THU0197 MONOTHERAPY WITH UPADACITINIB IN MTX-NAÏVE PATIENTS WITH RHEUMATOID ARTHRITIS: RESULTS AT 48 WEEKS FROM THE SELECT-EARLY STUDY
Authors: Ronald van Vollenhoven, Tsutomu Takeuchi, Aileen Pangan, Alan Friedman, Su Chen, Maureen Rischmueller, Ricardo Blanco, Ricardo Xavier, Vibeke Strand
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Upadacitinib (UPA), a JAK1-selective inhibitor, was efficacious as monotherapy upto 24 weeks (wks) in MTX-naive patients (pts) with active RA.<sup>1</sup> <h3>Objectives</h3> To assess safety and efficacy of UPA through 48 wks in an ongoing extension of the ph 3 SELECT-EARLY RCT. <h3>Methods</h3> SELECT-EARLY had a 48-wk double-blind active comparator-controlled period. Pts were initially randomized to monotherapy (mono) with UPA 15 or 30 mg or MTX (titrated up to Wk8). Rescue therapy was offered if pts met the following: (1) From Wk 12-24, pts without ≥20% improvement from BL (Δ) in both TJC and SJC at 2 consecutive visits continued blinded study drug with optimized background RA medications. (2) At Wk26, pts with CDAI ≤2.8 continued their original study drug; in pts with CDAI &gt;2.8 and &lt;20% Δ in TJC and SJC, for those on MTX, UPA15/30mg was added; for those on UPA15/30mg, MTX was added. For pts with CDAI&gt;2.8 but ≥20%Δ in TJC and SJC, background medications were optimized. Background csDMARDs could be initiated after Wk26. After Wk48, pts could continue in a long-term extension. Efficacy data up to the Wk48 visit are reported based on initial randomized treatment. For binary non-radiographic endpoints, NRI was used for missing data and rescue handling; for continuous non- radiographic endpoints, LOCF was used for rescue handling. Radiographic analyses are based on linear extrapolation for missing data imputation and rescue handling. Adverse events (AE) per 100 pt yrs (PY) are summarized up to a cut-off date of Aug 16 2018. <h3>Results</h3> Of 945 pts randomized and treated, 747(79%) completed Wk48 treatment, 163 (17.2%) discontinued (D/C) study drug prior to Wk48, 35 pts (4%) had not completed the Wk48 treatment as of this analysis. Primary reasons for D/C were AEs for 62 pts (6.5%), and lack of efficacy in 20 pts (2.1%). At Wk26, UPA15/30 was added for 37 (12%) of pts on MTX; MTX was added for 19 (6%) and 9 (3%) of pts on UPA15 and UPA30, respectively. Cumulative exposures to MTX mono, UPA15 mono and UPA30 mono were 314.4, 343.1 and 336.7 PYs, respectively. Through Wk48, pts on UPA15 and 30 vs MTX continued to have significantly greater improvements in clinical, functional and pt-reported outcomes (except FACIT-F for UPA15, p=.058 vs MTX) (Table 1). At Wk 48, CDAI Remission (REM) was achieved by 33% and 40% of pts on UPA15 and 30 respectively vs 17% on MTX; 28% and 33% vs 13% achieved Boolean REM. At Wk48, ΔmTSS were significantly less on UPA15 and UPA30 vs MTX. The safety profile of UPA15 and UPA30 mono was generally similar to MTX, except for total AEs and herpes zoster, which were higher with UPA15 and 30 vs MTX (Table 2). There were 11 deaths (including 3 non-treatment emergent deaths) due to varied causes. <h3>Conclusion</h3> UPA15 and 30 monotherapy continued to show significant improvements in RA signs and symptoms and inhibition of structural damage vs MTX through 48 wks. Only a small proportion of pts required MTX addition to UPA mono at Wk26 to achieve and maintain response. The safety profile based on all exposure remained consistent with ph 2 and 3 RCTs in RA, although an integrated safety analysis of UPA across the full ph 3 RA program will provide a more comprehensive understanding of the benefit:risk profile of UPA in RA. <h3>Reference</h3> [1] van Vollenhoven R, et al. Arthritis Rheum2018;70 <h3>Acknowledgement</h3> AbbVie, Inc was the study sponsor, contributed to study design, data collection, analysis &amp; interpretation, and to writing, reviewing, and approval of final version. Medical writing support was provided by Naina Barretto of AbbVie, Inc. <h3>Disclosure of Interests</h3> Ronald van Vollenhoven Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, and UCB, Consultant for: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, and Vertex., Speakers bureau: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, and Vertex., 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., Aileen Pangan Shareholder of: AbbVie, Employee of: AbbVie, Alan Friedman Shareholder of: AbbVie, Employee of: AbbVie, Su Chen Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Maureen Rischmueller Consultant for: Abbvie, Bristol-Meyer-Squibb, Celgene, Glaxo Smith Kline, Hospira, Janssen Cilag, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Ricardo Blanco Grant/research support from: Abbvie, MSD and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Ricardo Xavier Consultant for: Abbvie, Pfizer, Novartis, Janssen, Lilly, Roche, Vibeke Strand Consultant for: AbbVie, Amgen, Bayer, BMS, Boehringer Ingelheim, Celgene, Celltrion, CORRONA, Crescendo, EMD Serono, Genentech/Roche, GSK, Horizon, Inmedix, Janssen, Kezar, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Servier, UCB.