S3079 Treatment Strategies for Refractory Celiac Disease: A Systematic Review and Meta-Analysis

Introduction: Refractory celiac disease (RCD) is a severe complication of celiac disease defined by persistent symptoms and intestinal damage despite strict adherence to a gluten-free diet. With no FDA-approved therapies and limited evidence, treatment remains challenging. This systematic review and meta-analysis evaluated current treatment strategies for RCD to guide clinical care. Methods: We systematically searched MEDLINE, Embase, Scopus, the Cochrane Library, and ClinicalTrials.gov through November 2024 for studies evaluating therapeutic interventions in RCD, including clinical trials, cohort studies, and case series with ≥5 patients. The main outcomes were clinical response, defined as improvement in symptoms, and clinical remission, defined as sustained complete resolution of symptoms. Pooled proportions were estimated using a fixed-effects model. Results: Thirty-two studies (1,038 patients) were included, with 5 focusing solely on type I RCD, 11 on type II RCD, and 16 reporting on both subtypes. In patients with RCD I, budesonide led to clinical response in 88% (95% CI, 82–94%; N/n = 6/144; I² = 61.8%) and remission in 65% (55–73%; N/n = 6/119; I² = 82.8%) of patients. Open-capsule budesonide led to clinical response in 87% (80–93%; N/n = 3/110; I² = 71.6%) and remission in 60% (51–69%; N/n = 3/110; I² = 74.4%). A clinical response was achieved in 97% (77–100%; N/n = 3/16; I² = 0.0%) and 100% (91–100%; N/n = 2/11; I² = 0.0%) of patients that received systematic steroids alone and combined with azathioprine, consecutively. In patients with RCD II, budesonide was associated with a clinical response in 96% (83–100%; N/n = 4/32; I² = 44.7%) and remission in 27% (10–46%; N/n = 3/28; I² = 91.2%). Systemic steroids led to a response in 76% (60–89%; N/n = 2/40; I² = 0.0%) and remission in 6% (0–17%; N/n = 2/40; I² = 0.0%) of patients. Combination therapy resulted in clinical response in 100% (94–100%; N/n = 3/27; I² = 12.3%) and remission in 79% (56–97%; N/n = 3/27; I² = 95.1%). Cladribine demonstrated response in 71% (57–83%) and remission in 45% (27–64%; N/n = 2/34; I² = 81.4%) of patients, while stem cell transplantation led to response in 78% (56–95%; N/n = 3/29; I² = 3.9%) and remission in 67% (33–95%; N/n = 2/16; I² = 0.0%). Conclusion: RCD I often responds well to budesonide and systemic steroids, whereas RCD II poses a therapeutic challenge with limited effective options. Further studies are needed to validate emerging therapies and develop standardized treatment algorithms.