Targeting the unmet needs in IBD: Emerging therapies beyond biologics and small molecules

Despite progress with biologics and small molecules, a substantial proportion of patients with inflammatory bowel disease (IBD) continue to face unmet needs, including non-response, disease recurrence, and impaired quality of life. These limitations highlight the need for novel therapeutic strategies that go beyond current pharmacological approaches, including biologics and small molecules. This review explores emerging therapies aimed at restoring immune balance, repairing intestinal function and improving long-term outcomes in IBD. Cellular and genetic therapies offer promising avenues to restore immune tolerance and promote mucosal healing in IBD. Likewise, microbiome-based interventions aim to rebalance gut inflammation and host-microbe interactions. Additional strategies focus on targeted immunomodulation through therapeutic peptides, RNA-based agents, and vaccines directed against intestinal antigens. Complementary and alternative medicine, including dietary approaches, nutraceuticals and psychological therapies is also gaining attention within integrative care models. While these approaches are conceptually compelling, most remain in the early stages of clinical or preclinical development. Their therapeutic potential has yet to be fully validated and further research is essential to establish their efficacy, safety, and long-term impact. Taken together, these emerging strategies represent a shift beyond conventional therapies, moving toward modifying disease trajectory and improving patient-centered outcomes. However, their successful integration into IBD clinical practice will require robust evidence, standardized protocols, and a multidisciplinary framework grounded in real-world applicability.