Although numbers were low, mucosal IgA-tTG deposits increased in four patients on placebo and one on AN-PEP and decreased in Sorafenib Tosylate chemical structure one patient on AN-PEP, compared to baseline values, suggesting that AN-PEP may mitigate gluten exposure. Some gastrointestinal-related symptoms, mostly mild and transient, were reported during gluten challenge and symptoms between the two groups were comparable suggesting no treatment-related effects on gastrointestinal symptoms. Besides the substantial gluten intake, emotional stress as a consequence of having to ingest gluten might have triggered some of the reported gastrointestinal complaints. The celiac patients consumed approximately 7 g of gluten daily, which is about half of the average adult daily gluten intake in The Netherlands.
Despite this high gluten dose, no substantial histological, serological, or symptom changes were observed with placebo after 2 wk. In another study in which adult CD patients consumed approximately 3.5 g/d of gluten from cracker biscuits for 2 wk, only few patients consuming gluten on placebo showed deterioration on histology, serology, and symptoms. Two other studies investigating a gluten challenge in adult patients, based on either lower gluten intake (2.5-5.0 g/d for at least 3 mo) or comparable gluten intake (4 slices of white bread daily; approximately 8 g/d) showed that a moderate gluten intake can be tolerated by some patients for several weeks-to-months without significant changes in symptoms, serology and histology[26,27].
The time to serological and mucosal relapse and recovery after gluten re-introduction and elimination, respectively, can be highly variable among adult CD patients from several weeks up to many years[27-30]. Excluding 2 out of 16 patients that may have been more sensitive to gluten from the efficacy phase may, to a small extent, have caused sample bias by selecting patients being less sensitive to gluten. Nevertheless, the same population of patients that entered the efficacy phase was randomly allocated to the AN-PEP or placebo arm. Also attrition bias can be excluded since all patients remained in the study. The lack of substantial clinical response to gluten observed in this study indicates that a longer gluten challenge is likely necessary to induce a significant clinical response to gluten in the majority of patients. For the same reason a longer wash-out period should be considered. Moreover, unresponsiveness to gluten of patients being diagnosed for Dacomitinib more than 10 years ago, suggests that future studies may benefit from selecting more recently diagnosed patients. In conclusion, AN-PEP appeared to be safe in celiac patients.