Efficacy And Safety Of Ruxolitinib And New Generation Of JAK2 Inhibitors In Patients With Myelofibrosis:a Meta-analysis

OBJECTIVES:To evaluate the efficacy and safety of ruxolitinib and new generation of(Janus Kinase)JAK2 inhibitors in patients with myelofibrosis(MF),compared with the best available treatment(BAT)/ placebo,in order to provide strong support for clinical treatment of MF and provide research directions for future randomized controlled trials(RCT).METHODS:Through the literature search of domestic and foreign databases,with the retrieval time from inception to January 2020,all the randomized controlled trials about ruxolitinib and the new generation of JAK2 inhibitors in the treatment of MF were screened.Then the included literatures were analyzed by Revman 5.3.RESULTS:Of the 8 studies included,there were 2,139 participants and 1,440 events.Compared with BAT/placebo,ruxolitinib was efficacious in relieving splenomegaly[RR=57.26,95%CI(11.56,283.55),P<0.00001].Compared with BAT/ placebo,the new generation of JAK2 inhibitors have effect on relieving splenomegaly[RR=5.07,95%CI(1.42,18.09),P=0.01] and improvement of symptoms[RR=2.93,95%CI(1.95,4.40),P<0.00001].In terms of safety,after the treatment of the new generation of JAK2 inhibitors,the anemia[RR=1.60,95%CI(1.24,2.05),P= 0.0003],the thrombocytopenia [RR=1.61,95%CI(1.17,2.21),P=0.003]were higher than those of BAT/ placebo.Neutropenia[RR=1.82,95%CI(0.83,3.98),P= 0.13],gastrointestinal reactions [RR=6.31,95%CI(0.96,41.52),P= 0.06],infection [RR=1.48,95%CI(0.95,2.28),P= 0.08]and other common adverse reactions,included fatigue,abdominal pain,pyrexia,dyspnoea,cardiac toxicity and peripheral neuropathy,were no significant difference compared with BAT/ placebo.The incidence of secondary tumor in Ruxolitinib[RR=3.12,95%CI(1.87),P< 0.0001)]was higher than that in BAT/ placebo,and the difference was statistically significant.There was no increased risk of conversion to acute myelocytic leukemia(AML)in patients with the new generation of JAK2 inhibitors[RR=1.79,95%CI(0.60,5.33),P=0.29] compared with BAT/ placebo.CONCLUSIONS:1.The effect on relieving splenomegaly in patients with MF treated with ruxolitinib were superior to those of BAT/ placebo group.2.Compared with the BAT/ placebo group,the new generation of JAK2 inhibitors in the treatment of MF has an advantage in improvement of symptoms,and there are possible in relieving splenomegaly.They have more bone marrow toxicity,but have no significant difference in other adverse reactions.3.Ruxolitinib probably increased the risk of secondary tumor in patients with MF,and the new generation of JAK2 inhibitors did not increase the risk of conversion from MF to AML.