Long-Term Efficacy and Safety of Upadacitinib in Patients with Rheumatoid Arthritis: 3-year Results from the SELECT-EARLY Study

Ronald F van Vollenhoven¹, Tsutomu Takeuchi², Jacob Aelion³, Nilmo Chavez⁴, Pablo Mannucci⁵, Atul Singhal⁶, Jerzy Swierkot⁷, Alan Friedman⁸, Nasser Khan⁸, Yihan Li⁹, Xianwei Bu⁹, Justin Klaff⁸ and Vibeke Strand¹⁰, ¹Amsterdam University Medical Centers, Department of Rheumatology and Clinical Immunology, Rheumatology and Immunology Center ARC, Amsterdam, Netherlands, ²Div. Rheumatology, Keio University, Tokyo, Japan, ³Arthritis Clinic and West Tennessee Research Institute, Jackson, TN, ⁴Instituto Guatemalteco de Seguridad Social, Ciudad de Guatemala, Guatemala, ⁵Aprillus Asistencia e Investigación, Buenos Aires, Argentina, ⁶Southwest Rheumatology Research LLC, Dallas, TX, ⁷Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland, ⁸AbbVie Inc., North Chicago, IL, ⁹AbbVie Inc., North Chicago, ¹⁰Stanford University School of Medicine, Portola Valley, CA

Meeting: ACR Convergence 2021

Keywords: clinical trial, Randomized Trial, rheumatoid arthritis

Session Information

Date: Tuesday, November 9, 2021

Title: RA – Treatments Poster III: RA Treatments & Their Safety (1674–1710)

Session Type: Poster Session D

Session Time: 8:30AM-10:30AM

Background/Purpose: Upadacitinib (UPA), an oral Janus kinase inhibitor, demonstrated significant improvements in signs, symptoms, and structural inhibition as monotherapy (mono) vs methotrexate (MTX) in MTX-naïve patients (pts) with rheumatoid arthritis (RA) through 48 weeks (wks).¹ The objective of this analysis was to report the efficacy and safety of UPA vs MTX mono up to 156 wks in pts with RA from the ongoing long-term extension (LTE) of the SELECT-EARLY trial.

Methods: During the 48-wk double-blind study period, pts were randomized to UPA 15 or 30 mg once daily (QD) or MTX (titrated to 20 mg/wk by Wk 8). At Wk 26, pts who did not achieve Clinical Disease Activity Index (CDAI) remission (≤2.8) and had < 20% improvement from baseline in tender or swollen joint count received blinded rescue therapy (addition of MTX for UPA groups and UPA 15 or 30 mg for the MTX group). In the LTE, pts received open-label treatment once the last pt reached Wk 48. Efficacy assessments up to Wk 156 were summarized by randomized group and included American College of Rheumatology (ACR) responses, remission and low disease activity (LDA) measures, and change in modified Total Sharp Score (mTSS; up to 96 wks). Treatment-emergent adverse events (AEs) per 100 pt-years (PY) for pts on continuous mono were summarized through 156 wks. Non-responder imputation was used for binary endpoints for missing data and when pts received rescue therapy or prematurely discontinued the study drug.

Results: Of 945 pts randomized and treated, 775 entered the LTE on study drug (including 57 rescued pts; MTX, 33; UPA 15 mg, 17; UPA 30 mg, 7). Overall, 161 (21%) pts discontinued during the LTE. At Wk 156, higher proportions of pts randomized to UPA achieved a 20/50/70% improvement in ACR response (ACR20/50/70), LDA, and remission vs MTX (Figure). Change from baseline in mTSS at Wk 96 favored UPA vs MTX (data not shown). Most AEs were numerically more frequent with UPA 30 mg. The overall rate of serious infection was numerically higher with UPA vs MTX (Table). Herpes zoster (HZ), neutropenia, non-melanoma skin cancer (NMSC), and creatine phosphokinase (CPK) elevation were more frequent with UPA vs MTX. Two active tuberculosis (TB) events were reported in each UPA arm; 3 adjudicated gastrointestinal (GI) perforation events were observed in the UPA 30 mg arm. Adjudicated major adverse cardiovascular event (MACE) or venous thromboembolism (VTE) were comparable across treatment arms.

Conclusion: UPA monotherapy showed sustained superior clinical responses including remission vs MTX through Wk 156 but higher rates of several AEs, including HZ, neutropenia, and CPK elevations; no new safety risks were observed compared with previous results.^1,2

References:

1. van Vollenhoven R, et al. Ann Rheum Dis 2019;78:376–377.
2. Cohen SB, et al. Ann Rheum Dis 2020;annrheumdis-2020-218510.

Disclosures: R. van Vollenhoven, Bristol-Myers Squibb, 2, 5, 6, GlaxoSmithKline, 2, 5, 6, Eli Lilly, 5, Pfizer, 2, 5, 6, Roche, 5, UCB, 2, 5, 6, AbbVie, 2, 6, AstraZeneca, 2, 6, Biogen, 2, 6, Biotest,, 2, 6, Galapagos, 2, 6, Gilead, 2, 6, Janssen, 2, 6, Sanofi, 2, 6, Servier, 2, 6, Velabio, 2, 6, BMS, 5, GSK, 5, Celgene, 2, 6; T. Takeuchi, Astellas Pharma, 2, 5, 6, Chugai Pharmaceutical, 2, 5, 6, Asahi Kasei Pharma, 5, Mitsubishi Tanabe, 2, 5, 6, AbbVie, 5, 6, Daiichi Sankyo, 5, 6, Eisai, 5, 6, Shionogi, 5, Takeda, 5, UCB Japan, 5, Eli Lilly Japan, 2, 6, AYUMI, 6, Bristol-Myers Squibb, 6, Gilead Sciences, Inc., 6, Novartis, 6, Pfizer Japan, 6, Sanofi, 6, Dainippon Sumitomo, 6; J. Aelion, AbbVie, 5, Amgen, 5, AstraZeneca, 5, Bristol-Myers Squibb, 5, Celgene, 5, Eli Lilly, 5, Galapagos/Gilead, 5, Genentech, 5, GlaxoSmithKline,, 5, Horizon, 5, Janssen, 5, Mallinckrodt, 5, Nektar, 5, Nichi-Iko, 5, Novartis, 5, Pfizer, 5, Regeneron, 5, Roche, 5, Sanofi-Aventis, 5, Selecta, 5, UCB, 5; N. Chavez, AbbVie, 2, 5, 6, Galapagos, 5, Gilead, 5, Pfizer, 2, 5, 6, Sanofi, 5, Janssen, 2, 6; P. Mannucci, AbbVie, 2, 5, Bristol-Myers Squibb, 5, Eli Lilly, 5, Genentech/Roche, 5, GlaxoSmithKline, 5, Janssen, 5, UCB, 5; A. Singhal, AbbVie, 2, 5, Aclaris, 2, 5, Amgen, 2, 5, AstraZeneca, 2, 5, Bristol-Myers Squibb, 2, 5, Gilead, 2, 5, Eli Lilly, 2, 5, Idorsia, 2, 5, Novartis, Oscotec, 2, 5, Pfizer, 2, 5, Regeneron-Sanofi, 2, 5, Roche/Genentech, 2, 5, Selecta, 2, 5, Takeda, 2, 5, UCB, 2, 5, Vielabio, 2, 5; J. Swierkot, AbbVie, 2, 5, 6, Sandoz, 2, 5, 6, Pfizer, 2, 5, 6, Roche, 2, 5, 6, Bristol-Myers Squibb, 2, 5, 6, UCB, 2, 5, 6, MSD, 2, 5, 6, Accord, 2, 5, 6, Janssen, 2, 5, 6; A. Friedman, AbbVie, 3, 11; N. Khan, AbbVie, 3, 11; Y. Li, AbbVie, 3, 11; X. Bu, AbbVie, 3, 11; J. Klaff, AbbVie, 3, 11; V. Strand, Abbvie, 2, Amgen, 2, Genentech / Roche, 2, Janssen, 2, Novartis, 2, Pfizer, 2, Sanofi, 2, UCB, 2, Bristol-Myers Squibb, 2, Boehringer Ingelheim, 2, Celltrion, 2, Arena, 2, Gilead, 2, GlaxoSmithKline, 2, Ichnos, 2, Inmedix, 2, Kiniksa, 2, Merck, 2, Myriad Genetics, 2, Regeneron Pharmaceuticals, Inc., 2, Samsung, 2, Sandoz, 2, Setpoint, 2, Galapagos, 2, Horizon, 2, Lilly, 2, Rheos, 2, R-Pharma, 2, Scipher, 2, Sun Pharma, 2.

To cite this abstract in AMA style:

van Vollenhoven R, Takeuchi T, Aelion J, Chavez N, Mannucci P, Singhal A, Swierkot J, Friedman A, Khan N, Li Y, Bu X, Klaff J, Strand V. Long-Term Efficacy and Safety of Upadacitinib in Patients with Rheumatoid Arthritis: 3-year Results from the SELECT-EARLY Study [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/long-term-efficacy-and-safety-of-upadacitinib-in-patients-with-rheumatoid-arthritis-3-year-results-from-the-select-early-study/. Accessed .

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