The treatment outcomes with tofacitinib monotherapy were not significantly different from the combination of tofacitinib with background methotrexate. Similarly, linear meta regressions based on the duration of therapy and doses of tofacitinib did not show a significant variation in the therapeutic outcome across studies. How ever, sensitivity analysis has confirmed the robustness of the overall value. when any of the study was excluded from the analysis the overall odds ratio swings within the range of 3. 63 to 4. 79. The meta analysis of change in HAQ DI scores from baseline presents further evidence that supports the efficacy of tofacitinib in the treatment of rheumatoid arthritis. This is to mean, a statistically sig nificant improvement in HAQ DI scores were seen in patients who were on tofacitinib than placebo treated pa tients.

Furthermore, in all the included studies, patients who were treated with a greater than or equal to 5 mg of tofa citinib BID have shown a statistically significant reduction in HAQ DI scores. Heterogeneity testing showed no significant variation among the included studies. Safety and tolerability As shown in Figure 4, the proportion of infections was higher in the tofacitinib treated groups than in the placebo groups. Nonetheless, unlike in the subgroups of tofacitinib 10 mg and 15 mg, the proportion of infections in the subgroups of tofacitinib 3 mg and 5 mg were not significantly different from placebo. Whilst, with a significant heterogeneity, tofa citinib treatment was significantly associated with re duction in neutrophil counts.

The subgroups SMDs were not significant in the subgroups of tofacitinib Carfilzomib 3 mg and 15 mg. but the numbers of studies in the subgroups were very small. On the contrary, the mean hemoglobin level has in creased significantly from baselines in tofacitinib treated groups. Even though the overall SMD was statistically significant, the mean hemoglobin level was increased significantly only in the subgroup of tofacitinib 5 mg. Similarly, mean serum creatinine , HDL cholesterol , and LDL cholesterol levels have increased significantly in tofacitinib treated groups. The significant increments in mean serum creatinine, HDL cholesterol, and LDL cholesterol levels were con sistent in tofacitinib 5 mg and 10 mg treated groups. Furthermore, a significant number of patients with ALT 1 X ULN and AST 1 X ULN were reported among tofacitinib treated groups.

Yet, unlike in the subgroups of 10 mg and 15 mg the number of patients who were treated with tofacitinib and had elevated levels of both liver enzymes in the subgroup of 3 mg were not significantly different from placebo treated. In the 5 mg subgroup, a significant number of patients have had an increased level of AST level but not ALT level.