The standard of care for treatment of celiac disease (CD) is a stringent lifetime gluten-free diet (GFD). Larazotide acetate (AT-1001) is an anti-zonulin which functions as a gut permeability regulator for treatment of CD. We endeavored to conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) which studied the efficacy and safety of AT-1001 in patients with CD.

We examined four databases from inception to 20-August-2020. We pooled continuous outcomes as mean difference and dichotomous outcomes as risk ratio with 95% confidence interval under the fixed-effects meta-analysis model.

Four RCTs met our eligibility criteria, comprising 626 patients (AT-1001, n=465, placebo, n=161). Three and two RCTs reported outcomes of patients undergoing gluten challenge (intake of 2.4–2.7 grams of gluten/day) and GFD, respectively. For change in lactulose-to-mannitol ratio, the endpoint did not significantly differ between AT-1001 and placebo groups, irrespective of the gluten status. Subgroup analysis of patients undergoing gluten challenge showed AT-1001 treatment (compared with placebo) significantly correlated with better symptomatic improvement in the two endpoints of change in total gastrointestinal symptom rating scale (total GSRS) and CD-specific GSRS (CD-GSRS). However, no significant difference was noted among patients undergoing GFD for the abovementioned two efficacy endpoints. Compared with placebo, AT-1001 favorably reduced the adverse event (AE) of gluten-related diarrhea in patients who underwent gluten challenge. Other AEs were comparable between both AT-1001 and placebo groups.

AT-1001 is largely well-endured and seems somehow superior to placebo in alleviating gastrointestinal symptoms among CD patients undergoing gluten challenge. Nevertheless, additional RCTs are warranted to validate these findings.