THU0193 EFFICACY OF TOFACITINIB MONOTHERAPY, TOFACITINIB WITH METHOTREXATE AND ADALIMUMAB WITH METHOTREXATE IN PATIENTS WITH EARLY (≤2 YEARS) VS ESTABLISHED (&gt;2 YEARS) RHEUMATOID ARTHRITIS: A POST HOC ANALYSIS OF DATA FROM ORAL STRATEGY
Authors: Tsutomu Takeuchi, Yoshiya Tanaka, Naonobu Sugiyama, Noriko Iikuni, Koshika Soma, Harry Shi, Eduardo Mysler, Robert J Moots, Josef S. Smolen, Roy Fleischmann
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Tofacitinib is an oral JAK inhibitor for the treatment of RA. Greater improvements in efficacy outcomes have been reported with tofacitinib 5 mg BID ± csDMARDs in patients (pts) with early vs established RA.<sup>1</sup>,<sup>2</sup> <h3>Objectives:</h3> This post hoc analysis of ORAL Strategy data evaluated the efficacy and safety of tofacitinib monotherapy, tofacitinib + methotrexate (MTX) and adalimumab (ADA) + MTX, stratified by baseline (BL) RA duration. <h3>Methods:</h3> ORAL Strategy (NCT02187055) was a P3b/4, 1-yr, double–blind, triple-dummy, active comparator-controlled study. MTX inadequate-responder pts were randomised 1:1:1 to receive tofacitinib 5 mg BID (tofa mono), tofacitinib 5 mg BID + MTX (tofa+MTX), or ADA SC 40 mg Q2W + MTX (ADA+MTX); MTX was dosed at 15–25 mg/wk except in cases of intolerance/toxicity. In this analysis, pts were stratified by BL RA duration as having early (≤2 yrs) or established (&gt;2 yrs) RA. Efficacy outcomes (Months [M]3, 6 and 12): ACR20/50/70; change from BL (Δ) in DAS28–4(ESR), SDAI and CDAI; and rates of DAS28-4(ESR)-, SDAI- and CDAI–defined LDA (≤3.2, ≤11 and ≤10, respectively) and remission (&lt;2.6, ≤3.3 and ≤2.8, respectively). Nominal p values for treatment comparisons were calculated without multiplicity adjustment; p&lt;0.05 was considered significant. Treatment-emergent AEs and serious AEs (SAEs) were assessed throughout the study. <h3>Results:</h3> 241 pts had early RA (tofa mono: N=80; tofa+MTX: N=83; ADA+MTX: N=78; mean RA duration: 1.0–1.1 yrs); 905 pts had established RA (tofa mono: N=304; tofa+MTX: N=293; ADA+MTX: N=308; mean RA duration: 9.4–10.4 yrs). BL demographics and disease characteristics were generally comparable for early vs established RA pts, with some expected differences (the latter were slightly older, and a greater proportion had received prior bDMARDs); RF+ and anti-CCP+ rates were higher for established RA pts (Table). ACR50 and ΔDAS28-4(ESR) were generally similar for tofa mono and tofa+MTX up to M12 in early RA but significantly greater with tofa+MTX in established RA (p&lt;0.05); ADA+MTX was not statistically different vs tofa+MTX in early RA (Figure). Trends were similar for all outcomes. AE rates were generally similar in early vs established RA. Trends for SAEs were less clear; rates were lowest for tofa+MTX in early RA and slightly higher for both tofacitinib arms vs ADA+MTX in established RA (Table). <h3>Conclusion:</h3> Efficacy was similar for tofa mono and tofa+MTX in early RA, and significantly higher with tofa+MTX in established RA. ADA+MTX was numerically but not always significantly more effective than tofacitinib in early RA. AE rates were generally similar regardless of BL RA duration. These findings, especially in established RA, are consistent with the conclusion of the primary analysis.<sup>3</sup> Limitations to this post hoc analysis include low numbers of early RA pts. <h3>References:</h3> [1] Hall S, et al. Arthritis Rheum2016; 68(S10): 1999-2001. [2] Fleischmann RM, et al. RMD Open2016; 2: e000262. [3] Fleischmann RM, et al. Lancet2017; 390: 457-468. <h3>Acknowledgement:</h3> Study sponsored by Pfizer Inc. Medical writing support was provided by Christina Viegelmann of CMC Connect and funded by Pfizer Inc. <h3>Disclosure of Interests:</h3> Tsutomu Takeuchi Grant/research support from: Astellas Pharma Inc, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Asahikasei Pharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Eisai Co., Ltd., AYUMI Pharmaceutical Corporation, Nipponkayaku Co. Ltd., Novartis Pharma K.K., Grant/research support from: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Grant/research support from: Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCB Japan, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Abbivie GK, Nipponkayaku Co.Ltd, Janssen Pharmaceutical K.K., Astellas Pharma Inc., Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Taisho Toyama Pharmaceutical Co. Ltd., GlaxoSmithKline K.K., UCB Japan Co. Ltd., Consultant for: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., AbbVie GK, Daiichi Sankyo Co., Ltd., Bristol Myers Squibb, and Nipponkayaku Co. Ltd., Speakers bureau: Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCB Japan, Speakers bureau: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Astellas Pharma Inc, Diaichi Sankyo Co. Ltd., Eisai Co. Ltd., Sanofi K.K., Teijin Pharma Ltd., Takeda Pharmaceutical Co. Ltd., Novartis Pharma K.K., Yoshiya Tanaka Grant/research support from: Abbvie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, MSD, Ono, Taisho-Toyama, Takeda, Speakers bureau: Abbvie, Asahi-kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Eisai, Glaxo-Smithkline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer Japan Inc, Sanofi, Takeda, UCB, YL Biologics, Naonobu Sugiyama Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Noriko Iikuni Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Koshika Soma Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Harry Shi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Eduardo Mysler Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Pfizer, Novartis, Janssen, Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lily, Janssen, Medimmune, Pfizer Inc, and Roche, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lily, Janssen, Medimmune, Pfizer Inc, and Roche, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Pfizer, Novartis, Janssen, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lily, Janssen, Medimmune, Pfizer Inc, and Roche, Robert J Moots Grant/research support from: Biogen, Bristol-Myers Squibb, Chugai, Novartis, Pfizer Inc, Roche, Sandoz, and UCB, Consultant for: Biogen, Bristol-Myers Squibb, Chugai, Novartis, Pfizer Inc, Roche, Sandoz, and UCB, Speakers bureau: Biogen, Bristol-Myers Squibb, Chugai, Novartis, Pfizer Inc, Roche, Sandoz, and UCB, Josef S. Smolen Grant/research support from: AbbVie, Eli Lilly, Janssen, MSD, Pfizer Inc, Roche, Consultant for: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, Eli Lilly, GlaxoSmithKline, ILTOO, Janssen, Medimmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, Eli Lilly, GlaxoSmithKline, ILTOO, Janssen, Medimmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, Roy Fleischmann Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celtrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer Inc, Sanofi-Aventis, UCB, Consultant for: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celtrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer Inc, Sanofi-Aventis, UCB