful hierarchy of efficacy and safety of treatments for newly diagnosed primary immune thrombocytopenia in adults. Randomized controlled trials evaluating medical treatments for newly diagnosed immune thrombocytopenia were included. Reviewers independently extracted data and assessed the risk of bias. The main outcome was the sustained response (platelet count >30×109/L for 3-6 months after completion of treatments), while overall response (platelet count >30×109/L for 2-4 weeks after initiation of the up-front treatment) and therapy-related adverse events were the secondary endpoints. A total of 21 randomized controlled trials (1898 patients) were included in this study. Our main findings were a significantly better sustained response in the recombinant human thrombopoietin+dexamethasone and rituximab+dexamethasone arms compared to those of conventional therapies (prednisolone and dexamethasone monotherapy). Moreover, recombinant human thrombopoietin+dexamethasone and +prednisolone improved early overall response compared to prednisolone, dexamethasone, and rituximab-containing regimens. Therapy-related adverse events showed similar profiles and were tolerable in all treatment arms. Regimens containing recombinant human thrombopoietin agonist may be beneficial up-front therapies in addition to the conventional corticosteroid monotherapies. Future head-to-head trials including these regimens and rituximab-containing treatments are necessary in order to overcome the limitations of the small number in our study and determine the most suitable initial therapies for newly diagnosed immune thrombocytopenia.

Dataset Information

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

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

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