| Objective: In order to understand the difference of clinical efficacy between original TNF-α inhibitors(TNFi)and their biosimilars,Bayesian mesh meta-analysis was used to compare Enbrel,Remicade,Humira with their biosimilars in the treatment of ankylosing spondylitis(AS).Methods: A systematic literature search was performed,using Ovid Biomedical,Embase,Cochrane Library,CNKI,Wanfang Database and Weipu Database(up to December 13,2019 for all resources above),to search any language publications of randomized controlled trial(RCT)about all original and biosimilar TNFi for the treatment of AS.Two reviewers independently identified the eligible trials,evaluated bias risk using The Cochrane Collaboration’s tool for assessing risk of bias and extracted relevant data.Bayesian mesh meta-analysis(NMA)method was used to comprehensively evaluate the efficacy of Enbrel,Remicade,Humira and their biosimilar in the treatment of AS,Assessments in Ankylosing Spondylitis 20% response criteria(ASAS20),Bath Ankylosing Spondylitis Disease Activity Index(BASDAI),Bath Ankylosing Spondylitis Functional Index(BASFI)as the main outcome indexes and C-reactive protein(CRP)and erythrocyte sedimentation rate(ESR)as the secondary outcome indexes.The R3.6.1 and RStudio software were used for data analysis.Results: A total of 33 RCTs were included.Third of these RCTs were of low risk bias,the others were of high risk bias.Among the included RCTs,more RCTs were those of comparison between the original TNFi and the placebo,including Enbrel vs the placebo and Humira vs the placebo.Only few RCTs compared the TNFi biosimilars with its original drug.The sample size ranged from 30 to 566 with a total number of 5948.About 75% of the patients were male,and the positive rate of HLA-B27 was about 85%.The treatment duration ranged from 6 weeks to 24 weeks.Based on this NMA of clinical trials,Enbrel,Remicade,Humira,Yi sai pu and An bai nuo were significantly superior to placebo and sulfasalazine in terms of ASAS20,BASDAI,BASFI,CRP and ESR,but the order of efficacy was different among these outcomes.The comparison of biosimilars with their corresponding original drugs showed that there was no significant difference in main outcome indexes(ASAS20,BASDAI,BASFI)in the comparison of Yi sai pu vs Enbrel,An bai nuo vs d Enbrel,Qiang ke vs Enbrel,CT-P13 vs Remicade,B-CD55 vs Remicade,An jian ning vs d Humira and Ge le li vs Humira.Neither difference was found in the comparison of Yi sai pu vs Enbrel,An bai nuo vs Enbrel and Qiang ke vs Enbrel in terms of secondary outcome indexes CRP and ESR.Few RCTs compared of biological biosimilars with their original drugs and their methodology were flawed and the risk of bias was higher.Therefore,more studies are needed to confirm whether these biosimilars own the efficacy comparable to their original drugs.Conclusion: Enbrel,Remicade,Humira as well as their biosimilars,including Yi sai pu,An bai nuo and CT-P13,were significantly superior to placebo and sulfasalazine in terms of ASAS20,BASDAI,BASFI,CRP and ESR.Limited evidence shows that the efficacy of biological biosimilars Yi sai pu,An bai nuo,CT-P13 and Ge le li might be similar to their corresponding original drugs in those outcomes mentioned above. |
