Outcomes of Dose Reduction, Withdrawal, and Restart of Tofacitinib in Patients with Rheumatoid Arthritis: A Prospective Observational Study


This study was designed to compare outcomes of dose reduction, withdrawal, and continuation of tofacitinib in patients with rheumatoid arthritis (RA) and to examine effectiveness of rescue with an original treatment regimen for disease flare.


We prospectively enrolled 100 patients who had high or moderate disease activity and treated them with tofacitinib at 5 mg twice daily for 1 year. All patients achieving remission or low disease activity (LDA) were assigned to a withdrawal, dose-reduction, or continuation group, then followed until disease flare or end of the study. For flare cases, the original treatment regimen was reintroduced.


During the first year, 68 patients achieved remission or LDA (median sustained time 49.0 weeks). Subsequently, disease flare occurred at the following crude incidence rates per person-year (95% confidence interval [CI]): 0.73 (0.43-1.22) after withdrawal, 0.44 (0.25-0.77) after dose reduction, and 0.04 (0.01-0.27) during continuation. Kaplan-Meier estimates of median flare-free time (95% CI) were 7.0 months (2.8-11.2) for withdrawal and 21.0 months (4.1-37.9) for dose reduction. In the Cox regression analysis, adjusted hazard ratios (95% CIs) were 18.11 (2.38-138) for withdrawal and 9.13 (1.19-70.4) for dose reduction compared with continuation. Restart of the original treatment regimen led to rapid remission in flare cases (93% for withdrawal and 100% for dose reduction).


After achievement of remission or LDA, the dose-reduction strategy seems preferable to immediate withdrawal of tofacitinib. Restart of the original regimen can reinduce RA control in flare cases.

Key Points

  • During the 1-year tofacitinib therapy, two-thirds of RA patients with high or moderate disease activity achieved rapid and sustained remission or low disease activity.
  • During subsequent years, the incidence rate and adjusted hazard ratio for disease flare were significantly higher following tofacitinib immediate withdrawal than following dose reduction.
  • Half of the patients were estimated to remain flare-free for 21 months after dose reduction and for 7 months after withdrawal of tofacitinib.
  • Restart of the original treatment regimen rapidly restored disease control in almost all flare cases.