J Crohns Colitis. 2023 Dec 2:jjad203. doi: 10.1093/ecco-jcc/jjad203. Online ahead of print.

Christina Kapizioni ^1 2, Rofaida Desoki ^1 3, Danielle Lam ^1 4, Karthiha Balendran ^1 5, Eman Al-Sulais ^1 6, Sreedhar Subramanian ¹, Joanna E Rimmer ⁷, Juan De La Revilla Negro ¹, Holly Pavey ^8 9, Laetitia Pele ^10 11, Johanne Brooks ^12 13, Gordon W Moran ¹⁴, Peter M Irving ^15 16, Jimmy K Limdi ^17 18, Christopher A Lamb ^19 20; UK IBD BioResource Investigators; Miles Parkes ¹, Tim Raine ¹

Author information

¹Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

²Department of Gastroenterology, Attikon University Hospital, Athens, Greece.

³Department of Genetics, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

⁴Department of Gastroenterology, Sir Charles Gairdner Hospital, Perth, Australia.

⁵Department of Clinical Medicine, University of Jaffna, Sri Lanka.

⁶King Fahad Specialist Hospital, Dammam, Saudi Arabia.

⁷Academic Department of Military Medicine, Royal Centre for Defence Medicine, Medical Directorate, Joint Medical Command, Birmingham Research Park, Birmingham, UK.

⁸Division of Experimental Medicine and Immunotherapeutics, Department of Medicine, University of Cambridge, Cambridge, UK.

⁹Institute of Health Economics, Medical University Innsbruck, Innsbruck, Austria.

¹⁰Department of Medicine, University of Cambridge, UK.

¹¹IBD BioResource, NIHR BioResource, Cambridge, UK.

¹²Department of Clinical Pharmacology and Biological Sciences, University of Hertfordshire, Hatfield, UK.

¹³Gastroenterology Department, Lister Hospital, Stevenage, UK.

¹⁴University of Nottingham, NIHR Nottingham Biomedical Research Centre, Nottingham, Nottinghamshire, UK.

¹⁵Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

¹⁶School of Immunology and Microbial Sciences, King's College London, London, UK.

¹⁷IBD Section- Northern Care Alliance NHS Foundation Trust, Manchester, UK.

¹⁸Faculty of Biology, Medicine & Health,University of Manchester.

¹⁹Clinical and Translational Research Institute, Newcastle University, Newcastle upon Tyne, UK.

²⁰Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

Abstract

Background and aims: To compare effectiveness of different biologic therapies and sequences in patients with Inflammatory Bowel Disease (IBD) using real-world data from a large cohort with long exposure.

Methods: Demographic, disease, treatment and outcome data were retrieved for patients in the UK IBD BioResource. Effectiveness of treatment was based on persistence free of discontinuation or failure, analysed by Kaplan-Meier survival analysis with inverse probability of treatment weighting to adjust for differences between groups.

Results: 13,222 evaluable patients received at least one biologic. In ulcerative colitis (UC) first line vedolizumab (VDZ) demonstrated superior effectiveness over five years compared to anti-TNF agents (p=0.006). VDZ was superior to both infliximab (IFX) and adalimumab (ADA) after ADA and IFX failure respectively (p<0.001 and p<0.001). Anti-TNF therapy showed similar effectiveness when used first-line, or after failure of VDZ. In Crohn's disease (CD) we found significant differences between first line treatments over ten years (p=0.045), with superior effectiveness of IFX compared to ADA in perianal CD. Non-anti-TNF biologics were superior to a second anti-TNF after first line anti-TNF failure in CD (p=0.035). Patients with UC or CD experiencing TNF-failure due to delayed loss of response or intolerance had superior outcomes when switching to a non-anti-TNF biologic, rather than a second anti-TNF.

Conclusions: We provide real-world evidence to guide biologic selection and sequencing in a range of common scenarios. Our findings challenge current guidelines regarding drug selection after loss of response to first anti-TNF.