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High body mass index is associated with increased risk of treatment failure and surgery in biologic-treated patients with ulcerative colitis.

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.

SUBMITTER: Kurnool S

PROVIDER: S-EPMC5992082 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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High body mass index is associated with increased risk of treatment failure and surgery in biologic-treated patients with ulcerative colitis.

Kurnool S S Nguyen N H NH Proudfoot J J Dulai P S PS Boland B S BS Vande Casteele N N Evans E E Grunvald E L EL Zarrinpar A A Sandborn W J WJ Singh S S

Alimentary pharmacology & therapeutics 20180417 11

<h4>Background</h4>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.<h4>Aim</h4>To evaluate the impact of obesity on real world response to biological therapy in patients with UC.<h4>Methods</h4>In a single-centre retrospective cohort study between 2011-2016 of biologic-treated patients with UC, we evaluated treatment r ...[more]

PMID: 29665045

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Project description:AimsThere are limited data examining whether body mass index (BMI) influences the association between cardiovascular biomarkers and incident heart failure (HF).Methods and resultsThirteen biomarkers representing key HF domains were measured: N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-A-type natriuretic peptide (MR-proANP), cardiac troponin T (cTnT), C-reactive protein, procalcitonin, galectin-3, C-terminal pro-endothelin-1 (CT-proET-1), mid-regional pro-adrenomedullin, plasminogen activator inhibitor-1, copeptin, renin, aldosterone, and cystatin-C. Associations of biomarkers with BMI were examined using linear regression models, and with incident HF using Cox regression models. We selected biomarkers significantly associated with incident HF, and evaluated whether BMI modified these associations. Among 8202 individuals, 41% were overweight (BMI 25-30 kg/m2 ), and 16% were obese (BMI ≥30 kg/m2 ). Mean age of the cohort was 49 years (range 28-75), and 50% were women. All biomarkers except renin were associated with BMI: inverse associations were observed with NT-proBNP, MR-proANP, CT-proET-1 and aldosterone whereas positive associations were observed with the remaining biomarkers (all P ≤ 0.001). During 11.3 ± 3.1 years of follow-up, 357 HF events were recorded. Only NT-proBNP, MR-proANP and cTnT remained associated with incident HF (P < 0.001), and a significant biomarker*BMI interaction was not observed (interaction P > 0.1). Combined NT-proBNP and cTnT measurements modestly improved performance metrics of the clinical HF model in overweight (ΔC-statistic = 0.024; likelihood ratio χ2 = 38; P < 0.001) and obese (ΔC-statistic = 0.020; likelihood ratio χ2 = 32; P < 0.001) individuals.ConclusionsPlasma concentrations of several cardiovascular biomarkers are influenced by obesity. Only NT-proBNP, MR-proANP and cTnT were associated with incident HF, and BMI did not modify these associations. A combination of NT-proBNP and cTnT improves HF risk prediction in overweight and obese individuals.

Dataset Information

High body mass index is associated with increased risk of treatment failure and surgery in biologic-treated patients with ulcerative colitis.

Publications

High body mass index is associated with increased risk of treatment failure and surgery in biologic-treated patients with ulcerative colitis.

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