P4935 - Efficacy and Safety of Latiglutinase In Celiac Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Fouad Jaber, MD, MS¹, Mohammed Ayyad, MD², Saqr Alsakarneh, MD¹, Mohammad Jaber, MD³, Anas Alselek, MD⁴, Mohammad Adam, MD⁵, Manesh Kumar Gangwani, MD⁶, Hassam Ali, MD⁷, Yazan Sallam, MD⁵, Raed Darwish, MD⁸, Ahmed Fares, MD⁹, Dushyant S. Dahiya, MD^10
1University of Missouri - Kansas City School of Medicine, Kansas City, MO; ²Rutgers New Jersey Medical School, Newark, NJ; ³Al-Azhar University, Gaza, Palestinian Territories; ⁴Cairo University School of Medicine, Cairo, Al Jizah, Egypt; ⁵University of Missouri, Kansas City, MO; ⁶University of Toledo, Toledo, OH; ⁷ECU Health Medical Center, Greenville, NC; ⁸Ain Shams University, Cairo, Al Qahirah, Egypt; ⁹Tufts Medical Center, Boston, MA; ¹⁰The University of Kansas School of Medicine, Kansas City, KS

Introduction: Celiac disease is a chronic immune disorder triggered by dietary gluten, leading to mucosal inflammation in genetically predisposed individuals. Despite adherence to a gluten-free diet (GFD), many patients experience persistent symptoms and mucosal damage, prompting the exploration of non-dietary therapeutic approaches like latiglutenase. Latiglutenase is an enzyme therapy designed to degrade gluten proteins into non-immunogenic fragments, potentially reducing gut mucosa inflammation. This meta-analysis aimed to evaluate the efficacy and safety of latiglutenase in treating celiac disease.

Methods: A systematic review of major databases, including Cochrane, SCOPUS, PubMed, Web of Science, and EMBASE till April 2024 was conducted, adhering to PRISMA guidelines. Randomized controlled trials (RCTs) comparing latiglutenase to placebo in celiac disease patients were included. Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were calculated using the DerSimonian–Laird method. Primary outcomes were the villus height to crypt depth ratio and intraepithelial lymphocyte densities; secondary outcomes included adverse events (AEs).

Results: Three RCTs involving 253 patients were analyzed (Table 1). No significant difference was observed between latiglutenase and placebo in the villus height to crypt depth ratio (MD: 0.05, 95% CI [-0.41, 0.51], P = 0.82) (Figure 1-A) or intraepithelial lymphocyte densities (MD: -11.82, 95% CI [-28.41, 4.78], P = 0.16) (Figure 1-B). Additionally, there were no significant differences in overall AEs (RR: 0.99, 95% CI [0.81, 1.21], P = 0.90), medication-related AEs (RR: 1.33, 95% CI [0.71, 2.49], P = 0.37), or gastrointestinal-related AEs (RR: 1.05, 95% CI [0.82, 1.34], P = 0.70) (Figure 1-C). Specific symptoms like diarrhea, nausea, headache, fatigue/tiredness, and abdominal distension did not differ between groups. Stratified by severity, both latiglutenase and placebo displayed comparable outcomes for mild, moderate, and severe AEs.

Discussion: While no significant differences were found in symptomatic, histological, and serological parameters between latiglutenase and placebo groups, previous trials indicated symptom improvements. This suggests that histological and serological parameters may require more time to normalize compared to symptomatic improvements. Longer-term RCTs are essential to comprehensively evaluate latiglutenase's effects on symptomatic, histological, and serological outcomes, along with its long-term safety profile.



Disclosures:


Fouad Jaber, MD, MS¹, Mohammed Ayyad, MD², Saqr Alsakarneh, MD¹, Mohammad Jaber, MD³, Anas Alselek, MD⁴, Mohammad Adam, MD⁵, Manesh Kumar Gangwani, MD⁶, Hassam Ali, MD⁷, Yazan Sallam, MD⁵, Raed Darwish, MD⁸, Ahmed Fares, MD⁹, Dushyant S. Dahiya, MD¹⁰. P4935 - Efficacy and Safety of Latiglutinase In Celiac Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.