Larazotide Acetate for Treatment of Celiac Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

ABSTRACT Purpose The standard of care for treatment of celiac disease (CD) is a stringent lifetime glutenfree diet (GFD), which is very challenging. 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 larazotide acetate in patients with CD. Methods We examined four databases from inception to 20-August-2020 using related keywords. We identified all relevant RCTs and judged their risk of bias. We pooled continuous outcomes as mean difference and dichotomous outcomes as risk ratio with 95% confidence interval under fixed-effects meta-analysis model. Results Four RCTs met our eligibility criteria, comprising 626 patients (larazotide acetate, n = 465, placebo, n = 161). Three and two studies reported outcomes of patients undergoing gluten challenge and GFD, respectively. For change in lactulose-to-mannitol ratio, the overall effect estimate did not reveal a significant difference between larazotide acetate and placebo groups. For change in total gastrointestinal symptom rating scale (GSRS), subgroup analysis showed that larazotide acetate significantly yielded better symptomatic improvement in the gluten challenge but not gluten free subgroup. Similar finding was found for change in celiac-disease GSRS (CD-GSRS) favoring the gluten challenge over gluten free subgroup. When compared to placebo, larazotide acetate favorably reduced the adverse event (AE) of gluten-related diarrhea in patients who underwent gluten challenge. Other AEs were comparable between both treatment groups. Conclusions Larazotide acetate is well-endured and superior to placebo in alleviating gastrointestinal symptoms.