Background/Purpose: Little is known about the real-world safety of tofacitinib, an oral Janus kinase inhibitor. We compared serious infections associated with tofacitinib, disease-modifying antirheumatic drugs (DMARDs), tumor necrosis factor inhibitors (TNFi) and non-TNF biologics in rheumatoid arthritis (RA) patients previously treated with methotrexate (MTX).

Methods: We performed a retrospective cohort study using MarketScan® Databases from 2010-2014. We studied adults with RA, previously treated with MTX, and newly prescribed one of the medications under study between January 2011 and December 2014. Cohort entry was the date of first prescription or infusion of drug. We required subjects to be continuously enrolled with medical and pharmacy coverage for 12 months before cohort entry and to have had no use of biologics or tofacitinib at any point prior to cohort entry. We defined serious infection as one associated with a hospitalization. We assessed current drug exposure considering prescription days’ supply or infusion intervals in a time-dependent manner, thereby classifying patients into one of the five groups: 1) DMARDs without biologics or tofacitinib; 2) TNFi +/- DMARDs, 3) non-TNF biologics +/- DMARDs; 4) tofacitinib +/- DMARDs, or 5) non-use (time within none of the previous groups). Subjects remained exposed for the most recently presented drug group until 90 days or until the start of a new drug. This classification was independent of whether the patient did or did not continue to use MTX, including the group 5. We estimated the rate of serious infection and hazard ratios (HR) with 95% confidence intervals (CI) to assess the risk of serious infections between the exposure groups, using group 5 as a reference. We adjusted the analysis for covariates such as sex, age, year of cohort entry, current use of MTX, and confounders in the one-year prior to cohort entry: Charlson comorbity index; use of selective COX-2 inhibitors, nonsteroidal anti-inflammatory drugs, and oral glucocorticoid (none, ≤7.5mg/day, >7.5mg/day); hospitalization for infection and for all reasons; physician, rheumatology, and emergency department visits. Patients were followed from cohort entry until the earliest date of loss of medical or pharmacy coverage, death, end of the study, or the first hospitalized infection.

Results: We included 21,832 RA patients; 0.8% with tofacitinib, 24.7% with other DMARDs, 61.2% with TNFi, and 13.3% with non-TNF biologics. Among all patients, 77.0% were female and the median age was 56 (interquartile interval 48-63) years. The incidence of serious infection with tofacitinib was 3.7 per 100 patient-years. The adjusted HR for hospitalized infection was 1.81 (95% CI 1.08-3.01) for tofacitinib compared to the reference group (Table 1).

Conclusion:

Tofacitinib was associated with more hospitalized infections, but this could represent channelling. Further analyses are underway.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/serious-infections-associated-with-tofacitinib-in-rheumatoid-arthritis-patients-previously-treated-with-methotrexate/