Available online 25 November 2025, 102596

There has been significant progress made in inflammatory bowel disease (IBD) over the last couple of decades, with a rapidly increasing number of biologic and small molecules treatments. Coupled with a better understanding of when and how to use treatments appropriately, has resulted in substantial and meaningful improvement in outcomes for many patients. However, an ongoing issue is that around 30-40% of patients either do not respond or lose response to currently available treatments over time, underscoring the need for further novel therapeutic targets and approaches.

Two particularly exciting novel approaches include a novel class of medications targeting tumour necrosis factor-like ligand 1A (TL1A) and engaging in two pathogenic pathways simultaneously through the use of bispecific antibodies. The development of both of these potential treatment approaches have been built on decades of translational studies including initial genetic discovery and immune functional validation. The class of molecules targeting TL1A have shown high potency in the pre-clinical setting and emerging data from early-phase interventional clinical trials have been encouraging. Bispecific antibodies have been used to date mostly in the fields of haematology and oncology, but with promising initial findings in IBD that targeting multiple pathways at once, may offer the prospect of greater remission rates or more durable remission, than current strategies seeking to target single immunological pathways in isolation. This narrative review presents the latest evidence evaluating TL1A inhibition and bispecific antibodies, including the development pipeline for these molecules, as innovative approaches for the next generation of IBD treatments.

Crohn’s disease

ulcerative colitis

inflammatory bowel disease

IBD

therapeutics

TL1A

bispecific antibodies

© 2025 The Author(s). Published by Elsevier Ltd.