SAT0252 Clinical and functional response to tofacitinib and adalimumab in patients with rheumatoid arthritis: probability plot analysis of results from the oral strategy trial

Abstract

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). ORAL Strategy (NCT02187055), a 12-month, global, Phase 3b/4 study, demonstrated that in patients with RA and an inadequate response to methotrexate (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 Objectives: To assess 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 (DHAQ-DI) score at Month 12. Cumulative probability plots for ACR-n (where ACR is the % improvement from baseline in ACR components, and n represents the mimimum % achieved by each patient) and DHAQ-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). The cumulative probability plots of DHAQ-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. (Figure Presented) Conclusions: 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