Interrogating host immunity to predict treatment response in inflammatory bowel disease

• Published in: Nature reviews. Gastroenterology & hepatology Vol. 17; no. 1; pp. 9 - 20
• Main Authors: Digby-Bell, Jonathan L, Atreya, Raja, Monteleone, Giovanni, Powell, Nick
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.01.2020
• Subjects: Care and treatment; Cell Movement; Clinical trials; Corticosteroids; Cytokines; Cytokines - immunology; Development and progression; Drug delivery; Drug development; Drugs; Endoscopy; Endoscopy, Gastrointestinal; Evaluation; Gastrointestinal Agents - therapeutic use; Gene Expression Profiling; Humans; Immune response; Immunity (Disease); Immunohistochemistry; Immunosuppressive agents; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - immunology; Inflammatory Bowel Diseases - pathology; Interleukin 23; Interleukin 6; Intestinal microflora; Intestine; Intravital Microscopy; Janus Kinases - immunology; Lymphocytes - immunology; Lymphocytes - pathology; Microbiomes; Microscopy, Confocal; Monoclonal antibodies; Mucosal immunity; Observations; Pathogenesis; Patients; Precision Medicine; Prognosis; Signal Transduction; Treatment Outcome; Tumor Necrosis Factor Inhibitors - therapeutic use; Ulcerative colitis; United Kingdom
• ISSN: 1759-5045; 1759-5053
• DOI: 10.1038/s41575-019-0228-5

IBD treatment is undergoing a transformation with an expanding repertoire of drugs targeting different aspects of the immune response. Three novel classes of drugs have emerged in the past decade that target leukocyte trafficking to the gut (vedolizumab), neutralize key cytokines with antibodies (ustekinumab) and inhibit cytokine signalling pathways (tofacitinib). In advanced development are other drugs for IBD, including therapies targeting other cytokines such as IL-23 and IL-6. However, all agents tested so far are hampered by primary and secondary loss of response, so it is desirable to develop personalized strategies to identify which patients should be treated with which drugs. Stratification of patients with IBD by clinical parameters alone lacks sensitivity, and alternative modalities are now needed to deliver precision medicine in IBD. High-resolution profiling of immune response networks in individual patients is a promising approach and different technical platforms, including in vivo real-time molecular endoscopy, tissue transcriptomics and germline genetics, are promising tools to help predict responses to specific therapies. However, important challenges remain regarding the clinical utility of these technologies, including their scalability and accessibility. This Review focuses on unravelling some of the complexity of mucosal immune responses in IBD pathogenesis and how current and emerging analytical platforms might be harnessed to effectively stratify and individualise IBD therapy.