gov since 2010 but peer reviewed published results were yet to be available. Consequently, the possibility of publication bias and time lag bias cannot be excluded. Although we have generated funnel plots to ac cess publication bias, the paucity of the literature makes it difficult to warrant its reliability. Secondly, the patient in the included studies all had an inadequate response to MTX treatment, which may limit the generalisability of study findings to DMARD na ve patients. Thirdly, there is substantial statistical heterogeneity between studies in the outcomes of ACR20 and ACR50 response rates. This ap parent heterogeneity was likely to be attributed to data from a single study by the Tanaka et al. However, sen sitivity analysis showed that its exclusion resulted in reduc tion in heterogeneity without materially affecting the overall conclusions.

The setting of this study was similar to all other studies in terms of concomitant medication and study duration. However we observed a high RR of ACR20 response rate, which implied that the heterogeneity may be due to the difference in study populations as this study was conducted among the Japanese population only. The other studies were conducted internationally, mainly in North America. Pharmacogenomics studies are recommended to investigate the apparent differences in efficacy. In addition, some important information was not reported in the included studies, which limit our further understanding of the efficacy and safety of tofacitinib treat ment in some circumstances. First, data according to differ ent age groups should be reported.

The manufacturer reported that elderly people receiving tofacitinib might have a higher risk of developing serious infections and more severe RA symptoms, which may render different efficacy and safety of tofacitinib. GSK-3 However, there was a lack of published information reporting the outcomes of this specific age group. Second, radiographic outcomes such as erosions, joint space narrowing and Sharp van der Heijde should be reported at least at baseline, during and at the end of the trial for assessing the efficacy but they were not reported in the included trials. Conclusions In conclusion, tofacitinib is more effective than placebo in the treatment of MTA resistant RA up to 24 weeks.

Tofacitinib is well tolerated as no statistically significant AEs impacting the immune or hematologic system were observed in short term studies compared with placebo. Despite significantly lower neutrophil counts in tofacitinib group, there were no associated treatment withdrawals. However, further studies on long term effi cacy and pharmacovigilance studies are still needed to support long term use. Background Rheumatoid arthritis is a progressive autoimmune disease that results in a systemic chronic inflammation and de struction of the joints.