Latiglutenase Improves Symptoms in Seropositive Celiac Disease Patients While on a Gluten-Free Diet
Background and Aims
Celiac disease (CD) is a widespread condition triggered by dietary gluten and treated with a lifelong gluten-free diet (GFD); however, inadvertent exposure to gluten can result in episodic symptoms. A previous trial of latiglutenase (clinicaltrials.gov; NCT01917630), an orally administered mixture of two recombinant gluten-specific proteases, was undertaken in symptomatic subjects with persistent injury. The primary endpoint for histologic improvement was not met, presumably due to a trial effect. In this post hoc analysis, we investigated the efficacy of latiglutenase for reducing symptoms in subgroups of the study participants based on their seropositivity.
The study involved symptomatic CD patients following a GFD for at least one year prior to randomization. Patients were treated for 12 weeks with latiglutenase or placebo. Of 398 completed patients, 173 (43%) were seropositive at baseline. Symptoms were recorded daily, and weekly symptom scores were compiled. p values were calculated by analysis of covariance.
A statistically significant, dose-dependent reduction was detected in the severity and frequency of symptoms in seropositive but not seronegative patients. The severity of abdominal pain and bloating was reduced by 58 and 44%, respectively, in the cohort receiving the highest latiglutenase dose (900 mg, n = 14) relative to placebo (n = 54). Symptom improvement increased from week 6 to week 12. There was also a trend toward greater symptom improvement with greater baseline symptom severity.
Seropositive CD patients show symptomatic improvement from latiglutenase taken with meals and would benefit from the availability of this treatment.
KeywordsCeliac disease Latiglutenase Therapy Symptoms
Clinical trial NCT01917630 was sponsored by Alvine Pharmaceuticals; all data from this trial are presently owned by ImmunogenX. The data analysis reported here was supported in part by a Grant from the National Institutes of Health (R01 DK063158 to C.K.).
JAS, JAM, PHRG, and CK were involved in the acquisition of data; JAS and CK analyzed and interpreted the data; JAS, and CK provided technical and material support; JAS, PHRG, and CK were involved in drafting of manuscript; JAS, JAM, PHRG, and CK were involved in the critical revision of the manuscript and important intellectual content.
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Conflict of interest
JAS is a founder of and owns stock in ImmunogenX. JAM has received grant support from the National Institutes of Health, Alvine Pharmaceuticals, and Alba Therapeutics; receives ongoing support from Oberkotter Foundation and Broad Medical Research Program at CCFA; serves on the advisory board of Celimmune, LLC and ImmunogenX; was a consultant to, BioLineRx, GlaxoSmithKline (GSK), Genentech, and Glenmark Pharmaceuticals Ltd; and is a consultant to ImmunosanT, Institute for Protein Design (PvP Biologics), Takeda Pharmaceutical Company, Ltd., Innovate Biopharmaceuticals, Inc., and Intrexon. PHRG is an advisor to ImmusanT and ImmunogenX. CK is a director of Protagonist Pharmaceuticals and an advisor to Sitari Pharmaceuticals and holds stock in both companies.