P Hindryckx1,2, G Novak1,3, N Vande Casteele1, D Laukens2, C Parker1, L M Shackelton1, N Narula4, R Khanna1,5, P Dulai6, B G Levesque1,6, W J Sandborn1,6, G D'Haens1,7, B G Feagan1,5,8, V Jairath1,5,8. 1. Robarts Clinical Trials Inc., University of Western Ontario, London, Ontario, Canada. 2. Department of Gastroenterology, University of Ghent, Ghent, Belgium. 3. Department of Gastroenterology, Ljubljana University Medical Centre, Ljubljana, Slovenia. 4. Department of Medicine and Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada. 5. Department of Medicine, University of Western Ontario, London, Ontario, Canada. 6. Division of Gastroenterology, University of California San Diego, La Jolla, California, USA. 7. Inflammatory Bowel Disease Centre, Academic Medical Centre, Amsterdam, The Netherlands. 8. Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada.
Abstract
BACKGROUND: Although optimal medical management of acute severe ulcerative colitis (UC) is ill-defined, infliximab has become a standard of care. Accumulating evidence suggests an increased rate of infliximab clearance in patients with acute severe UC and a reduced colectomy rate with an intensified infliximab induction regimen. AIM: To assess the strength of the current evidence for the relationship between infliximab pharmacokinetics, dosing strategies and disease behaviour in patients with acute severe UC. METHODS: We systematically searched MEDLINE and conference proceedings from 2000 to 2016 for relevant articles describing the pharmacokinetics of infliximab in acute severe UC and/or infliximab dose intensification strategies in acute severe UC. Eligible articles described randomised controlled trials, and cohort, cross-sectional, and case-controlled studies. RESULTS: Of 400 citations identified, 76 studies were eligible. Increased infliximab clearance occurs in patients with acute severe UC, and is driven by the total inflammatory burden and leakage of drug into the colonic lumen. Several cohort studies suggest that infliximab dose intensification is beneficial to at least 50% of acute severe UC patients and the results of case-controlled studies indicate that an intensified infliximab dosing regimen with 1-2 additional infusions in the first 3 weeks of treatment could reduce the early (3-month) colectomy rate by up to 80%, although these data require prospective validation. CONCLUSIONS: Uncontrolled studies suggest a benefit for infliximab dose optimisation in patients with acute severe UC. A randomised controlled trial in acute severe UC patients comparing a personalised infliximab dose-optimisation strategy with conventional dosing is a research priority.
BACKGROUND: Although optimal medical management of acute severe ulcerative colitis (UC) is ill-defined, infliximab has become a standard of care. Accumulating evidence suggests an increased rate of infliximab clearance in patients with acute severe UC and a reduced colectomy rate with an intensified infliximab induction regimen. AIM: To assess the strength of the current evidence for the relationship between infliximab pharmacokinetics, dosing strategies and disease behaviour in patients with acute severe UC. METHODS: We systematically searched MEDLINE and conference proceedings from 2000 to 2016 for relevant articles describing the pharmacokinetics of infliximab in acute severe UC and/or infliximab dose intensification strategies in acute severe UC. Eligible articles described randomised controlled trials, and cohort, cross-sectional, and case-controlled studies. RESULTS: Of 400 citations identified, 76 studies were eligible. Increased infliximab clearance occurs in patients with acute severe UC, and is driven by the total inflammatory burden and leakage of drug into the colonic lumen. Several cohort studies suggest that infliximab dose intensification is beneficial to at least 50% of acute severe UC patients and the results of case-controlled studies indicate that an intensified infliximab dosing regimen with 1-2 additional infusions in the first 3 weeks of treatment could reduce the early (3-month) colectomy rate by up to 80%, although these data require prospective validation. CONCLUSIONS: Uncontrolled studies suggest a benefit for infliximab dose optimisation in patients with acute severe UC. A randomised controlled trial in acute severe UC patients comparing a personalised infliximab dose-optimisation strategy with conventional dosing is a research priority.
Authors: Christopher Andrew Lamb; Nicholas A Kennedy; Tim Raine; Philip Anthony Hendy; Philip J Smith; Jimmy K Limdi; Bu'Hussain Hayee; Miranda C E Lomer; Gareth C Parkes; Christian Selinger; Kevin J Barrett; R Justin Davies; Cathy Bennett; Stuart Gittens; Malcolm G Dunlop; Omar Faiz; Aileen Fraser; Vikki Garrick; Paul D Johnston; Miles Parkes; Jeremy Sanderson; Helen Terry; Daniel R Gaya; Tariq H Iqbal; Stuart A Taylor; Melissa Smith; Matthew Brookes; Richard Hansen; A Barney Hawthorne Journal: Gut Date: 2019-09-27 Impact factor: 23.059
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Authors: G Pellino; D S Keller; G M Sampietro; M Carvello; V Celentano; C Coco; F Colombo; A Geccherle; G Luglio; M Rottoli; M Scarpa; G Sciaudone; G Sica; L Sofo; R Zinicola; S Leone; S Danese; A Spinelli; G Delaini; F Selvaggi Journal: Tech Coloproctol Date: 2020-03-02 Impact factor: 3.781
Authors: Matthew C Choy; Dean Seah; David M Faleck; Shailja C Shah; Che-Yung Chao; Yoon-Kyo An; Graham Radford-Smith; Talat Bessissow; Marla C Dubinsky; Alexander C Ford; Leonid Churilov; Neville D Yeomans; Peter P De Cruz Journal: Inflamm Bowel Dis Date: 2019-06-18 Impact factor: 5.325