TY - JOUR
T1 - Patients With Inflammatory Bowel Diseases and Higher Visceral Adipose Tissue Burden May Benefit From Higher Infliximab Concentrations to Achieve Remission
AU - Yarur, Andres J.
AU - Abreu, Maria T.
AU - Deepak, Parakkal
AU - Beniwal-Patel, Poonam
AU - Papamichael, Konstantinos
AU - Vaughn, Byron
AU - Bruss, Alexandra
AU - Sekhri, Shaina
AU - Moosreiner, Andrea
AU - Gu, Phillip
AU - Kennedy, William
AU - Dubinsky, Marla
AU - Cheifetz, Adam
AU - Melmed, Gil Y.
N1 - Publisher Copyright:
© 2023 by The American College of Gastroenterology.
PY - 2023/11/1
Y1 - 2023/11/1
N2 - INTRODUCTION: In patients with inflammatory bowel diseases (IBDs), high visceral adipose tissue (VAT) burden is associated with a lower response to infliximab, potentially through alterations in volume distribution and/or clearance. Differences in VAT may also explain the heterogeneity in target trough levels of infliximab associated with favorable outcomes. The aim of this study was to assess whether VAT burden may be associated with infliximab cutoffs associated with efficacy in patients with IBD. METHODS: We conducted a prospective cross-sectional study of patients with IBD receiving maintenance infliximab therapy. We measured baseline body composition parameters (Lunar iDXA), disease activity, trough levels of infliximab, and biomarkers. The primary outcome was steroid-free deep remission. The secondary outcome was endoscopic remission within 8 weeks of infliximab level measurement. RESULTS: Overall, 142 patients were enrolled. The optimal trough levels of infliximab cutoffs associated with steroid-free deep remission and endoscopic remission were 3.9 mcg/mL (Youden Index [J]: 0.52) for patients in the lowest 2 VAT % quartiles (<1.2%) while optimal infliximab level cutoffs associated with steroid-free deep remission for those patients in the highest 2 VAT % quartiles was 15.3 mcg/mL (J: 0.63). In a multivariable analysis, only VAT % and infliximab level remained independently associated with steroid-free deep remission (odds ratio per % of VAT: 0.3 [95% confidence interval: 0.17–0.64], P < 0.001 and odds ratio per mg/mL: 1.11 [95% confidence interval: 1.05–1.19], P < 0.001). DISCUSSION: The results may suggest that patients with higher visceral adipose tissue burden may benefit from achieving higher infliximab levels to achieve remission.
AB - INTRODUCTION: In patients with inflammatory bowel diseases (IBDs), high visceral adipose tissue (VAT) burden is associated with a lower response to infliximab, potentially through alterations in volume distribution and/or clearance. Differences in VAT may also explain the heterogeneity in target trough levels of infliximab associated with favorable outcomes. The aim of this study was to assess whether VAT burden may be associated with infliximab cutoffs associated with efficacy in patients with IBD. METHODS: We conducted a prospective cross-sectional study of patients with IBD receiving maintenance infliximab therapy. We measured baseline body composition parameters (Lunar iDXA), disease activity, trough levels of infliximab, and biomarkers. The primary outcome was steroid-free deep remission. The secondary outcome was endoscopic remission within 8 weeks of infliximab level measurement. RESULTS: Overall, 142 patients were enrolled. The optimal trough levels of infliximab cutoffs associated with steroid-free deep remission and endoscopic remission were 3.9 mcg/mL (Youden Index [J]: 0.52) for patients in the lowest 2 VAT % quartiles (<1.2%) while optimal infliximab level cutoffs associated with steroid-free deep remission for those patients in the highest 2 VAT % quartiles was 15.3 mcg/mL (J: 0.63). In a multivariable analysis, only VAT % and infliximab level remained independently associated with steroid-free deep remission (odds ratio per % of VAT: 0.3 [95% confidence interval: 0.17–0.64], P < 0.001 and odds ratio per mg/mL: 1.11 [95% confidence interval: 1.05–1.19], P < 0.001). DISCUSSION: The results may suggest that patients with higher visceral adipose tissue burden may benefit from achieving higher infliximab levels to achieve remission.
KW - Crohn’s disease
KW - Infliximab
KW - anti-infliximab antibodies
KW - obesity
KW - outcomes
KW - remission
KW - therapeutic drug monitoring
KW - ulcerative colitis
KW - visceral adipose tissue
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U2 - 10.14309/ajg.0000000000002330
DO - 10.14309/ajg.0000000000002330
M3 - Article
C2 - 37207314
AN - SCOPUS:85175376052
SN - 0002-9270
VL - 118
SP - 2005
EP - 2013
JO - American Journal of Gastroenterology
JF - American Journal of Gastroenterology
IS - 11
ER -