Aze Wilson1,2,3, Bethany Choi4, Michael Sey5, Terry Ponich5, Melanie Beaton5, Richard B Kim6,4. 1. Divisions of Clinical Pharmacology, Department of Medicine, Western University, 339 A Wilson 339 Windermere Road A10-221a, London, ON, N6A 5A5, Canada. awilson2008@meds.uwo.ca. 2. Divisions of Gastroenterology, Department of Medicine, Western University, 339 Windermere Rd, London, ON, N6A 5A5, Canada. awilson2008@meds.uwo.ca. 3. Department of Physiology and Pharmacology, Western University, Medical Sciences Building, Rm 216, London, ON, N6A 5C1, Canada. awilson2008@meds.uwo.ca. 4. Department of Physiology and Pharmacology, Western University, Medical Sciences Building, Rm 216, London, ON, N6A 5C1, Canada. 5. Divisions of Gastroenterology, Department of Medicine, Western University, 339 Windermere Rd, London, ON, N6A 5A5, Canada. 6. Divisions of Clinical Pharmacology, Department of Medicine, Western University, 339 A Wilson 339 Windermere Road A10-221a, London, ON, N6A 5A5, Canada.
Abstract
BACKGROUND: The threshold concentration of infliximab during maintenance therapy has not been well-defined in relation to histologic remission. The aim of the study is to dentify the maintenance-phase infliximab concentration associated with histologic remission in inflammatory bowel disease patients (IBD). METHODS: A prospective cohort study was carried out in 104 IBD patients seen at a tertiary care centre in London, Canada. Infliximab trough concentrations were collected during the maintenance phase of treatment and compared between participants with and without evidence of histologic remission. Participants were additionally evaluated for sustained histologic remission, and relapse to active disease. RESULTS: Participants in histologic remission attained higher mean concentrations of infliximab during the maintenance phase (10.34 ± 0.69 μg/ml) compared to those with persistent disease activity (6.23 ± 0.67 μg/ml, p-value < 0.0001). Additionally, during the maintenance phase, sustained histologic remission was also associated with a higher mean concentration of infliximab (10.81 ± 5.46 μg/ml) compared to those who relapsed to active disease (5.68 ± 3.70, p < 0.001). Overall, participants with a mean infliximab trough concentration greater than 8ug/ml were more likely to have histologic remission (area under the receiver operating characteristic curve, AUROC = 0.72, 95%CI = 0.65-0.84, p < 0.0001) and sustained histologic remission (AUC = 0.77, 95%CI = 0.63-0.91, p = 0.002). CONCLUSION: Maintenance-phase infliximab trough concentrations greater than 8 μg/ml, which is higher than the currently recommended target concentration, are highly associated with histologic remission and sustained histologic remission.
BACKGROUND: The threshold concentration of infliximab during maintenance therapy has not been well-defined in relation to histologic remission. The aim of the study is to dentify the maintenance-phase infliximab concentration associated with histologic remission in inflammatory bowel diseasepatients (IBD). METHODS: A prospective cohort study was carried out in 104 IBDpatients seen at a tertiary care centre in London, Canada. Infliximab trough concentrations were collected during the maintenance phase of treatment and compared between participants with and without evidence of histologic remission. Participants were additionally evaluated for sustained histologic remission, and relapse to active disease. RESULTS:Participants in histologic remission attained higher mean concentrations of infliximab during the maintenance phase (10.34 ± 0.69 μg/ml) compared to those with persistent disease activity (6.23 ± 0.67 μg/ml, p-value < 0.0001). Additionally, during the maintenance phase, sustained histologic remission was also associated with a higher mean concentration of infliximab (10.81 ± 5.46 μg/ml) compared to those who relapsed to active disease (5.68 ± 3.70, p < 0.001). Overall, participants with a mean infliximab trough concentration greater than 8ug/ml were more likely to have histologic remission (area under the receiver operating characteristic curve, AUROC = 0.72, 95%CI = 0.65-0.84, p < 0.0001) and sustained histologic remission (AUC = 0.77, 95%CI = 0.63-0.91, p = 0.002). CONCLUSION: Maintenance-phase infliximab trough concentrations greater than 8 μg/ml, which is higher than the currently recommended target concentration, are highly associated with histologic remission and sustained histologic remission.
Authors: Cynthia W Ko; Siddharth Singh; Joseph D Feuerstein; Corinna Falck-Ytter; Yngve Falck-Ytter; Raymond K Cross Journal: Gastroenterology Date: 2018-12-18 Impact factor: 22.682
Authors: Talat Bessissow; Bart Lemmens; Marc Ferrante; Raf Bisschops; Kristel Van Steen; Karel Geboes; Gert Van Assche; Séverine Vermeire; Paul Rutgeerts; Gert De Hertogh Journal: Am J Gastroenterol Date: 2012-11-13 Impact factor: 10.864
Authors: Paul Rutgeerts; William J Sandborn; Brian G Feagan; Walter Reinisch; Allan Olson; Jewel Johanns; Suzanne Travers; Daniel Rachmilewitz; Stephen B Hanauer; Gary R Lichtenstein; Willem J S de Villiers; Daniel Present; Bruce E Sands; Jean Frédéric Colombel Journal: N Engl J Med Date: 2005-12-08 Impact factor: 91.245
Authors: C Cellier; T Sahmoud; E Froguel; A Adenis; J Belaiche; J F Bretagne; C Florent; M Bouvry; J Y Mary; R Modigliani Journal: Gut Date: 1994-02 Impact factor: 23.059
Authors: Talia Zenlea; Eric U Yee; Laura Rosenberg; Marie Boyle; Kavinderjit S Nanda; Jacqueline L Wolf; Kenneth R Falchuk; Adam S Cheifetz; Jeffrey D Goldsmith; Alan C Moss Journal: Am J Gastroenterol Date: 2016-03-15 Impact factor: 10.864
Authors: Laurent Peyrin-Biroulet; Walter Reinisch; Jean-Frederic Colombel; Gerassimos J Mantzaris; Asher Kornbluth; Robert Diamond; Paul Rutgeerts; Linda K Tang; Freddy J Cornillie; William J Sandborn Journal: Gut Date: 2013-08-23 Impact factor: 23.059