Introduction:
Refractory celiac disease (RCD) is a rare but severe complication of celiac disease. RCD is classified into two subtypes:RCD-1 and RCD-2. Budesonide, a locally acting corticosteroid with limited systemic absorption, has been increasingly used in RCD management. We conducted a systematic review and meta-analysis to evaluate the efficacy of budesonide in RCD.
Methods:
Following PRISMA guidelines, we systematically searched PubMed, Embase, Scopus, and Google Scholar from inception through April 2026 using predefined search terms. Studies evaluating budesonide therapy in adult patients with RCD were included. Two independent investigators performed study selection, data extraction, and quality assessment using JBI critical appraisal checklist. Publication bias and certainty of evidence were assessed using funnel plots and GRADE, respectively. Pooled proportions with 95% confidence intervals(CI) were calculated using a random-effects model with Freeman Tukey transformation. Heterogeneity was assessed using the I² statistic, and subgroup analyses were performed to explore potential sources of substantial heterogeneity. Statistical analyses were performed using STATA version 17.0.
Result:
Seven retrospective studies involving 192 patients were included. The pooled clinical improvement rate with budesonide therapy was 82% (95%CI: 72%–91%; I²=66%), while the histological improvement rate was 55% (95%CI: 25%–86%; I²=91%). In patients with RCD-1, clinical improvement with budesonide was 82% (95%CI: 69%–95%; I²=82.4%), increasing to 93% (95% CI: 88%–98%; I²=0%) with open-capsule budesonide (OCB) formulation. Histological improvement in RCD-1 was 57% (95%CI: 24%–90%; I²=92%) and 87% (95% CI:77%–97%; I²=0%) with OCB. Among patients with RCD-2, clinical improvement with any budesonide formulation was 65% (95% CI: 30%–100%; I²=54%), while OCB demonstrated a pooled clinical response of 91% (95%CI:76%–100%; I²=0%). Histological improvement in RCD-2 was 59% (95%CI: 11%–100%; I²=77%) overall and 82% (95%CI: 66%-98%; I²=0%) with OCB.
Conclusion:
Budesonide, particularly open-capsule budesonide, represent a promising therapeutic option for RCD, especially RCD-1; however, larger prospective studies are required to validate these findings.