This is to mean, the number of patients who discontinued medica tion because of treatment emergent adverse events in the tofacitinib treated groups was not significantly different from placebo treated groups. As shown on the forest plot, patients who were treated with tofacitinib 15 mg BID was more likely to discontinue medication than those patients who were on other smaller doses of tofacitinib. Discussion This meta analysis has demonstrated the efficacy of tofa citinib in the treatment of active rheumatoid arthritis in patients with an inadequate response to at least one DMARDs. That is, although all the recruited patients with rheumatoid arthritis had an inadequate response or intolerance to at least one DMARDs and had active disease on the basis of the ACR 1987 revised criteria, a significant improvement in physical functions and a significant reduction in the signs and symptoms of the disease were seen in tofacitinib treated patients.

ACR20 response rates and change in HAQ DI were sig nificant in all tofacitinib treatment groups 3 mg BID than placebo groups. However, there was a significant heterogeneity among the included studies. But sensitivity analysis has demonstrated the stability of the pooled values. Accordingly the conclusiveness of the results of this meta analysis did not seem compromised. When there was a significant heterogeneity among the included studies whilst the number of included studies was small, the robustness of the pooled values was best assessed with sensitivity analysis. Tofacitinib monotherapy was as effective as tofacitinib with background methotrexate.

However, this finding must be interpreted with great cau tion. Most of the studies which evaluated the efficacy of tofacitinib in combination with methotrexate recruited patients with a criterion of inadequate response to at least one nonbiologic or biologic disease modifying drug . In contrary, studies which compared the efficacy of tofacitinib monotherapy against placebo did not clearly state this criterion. Anacetrapib As a result, the disease state in the recruited patients may be at the earlier stage and could respond better to treatment. Additionally, a previous systematic review and meta analysis of combin ation and monotherapy treatments in DMARD experienced patients with rheumatoid arthritis has shown the superiority of combination therapy to monotherapy.

Even though the primary studies reported the manage able safety profile of tofacitinib over the treatment periods, this meta analysis has established the signifi cant association of tofacitinib with infections, decreased level of neutrophil and increased levels of hemoglobin, creatinine and liver enzymes. Similarly, an increase in HDL and LDL cholesterol were observed in patients with rheumatoid arthritis who were treated with tofacitinib.