Etanercept Withdrawal and Retreatment in Nonradiographic Axial Spondyloarthritis: Results of RE-EMBARK, an Open-Label Phase IV Trial

Filip Van den Bosch; James Cheng-Chung Wei; Peter Nash; Francisco J Blanco; Daniela Graham; Chuanbo Zang; Edmund Arthur; Cecilia Borlenghi; Vassilis Tsekouras; Bonnie Vlahos; Atul Deodhar

doi:10.3899/jrheum.220353

Etanercept Withdrawal and Retreatment in Nonradiographic Axial Spondyloarthritis: Results of RE-EMBARK, an Open-Label Phase IV Trial

J Rheumatol. 2023 Apr;50(4):478-487. doi: 10.3899/jrheum.220353. Epub 2022 Nov 15.

Authors

Affiliations

¹ F. Van den Bosch, MD, PhD, Department of Internal Medicine and Pediatrics, Ghent University, and VIB Center for Inflammation Research, Ghent, Belgium; filip.vandenbosch@ugent.be.
² J.C.C. Wei, MD, PhD, Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Institute of Medicine, College of Medicine, Chung Shan Medical University, and Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
³ P. Nash, MD, Department of Medicine, Griffith University, Brisbane, Australia.
⁴ F.J. Blanco, MD, PhD, Universidad de A Coruña, Grupo de Investigación de Reumatología (GIR), INIBIC - Complejo Hospitalario Universitario de A Coruña, SERGAS, Departamento de Fisioterapia y Medicina, A Coruña, Spain.
⁵ D. Graham, MD, Global Product Development, Pfizer, Groton, Connecticut, USA.
⁶ C. Zang, PhD, Global Biometrics and Data Management, Pfizer, Collegeville, Pennsylvania, USA.
⁷ E. Arthur, PharmD, Clinical Development and Operations, Pfizer, Peapack, New Jersey, USA.
⁸ C. Borlenghi, MD, Inflammation & Immunology, Pfizer Global Medical Affairs, Buenos Aires, Argentina.
⁹ V. Tsekouras, MD, PhD, Inflammation & Immunology, Pfizer Global Medical Affairs, Strovolos, Cyprus.
¹⁰ B. Vlahos, BSN, MBA, Global Product Development, Pfizer, Collegeville, Pennsylvania, USA.
¹¹ A. Deodhar, MD, Division of Arthritis & Rheumatic Diseases, Oregon Health & Science University, Portland, Oregon, USA.

PMID: 36379575
DOI: 10.3899/jrheum.220353

Abstract

Objective: RE-EMBARK investigated etanercept (ETN) withdrawal and retreatment in patients with nonradiographic axial spondyloarthritis (nr-axSpA) achieving inactive disease.

Methods: Patients received ETN and a background nonsteroidal antiinflammatory drug for 24 weeks in period 1 (P1); those achieving inactive disease (Ankylosing Spondylitis Disease Activity Score [ASDAS] with C-reactive protein [CRP] < 1.3) discontinued ETN for 40 weeks or less (period 2 [P2]). Patients who flared (ASDAS with erythrocyte sedimentation rate [ESR] ≥ 2.1) were retreated for 12 weeks in period 3 (P3). The primary endpoint was the proportion of patients with inactive disease who flared within 40 weeks of ETN withdrawal. Baseline characteristics were analyzed post hoc as predictors of maintenance and regaining of inactive disease, respectively, using univariate logistic and stepwise multivariable logistic regression models.

Results: The proportion of patients experiencing flare following ETN withdrawal (P2) increased from 22.3% (25/112) after 4 weeks to 67% (77/115) after 40 weeks; 74.8% (86/115) experienced flare at any time during P2. Median time to flare was 16.1 weeks. Most patients (54/87, 62.1%) who were retreated with ETN in P3 reachieved inactive disease. Absence of both sacroiliitis detected on magnetic resonance imaging (MRI) and high-sensitivity CRP (hs-CRP) > 3 mg/L at baseline predicted inactive disease maintenance in P2 following ETN withdrawal in multivariable analysis; male sex and age younger than 40 years predicted regaining of inactive disease in P3 after flare/retreatment. There were no unexpected safety signals.

Conclusion: Approximately 25% of patients maintained inactive disease for 40 weeks after discontinuing ETN. Absence of both MRI sacroiliitis and high hs-CRP at baseline predicted response maintenance after ETN withdrawal. (ClinicalTrials.gov: NCT02509026).

Keywords: ankylosing spondylitis; biological therapy; etanercept; nonradiographic axial spondyloarthritis; retreatment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
C-Reactive Protein
Etanercept / therapeutic use
Humans
Male
Non-Radiographic Axial Spondyloarthritis*
Sacroiliitis* / diagnostic imaging
Sacroiliitis* / drug therapy
Severity of Illness Index
Spondylarthritis* / diagnostic imaging
Spondylarthritis* / drug therapy
Spondylitis, Ankylosing* / drug therapy
Treatment Outcome

Substances

Etanercept
C-Reactive Protein

Associated data

ClinicalTrials.gov/NCT02509026