Effect of the aspergillus niger prolyl endoprotease on involuntary gluten intake and clinical aspects in the real-life of long-term treated celiac disease patients

GRIZZUTI, M.; SEGURA MONTERO, V.; STEFANOLO, J.P.; HEREDIA BARROSO, A.; COMINO MONTILLA, I.; COSTA, A.F.; ESPINET, M.L.; PUEBLA, R.; TEMPRANO, M.P.; NIVELONI, S.; DE DIEGO, G.A.; OREGUI, M.E.; MORENO, M.L.; SMECUOL, E.; DE MARZI, M.C.; VERDÚ, E.F.; SOUZA, C.; BAI, J.C.

Copenhagen

Congreso; United European Gastroenterology Week.; 2023

Introduction: The only treatment for celiac disease (CeD) is strict adherence to a gluten-free diet (GFD). New adjuvant therapies areunder investigation. The enzyme Aspergillus niger prolyl endoprotease (AN-PEP) has been shown to degrade luminal gluten in apreclinical model.Aims & Methods: We here explore whether oral administration of AN-PEP may affect involuntary gluten exposure and preventssymptoms in adult CeD patients who were on their usual GFD in a context mimicking a real-life scenario. This is an exploratory,double-blind, randomized, placebo-controlled trial that enrolled patients with CeD on a long-term GFD. After a four-week run-inperiod, patients were randomized to a 4-week treatment with 2 AN-PEP capsules at each of 3 meals/day, or placebo. AN-PEP capsulecontained 325 mg of 70% AN-PEP, 30% maltodextrin, and citric acid (GliadinX, AVI Research, LLC, USA). We investigated the followingendpoints at run-in and end of trial: 1- Average weekly stool gluten immunogenic peptides (GIP) between the run-in and treatmentperiods, as well as between AN-PEP and placebo; 2- Celiac Symptom Index (CSI) (> 38 indicated symptomatic status), 3- CeD-specificserology (IgA tTG and DGP). Patients returning >30% capsules were excluded from the intention-to-treat analysis. Stool samples werecollected for GIP measurement by ELISA (Biomedal S.L., Seville, Spain) every Tuesday and Friday during run-in and treatment.Results: Between April 2021 and July 2022, 40 patients were randomized to the intention-to-treat analysis. Due to noncompliancewith the study protocol, 3 patients (1 placebo, 2 AN-PEP) were excluded. Overall, 645 of 656 stool samples were collected in thecomplete trial. GIP was undetectable (0.32μg/g) tocause mucosal damage potentially. When compared to the run-in period, the median GIP concentration in the AN-PEP group was44.7% lower after treatment. Furthermore, 35.6% of patients in the AN-PEP arm with an average stool GIP >0.180 μg/g had a reduced(>50% of run-in concentrations) or exhibited undetectable stool GIP after treatment. The AN-PEP significantly reduced the proportionof patients with a CSI >38 when compared to the run-in period for both the intention-to-treat and per-protocol analyses (McNemar:p0.180 μg/g. The significantly lower number of symptomatic cases in the AN-PEP arm compared to placebosuggests that symptomatic improvement could be the result of a therapeutic effect of AN-PEP. The current results warrant to beconfirmed by larger studies and also gluten challenge trials.