Progressing advanced therapies for inflammatory bowel disease: Current status including dual biologic therapy and discontinuation of biologics

Advanced therapies (ADT) that encompass biological agents and small molecules have been approved for the treatment of inflammatory bowel disease (IBD), broadening the spectrum of available treatment options. Nevertheless, a substantial proportion of patients fail to achieve satisfactory responses, necessitating surgical intervention. Treatment objectives have evolved beyond clinical remission, reduction of inflammation, and mucosal healing, shifting focus toward enhancing the quality of life, acknowledging the profound impact of IBD on physical and mental well-being. This comprehensive review describes the current landscape of ADT for IBD, including dual biologic therapy (DBT), which involves the combination of two biologics or a single biologic with a small-molecule compound, as well as considerations surrounding the discontinuation of biologics. ADT is the standard treatment for moderate to severe IBD, while DBT appears promising for specific subsets of patients, including those with refractory disease or extraintestinal manifestations. However, these approaches may increase the risk of adverse effects, including malignancy. To optimize individualized treatment strategies in patients with refractory IBD, further trials are needed to refine ADT's predictive value, establish DBT's safety and indications, define biologic discontinuation criteria, and evaluate emerging biomarkers, artificial intelligence, and bowel ultrasound in patient management.