Predicting response to infliximab and interferon-alpha in Behcet's syndrome: An exploratory analysis from the BIO-BEHCET'S randomized controlled trial.
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All Authors
Moots, RJ.
Fortune, F.
Jackson, R.
Thornburn, T.
Morgan, AW.
Carr, DF.
Murray, PI.
Ludwig, C.
Wallace, G.
Situnayake, D.
LTHT Author
Morgan, Ann-Wendy
LTHT Department
Rheumatology
NIHR Leeds Biomedical Research Centre
NIHR Leeds Biomedical Research Centre
Non Medic
Publication Date
2025
Item Type
Journal Article
Language
Subject
Subject Headings
Abstract
Background and Objectives: Biologic therapy has been used for Behcet's Syndrome after first-line immunomodulation, but in the absence of high-quality evidence or predictive biomarkers. BIO-BEHCET'S was a randomized controlled clinical trial to compare the two most widely used biologics for Behcet's Syndrome at that time, infliximab versus interferon-alpha2a, and identify potential biomarkers for response.
Methods: A total of 79 patients with active Behcet's Syndrome were randomized to either infliximab (REMICADE) or interferon-alpha2a (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-alpha2a 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-BEHCET'S suggests there is potential for a novel metabolomic biomarker that can identify response to infliximab in patients with Behcet'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.
Journal
Rheumatology & Immunology Research