Predicting response to infliximab and interferon-α in Behçet's syndrome: An exploratory analysis from the BIO-BEHÇET'S randomized controlled trial

Robert J Moots; Farida Fortune; Richard Jackson; Tony Thornburn; Ann W Morgan; Daniel F Carr; Philip I Murray; Christian Ludwig; Graham Wallace; Deva Situnayake

doi:10.1515/rir-2025-0010

Predicting response to infliximab and interferon-α in Behçet's syndrome: An exploratory analysis from the BIO-BEHÇET'S randomized controlled trial

Rheumatol Immunol Res. 2025 Jul 1;6(2):70-79. doi: 10.1515/rir-2025-0010. eCollection 2025 Jun.

Authors

Robert J Moots^{1

2}, Farida Fortune³, Richard Jackson⁴, Tony Thornburn⁵, Ann W Morgan⁶, Daniel F Carr⁷, Philip I Murray⁸, Christian Ludwig⁸, Graham Wallace⁸, Deva Situnayake⁹

Affiliations

¹ Faculty of Health, Social Care and Medicine, Edge Hill University, Ormskirk, UK.
² Department of Academic Rheumatology, Liverpool University Hospitals NHS Foundation Trust, Aintree University Hospital, Longmoor Lane, Liverpool, L9 7AL, UK.
³ Queen Mary University of London, UK; Barts Health NHS Trust, The London Hospital, London UK.
⁴ Liverpool Clinical Trials Centre, University of Liverpool, Liverpool UK.
⁵ Behçet's UK, Kemp House, 152-160 City Road, London, UK.
⁶ Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, UK and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds UK.
⁷ Institute of Systems, Molecular and Integrated Biology, University of Liverpool, Liverpool UK.
⁸ Department of Inflammation and Ageing, University of Birmingham, Birmingham UK.
⁹ Department of Rheumatology, Sandwell and West Birmingham Hospitals, Birmingham UK.

Abstract

Background and objectives: Biologic therapy has been used for Behçet's Syndrome after first-line immunomodulation, but in the absence of high-quality evidence or predictive biomarkers. BIO-BEHÇET'S was a randomized controlled clinical trial to compare the two most widely used biologics for Behçet's Syndrome at that time, infliximab versus interferon-α2a, and identify potential biomarkers for response.

Methods: A total of 79 patients with active Behçet's Syndrome were randomized to either infliximab (REMICADE) or interferon-α2a (ROFERON) according to the UK national treatment pathway, and follow-up with symptom-directed examination undertaken at Weeks 12 and 24. The head-to-head trial included an exploratory analysis on the potential role of single nucleotide polymorphisms (SNPs) and urinary metabolomic to act as biomarkers for drug response. Genotypic analysis was performed to determine whether four SNPs in IFNL3 and IFNL4 - selected based on known effects - impacted primary and secondary outcomes. For metabolomic analyses, urine samples were analyzed by nuclear magnetic resonance spectroscopy and principal component analysis.

Results: Genetic data suggested potential association between outcomes and carriage of rs4803221 or rs7248668 variants in the IFNL3 (IL-28B) gene locus for interferon-α2a patients; however, with the relatively small sample, statistical significance was lost when corrected for multiple testing. Metabolomic analysis identified potential markers of metabolic response to infliximab.

Conclusion: BIO-BEHÇET'S suggests there is potential for a novel metabolomic biomarker that can identify response to infliximab in patients with Behçet's Syndrome. Further work will characterize the appropriate metabolite (s) from existing samples to inform future prospective trials to study this in more detail clinically.

Keywords: Behçet’s; IFNL3; infliximab; interferon; metabolomic.

© 2025 Robert J. Moots, Farida Fortune, Richard Jackson, Tony Thornburn, Ann W. Morgan, Daniel F. Carr, Philip I. Murray, Christian Ludwig, Graham Wallace, Deva Situnayake, published by De Gruyter on behalf of NCRC-DID.