Meta Analysis Of Efficacy And Safety Of Interleukin-6 Receptor Antagonist For The Treatment Of Rheumatoid Arthritis

Objective:To compare the efficacy and safety of placebo and MTX with different doses regimens of interleukin-6 receptor antagonist for the treatment of Rheumatoid Arthritis.Methods:A systematic search of PubMed, High Wire, Cochrane Library, CNKI, WanFang data was performed to identify published articles of randomised, double blind, controlled trial. The quality of the articles were evaluated. Meta-analysis on the results of every trial was conducted through software RevMan 4.2.2 in terms of ACR20, ACR50, ACR70, the adverse event(AE) and other parameters, evaluated the efficacy and safety of MRA to treat RA. Then proper analysis model were chosen to merge effect size, and carried out sensitivity analysis to the results when necessary.Results:Seven trials were included, including 3,383 patients. The control groups were with placebo or MTX. According to the different dose regimens of MRA in the trial groups and the category of the medicine in the control groups, all the arms were divided into four groups, namely, high dose MRA group(8mg/kg every four weeks) and placebo group, low dose MRA group (4 mg/kg, every four weeks) and placebo group, low dose MRA group and high dose MRA group, and high dose MRA group and MTX group. According to the statistical analysis. High dose MRA was more effective than placebo(OR=6.17[3.88,9.82] for reaching ACR20). The same result was showed after conducting sensitivity analysis using a different statistical model structure(OR=4.89[3.99,5.99] for reaching ACR20). High dose MRA had more risks than placebo(OR=1.51[1.25,1.82] for AE). Low dose MRA was more effective than placebo(OR=3.61 [2.14,6.08] for reaching ACR20). There was no significant differences in safe profile between low dose MRA and placebo(OR=1.30 [0.98,1.74] for AE). Low dose MRA was less effective than high dose MRA(OR=0.54[0.42,0.70] for reaching ACR20). There was no significant differences in safe profile between low dose MRA and high dose MRA(OR=0.94[0.55,1.62] for AE). High dose MRA was more effective than MTX(OR=3.83[1.40,10.51] for reaching ACR20). There was no significant differences in safe profile between high dose MRA and MTX(OR=2.49[0.90,6.86] for AE).Conclusion:1. Intravenous infusion of MRA of 4mg/kg or 8 mg/kg every four weeks has better efficacy for the RA patients. The safety of the group with high dose of MRA is poorer than that of the placebo group. The safety of the group with low dose of MRA and that of placebo group are similar.2. The group with high dose of MRA is more effective than the group with low dose of MRA, and the safety of the two groups are similar.3. The group with high dose of MRA has better efficacy than the classic antirheumatic drug MTX during a short period of time (less than 24 weeks), and the safety of the two groups are similar. MRA is a new biologics with better efficacy and safety to treat RA.