1. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study
- Author
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Nicholas A Kennedy, Graham A Heap, Harry D Green, Benjamin Hamilton, Claire Bewshea, Gareth J Walker, Amanda Thomas, Rachel Nice, Mandy H Perry, Sonia Bouri, Neil Chanchlani, Neel M Heerasing, Peter Hendy, Simeng Lin, Daniel R Gaya, J R Fraser Cummings, Christian P Selinger, Charlie W Lees, Ailsa L Hart, Miles Parkes, Shaji Sebastian, John C Mansfield, Peter M Irving, James Lindsay, Richard K Russell, Timothy J McDonald, Dermot McGovern, James R Goodhand, Tariq Ahmad, Vinod Patel, Zia Mazhar, Rebecca Saich, Ben Colleypriest, Tony C Tham, Tariq H Iqbal, Vishal Kaushik, Senthil Murugesan, Salil Singh, Sean Weaver, Cathryn Preston, Assad Butt, Melissa Smith, Dharamveer Basude, Amanda Beale, Sarah Langlands, Natalie Direkze, Franco Torrente, Juan De La Revella Negro, Chris Ewen MacDonald, Stephen M Evans, Anton V J Gunasekera, Alka Thakur, David Elphick, Achuth Shenoy, Chuka U Nwokolo, Anjan Dhar, Andrew T Cole, Anurag Agrawal, Stephen Bridger, Julie Doherty, Sheldon C Cooper, Shanika de Silva, Craig Mowat, Phillip Mayhead, Charlie Lees, Gareth Jones, James W Hart, Lisa Gervais, Paul Dunckley, Tariq Mahmood, Paul J R Banim, Sunil Sonwalkar, Deb Ghosh, Rosemary H Phillips, Amer Azaz, Richard Shenderey, Lawrence Armstrong, Claire Bell, Radhakrishnan Hariraj, Helen Matthews, Hasnain Jafferbhoy, Veena Zamvar, John S De Caestecker, Anne Willmott, Richard Miller, Palani Sathish Babu, Christos Tzivinikos, Stuart L Bloom, Guy Chung-Faye, Nicholas M Croft, John ME Fell, Marcus Harbord, Ailsa Hart, Ben Hope, James O Lindsay, Joel E Mawdsley, Alistair McNair, Kevin J Monahan, Charles D Murray, Timothy Orchard, Thankam Paul, Richard Pollok, Neil Shah, Matt W Johnson, Anita Modi, Kasamu Dawa Kabiru, B K Baburajan, Bim Bhaduri, Andrew Adebayo Fagbemi, Scott Levison, Jimmy K Limdi, Gill Watts, Stephen Foley, Arvind Ramadas, George MacFaul, John Mansfield, Leonie Grellier, Mary-Anne Morris, Mark Tremelling, Chris Hawkey, Sian Kirkham, Charles PJ Charlton, Astor Rodrigues, Alison Simmons, Stephen J Lewis, Jonathon Snook, Mark Tighe, Patrick M Goggin, Aminda N De Silva, Simon Lal, Mark S Smith, Simon Panter, Suranga Dharmisari, Martyn Carter, David Watts, Zahid Mahmood, Bruce McLain, Sandip Sen, Anna J Pigott, David Hobday, Emma Wesley, Richard Johnston, Cathryn Edwards, John Beckly, Deven Vani, Subramaniam Ramakrishnan, Rakesh Chaudhary, Nigel J Trudgill, Rachel Cooney, Andy Bell, Neeraj Prasad, John N Gordon, Matthew J Brookes, Andy Li, Stephen Gore, and Simmons, A
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Adult ,Male ,medicine.medical_specialty ,Antibodies ,Cohort Studies ,Leukocyte Count ,Young Adult ,03 medical and health sciences ,Drug withdrawal ,0302 clinical medicine ,Crohn Disease ,Risk Factors ,Internal medicine ,Azathioprine ,medicine ,Adalimumab ,Humans ,Prospective Studies ,Treatment Failure ,Adverse effect ,Prospective cohort study ,Serum Albumin ,Proportional Hazards Models ,Crohn's disease ,Hepatology ,Mercaptopurine ,business.industry ,Smoking ,Age Factors ,Gastroenterology ,Middle Aged ,medicine.disease ,Infliximab ,Clinical trial ,Methotrexate ,Treatment Outcome ,030220 oncology & carcinogenesis ,Drug Therapy, Combination ,Female ,Tumor Necrosis Factor Inhibitors ,030211 gastroenterology & hepatology ,business ,Immunosuppressive Agents ,Cohort study ,medicine.drug - Abstract
BACKGROUND: Anti-TNF drugs are effective treatments for the management of Crohn's disease but treatment failure is common. We aimed to identify clinical and pharmacokinetic factors that predict primary non-response at week 14 after starting treatment, non-remission at week 54, and adverse events leading to drug withdrawal. METHODS: The personalised anti-TNF therapy in Crohn's disease study (PANTS) is a prospective observational UK-wide study. We enrolled anti-TNF-naive patients (aged ≥6 years) with active luminal Crohn's disease at the time of first exposure to infliximab or adalimumab between March 7, 2013, and July 15, 2016. Patients were evaluated for 12 months or until drug withdrawal. Demographic data, smoking status, age at diagnosis, disease duration, location, and behaviour, previous medical and drug history, and previous Crohn's disease-related surgeries were recorded at baseline. At every visit, disease activity score, weight, therapy, and adverse events were recorded; drug and total anti-drug antibody concentrations were also measured. Treatment failure endpoints were primary non-response at week 14, non-remission at week 54, and adverse events leading to drug withdrawal. We used regression analyses to identify which factors were associated with treatment failure. FINDINGS:We enrolled 955 patients treated with infliximab (753 with originator; 202 with biosimilar) and 655 treated with adalimumab. Primary non-response occurred in 295 (23·8%, 95% CI 21·4-26·2) of 1241 patients who were assessable at week 14. Non-remission at week 54 occurred in 764 (63·1%, 60·3-65·8) of 1211 patients who were assessable, and adverse events curtailed treatment in 126 (7·8%, 6·6-9·2) of 1610 patients. In multivariable analysis, the only factor independently associated with primary non-response was low drug concentration at week 14 (infliximab: odds ratio 0·35 [95% CI 0·20-0·62], p=0·00038; adalimumab: 0·13 [0·06-0·28], p
- Published
- 2019