S Kurnool1, N H Nguyen2, J Proudfoot3, P S Dulai4, B S Boland4, N Vande Casteele4, E Evans4, E L Grunvald5, A Zarrinpar4,6,7, W J Sandborn4, S Singh4,8. 1. School of Medicine, University of California San Diego, La Jolla, CA, USA. 2. Department of Internal Medicine, University of California San Diego, La Jolla, CA, USA. 3. Biostatistics Unit, Altman Clinical and Translational Research Institute, University of California San Diego, La Jolla, CA, USA. 4. Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA. 5. Weight Management Program, Department of Medicine, University of California San Diego, La Jolla, CA, USA. 6. Institute for Diabetes and Metabolic Health, University of California San Diego, La Jolla, CA, USA. 7. VA San Diego Health Systems, La Jolla, CA, USA. 8. Division of Biomedical Informatics, University of California San Diego, La Jolla, CA, USA.
Abstract
BACKGROUND: Though pharmacokinetic studies suggest accelerated biologic drug clearance with increasing body weight, evidence of obesity's impact on clinical outcomes in biologic-treated patients with ulcerative colitis (UC) is inconsistent. AIM: To evaluate the impact of obesity on real world response to biological therapy in patients with UC. METHODS: In a single-centre retrospective cohort study between 2011-2016 of biologic-treated patients with UC, we evaluated treatment response by baseline body mass index (BMI). Primary outcome was treatment failure (composite outcome of IBD-related surgery/hospitalisation or treatment modification including dose escalation, treatment discontinuation or addition of corticosteroids); secondary outcomes were risk of IBD-related surgery/hospitalisation and endoscopic remission. We conducted multivariate Cox proportional hazard analyses to evaluate the independent impact of BMI on clinical outcomes. Stratified analysis by weight-based regimens (infliximab) or fixed-dose regimens (adalimumab, golimumab, vedolizumab, certolizumab pegol) was performed. RESULTS: We included 160 biologic-treated UC patients (50% males, 55% on infliximab) with median (IQR) age 36 y (26-52) and BMI 24.3 kg/m2 (21.4-28.7). On multivariate analysis, each 1 kg/m2 increase in BMI was associated with 4% increase in the risk of treatment failure (adjusted hazard ratio [aHR], 1.04 [95% CI, 1.00-1.08]) and 8% increase in the risk of surgery/hospitalisation (aHR, 1.08 [1.02-1.14]). The effect on treatment failure was seen in patients on weight-based dosing regimens or fixed-dose therapies. CONCLUSION: BMI is independently associated with increased risk of treatment failure in biologic-treated patients with UC, independent of dosing regimen.
BACKGROUND: Though pharmacokinetic studies suggest accelerated biologic drug clearance with increasing body weight, evidence of obesity's impact on clinical outcomes in biologic-treated patients with ulcerative colitis (UC) is inconsistent. AIM: To evaluate the impact of obesity on real world response to biological therapy in patients with UC. METHODS: In a single-centre retrospective cohort study between 2011-2016 of biologic-treated patients with UC, we evaluated treatment response by baseline body mass index (BMI). Primary outcome was treatment failure (composite outcome of IBD-related surgery/hospitalisation or treatment modification including dose escalation, treatment discontinuation or addition of corticosteroids); secondary outcomes were risk of IBD-related surgery/hospitalisation and endoscopic remission. We conducted multivariate Cox proportional hazard analyses to evaluate the independent impact of BMI on clinical outcomes. Stratified analysis by weight-based regimens (infliximab) or fixed-dose regimens (adalimumab, golimumab, vedolizumab, certolizumab pegol) was performed. RESULTS: We included 160 biologic-treated UC patients (50% males, 55% on infliximab) with median (IQR) age 36 y (26-52) and BMI 24.3 kg/m2 (21.4-28.7). On multivariate analysis, each 1 kg/m2 increase in BMI was associated with 4% increase in the risk of treatment failure (adjusted hazard ratio [aHR], 1.04 [95% CI, 1.00-1.08]) and 8% increase in the risk of surgery/hospitalisation (aHR, 1.08 [1.02-1.14]). The effect on treatment failure was seen in patients on weight-based dosing regimens or fixed-dose therapies. CONCLUSION: BMI is independently associated with increased risk of treatment failure in biologic-treated patients with UC, independent of dosing regimen.
Authors: Shringi Sharma; Doerthe Eckert; Jeffrey S Hyams; Sven Mensing; Roopal B Thakkar; Anne M Robinson; Joel R Rosh; Frank M Ruemmele; Walid M Awni Journal: Inflamm Bowel Dis Date: 2015-04 Impact factor: 5.325
Authors: Hamed Khalili; Ashwin N Ananthakrishnan; Gauree G Konijeti; Leslie M Higuchi; Charles S Fuchs; James M Richter; Andrew T Chan Journal: Inflamm Bowel Dis Date: 2015-02 Impact factor: 5.325
Authors: Johannan F Brandse; Gijs R van den Brink; Manon E Wildenberg; Desiree van der Kleij; Theo Rispens; Jeroen M Jansen; Ron A Mathôt; Cyriel Y Ponsioen; Mark Löwenberg; Geert R A M D'Haens Journal: Gastroenterology Date: 2015-04-25 Impact factor: 22.682
Authors: T Billiet; I Cleynen; V Ballet; M Ferrante; G Van Assche; A Gils; S Vermeire Journal: Aliment Pharmacol Ther Date: 2016-08-09 Impact factor: 8.171
Authors: Jennifer L Seminerio; Ioannis E Koutroubakis; Claudia Ramos-Rivers; Jana G Hashash; Anwar Dudekula; Miguel Regueiro; Leonard Baidoo; Arthur Barrie; Jason Swoger; Marc Schwartz; Katherine Weyant; Michael A Dunn; David G Binion Journal: Inflamm Bowel Dis Date: 2015-12 Impact factor: 5.325
Authors: Animesh Jain; Nghia H Nguyen; James A Proudfoot; Christopher F Martin; William J Sandborn; Michael D Kappelman; Millie D Long; Siddharth Singh Journal: Am J Gastroenterol Date: 2019-04 Impact factor: 10.864
Authors: Stephan C Bischoff; Rocco Barazzoni; Luca Busetto; Marjo Campmans-Kuijpers; Vincenzo Cardinale; Irit Chermesh; Ahad Eshraghian; Haluk Tarik Kani; Wafaa Khannoussi; Laurence Lacaze; Miguel Léon-Sanz; Juan M Mendive; Michael W Müller; Johann Ockenga; Frank Tacke; Anders Thorell; Darija Vranesic Bender; Arved Weimann; Cristina Cuerda Journal: United European Gastroenterol J Date: 2022-08-12 Impact factor: 6.866