Efficacy and Safety of the Combination Treatment of Rituximab and Dexamethasone for Adults with Primary Immune Thrombocytopenia (ITP): A Meta-Analysis

Abstract

Objective. To conduct a meta-analysis, assessing the efficacy and safety of the combination treatment of dexamethasone and rituximab for adults with ITP (primary immune thrombocytopenia). Methods. Randomized controlled trials that compared rituximab and dexamethasone combination treatment to dexamethasone monotherapy in the treatment of adults with ITP were collected by searching Pubmed, Embase, Cochrane, China National Knowledge (CNKI), Wanfang database, and Sino Med. We conducted pooled analyses on OR (overall response) rate, CR (complete response) rate, PR (partial response) rate, SR (sustained response) rate, R (relapse) rate, change in Treg cell count (mean [SD]), and AE (adverse event). GRADE pro scale was used to assess the quality of the evidence. Publication bias was assessed with Egger's test method. Results. A total of 11 randomized controlled trials were eligible for inclusion. The overall efficacy estimates favored combination arm in terms of OR rate at month 3, CR rate at week 4 and month 3, SR rate, and Treg cell count at week 2. Subgroup analysis showed that females obtained a higher OR rate than males did at week 4. No significant difference was found in pooled analysis of relapse rate between combination arm and monotherapy arm. The comparison of serious AE and other AEs showed no significant difference either. A total of 19 outcomes were assessed by GRADE pro software, of which 79% (15/19) was scaled as moderate-to-high level. Publication bias existed in studies on OR at week 4 (P=0.025), CR at week 4 (P=0.017), infection (P=0.006), and rash (P=0.028) of the AEs. Conclusion. Dexamethasone combined with rituximab can provide a better long-term response in the treatment of adults with ITP and will not increase the risk of adverse effects.

High‐dose dexamethasone plus recombinant human thrombopoietin vs high‐dose dexamethasone alone as frontline treatment for newly diagnosed adult primary immune thrombocytopenia: A prospective, multicenter, randomized trial

“…For example, high-dose dexamethasone (HD-DXM) plus rituximab yielded a SR rate of 63% to 76%, which was significantly higher than HD-DXM monotherapy, whereas early response rates showed no statistical difference between combination and monotherapy. [10][11][12] Thrombopoietin (TPO) is the primary regulator of megakaryocyte development and platelet production. 13 Relative TPO deficiency is an important reason for insufficient thrombopoiesis in ITP.…”

“…Recently, combination therapies have shown encouraging results in newly diagnosed ITP patients. For example, high‐dose dexamethasone (HD‐DXM) plus rituximab yielded a SR rate of 63% to 76%, which was significantly higher than HD‐DXM monotherapy, whereas early response rates showed no statistical difference between combination and monotherapy 10‐12 …”

Primary Immune Thrombocytopenia: Novel Insights into Pathophysiology and Disease Management

“…To increase the rate of sustained response, combination of dexamethasone with second line treatments such as rituximab have been investigated. A recent meta-analysis compared the effectiveness of the combination of high-dose dexamethasone and rituximab with dexamethasone alone in ITP [ 83 ]. Overall response rate at month 3 (RR = 5.07, 95% CI: 2.91–8.86, and p < 0.00001) and sustained response rate at 12 months (RR = 1.73, 95% CI: 1.36–2.91, and p < 0.00001) was significantly higher in combination arm than that in monotherapy.…”

“…Overall response rate at month 3 (RR = 5.07, 95% CI: 2.91–8.86, and p < 0.00001) and sustained response rate at 12 months (RR = 1.73, 95% CI: 1.36–2.91, and p < 0.00001) was significantly higher in combination arm than that in monotherapy. Furthermore, the rate of adverse events has not significantly increased with combination therapy [ 83 ].…”

Short-term dose-escalated romiplostim for preparing an adult patient with persistent newly diagnosed primary immune thrombocytopenia for splenectomy

“… 3 The combination provides a sustained response rate of 58% at six months and is superior to mono-therapy. 4 Splenectomy is indicated for patients failing first- and second-line treatment. 1 IVIG plus platelet transfusions may increase the platelet count sufficiently to decrease the risk of hemorrhage and permit surgery.…”