Noninvasive Targeted Crohn Disease Management by Combining Endoscopic Healing Index and Therapeutic Drug Monitoring. Issue 3 (9th June 2021)

• Record Type: Journal Article
• Authors: Hemperly, Amy; Dubinsky, Marla C; Yarur, Andres; Afzali, Anita; Hanauer, Stephen; Kugathasan, Subra; Long, Millie D; Rabizadeh, Shervin; Sockolow, Robbyn; Okada, Lauren; Jain, Anjali; Abreu, Maria T; Vande Casteele, Niels
• Is Part Of: Crohn's & colitis 360. Volume 3:Issue 3(2021)
• Publication Date: 2021-06-09
• Subjects: inflammatory bowel disease -- endoscopic remission -- treat-to-target -- biomarker; Crohn's disease -- Periodicals; Colitis -- Periodicals; 616.344
• DOI: 10.1093/crocol/otab035
• Languages: English
• ISSNs: 2631-827X

Abstract

Abstract: Background and Aims: Therapeutic drug monitoring (TDM) with measurement of serum drug and antidrug antibody concentrations is used to optimize tumor necrosis factor antagonists (anti-TNF). The endoscopic healing index (EHI) is a validated serum-based assay to measure mucosal inflammation in adults with Crohn disease (CD). Our objectives were to evaluate the relationship between EHI and TDM results and to determine the anti-TNF concentration range associated with EHI <20 (consistent with endoscopic remission). Methods: Adult and pediatric patients with CD (N = 1731) were selected retrospectively from a clinical laboratory cohort. Patients were selected if they had an ICD-10 code for CD and if results for EHI and TDM were available within 30 days of each other. The relationship between EHI and TDM results was examined and the anti-TNF concentration range associated with EHI <20 vs >50 was evaluated. Results: Median anti-TNF concentration was higher in patients with EHI <20 vs >50 for infliximab (N = 796): 11.1 vs 3.4 µg/mL and for adalimumab (N = 935): 9.2 vs 5.0 µg/mL ( P < 0.0001 both drugs). Patients with antibodies to infliximab (12.8%) or adalimumab (14.9%) had lower anti-TNF concentrations ( P < 0.001 both drugs) and higher EHI ( P < 0.01 both drugs). The concentration range for infliximab: 5–15 µg/mL (5–9 µg/mL in pediatric patients) and for adalimumab: 5–10 µg/mL (8 µg/mL in pediatric patients) best discriminated EHI <20 vs >50. Conclusions: We report the anti-TNF concentration range associated with EHI <20. Combined testing of EHI and TDM is proposed as a noninvasive approach for treat-to-target management which could improve the ability to monitor disease and optimize anti-TNF therapy. Lay Summary: In a large clinical cohort of 1731 adult and pediatric patients with Crohn disease, we evaluated the correlation between serum drug concentrations of biologics infliximab or adalimumab and a serum biomarker for mucosal inflammation and propose a noninvasive approach for treat-to-target management to optimize therapy with biologics.