CHICAGO – according to a lecture delivered at the 2019 James W. Freston Conference: Food at the Intersection of Gut Health and Disease.
Dr. Benjamin Lebwohl
Home testing services and portable gluten-detection devices enable patients to diagnose and manage themselves without medical supervision, but these strategies raise concerns about accuracy and efficacy, said Benjamin Lebwohl, MD, director of clinical research at the Celiac Disease Center at Columbia University in New York.
Potential treatments on the horizon
The gluten-free diet is the only treatment proven effective for celiac disease, but it can be expensive or unpalatable for some patients. The diet also entails risks of bowel irregularity and weight gain. “The gluten-free diet remains an inadequate treatment for many people with celiac disease,” said Dr. Lebwohl.
Tennyson et al. found that 66% of patients with biopsy-proven celiac disease are interested in nondietary therapy (Therap Adv Gastroenterol. 2013;6[5]:358-64.). Such patients are more likely to be male and older than 50 years.
Latiglutenase, a gluten enzyme derived from bacteria and cereal, is among the pharmacotherapies being investigated as a treatment for nonresponsive celiac disease. It reduces or eliminates the toxicity of gluten. In a recent phase 2b trial, however, the treatment did not achieve the primary outcome measure of histologic improvement (Gastroenterology. 2017;152[4]:787-98.). Compared with placebo, the drug was not associated with significant improvements in histologic and symptom scores.
Another drug in development is the tight-junction modulator larazotide acetate. Studies of zonula occludens toxin and its mammalian analogue zonulin led to the development of larazotide acetate. Leffler et al. found that a 0.5-mg dose of the drug reduced symptoms of nonresponsive celiac disease in patients who were following a gluten-free diet, compared with patients treated with the diet alone (Gastroenterology. 2015;148[7]:1311-9.). Innovate Pharmaceuticals plans to study the drug in phase 3 trials, said Dr. Lebwohl.
ImmunosanT has studied Nexvax2, which promotes gluten peptide desensitization. A phase 2 study examined the drug’s efficacy in reducing symptoms during a masked food challenge. The company discontinued this study when an interim analysis showed that the drug provided no more protection from gluten exposure than placebo. Nexvax2 was safe and well tolerated, and the study revealed no new safety signals.
In addition to newly developed therapies, researchers are studying whether drugs marketed for other indications could be effective treatments for celiac disease. For example, budesonide, a treatment for asthma and chronic obstructive pulmonary disease, is being investigated for nonresponsive celiac disease and refractory celiac disease. Other research is examining whether budesonide could provide effective protection after inadvertent gluten exposure. Systemic steroids, immunosuppressants such as azathioprine, chemotherapeutics such as cladribine, and mesalamine, which is a treatment for inflammatory bowel disease, also are under investigation.
But several questions related to drug development for celiac disease remain unanswered. For example, whether researchers should choose clinical or histologic endpoints for their trials is a subject of debate. “Probably, we’re going to be looking for two endpoints,” said Dr. Lebwohl. No consensus has been established about whether trials should include patients for whom diagnosis is based on a test other than a biopsy. Also, the effect of nondietary therapy on adherence to the gluten-free diet remains to be clarified.