EARLY DISCONTINUATION OF TOFACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS CO-TREATED WITH RIFAMPIN FOR LATENT TUBERCULOSIS: RESULTS FROM THE REAL-WORLD DATA

Background: Rheumatoid arthritis (RA) patients need to undergo screening and receive treatment for latent tuberculosis infection (LTBI) before starting tofacitinib, which is primarily metabolized by cytochrome P450 (CYP) 3A4. Among chemoprophylactic agents, rifampin is known to be a potent CYP3A4 inducer; therefore, it is expected to decrease the efficacy of tofacitinib. However, tofacitinib and rifampin have been co-administered practically because of the short duration of chemoprophylaxis. Objectives: The aim of this study was to determine the efficacy of tofacitinib on co-administration with rifampin. Methods: Biologic-naive RA patients treated with tofacitinib were selected, and electronic medical reports were reviewed retrospectively. All patients underwent screening for LTBI before starting tofacitinib, and patients with positive results were treated to prevent progression to active tuberculosis. To evaluate the efficacy of tofacitinib with or without rifampin, the discontinuation rates of tofacitinib were examined during the first 6 months. Kaplan–Meier analysis was used to construct cumulative discontinuation curves, and comparisons were performed using the log-rank test. Results: Among 81 patients who started tofacitinib, 21 (25.9%) were LTBI-positive and 18 (22.2%) were administered rifampin concomitantly with tofacitinib. The median follow-up time was 6 months in both patients who received rifampin (interquartile range [IQR] 2.21, 6.00) and those who did not receive rifampin (IQR 5.97, 6.00) (p = 0.083). There were no significant differences between patients who received rifampin and those who did not receive rifampin in all baseline characteristics, except the swollen joint count (3.00 [1.75, 5.25] vs. 5.00 [4.00, 7.00]; p = 0.025), at the time of starting tofacitinib. In patients who received rifampin at the time of starting tofacitinib, the mean duration of co-administration was 47.00 ± 23.54 days (median 56; IQR 28.75, 59.00). During follow-up, 14 of the 81 patients (17.3%) discontinued tofacitinib. As shown in the Figures 1 and 2, the discontinuation rate of tofacitinib within the first 6 months was significantly higher among patients who received rifampin for LTBI than among those who did not receive rifampin (lack of efficacy: 24.7% vs. 5.1%, p = 0.008; all causes: 38.9% vs. 11.2%, p = 0.002). Seven patients discontinued tofacitinib because of uncontrolled RA activity, and rifampin had been administered concomitantly in four of these seven patients. Of the four patients, three stopped taking tofacitinib in the middle of LTBI treatment, and the DAS28-ESR scores of these patients were higher at discontinuation than at baseline. Conclusion: Discontinuation rates were higher in RA patients who started tofacitinib during chemoprophylaxis involving rifampin than in those who did not receive rifampin. Physicians should be aware that the efficacy of tofacitinib could be decreased by the chemoprophylactic regimen for tuberculosis. Disclosure of Interests:None declared