Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA, originally approved at 5 mg twice daily (BID). In 2016, an extended-release (XR) dose of tofacitinib 11 mg once daily (QD) was approved. Limited clinical or real-world data exist comparing efficacy outcomes between 11 mg QD and 5 mg BID doses. We aimed to compare the efficacy of these formulations.

Methods: Treatment effectiveness at 6 (±3) months (mos) after initiation (baseline) was evaluated in an observational cohort of patients (pts) initiating tofacitinib 5 mg BID or 11 mg QD between February 2016 and March 2018, identified from the Corrona US RA Registry. The primary outcome was achievement of a minimum clinically important difference (MCID) in Clinical Disease Activity Index (CDAI) improvement at approximately the 6-mo visit following initiation. The MCID was dependent on baseline disease activity (≥2 if low baseline CDAI [≤10], ≥6 if moderate baseline CDAI [10<CDAI≤22], and ≥11 if high baseline CDAI [>22]). Secondary outcomes included: CDAI change from baseline to 6-mo visit, Pt Pain, and Pt Fatigue; achievement of low disease activity (LDA; CDAI ≤10) in pts without baseline LDA, or remission (CDAI ≤2.8) in pts without baseline remission, at 6 mos; and improvement ≥MCID in HAQ (≥0.22) at 6 mos. Outcomes were compared between groups in unadjusted analyses and adjusted linear and logistic regression models (covariates: age, sex, baseline CDAI, duration of RA [a priori decision], and additional covariates with standardized differences >0.2). An exploratory analysis (limited sample size) was conducted to examine 6-mo outcomes in pts who switched to 11 mg QD after 5 mg BID initiation.

Results: 791 pts initiated tofacitinib (11 mg QD: n=460; 5 mg BID: n=234), of whom 334 pts (11 mg QD: n=196; 5 mg BID: n=138) had a registry visit and thus CDAI data at 6 mos after initiation. Baseline characteristics are shown in the Table. There were no significant differences in the proportion of pts with CDAI improvements ≥MCID between formulations with and without adjustment (23.5% vs 21.0%; odds ratio 1.23; 95% confidence interval 0.70, 2.15; covariates added in the model were prior number of non-TNF inhibitors and biologic DMARDs). There were no significant differences in the odds of achieving LDA, remission or improvement in HAQ ≥0.22 between formulations with adjustment (Table). Similar proportions of pts initiating 11 mg QD and 5 mg BID remained on tofacitinib at 6 mos (61.2% vs 67.4%; p=0.43). There were 135 switchers (5 mg BID to 11 mg QD); their post-6-mo outcomes were similar to those at the time of switch.

Conclusion: Results suggest that pts with RA who initiated treatment with tofacitinib 11 mg QD achieved comparable efficacy outcomes with pts who initiated with 5 mg BID. Although currently available person years of exposure is limited, data do not suggest the emergence of any new or unexpected safety risks for the XR formulation.