Monotherapy with Upadacitinib in MTX-naïve Patients with Rheumatoid Arthritis: Results at 48 Weeks

Ronald van Vollenhoven¹, Tsutomu Takeuchi ², Aileen Pangan ³, Alan Friedman ³, Su Chen ³, Maureen Rischmueller ⁴, Ricardo Blanco ⁵, Ricardo Machado Xavier ⁶ and Vibeke Strand ⁷, ¹Amsterdam Rheumatology and Immunology Center, Amsterdam, Netherlands, ²Keio University School of Medicine, Tokyo, Japan, ³AbbVie Inc., North Chicago, ⁴Department of Rheumatology, The Queen Elizabeth Hospital and University of Adelaide, South Australia, Australia, ⁵Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, Spain, ⁶Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil, ⁷Division of Immunology/Rheumatology, Stanford University, Stanford, CA

Meeting: ACR/ARP Annual Meeting 2019

Keywords: rheumatoid arthritis, treatment and clinical trials

Session Information

Date: Sunday, November 10, 2019

Title: 3S109: RA – Treatments II: Novel Treatments for RA (927–932)

Session Type: ACR Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Upadacitinib (UPA), a JAK1-selective inhibitor, was efficacious as monotherapy upto 24 weeks (wks) in MTX-naive patients (pts) with active RA.¹

To assess safety and efficacy of UPA through 48 wks in an ongoing extension of the ph 3 SELECT-EARLY RCT.

Methods: 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 >2.8 and < 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 >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.

Results: 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.

Conclusion: 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.

Disclosure: R. van Vollenhoven, AbbVie, 2, 5, 8, AbbVie, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline (GSK), Lilly, Pfizer, and UCB, 2, AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB., 5, Amgen, 2, AstraZeneca, 5, 8, Biotest, 5, 8, Bristol-Myers Squibb, 2, 5, 8, Celgene, 5, 8, Crescendo Bioscience, 5, 8, GlaxoSmithKline, 2, 5, 8, Janssen, 5, 8, Janssen Research & Development, LLC, 2, Lilly, 5, 8, Merck, 5, 8, Novartis, 5, 8, Pfizer, 2, 5, 8, Roche, 2, 5, 8, UCB, 2, 5, 8, Vertex, 5, 8; T. Takeuchi, AbbVie, 2, 5, 8, AbbVie GK, 2, 9, Asahi Kasei, 2, Asahikasei, 2, Asahikasei Pharma Corp., 2, Astellas, 2, 8, 9, Astellas Pharma Inc, 2, Astellas Pharma, Inc., 2, 5, 8, 9, Astra Zeneca, 2, AstraZeneca, 8, AYUMI, 2, 9, AYUMI Pharmaceutical Corporation, 2, BMS, 2, 8, Boehringer-ingelheim, 9, Bristol–Myers K.K., 9, Bristol-Myers, 2, Bristol-Myers Squibb, 8, Chugai, 2, 8, 9, Chugai Pharmaceutical Co, Ltd., 2, Daiichi Sankyo, 2, 8, 9, Daiichi Sankyo Co., Ltd., 2, Eisai, 2, 5, 8, 9, Eisai Co., Ltd., 2, Eli Lilly, 2, 8, Eli Lilly Japan, 9, Gilead Sciences, Inc., 9, GlaxoSmithKline K.K, 9, GSK, 8, Janssen, 2, 8, Janssen Pharmaceutical K.K, 9, Mitsubishi Tanabe, 2, 9, Mitsubishi Tanabe Pharma Co., 2, Mitsubishi-Tanabe Pharma Corp, 2, 8, 9, Nippon Kayaku, 2, Nipponkayaku, 2, 9, Nipponkayaku Co.Ltd., 2, Novartis, 2, 8, Novartis Pharma K.K, 2, 9, Novartis Pharma K.K., 2, Pfizer, 2, 8, Pfizer Japan, 2, 9, Pfizer Japan Inc., 2, Sanofi, 8, Sanofi K.K, 9, Shionogi & Co., 2, Shionogi & Co., LTD., 2, Taiho, 2, 8, 9, Taisho, 9, Taisho Toyama, 2, 8, Takahashi Industrial and Economic Research Foundation, 2, Takeda, 2, 8, Takeda Pharmaceutical Co., Ltd., 2, Teijin, 2, 8, UCB, 8, 9, UCB Japan, 9; A. Pangan, AbbVie, 3, 4, AbbVie Inc., 3, 4; A. Friedman, AbbVie, 1, 3, Abbvie, 1, 4; S. Chen, AbbVie, 3, 4; M. Rischmueller, AbbVie, 5, Bristol-Myers Squibb, 5, Celgene, 5, GlaxoSmithKline, 5, Hospira, 5, Janssen, 5, MSD, 5, Novartis, 5, Pfizer, 5, Roche, 5, Sanofi, 5, UCB, 5; R. Blanco, AbbVie, 2, 5, 8, AbbVie, MSD, Roche, Pfizer, Bristol-Myers, Janssen., 2, 8, Bristol-Myers Squibb, 5, 8, Janssen, 5, 8, MSD, 2, 5, 8, Pfizer, 5, 8, Roche, 2, 5, 8; R. Xavier, AbbVie, 5, 8, BMS, 8, Janssen, 5, 8, Lilly, 5, 8, Novartis, 5, 8, Pfizer, 5, 8, Roche, 5, 8; V. Strand, Abbvie, 5, AbbVie, 5, Amgen, 5, Amgen, Abbvie, Bayer, BMS, Boehringer Ingelheim, Celltrion, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, UCB, 5, AstraZeneca, 5, AURA, 8, Bayer, 5, BMS, 5, Boehringer Ingelheim, 5, Celgene, 5, Celltrion, 5, Cleveland Clinic, 8, CORRONA, 5, Crescendo, 5, Crescendo Bioscience, 5, Eli Lilly, 5, EMD Serono, 5, Genentech, 5, GlaxoSmithKline, 5, GSK, 5, Horizon, 5, Inmedix, 5, Janssen, 5, Kezar, 5, Lilly, 5, Merck, 5, NACCME, 8, Novartis, 5, Pfizer, 5, Purdue, 8, RA Forum, 8, RAN, 8, Regeneron, 5, Roche, 5, Samsung, 5, Sandoz, 5, Sanofi, 5, Servier, 5, Setpoint, 5, SLRA, 8, UCB, 5, Up to Date, 7, Washington University, 8, WIR, 8, WRA, 8.

To cite this abstract in AMA style:

van Vollenhoven R, Takeuchi T, Pangan A, Friedman A, Chen S, Rischmueller M, Blanco R, Xavier R, Strand V. Monotherapy with Upadacitinib in MTX-naïve Patients with Rheumatoid Arthritis: Results at 48 Weeks [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/monotherapy-with-upadacitinib-in-mtx-naive-patients-with-rheumatoid-arthritis-results-at-48-weeks/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/monotherapy-with-upadacitinib-in-mtx-naive-patients-with-rheumatoid-arthritis-results-at-48-weeks/