| Summary: | It was predicted that the biological era might alter the natural history of Crohn’s disease, preventing the well-documented inflammation–fibrosis–fistulisation sequence. However, despite the development of novel biological therapies, average efficacy at 1 year remains at 30–50%, with this number decreasing as second-line therapies are regularly required. Currently, new advanced therapies are under investigation to provide alternatives to available treatments. In addition, novel, nonpharmacological strategies are also being explored. Surgical intervention, currently inevitable in a significant proportion of patients, necessitates that prevention of postoperative recurrence is an important research focus and recent studies have shed light on the long-term efficacy of early operative interventions and emerging surgical techniques. Cellular therapies, including stem cell therapy for perianal disease, stem cell transplantation, and harnessing the therapeutic potential of regulatory T cells, are in various stages of development. These could conceivably change the landscape of Crohn’s disease management. Dietetic interventions offer a lower risk alternative that may be used as an adjunct to other therapies or where immunosuppression is unfavourable. Choosing between these therapeutic options depends on multiple factors, including the associated risk–benefit profile, available alternatives, as well as patient preference. In practice, optimal management is guided by a multidisciplinary team where pharmacological, nonpharmacological, and surgical strategies can be simultaneously explored. This narrative review aims to provide an update on advanced therapies under investigation in clinical trials and offer insights into novel, nonpharmacological approaches with a focus on interventions entering late-phase trials that will be relevant to clinical practice in the near future.
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