Abstract Crohn's disease (CD) is a chronic inflammatory bowel disease with increasing global prevalence, significantly impacting patients' quality of life and healthcare costs. The introduction of monoclonal antibodies has revolutionized CD management, offering targeted therapy against specific inflammatory pathways. This review systematically analyzes the current state of monoclonal antibody therapy, including anti-TNF-α agents (infliximab, adalimumab, certolizumab pegol), anti-integrin antibodies (vedolizumab), and anti-cytokine therapies (ustekinumab, risankizumab). Despite remarkable therapeutic advances, significant limitations persist, including primary non-response (20-40%), secondary loss of response (13-20% annually), immunogenicity, safety concerns, and substantial economic burden. We propose evidence-based strategies to address these challenges, including therapeutic drug monitoring, combination therapy, and personalized medicine approaches. Furthermore, we identify promising novel therapeutic targets such as IL-36, IL-17C, SMAD7, TL1A, complement components, and microbiome-related factors. Targeting two or more specific targets simultaneously appears to be a promising direction of research for the development of bi- and polyspecific monoclonal antibodies capable of interfering with multiple pathological pathways in Crohn's disease. The integration of advanced antibody engineering, personalized medicine, and innovative delivery systems represents the future direction for overcoming current limitations. Achieving sustained remission for all patients through safe, effective, and accessible therapeutic interventions remains the ultimate goal in CD management.
Blagov et al. (Tue,) studied this question.
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