Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. ORAL Strategy (NCT02187055), a 12-month, global, Phase 3b/4 study, demonstrated that in patients with RA and an inadequate response to MTX, tofacitinib + MTX was non-inferior to adalimumab + MTX, while tofacitinib monotherapy was not non-inferior to either combination based on American College of Rheumatology (ACR)50 response rates at Month 6.¹ This post hoc analysis aimed to assess the clinical and functional efficacy across treatments in the ORAL Strategy trial using cumulative probability plots.

Methods: Efficacy was evaluated between patients who received tofacitinib 5 mg twice daily (BID) as monotherapy (N=384), tofacitinib 5 mg BID + MTX (N=376), and adalimumab 40 mg subcutaneously once every 2 weeks + MTX (N=386) based on ACR responses and changes from baseline in Health Assessment Questionnaire-Disability Index (ΔHAQ-DI) at Month 12. Cumulative probability plots for ACR-n (where ACR is the % improvement from baseline in ACR components, and n represents the minimum % achieved by each patient) and ΔHAQ-DI are presented. The area under the curve (AUC) was calculated for ACR-n up to Month 12 (in months), and an analysis of covariance model was used to assess treatment effects in terms of the AUC of ACR-n at Month 12; there was no adjustment for multiplicity for this post hoc analysis.

Results: The cumulative probability plots of ACR responses at Month 12 indicated that the proportion of patients who achieved responses of ACR20, ACR50, and ACR70 was similar for tofacitinib + MTX and adalimumab + MTX, but was numerically smaller for tofacitinib monotherapy (Figure A). Responses of approximately ≥ACR80 were achieved by a similar proportion of patients in each treatment group. Least squares mean (standard error) AUC of ACR-n up to Month 12 (in months) was similar for tofacitinib + MTX (437 [35]) and adalimumab + MTX (402 [35]), but was smaller for tofacitinib monotherapy (319 [35]; p<0.05; data not shown). The cumulative probability plots of ΔHAQ-DI suggested that, in general, reductions from baseline in HAQ-DI were similar across treatment groups (Figure B), although a slightly higher proportion of patients who received tofacitinib monotherapy reported an increase in HAQ-DI vs other treatments.

Conclusion: These data support the primary ORAL Strategy findings,¹ indicating that in patients with RA, clinical efficacy, based on ACR response, was generally similar for tofacitinib + MTX and adalimumab + MTX, while a smaller proportion of patients who received tofacitinib monotherapy achieved ACR response in general, and particularly for <ACR80. Functional efficacy, based on ΔHAQ-DI, was generally similar across all treatment groups. Cumulative probability analyses for CDAI will be further evaluated.

1. Fleischmann et al. Lancet 2017; 390: 457–68.