POS0650 PREDICTORS OF DURABLE CLINICAL RESPONSE TO TOFACITINIB 11 MG ONCE DAILY WITH OR WITHOUT METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS: POST HOC ANALYSIS OF DATA FROM A PHASE 3b/4 METHOTREXATE WITHDRAWAL STUDY
Authors: K. Yamaoka, S. B. Cohen, N. Sugiyama, H. Shi, J. L. Rivas, A. Diehl, J. S. Smolen
Journal: Annals of the Rheumatic Diseases (2021)

Background: ORAL Shift, a global Phase 3b/4 non-inferiority study, demonstrated sustained efficacy and safety of tofacitinib modified-release (MR) 11 mg once daily (QD) following methotrexate (MTX) withdrawal in patients with rheumatoid arthritis (RA) who achieved Clinical Disease Activity Index (CDAI) low disease activity (LDA) after treatment with tofacitinib + MTX. 1 Objectives: To assess predictors of durable clinical response in patients receiving tofacitinib MR 11 mg QD in ORAL Shift. Methods: ORAL Shift ( NCT02831855 ) enrolled patients aged ≥18 years with moderate to severe RA and an inadequate response to MTX. Patients received open-label tofacitinib MR 11 mg QD + MTX for 24 weeks. Patients achieving LDA (CDAI score ≤10) at Week (W)24 entered the 24-week double-blind MTX withdrawal phase and were randomised 1:1 to receive tofacitinib MR 11 mg QD + placebo (tofacitinib monotherapy; ie blinded MTX withdrawal) or continue tofacitinib + MTX. In this post hoc analysis of randomised patients, we assessed predictors of durable response (maintenance of response from W24–48) per CDAI LDA and remission (CDAI score ≤2.8) criteria. All covariates were initially assessed for significance in a univariate logistic regression. Highly correlated covariates were reviewed to assess which would be removed prior to modelling in a multivariable logistic regression. Remaining significant (p≤0.10) covariates in the univariate regression were selected in the model using a stepwise selection process with p≤0.15 entry and p≤0.05 stay criteria. From the final model, estimated odds ratios (ORs) with 95% confidence intervals (CIs) are presented. Results: In the double-blind phase of ORAL Shift, durable CDAI LDA and remission rates were: 66.2% and 14.7%, respectively, with tofacitinib + MTX (N=266); and 55.3% and 11.0%, respectively, with tofacitinib + placebo (N=264) (Table 1). In the multivariable analysis, five patient covariates significantly predicted durable CDAI LDA (Figure 1; discussed hereafter). Each unit increase in CDAI score at W24 reduced the likelihood of maintaining CDAI LDA by 22.0%. Each unit increase in C-reactive protein (CRP) at W24 increased the likelihood of maintaining CDAI LDA by 4.0%; this may have been due to imbalanced CRP levels at W24 (randomisation) between treatment groups (Figure 1, footnote c). The odds of durable CDAI LDA were 53.0% lower in the US vs Europe and 61.0% lower in the US vs ‘other’ regions. Each unit increase in baseline Health Assessment Questionnaire-Disability Index (HAQ-DI) score reduced the odds of durable CDAI LDA by 34.0%. Patients receiving tofacitinib + MTX had 66.0% greater odds of durable CDAI LDA vs patients receiving tofacitinib + placebo. CDAI at W24 was the only significant predictor of durable CDAI remission in the multivariable analysis: OR (95% CI) 0.32 (0.24, 0.43); p&lt;0.0001. Each unit increase in CDAI score at W24 reduced the odds of durable CDAI remission by 68.0%. Table 1. Durable CDAI LDA and remission a in patients receiving tofacitinib MR 11 mg QD with MTX or placebo in the double-blind phase of ORAL Shift Tofacitinib + MTX (N=266 ) Tofacitinib + placebo (N=264 ) Durable CDAI LDA, n (%) 176 (66.2) 146 (55.3) Durable CDAI remission, n (%) 39 (14.7) 29 (11.0) a Durable CDAI LDA or remission was defined as achievement of LDA (CDAI score ≤10) or remission (CDAI score ≤2.8), respectively, at W24–48 N, number of patients in each group; n, number of patients achieving outcome Conclusion: This post hoc analysis of data from ORAL Shift found that CDAI and CRP at W24, geographic region, baseline HAQ-DI and treatment could be predictors for durable CDAI LDA. As these findings were limited to patients who achieved CDAI LDA at W24 with tofacitinib MR 11 mg QD + MTX, additional data in the general patient population need to be investigated. References: [1]Cohen et al. Lancet Rheumatol 2019; 1: E23-34. Acknowledgements: Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott, CMC Connect, and funded by Pfizer Inc. Disclosure of Interests: Kunihiro Yamaoka Speakers bureau: Actelion, Astellas, Chugai, Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, Nippon Shinyaku, Pfizer Inc, Takeda, Consultant of: Actelion, Astellas, Chugai, Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, Nippon Shinyaku, Pfizer Inc, Takeda, Stanley B. Cohen Consultant of: AbbVie, Eli Lilly, Genentech, Gilead Sciences, Pfizer Inc, Grant/research support from: AbbVie, Eli Lilly, Genentech, Gilead Sciences, Pfizer Inc, Naonobu Sugiyama Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Harry Shi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jose Luis Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Annette Diehl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Josef S. Smolen Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead Sciences, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, Grant/research support from: AbbVie and AstraZeneca