S3090 Evaluating the Use of Latiglutenase as Gluten-Targeting Protease in Patients With Celiac Disease: A Meta-Analysis of Randomized Controlled Trials

Introduction: A gluten-free diet remains the treatment of choice for celiac disease, but due to cross-contamination and the difficulty in adherence, celiac symptoms do emerge. New pharmacological options are under investigation, and latiglutenase, a new investigational drug, is a recombinant protein with gluten-targeting protease that degrades gluten molecules. Methods: On November 17, 2024, related articles were searched in the following databases: PubMed, Scopus, and Cochrane. Our inclusion criteria were only randomized controlled clinical trials that evaluated the use of latiglutenase in celiac patients. Our outcomes were the mean change in villus height to crypt depth ratio to assess histologic impact of the treatment in villous atrophy, the mean change in the density of intraepithelial lymphocytes to assess inflammatory changes with the treatment, and the difference in the symptoms related to celiac disease. In this meta-analysis, we used the mean difference and the odds ratio (OR) with the 95% confidence interval to estimate the effect size. A random-effects model was applied. Results: Out of 143 articles screened, only 3 were eligible for inclusion, with a total of 253 patients. All included patients were on a strict gluten-free diet for at least 1 year prior to the trials. Two studies (Murray 2022 and Lahdeaho) administered a daily gluten challenge of approximately 2 grams for 6 weeks, along a gluten-free diet. In our analysis of the mean change in the villus height to crypt depth ratio, there was no statistical difference between the groups, with a mean difference of 0.05 (CI: -0.41 to 0.51, P = 0.82). The mean change in the density of intraepithelial lymphocytes also failed to show any statistical difference, with a mean difference of -11.82 (CI: -28.41 to 4.78, P = 0.16). Symptoms such as nausea, diarrhea, and abdominal distention showed no significant difference between the treatment groups, as all shared a P-value above 0.05. Finally, there were no statistical differences in the rates of any adverse events between the 2 groups with an odds ratio of 0.79 (CI: 0.45 to 1.39, P = 0.42). Conclusion: Latiglutenase has failed to show a meaningful difference in the histologic markers when compared to a placebo, indicating no impact on villous atrophy. Similar results were observed for symptoms related to celiac disease. There is a need for non-dietary pharmacological options for celiac disease.