S502 Clinical Features and Treatment Response to Topical Steroids in Ethnic and Racial Minority Patients With Eosinophilic Esophagitis

Ocampo, Adolfo A.; Xue, Zeyun; Chang, Nicole C.; Thakkar, Kisan; Reddy, Sumana; Greenberg, Sydney B.; Lee, Chris; Ketchem, Corey J.; Redd, Walker D.; Eluri, Swathi; Reed, Craig C.; Dellon, Evan S.

doi:10.14309/01.ajg.0000858648.17490.bb

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“…This may allow for a decreased need for upper endoscopies to monitor empirically chosen treatments or switching from one ineffective treatment to another option, depending on the complexity of the response outcomes assessed ( 37 ). Prior studies assessing clinical predictors of response have shown that nonresponse is associated with esophageal dilation ( 10 , 11 , 14 ), the so-called “extreme narrow caliber esophagus” ( 38 ), increased BMI ( 39 ), younger age ( 14 , 40 ), and minoritized racial groups ( 41 ). However, results have not yet been replicated, and these patient-based factors are not routinely considered when choosing treatments.…”

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confidence: 99%

Validation of epigenetic markers for prediction of response to topical corticosteroid treatment in eosinophilic esophagitis

Jensen

Langefeld

Howard

et al. 2023

Clin Transl Gastroenterol

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Background: We previously identified 18 CpG methylation biomarkers associated with treatment response to topical steroids (tCS) in eosinophilic esophagitis (EoE). Here, in an independent cohort, we assessed the validity of these CpG sites as treatment response biomarkers. Methods: DNA was extracted from prospectively biobanked esophageal biopsies from newly diagnosed EoE patients enrolled in a randomized trial of two tCS formulations. Histologic response was defined as <15 eosinophils per high-power field (eos/hpf). Pre-treatment DNA methylation was assayed on the Illumina Human MethylationEPIC BeadChip. Logistic regression and area under the ROC (AUC) analyses, adjusting for chip, position on the chip, age, sex, and baseline eosinophil count, were computed to test for an association between DNA methylation and treatment response at the 18 previously identified CpG sites. Results: We analyzed 88 patients (58 histologic responders, 30 non-responders), with a mean age of 38±16 years, 64% male, 97% White race. Of the 18 CpG sites, 13 met quality control criteria, and three were associated with responder status (p<0.012), including sites within UNC5B (cg26152017), ITGA6 (cg01044293), and LRRC8A (cg13962589). All three showed evidence of reduced methylation in treatment responders, consistent with the original discovery associations. The predictive probability for non-response with all three CpG sites was strong (AUC=0.79). Discussion: We validated epigenetic biomarkers (CpG methylation sites) for prediction of tCS response in EoE patients in an independent population. While not all previously identified markers replicated, three demonstrated a relatively high predictive probability for response to treatment and hold promise for guiding tCS treatment in EoE.

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