Children's Hospital of Philadelphia Philadelphia, PA, United States
Melanie A. Ruffner, MD, PhD1, Cary Cotton, MD, MPH2, Evan S. Dellon, MD, MPH, FACG2 1Children's Hospital of Philadelphia, Philadelphia, PA; 2University of North Carolina School of Medicine, Chapel Hill, NC
Introduction: The optimal thresholds to define histologic and endoscopic treatment responses in eosinophilic esophagitis (EoE) remain a subject of debate. We aimed to evaluate whether post-treatment gene expression profiles support previously proposed treatment response thresholds.
Methods: We performed post-hoc analysis of a prospective cohort study of newly diagnosed adult EoE patients. After enrollment, patients were treated with standard of care swallowed topical steroids (either oral viscous budesonide 2 mg total/day or swallowed fluticasone from an inhaler 1760 mcg total/day). During post-treatment follow-up endoscopy, a single mid-esophageal biopsy was preserved in RNA-later. RNA was isolated using standard techniques and analyzed using the 94-gene EoE diagnostic panel (EDP). The EDP summary expression score was calculated by adding the differences between the housekeeping gene and each gene CT value; a score < 333 has previously shown to reflect active EoE, with lower scores indicating more severe molecular disease activity. We then explored post-treatment EDP scores for a range of post-treatment histologic thresholds and EoE Endoscopic Reference Score (EREFS) thresholds.
Results: There were 89 incident EoE cases with post-treatment EDP data (mean age 37 years, 60% male, 94% white, 76% with an atopic condition). Baseline peak eosinophil counts were 137±124 eos/hpf and post-treatment counts were 48 ± 80; 59% of patients had histologic response (≤ 15 eos/hpf). EREFS data was available for 63 patients; 73% had endoscopic response (EREFS ≤2 cutoff). We observed a strong inverse correlation between post-treatment gene score and eosinophil count (Figure 1A, Pearson’s R = -0.66; p< 0.001). There was a clear distinction in gene scores at 15 eos/hpf (Figure 1B), with biopsies with < 15 eos/hpf having higher gene scores (425 or above) compared to those with ≥15 eos/hpf. We also saw a strong inverse correlation between post-treatment gene score and EREFS (Figure 1C, Pearson’s R = -0.61; p< 0.001), with EREFS ≤2 associated with EDP scores above 395 (Figure 1D).
Discussion: :Post-treatment EDP scores strongly correlate with post-treatment eosinophil counts and endoscopic severity measured by EREFS. There is clear differentiation of molecular severity at response thresholds of < 15 eos/hpf and EREFS ≤2, and gene scores do not further improve below these thresholds. This molecular approach supports use of these thresholds in clinical practice and trials.
Figure: Figure 1: Gene expression score from the EoE diagnostic panel negatively correlates with (A) biopsy eosinophil count (n=89, Pearson’s R=0.69, p <0.001) and (B) there is a clear distinction in gene scores at 15 eos/hpf (Figure 1B), with biopsies with <15 eos/hpf having higher gene scores (425 or above) compared to those with ≥15 eos/hpf. (C) EDP gene expression score negatively correlated with EoE Endoscopic Reference Score (EREFS, n=63, Pearson’s R=0.61, p <0.001). (D) EREFS ≤2 were associated with EDP scores above 395.
Melanie Ruffner indicated no relevant financial relationships.
Cary Cotton indicated no relevant financial relationships.
Evan Dellon indicated no relevant financial relationships.
Melanie A. Ruffner, MD, PhD1, Cary Cotton, MD, MPH2, Evan S. Dellon, MD, MPH, FACG2. P2388 - Post-Treatment Gene Scores Support Histologic and Endoscopic Response Thresholds in Eosinophilic Esophagitis, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.