Three-year safety and effectiveness of tofacitinib in patients with rheumatoid arthritis in Japan: final analysis of an all-case post-marketing surveillance study.

Objective: Evaluate tofacitinib real-world safety/effectiveness in patients with rheumatoid arthritis in Japan in a 3-year all-case post-marketing surveillance study.

Methods: All patients with rheumatoid arthritis who initiated tofacitinib (07/30/2013-12/03/2017) were registered in Japan. Serious infections/malignancy/mortality incidence were compared in patients with active rheumatoid arthritis after >8 mg methotrexate/week for ≥3 months who received tofacitinib or other drugs (control: methotrexate/other disease-modifying antirheumatic drugs/immunosuppressants). Disease activity was assessed over 3 years.

Results: The adherent comparative safety analysis set included 3731/2419 (tofacitinib/control) patients. Baseline (tofacitinib/control) biologic disease-modifying antirheumatic drug history (53.3%/12.2%), methotrexate history (81.4%/98.6%), and rheumatoid arthritis stage (I-II: 45.3%/67.1%) and class (1-2: 76.5%/90.8%) varied between groups. For tofacitinib vs control, incidence rates (patients with event/100 patient-years [95% confidence interval]) were 6.86 (5.96-7.86) vs 1.42 (0.97-2.00) for serious infections (adjusted hazard ratios 3.25-3.80); 1.40 (1.18-1.66) vs 0.88 (0.66-1.15) for malignancies (adjusted hazard ratios 1.37-1.53); 0.89 (0.72-1.10) vs 0.26 (0.15-0.43) for mortality (unadjusted hazard ratio 3.29). Remission/low disease activity rates with tofacitinib increased over 3 years.

Conclusions: Serious infection rates were higher, and malignancy rates were numerically higher with tofacitinib vs control. Results should be interpreted cautiously due to imbalanced groups and unmeasured confounders.