ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • Register
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 0239

Adjudicated MACE and VTE in the Filgotinib RA Program: Integrated Analysis from Phase 2 and 3 Clinical Trials

Christina Charles-Schoeman1, Sang-Cheol Bae2, Arvind Chopra3, Stanley Cohen4, Jeffrey R Curtis5, Jacques-Eric Gottenberg6, Edward C Keystone7, Kunihiro Yamaoka8, Peter Nash9, J-Abraham Simon-Campos10, William Stohl11, Michael Weinblatt12, Rene Westhovens13, Jeff Siegel14, Iyabode Tiamiyu14, Lei Ye14, Deyuan Jiang14, Franziska Matzkies14, Angelika Jahreis14, John S. Sundy14 and Jon Giles15, 1University of California, Los Angeles, Los Angeles, CA, 2Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea, 3Center for Rheumatic Diseases, Pune, India, 4University of Texas Southwestern Medical School at Dallas, and Metroplex Clinical Research Center, Dallas, TX, 5Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, 6Strasbourg University Hospital, Strasbourg, France, 7Mount Sinai Hospital, Toronto, ON, Canada, 8Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan, 9School of Medicine Griffith University, Brisbane, Queensland, Australia, 10Köhler & Milstein Research, Mérida, Mexico, 11University of Southern California Keck School of Medicine, Los Angeles, CA, 12Brigham and Women's Hospital, Boston, MA, 13University Hospitals Leuven, Belgium, Leuven, Belgium, 14Gilead Sciences, Inc., Foster City, CA, 15Columbia University, New York, NY

Meeting: ACR Convergence 2020

Keywords: Cardiovascular, Disease-Modifying Antirheumatic Drugs (Dmards), Myocardial Infarction, rheumatoid arthritis

  • Tweet
  • Email
  • Print
Save to PDF
Session Information

Date: Friday, November 6, 2020

Session Title: RA – Treatments Poster I: RA Treatments & Their Safety

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Filgotinib (FIL)—an oral, selective Janus kinase 1 inhibitor (JAKi)—improved RA signs and symptoms in three phase 3 trials. Despite the efficacy of FIL and other JAKi, there are some concerns regarding potential for venous thromboembolism (VTE); major adverse cardiac events (MACE); and elevated platelet levels, which may result from JAK2 inhibition and modulation of thrombopoietin and could be causally related to VTE.

Methods: Patients (pts) meeting 2010 ACR/EULAR criteria for RA who participated in the phase 2 DARWIN 1–2 (D1–2), phase 3 FINCH 1–3 (F1–3), and long-term extension studies (DARWIN 3 [D3] and FINCH 4 [F4]) and received FIL 100 mg, FIL 200 mg, adalimumab (ADA), or placebo (PBO) with or without MTX were included. Events were analyzed as-exposed according to treatment received.

The week (W)12 PBO-controlled safety analysis included data from pts who received FIL 100, FIL 200, or PBO for ≤12W (D1–2, F1–2); some PBO-treated pts had additional data through W24 (F1–2). The active-controlled analysis included data from pts who received FIL 100, FIL 200, or ADA with background MTX (F1) and pts who received FIL 100 + MTX, FIL 200 + MTX, FIL 200, or MTX (F3) for ≤52W. The FIL 200 vs FIL 100 analysis included data from pts (D1–3, F1–4) for ≤5.5 years.

Data were analyzed based on whether pts did/did not experience a MACE or VTE event. For active-controlled analysis sets (except MACE in the MTX-controlled analysis set), exposure-adjusted incidence rates (EAIRs) and 95% confidence intervals (CIs) were calculated using the exact Poisson method, and treatment differences were provided with corresponding CIs based on the confidence limits of individual point estimates. For FIL 200 vs FIL 100 analyses and MACE in the MTX-controlled analysis set, EAIRs, difference in EAIRs, and 95% CIs were calculated using Poisson regression with treatment group as a covariate. Suspected MACE (cardiovascular [CV] death, myocardial infarction, and stroke) and VTE (deep vein thrombosis and pulmonary embolism) were adjudicated by a blinded independent CV safety endpoint adjudication committee.

Results: CV risk factors were common at baseline (Table 1). No VTE occurred in the 12W PBO-controlled safety analysis (Figure 1). There were 13 total VTE events. EAIR/100 patient-years of exposure (PYE) were comparable for all treatments (EAIR [n]: FIL 200, 0.2 [7]; FIL 100, 0.1 [1]; ADA, 0.3 [1]; MTX, 0.5 [2]; PBO (up to W24), 0.7 [2]; Figure 1). Crude incidence of MACE in the PBO-controlled safety analysis is shown in Figure 2. There were 32 MACE events overall. EAIRs were comparable for all treatments (EAIR [n]: FIL 200, 0.6 [16]; FIL 100, 0.6 [10]; ADA, 0.3 [1]; MTX, 0.5 [2]; PBO (up to W24), 1.0 [3]; Figure 2). Platelet counts did not increase during the study; at W52, mean platelet counts slightly decreased in all treatment arms.

Conclusion: No safety signal for VTE or MACE was observed in the filgotinib RA program. EAIRs of positively adjudicated VTE and MACE were low and consistent with expectations in patients with RA (EAIR 0.4/100 PYE for VTE and 1.0/100 PYE for MACE).1,2

References

  1. Davies R et al. Ann Rheum Dis. 2011;70:1831–4.
  2. Cooksey R et al. Semin Arthritis Rheum. 2018;48:367–73.

Table 1. Prevalence of factors associated with cardiovascular risk at baseline in patients receiving FIL 200 mg or FIL 100 mg in pooled phase 3 studies (F1, 2 and 3)

Figure 1. VTE events during the PBO-controlled, active-controlled, and long-term periods

Figure 2. MACE during the PBO-controlled, active-controlled, and long-term periods


Disclosure: C. Charles-Schoeman, AbbVie, 2, 5, Regeneron-Sanofi, 5, Gilead, 5, Bristol-Myers Squibb, 2, Pfizer Inc, 2, 5; S. Bae, None; A. Chopra, None; S. Cohen, Abbvie, 2, 5, Pfizer, 2, 5, Gilead, 2, 5, Lilly, 2, 5; J. Curtis, AbbVie, 2, 5, Amgen, 2, 5, Bristol-Myers Squibb, 2, 5, Corrona, 2, 5, Janssen, 2, 5, Lilly, 2, 5, Myriad, 2, 5, Pfizer, 2, 5, Regeneron, 2, 5, Roche, 2, 5, UCB, 2, 5, Gilead Sciences, Inc., 5, Sanofi, 5; J. Gottenberg, Bristol-Myers Squibb, 2, 8, Pfizer, 2, 5, UCB, 5, 8, Eli Lilly, 2, 8, AbbVie, 2, 8, Roche, 2, 8, Sanofi-Genzyme, 5, 8; E. Keystone, AbbVie, 2, 5, 8, Celltrion, 2, 5, 8, Eli Lilly, 2, 5, 8, Pfizer Inc, 2, 5, 8, Merck, 2, 5, 8, Sandoz, 2, 5, 8, Samsung Bioepsis, 2, 5, 8, Myriad Autoimmune, 2, 5, 8, Purapharm, 2, 5, 8, Janssen, 2, 5, 8, Sanofi-Genzyme, 2, 5, 8, Amgen, 2, 5, 8, AstraZeneca, 2, 5, 8, Bristol-Myers Squibb, 2, 5, 8, F. Hoffman-La Roche Ltd., 2, 5, 8, Genentech, 2, 5, 8, Gilead, 2, 5, 8, UCB, 2, 5, 8; K. Yamaoka, AbbVie, 2, 5, 8, Astellas, 2, 5, 8, Bristol-Myers Squibb, 8, Mitsubishi Tanabe, 2, 5, 8, Pfizer Inc, 2, 5, 8, Takeda, 5, 8, Actelion, 5, 8, Chugai, 2, 5, 8, Eisai, 2, 5, 8, Eli Lilly, 2, 5, 8, GlaxoSmithKline, 5, 8, Janssen, 5, 8, Nippon Shinyaku, 5, 8, Daiichi Sankyo, 2, 8, Teijin Pharma, 2, Merck Sharp & Dohme, 2, 8, Shionogi, 2, Nippon Kayaku, 2, 8, Takeda Industrial Pharma, 2, 8, Asahikasei Pharma Corp, 5, 8, Gilead G. K., 5, 8, Eli Lilly Japan K. K., 5, Japan Tobacco Inc., 5, Actelion Pharmaceuticals Japan, 8, Ono Pharma, 8, Otsuka Pharma, 8, Boehringer Ingelheim Japan, 8, Hisamitsu Pharma Co., 8, Sanofi, 8, AYUMI Pharma Co., 8; P. Nash, AbbVie, 2, 5, 8, Bristol Myers Squibb, 2, 5, 8, Celgene, 2, 5, 8, Eli Lilly, 2, 5, 8, Janssen, 2, 5, 8, Novartis, 2, 5, 8, Pfizer, 2, 5, 8, Roche, 2, 5, 8, Sanofi, 2, 5, 8, UCB, 2, 5, 8; J. Simon-Campos, None; W. Stohl, Gilead Sciences, Inc., 2, GlaxoSmithKline, 2, Janssen Research & Development, 5; M. Weinblatt, Crescendo Bioscience, 1, Bristol Myers Squibb, 1, Sanofi, 2, Lilly, 1, Amgen, 1, AbbVie, 5, Amgen, 2, 5, Arena, 5, Bristol Myers Squibb, 2, 5, Canfite, 1, 5, Corrona, 5, Crescendo, 2, 5, GlaxoSmithKline, 5, Gilead, 9, Horizon, 9, Johnson and Johnson, 9, Lilly, 2, 9, Pfizer, 9, Scipher, 1, 9, Set Point, 9, Roche, 9, Canfite, 1, Inmedix, 1, Lycera, 1, Vorso, 1, Scipher, 1; R. Westhovens, Celltrion, Inc., 2, 5, Galapagos NV, 2, 5, Gilead Sciences, Inc., 2, 5; J. Siegel, Gilead Sciences, Inc., 1, 3, Gilead Sciences, Inc., 3, Roche, Inc., 1; I. Tiamiyu, Gilead Sciences, Inc., 1, 3; L. Ye, Gilead Sciences, Inc., 1, 3; D. Jiang, Gilead Sciences, Inc., 1, 3; F. Matzkies, Gilead Sciences, Inc., 1, 3; A. Jahreis, Gilead Sciences, Inc., 1, 3; J. Sundy, Gilead Sciences, Inc., 1, 9; J. Giles, AbbVie, 5, Bristol-Myers Squibb, 5, Eli Lilly, 5, Gilead, 5, Pfizer, 2.

To cite this abstract in AMA style:

Charles-Schoeman C, Bae S, Chopra A, Cohen S, Curtis J, Gottenberg J, Keystone E, Yamaoka K, Nash P, Simon-Campos J, Stohl W, Weinblatt M, Westhovens R, Siegel J, Tiamiyu I, Ye L, Jiang D, Matzkies F, Jahreis A, Sundy J, Giles J. Adjudicated MACE and VTE in the Filgotinib RA Program: Integrated Analysis from Phase 2 and 3 Clinical Trials [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/adjudicated-mace-and-vte-in-the-filgotinib-ra-program-integrated-analysis-from-phase-2-and-3-clinical-trials/. Accessed March 1, 2021.
  • Tweet
  • Email
  • Print
Save to PDF

« Back to ACR Convergence 2020

ACR Meeting Abstracts - https://acrabstracts.org/abstract/adjudicated-mace-and-vte-in-the-filgotinib-ra-program-integrated-analysis-from-phase-2-and-3-clinical-trials/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

ACR Convergence: Where Rheumatology Meets. All Virtual. November 5-9.

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2021 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.