POS0651 CLINICAL AND FUNCTIONAL RESPONSE TO TOFACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS: PROBABILITY PLOT ANALYSIS OF RESULTS FROM A 48-WEEK PHASE 3b/4 METHOTREXATE WITHDRAWAL STUDY

2021 
Background: The Phase 3b/4 study ORAL Shift (NCT02831855) demonstrated sustained efficacy/safety of tofacitinib modified-release 11 mg QD following MTX withdrawal, that was non-inferior to continued tofacitinib + MTX use, in patients (pts) with moderate to severe RA who achieved LDA with tofacitinib + MTX at Week (W)24.1 Objectives: To assess differences and similarities in clinical/functional responses in pts receiving tofacitinib ± MTX in ORAL Shift. Methods: In ORAL Shift, pts received open-label tofacitinib + MTX to W24; at W24, pts who achieved CDAI LDA were randomised to receive tofacitinib + MTX or tofacitinib + placebo (PBO) from W24–48. In this post hoc analysis, clinical efficacy endpoints were ACR-N (minimum % change from baseline [BL; Δ] at W48 achieved by each pt in 3 efficacy measures), ΔDAS28-4(ESR), and DAS28-4(ESR) remission/LDA (scores ≤3.2) and moderate/high disease activity (scores >3.2). Functional efficacy endpoints were ΔHAQ-DI and HAQ-DI clinically relevant functional progression (CRFP) status at W48, defined as failure to achieve improvement in HAQ-DI ≥ minimum clinically important difference (MCID; ≥0.22 decrease from BL in HAQ-DI). Thus, CRFP was defined as W24–48 were assessed by response subgroups. Results: 266 pts receiving tofacitinib + MTX and 264 pts receiving tofacitinib + PBO in W24–48 were included. At W48: mean ACR-N was numerically greater with tofacitinib + MTX vs tofacitinib + PBO (60.8 vs 53.1); mean decrease in HAQ-DI was generally similar between groups (-0.71 vs -0.67); mean decrease in DAS28-4(ESR) was numerically greater with tofacitinib + MTX vs tofacitinib + PBO (-2.95 vs -2.68). The differences/similarities between groups in ACR-N and ΔHAQ-DI were also seen in cumulative probability plots (Figure 1). CRFP rates were numerically lower with tofacitinib + MTX (18.7%) vs tofacitinib + PBO (23.5%), and in pts with remission/LDA (tofacitinib + MTX, 12.1%; tofacitinib + PBO, 16.8%) vs moderate/high disease activity (tofacitinib + MTX, 26.2%; tofacitinib + PBO, 30.8%). Median of mean CRP over time was generally numerically lower in pts with CRFP vs non-CRFP and DAS28-4(ESR)-defined remission/LDA vs moderate/high disease activity; and in those receiving tofacitinib + PBO vs tofacitinib + MTX, irrespective of CRFP or DAS28-4(ESR) disease status (Table 1). Conclusion: Although clinical/functional responses were generally similar between treatment groups, numerical improvements were seen for some efficacy endpoints with tofacitinib + MTX vs tofacitinib + PBO. A numerically higher CRFP rate may be associated with higher DAS28-4(ESR) disease activity. CRP changes up to W48 may not trend with CRFP status. References: [1]Cohen et al. Lancet Rheumatol 2019; 1: E23-34. Acknowledgements: Study sponsored by Pfizer Inc. Medical writing support was provided by Anthony G McCluskey, CMC Connect, and funded by Pfizer Inc. Disclosure of Interests: 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, Yi-Hsing Chen Grant/research support from: Bristol-Myers Squibb, GlaxoSmithKline, Pfizer Inc, Naonobu Sugiyama 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, Tatjana Lukic Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jerome Paulissen Consultant of: Pfizer Inc, Haiyun Fan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Tomohiro Hirose Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Edward Keystone Speakers bureau: AbbVie, Amgen, F. Hoffman-La Roche, Janssen, Merck, Novartis, Pfizer Inc, Sanofi Genzyme, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Eli Lilly, F. Hoffman-La Roche, Gilead Sciences, Janssen, Merck, Myriad Autoimmune, Pfizer Inc, Sandoz, Sanofi Genzyme, Samsung Bioepsis, Grant/research support from: Amgen, Merck, Pfizer Inc, PuraPharm
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