Kiryat Bialik

This research aims to test if giving a short course of the antibiotic azithromycin before starting anti-tumor necrosis factor-alpha (anti-TNF) therapy can reduce the development of anti-drug antibodies (ADA) in patients with Crohn's disease. Anti-TNF agents are key treatments for inflammatory bowel diseases but their effectiveness can be limited by ADA, which cause the treatment to stop working. Current methods to reduce ADA involve immunosuppressive drugs but carry risks like infections and cancer. Based on recent findings linking antibiotic use to ADA prevention, especially with macrolide antibiotics like azithromycin, this study explores whether altering the gut microbiome before anti-TNF therapy can improve treatment durability. Participants will be randomly assigned to receive either a tablet of 500 mg azithromycin or a placebo tablet that looks the same. The treatment is given before starting anti-TNF therapy with infliximab or adalimumab. Some patients may also receive thiopurine or corticosteroid co-therapy. The study is a phase 2 randomized placebo-controlled trial comparing these groups and also includes matched historical patient data for comparison. The main focus is on ADA development one year after starting anti-TNF treatment. During the study, participants will attend all visits and complete questionnaires. Researchers will monitor antibody development and other clinical and serological data over one year. They will also track safety and adherence to the study procedures. This study requires participants to be adults aged 18 to 80 with a confirmed diagnosis of Crohn's disease and a plan to start anti-TNF therapy. The total study period includes follow-up at one year to assess the primary outcome.