MedicalResearch.com Interview with:
Markku Mäki, MD, PhD
Professor (emeritus) at the University of Tampere and
Presently research director at the
Tampere University Hospital
MedicalResearch.com: What is the background for this study?
Response: The only treatment for this life-long gluten-induced autoimmune systemic disease is a strict avoidance of wheat, rye and barley, the food cereals which contain gluten, the environmental trigger and driving force in celiac disease. Gluten causes intestinal
inflammation, usually with (but sometimes without) gastrointestinal or
nutritional symptoms or signs, and with frequent extra-intestinal
diseases. However, it is impossible for celiac disease patients to
avoid gluten entirely and indefinitely and a third of patients report
symptoms on a strict gluten-free diet. Gut mucosal healing is not
optimal in half of the patients, and inflammation and injury is
detected for years after starting the diet, presumably due to
contamination with gluten in the diet. This is why patients are
requesting, and academia and industry are looking for novel adjunct
therapies for celiac disease. Initially, these therapies are tested to
prevent the consequences of hidden gluten; the ultimate goal being
that also celiacs could one day eat safely wheat, barley and rye
products. Some 20 novel experimental therapies are at present actively
being investigated (modifying wheat or different drugs, devices and
The present study investigated whether blocking interleukin 15, an
important mediator of celiac disease, reduces or prevents
gluten-driven ill health, both the inflammation and injury at the
small intestinal mucosal level and gluten-induced symptoms. The
experimental drug used was Amgen’s AMG 714, a human monoclonal
antibody, used at a low and high dose, in the presence or absence of a
high-dose gluten challenge.
MedicalResearch.com: What are the main findings?
Response: This 10-week randomized, double-blind, placebo-controlled, phase 2a
gluten challenge trial showed that AMG 714 reduced gluten-triggered
effects in the drug arms compared to placebo. The drug arm showed less
mucosal inflammation and patient reported outcome questionnaires
showed significantly less symptoms. None of the patients given the
gluten challenge who took the higher AMG 714 dose were deemed by the
principal investigator at three different study sites to have active
disease clinically (in the Physician Global Activity index), compared
to one third in the placebo group. However, the drug did not prevent
the gluten induced mucosal injury caused by the high-dose gluten. In
the non-challenge group exposed to hidden gluten contamination a trend
towards reduced intestinal damage was observed. No serious adverse
events or safety signals caused by AMG 714 were observed.
MedicalResearch.com: Might this treatment also work for Dermatitis Herpetiformis?
Response: DH is an extraintestinal manifestation of celiac disease and the small
intestinal mucosa is the site were disease mechanisms initiates in dermatitis herpetiformis.
While DH patienst were not specifically studied in the trial, the
effect on DH will at some point be studied. At this stage of drug
development flare ups of skin symptoms due to hidden gluten
contamination might be prevented in DH patients on an otherwise strict
gluten-free diet, but the information is not yet available.
MedicalResearch.com: What should readers take away from your report?
Response: The results confirm interleukin 15 to be an important mediator of
celiac disease. AMG 714 did not prevent gluten induced mucosal
injury when gluten was administered at this amount. The drug
significantly decreased mucosal inflammation and symptoms, in a
dose-dependent fashion. There is great potential for further
development of AMG 714 in celiac and also in refractory celiac disease
type 2 (a separate Phase 2 study will also be presented at DDW showing
promise in this intestinal lymphoma which complicates celiac
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Follow up studies in larger patient populations potentially using a
higher drug dose and for a longer period are warranted. The next
question to be answered is whether the clear effects on symptoms and
decrease in mucosal inflammation will over time and using a higher
dose translate also to improved small intestinal mucosal architectural
health, the gold standard outcome in gluten-free diet treatment of
As mentioned, a severe complication of the disease, refractory celiac
type 2 celiac disease is also a target for AMG 714. Interruption of
the disease process and symptom relief in this poor-outcome disease is
welcomed. Refractory celiac disease type 2 will be discussed at DDW,
oral presentation on Monday, June 4, abstract 616 (Presidential
Disclosures: Markku Maki is the member of the Scientific Advisory Board of Celimmune LLC.
Citation: DDW2018 week abstract:
AMG 714 (anti-IL-15 mAb) ameliorates the effects of gluten
consumption in celiac disease: A phase 2a, randomized, double-blind,
placebo-controlled study evaluating AMG 714 in adult patients with
celiac disease exposed to high-dose gluten challenge
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