The dysphagia symptom questionnaire is responsive and valid for measuring patient-reported outcomes in eosinophilic esophagitis: Analysis from a multicenter randomized placebo controlled trial

Background: A limitation of conducting clinical treatment trials for eosinophilic esophagitis (EoE) is the prior lack of validated patient reported outcome (PRO) measures. The Dysphagia Symptom Questionnaire (DSQ) is a daily dysphagia symptom diary for use in patients with EoE. The responsiveness of this instrument is unknown. Aim: To determine whether the DSQ is capable of measuring symptom response in patients treated with oral budesonide suspension (OBS) vs placebo in a clinical trial, and assess the association between symptomatic and histologic responses. Methods: This multicenter randomized, double-blind, placebocontrolled trial (NCT01642212) enrolled subjects ages 11-40 years with EoE diagnosed as per 2011 consensus guidelines, including ≥15 eos/hpf after a documented high-dose PPI trial, from 7/2012-5/2014. Eligibility criteria were ≥15 eos/hpf peak count from at least 2 esophageal levels on screening endoscopy, and at least 4 days with symptoms of dysphagia (as measured by the DSQ) over a 2 week period during a 4 week blinded run-in. Subjects were randomized to receive either OBS 2 mg BID or placebo BID for 12 weeks. The DSQ was completed daily during treatment. Follow-up endoscopy/biopsy was performed at week 12, with histologic response defined as ≤6 eos/hpf. Physician global assessment (PGA) was recorded pre and post-treatment. To assess responsiveness, DSQ scores were compared between OBS and placebo. To assess concurrent validity, DSQ scores were compared to histologic response rates and the PGA. Results: Of the 87 subjects with complete baseline and follow-up symptomatic and histologic data, 49 received OBS and 38 received placebo. Over the 12 week treatment phase, the DSQ score significantly decreased with OBS, while the response plateaued with placebo (Figure). A ≥30% reduction in DSQ score was achieved by 69% of OBS-treated subjects compared with 45% of placebo (p=0.0206); a ≥50% reduction was achieved by 63% and 40%, respectively (p=0.0275). The change in DSQ score was strongly associated with histologic response. Histologic responders had a mean change in DSQ score of-16.2, whereas non-responders had a mean change of-9.9 (p<0.001). DSQ and PGA were also associated. The end of treatment mean DSQ scores were 9.7, 22.2, and 37.9 for PGAs of none/mild, moderate, and worst possible disease activity (p<0.0001). DSQ compliance was excellent; for example, 98% of subjects completed at least 8 diary days in 14 day period at baseline. Conclusions: The DSQ, a daily dysphagia symptom PRO for patients with EoE, was found to be responsive in this multicenter randomized treatment trial. In addition, the DSQ was associated with both histologic response and with PGA, confirming excellent concurrent validity. The DSQ should be considered a valid and responsive PRO for EoE clinical trials. (Figure presented).