Although several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for celiac disease, there is currently no widely accepted measure of disease activity used in clinical trials.
Dr Pieter Hindryckx and colleagues conducted a systematic review of celiac disease activity indices to evaluate their operating properties, and potential as outcome measures in registration trials.
MEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or pediatric patients with celiac disease that included celiac disease activity markers in their outcome measures.
The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA).
|Patients with active disease had higher disability rates |
Of 19,123 citations, the researchers found that 286 studies were eligible, including 24 randomised-controlled trials.
The research team noted that 3 of 5 PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA.
All histological and endoscopic scores identified lacked content validity.
Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales.
The researchers observed that endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy.
Dr Hindryckx's team concludes, "Current best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in celiac disease registration trials."
"Morphometric histology should be included as a key secondary or co-primary end point."
"Further work is needed to optimize end point configuration to inform efficient drug development."