Efficacy And Safety Of Rituximab Combined With Glucocorticoid For Treating Primary Immune Thrombocytopenia: A Meta-analysis

Objective To systematically evaluate the efficacy and safety of rituximab combined with glucocorticoid for treating primary immune thrombocytopenia(ITP). Methods To search the databases from CNKI, VIP, Wanfang Data, CBM, CMCC, MEDLINE, PubMed, EMBASE, and Cochrane, in accordance with inclusion criteria and exclusion criteria for literature screening. To collect all studies of randomized controlled trials about rituximab combined with glucocorticoids and glucocorticoid alone therapy on ITP. To evaluate the quality of the literature individually and data extraction, using Review Manager 5.3 software for statistical analysis of the raw data. Results are expressed as relative risks(RR) and 95% confidence intervals(CI). The main outcome measures include overall response(OR), complete response(CR), partial response(PR), sustained response(SR), relapse and adverse event(AE). Each process is completed by two independent reviewers, the results mutually check to confirm no errors. Results Included 9 studies with 9 RCTs, a total of 785 cases of patients, the test group of patients contains 363 cases, and the control group patients contains 422 cases. According to results of metaanalyses, the OR of rituximab combined with glucocorticoids compared with glucocorticoid monotherapy at 28 days showed no statistical difference between the two treatment groups(RR=1.12, 95%CI[0.99,1.27], P=0.07). In the 3rd month OR showed a statistically significant difference between the two treatment groups(RR=2.41,95%CI[1.82,3.19],P<0.00001), the combination therapy precedes the monotherapy. CR at 28 days showed no statistical difference between the two treatment groups(RR=1.58, 95%CI[0.98,2.54], P=0.06). In the 3rd month CR showed a statistically significant difference between the two treatment groups(RR=5.07, 95%CI[3.22,15.22], P<0.00001), the combination therapy precedes the monotherapy. PR at 28 days showed no statistical difference between the two treatment groups(RR=1.01, 95%CI[0.61,1.65], P=0.98). In the 3rd month PR showed no statistically significant difference between the two treatment groups(RR=1.08, 95%CI[0.67,1.74], P=0.76). SR at 6th month showed a statistically significant difference between the two treatment groups(RR=1.73, 95%CI[1.36,2.19], P<0.00001), the combination therapy precedes the monotherapy. In the 12 th month SR showed a statistically significant difference between the two treatment groups(RR=2.10, 95%CI[1.59,2.75], P<0.00001), the combination therapy precedes the monotherapy. Relapse rate showed a statistically significant difference between the two treatment groups(RR=0.65, 95%CI[0.45,0.94], P=0.02), the combination therapy precedes the monotherapy. Infection rate showed no statistical significant difference between the two treatment groups(RR=1.02, 95%CI[0.73,1.43], P=0.89). The incidence of hyperglycemia showed no statistical significant difference between the two treatment groups(RR=0.90, 95%CI[0.58,1.38], P=0.63). The incidence of hypertension showed no statistical significant difference between the two treatment groups(RR=1.19, 95%CI[0.75,1.89], P=0.45). The incidence of electrolyte disturbances showed no statistical significant difference between the two treatment groups(RR=1.18, 95%CI[0.77,1.80], P=0.45). The incidence of serious adverse events showed a statistically significant difference between the two treatment groups(RR=2.10, 95%CI[1.07,4.13], P=0.03), combination therapy increased the incidence of serious adverse events. According to the results of meta-analyses, the OR of rituximab combined with dexamethasone compared with high dose dexamethasone monotherapy at 28 days showed no statistical difference between the two treatment groups(RR=1.13, 95%CI[0.97,1.32], P=0.11). CR at 28 days showed no statistical difference between the two treatment groups(RR=2.25, 95%CI[0.73,6.95], P=0.16). PR at 28 days showed no statistical difference between the two treatment groups(RR=1.13, 95%CI[0.65,1.95], P=0.67). SR at 6th month showed a statistically significant difference between the two treatment groups(RR=1.65, 95%CI[1.25,2.18], P=0.0004), the combination therapy precedes the monotherapy. In the 12 th month SR showed a statistically significant difference between the two treatment groups(RR=2.37, 95%CI[1.42,3.97], P=0.0010), the combination therapy precedes the monotherapy. Relapse rate showed a statistically significant difference between the two treatment groups(RR=0.63, 95%CI[0.41,0.96], P=0.03), the combination therapy precedes the monotherapy. The incidence of hyperglycemia showed no statistical significant difference between the two treatment groups(RR=0.92, 95%CI[0.60,1.43], P=0.72). The incidence of hypertension showed no statistical significant difference between the two treatment groups(RR=1.16, 95%CI[0.73,1.85], P=0.54). Conclusion The short-term efficacy is similar between Rituximab combined with glucocorticoid therapy and glucocorticoid monotherapy in ITP patients. However, the long-term efficacy of combination therapy benefit significantly, while reducing the relapse rate. The incidence of mild adverse events is similar. It increase the incidence of serious adverse events, but the incidence is still low. In summary, rituximab combined with glucocorticoids in clinical programs should be an effective and safe treatment option.