Comparison of up-front treatments for newly diagnosed immune thrombocytopenia -a systematic review and network meta-analysis

Abstract

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.

Figure 1.

Study schema. Flow diagram showing the process of identifying and selecting relevant studies.

Figure 2.

Results of the network of long-term sustained response comparison. (A) The network of comparisons included in the network meta-analysis for long-term sustained response (SR; platelet counts > 30×10⁹/L at 3 – 6 months). The circle size is proportional to the total number of patients in the treatment group. The line width is proportional to the number of trials comparing the treatment groups. (B) The summary effect estimate (risk ratio of SR) for each combination of treatments. Risk rations are indicated by dots, and 95% confidence intervals by bars. (C) The surface under the cumulative ranking curve (SUCRA) is shown for each treatment.

Figure 3.

Results of the network of long-term sustained response comparison. (A) The network of comparisons included in the network meta-analysis for long-term sustained response (SR; platelet counts > 30×10⁹/L at 3 – 6 months). The circle size is proportional to the total number of patients in the treatment group. The line width is proportional to the number of trials comparing the treatment groups. (B) The summary effect estimate (risk ratio of SR) for each combination of treatments. Risk ratios are indicated by dots, and 95% confidence intervals by bars. (C) The surface under the cumulative ranking curve (SUCRA) is shown for each treatment.