Management of patients with inflammatory bowel diseases: evaluating effectiveness, safety, and drug repurposing strategies

Inflammatory Bowel Diseases (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic, immune-mediated conditions characterized by gastrointestinal inflammation in genetically predisposed individuals. IBD has a global prevalence of approximately 4.9 million, progressing through distinct epidemiological phases, with Western countries experiencing compounding prevalence and approaching equilibrium due to aging populations and the impact of the COVID-19 pandemic. The clinical course of IBD, marked by relapse and remission, often leads to complications such as intestinal fibrosis, particularly in CD, which can result in bowel obstruction requiring surgical intervention. The treatment landscape for IBD has evolved significantly, transitioning from corticosteroids, immunomodulators, and aminosalicylates to biologics and small molecules targeting the inflammatory cascade. Monoclonal antibodies like anti-TNF agents (e.g., infliximab, adalimumab), anti-IL-12/23 (e.g., ustekinumab), anti-IL-23 (e.g., risankizumab), Janus kinase inhibitors (e.g., tofacitinib, upadacitinib), and anti-α4β7 integrins (e.g., vedolizumab) have revolutionized disease management. However, the high cost of biologics challenges the sustainability of healthcare systems, such as the Italian National Health Service (NHS). Biosimilars, introduced as cost-effective alternatives, have demonstrated comparable efficacy and safety to originators, yet their widespread adoption is hindered by the nocebo effect and variations in prescribing practices. Despite advancements, a significant proportion of patients fail to achieve optimal therapeutic responses, and concerns about adverse events (AEs), including infections, malignancies, and hypersensitivity, persist. Active pharmacovigilance programs play a critical role in refining the safety profiles of IBD therapies by identifying both anticipated and unexpected AEs through post-marketing surveillance. Recent multicenter studies have highlighted the importance of monitoring biologics to ensure their long-term safety and effectiveness in clinical practice. Additionally, therapeutic options remain limited for managing complications such as intestinal fibrosis in CD. Innovative approaches like drug repurposing, leveraging electronic healthcare records (EHRs), offer a promising avenue to accelerate the identification of new treatments and bypass the lengthy timelines of traditional drug development. To optimize IBD management, careful patient selection, individualized treatment strategies, and rigorous long-term monitoring are essential. Ensuring adherence to clinical guidelines, assessing real-world therapeutic outcomes, and embracing cost-effective solutions, including biosimilars and drug repurposing, are vital steps toward improving patient care and sustaining healthcare systems.