Predictors of Non-Response to Topical Steroids Treatment in Eosinophilic Esophagitis

Moawad, Fouad J.; Albert, Dustin; Heifert, Theresa; Min, Steve B.; Maydonovitch, Corinne; Wong, Roy K.H.

doi:10.14309/00000434-201310001-00037

Cited by 13 publications

(4 citation statements)

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“…Dilation was previously found to be a predictor of nonresponse in a retrospective cohort of EoE patients from our center 13 and in preliminary data from a separate study. 31 A steroid-resistant phenotype of EoE, an extreme narrowcaliber esophagus, has also been described. 12 In the context of these studies that show that the need for dilation is associated with a decreased likelihood of response to topical steroids, it is unclear whether swallowed fluticasone or oral viscous budesonide do not provide effective drug delivery in those with strictures or if fibrostenotic disease represents a more severe disease state that is treatment refractory.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Molecular Factors Associated With Histologic Response to Topical Steroid Treatment in Patients With Eosinophilic Esophagitis

Eluri

Selitsky

Perjar

et al. 2019

Clinical Gastroenterology and Hepatology

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Section: Discussionmentioning

confidence: 99%

Clinical and Molecular Factors Associated With Histologic Response to Topical Steroid Treatment in Patients With Eosinophilic Esophagitis

Eluri

Selitsky

Perjar

et al. 2019

Clinical Gastroenterology and Hepatology

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“…Prediction of treatment response related to tCS is an area of active research. Nonresponse has been associated with esophageal dilation (42–44), severe esophageal narrowing (45), increased BMI (30), younger age (31,44), and molecular features (46,47). In our analysis, the lower response rate in non-Whites persisted despite adjusting for these other known factors related to tCS response.…”

Section: Discussionmentioning

confidence: 99%

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

Ocampo,

Xue,

Chang

et al. 2023

Am J Gastroenterol

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Introduction: Differences in EoE presentation and outcomes by ethnicity or race remain understudied. We aimed to determine whether EoE patients of Hispanic/Latinx ethnicity or non-White race have differences in presentation at diagnosis or response to topical corticosteroid (tCS) treatment. Methods: This retrospective cohort study included subjects of any age with a new diagnosis of EoE and documentation of ethnicity or race. For those who had treatment with tCS and follow-up endoscopy/biopsy, we assessed histologic response (<15 eosinophils/hpf), global symptom response, and endoscopic responses. Hispanic EoE patients were compared to non-Hispanics at baseline, and before and after treatment. The same analyses were repeated for White vs non-Whites. Results: Of 1026 EoE patients with ethnicity data, just 23 (2%) were Hispanic. Most clinical features at presentation were similar to non-Hispanic EoE patients but histologic response to tCS was numerically lower (38% vs 57%). Non-White EoE patients (13%) were younger at diagnosis, had less insurance, lower zip code-level income, shorter symptom duration, more vomiting, less dysphagia and food impaction, fewer typical endoscopic features, and less dilation. Of 475 patients with race data treated with tCS, non-Whites had a significantly lower histologic response rate (41% vs 59%; p=0.01), and odds of histologic response remained lower after controlling for potential confounders (aOR 0.40, 95%CI: 0.19-0.87). Discussion: Few EoE patients at our center were Hispanic, and they had similar clinical presentations as non-Hispanics. The non-White EoE group was larger, and presentation was less dysphagia-specific. Non-White patients were also less than half as likely to respond to tCS.

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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.…”

Section: Discussionmentioning

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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Predictors of Non-Response to Topical Steroids Treatment in Eosinophilic Esophagitis

Cited by 13 publications

References 0 publications

Clinical and Molecular Factors Associated With Histologic Response to Topical Steroid Treatment in Patients With Eosinophilic Esophagitis

Clinical and Molecular Factors Associated With Histologic Response to Topical Steroid Treatment in Patients With Eosinophilic Esophagitis

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

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

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