Evaluating the role of capsule endoscopy for non-responsive, refractory and complicated celiac disease: a systematic review and meta-analysis

Abstract

Background Small-bowel capsule endoscopy (CE) is used in selected adults with nonresponsive, refractory, or complicated celiac disease (CD), but its diagnostic yield (DY), clinical impact, and safety remain uncertain.

Methods We searched Medline, EMBASE, CENTRAL, and PubMed from January 2000 to November 30, 2025, for studies of CE in adults with established CD and persistent symptoms, suspected refractory disease, or suspected complications. Two reviewers independently selected studies, extracted data, and assessed risk of bias using ROBINS-E; certainty was assessed using GRADE. Random-effects meta-analyses using generalized linear mixed models estimated pooled DY and secondary outcomes. Meta-regression and subgroup analyses were considered
exploratory.

Results Seventeen studies, including 994 adults, were eligible. The pooled DY of CE in complex CD was 82% (95% confidence interval [CI] 67-91%), with substantial heterogeneity (I2=82.5%). DY was highest in refractory CD cohorts. Pooled DY was 3% for ulcerative jejunitis and 3% for small-bowel malignancy. Capsule retention was uncommon. CE findings were associated with management changes in several studies; however, this outcome was reported in only 9 studies, and definitions varied. Egger’s test and trim-and-fill analysis suggested possible small-study effects, reducing the adjusted DY estimate to 79%. The pooled conversion to device-assisted enteroscopy
was estimated at 18% (95%CI 9-30%).

Conclusions CE may be a valuable second-line, noninvasive triage tool in selected high-risk patients with complex CD, particularly refractory CD. However, the available evidence remains of very low certainty and should be interpreted cautiously, given the substantial methodological and clinical heterogeneity across studies.

Keywords Capsule endoscopy, small bowel, diagnostic yield, refractory celiac disease, complicated celiac disease

Ann Gastroenterol 2026; 39 (5): 552-562