Biologic Therapy for Inflammatory Bowel Disease: Real-World Comparative Effectiveness and Impact of Drug Sequencing in 13 222 Patients within the UK IBD BioResource
Authors: Kapizioni Christina , Desoki Rofaida , Lam Danielle , Balendran Karthiha , Al-Sulais Eman , Subramanian Sreedhar , Rimmer Joanna E , De La Revilla Negro Juan , Pavey Holly , Pele Laetitia , Brooks Johanne , Moran Gordon W , Irving Peter M , Limdi Jimmy K , Lamb Christopher A ,   UK IBD BioResource Investigators, Alexakis Christopher , Allah-Ditta Mohammed , Appleby Richard , Baburajan Bijay , Baker-Moffatt Michelle , Banerjee Tyara , Banim Paul , Beckly John , Bevan Roisin , Bloom Stuart , Bose Monica , Brinkworth Elaine , Brooks Johanne , Butcher Deborah , Butterworth Jeffrey , Chan Monica , Clark Katie , Cole Andrew , Collum Joseph , Cooney Rachel , Cummings Fraser , Davies Albert , De Silva Aminda , DeCaestecker John , Dhar Anjan , Duffy Stacey , Durai Dharmaraj , Edwards Cathryn , Foley Stephen , Glazebrook Tessa , Gordon John , Grimes Michael , Gunasekera Anton , Hancock Laura , Hanna Mina , Hart Ailsa , Hay Gini , Hobday David , Hooper Patricia , Jarvis Mark , Javaid Babur , Johnson Matthew , Joy Lijo , Kassam Rzwan , Kennedy Nick , Kent Alexandra , Bel Kok Klaartje , Koss Konrad , Lancaster Nicola , Landy Jonathan , Lees Charlie , Lewis Wendy , Lewis Stephen , Li Andy , Lobo Alan , Loehry Juliette , Macdonald Chris , Macdonald Christopher , Macfaul George , Mahmood Zahid , Mansour Dina , McLaughlin Simon , McLaughlin John , Miao Yin , Muddu Ajay , Murray Charles , Nwokolo Chuka , O’Sullivan Susan , Oglesby Abby , Panter Simon , Patel Vinod , Patterson Linda , Penn Ruth , Phillips Anne , Phillis Kath , Pollok Richard , Powles Sam , Preston Cathryn , Rahman Monira , Ramadas Arvind , Ramage John , Ramakrishnan Subramaniam , Satsangi Jack , Saunders John , Scott Glyn , Sebastian Shali , Selinger Christian , Shabana Sherif , Shah Rakesh , Sharpstone Dan , Shedwell Sophy , Sheen Christopher , Shenderey Richard , Shenoy Achuth , Simmons Alison , Singh Salil , Sinha Leena , Sivaji Ganesh , Smith Melissa , Smith Paul , Smith Katherine , Steed Helen , Steel Alan , Theron Byron , Tidbury Jude , Tindall Theresa , Tremelling Mark , Vani Deven , Verma Ajay , Walker Gareth , Warner Ben , Watson Alastair , Wesley Emma , Wiles Alan , Wilkins Joy , Williams Horace , Parkes Miles , Raine Tim 
Published: December 2023

Abstract

Background and Aims
This study compares the 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
In total, 13 222 evaluable patients received at least one biologic. In ulcerative colitis [UC] first-line vedolizumab [VDZ] demonstrated superior effectiveness over 5 years compared to anti-tumour necrosis factor [anti-TNF] agents [p = 0.006]. VDZ was superior to both infliximab [IFX] and adalimumab [ADA] after ADA and IFX failure respectively [p &lt; 0.001 and p &lt; 0.001]. Anti-TNF therapy showed similar effectiveness when used as first-line treatment, or after failure of VDZ. In Crohn’s disease [CD] we found significant differences between first-line treatments over 10 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 treatment.