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

Background and Objectives Biologic therapy has been used for Beh & ccedil;et's Syndrome after first-line immunomodulation, but in the absence of high-quality evidence or predictive biomarkers. BIO-BEH & Ccedil;ET'S was a randomized controlled clinical trial to compare the two most widely used biologics for Beh & ccedil;et's Syndrome at that time, infliximab versus interferon-alpha 2a, and identify potential biomarkers for response.Methods A total of 79 patients with active Beh & ccedil;et's Syndrome were randomized to either infliximab (REMICADE) or interferon-alpha 2a (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-alpha 2a 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-BEH & Ccedil;ET'S suggests there is potential for a novel metabolomic biomarker that can identify response to infliximab in patients with Beh & ccedil;et'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.