Are we ready for an approved celiac disease treatment?
Once the first drug to treat celiac disease is approved and made available, patients and their health care providers will face a new and better world of treatment.
But even as a variety of drugs are moving through clinical trials, certain questions have yet to be addressed, including who will be eligible for the drugs and how health care providers will manage patients who now have medications in addition to the gluten-free diet.
These and other issues are tackled by the heads of three international celiac disease scientific organizations in the paper, “A look into the future: Are we ready for an approved therapy in celiac disease?,” published in the special celiac disease edition of the American Gastroenterological Association journal Gastroenterology.
Overall, anticipation of drug approval has “triggered reappraisal of the management of celiac disease,” the authors conclude.
Key points raised in the article include the likelihood that:
- The first drugs to treat celiac disease will be intended for use along with the gluten-free diet.
- Adults with persistent damage to the small intestine, called mucosal injury or villous atrophy, and persistent symptoms of celiac disease will be the first to receive the approved drugs.
- People with celiac disease who do not have symptoms and children with celiac disease would not be eligible for drugs at first.
- Health care providers who treat people with celiac disease will have to reassess the diagnosis of celiac disease in patients on a gluten-free diet, identify which patients have persistent intestinal damage, and determine if symptoms that continue on a gluten-free diet are due to celiac disease and not another factor.
- People who are following a gluten-free diet without a formal diagnosis of celiac disease would be more motivated to get a definitive diagnosis even as they resist having to go through a gluten challenge and an endoscopy with a biopsy.
- New methods of testing for and diagnosing celiac disease would be needed to handle the number of patients who went on a gluten-free diet without a diagnosis who now see a benefit in being diagnosed with a treatment available.
A landmark for patients
“A drug for celiac disease approved by the [U.S.] Food and Drug Administration (FDA), European Medicines Agency (EMEA) or any other rigorous medicines regulatory authority would be a landmark for patients with celiac disease,” wrote paper authors Robert Anderson, MD, Ritu Verma, MD, and Michael Schumann, MD, respectively presidents of the International, U.S. and European societies for the study of celiac disease.
They note “significant downsides of the gluten-free diet,” currently the only treatment for celiac disease, including the difficulty of avoiding gluten when eating in restaurants, at work and on vacation. Additionally, the expense and sometimes inferior taste of gluten-free foods and the social constraints of following the diet present challenges that may affect how completely someone with celiac disease avoids gluten, the article says. Persistent intestinal damage and continued symptoms can occur even when the diet is followed strictly.
Measuring intestinal damage
Symptoms may not be related to persistent damage to the intestine and blood tests for the antibodies that indicate celiac disease is active also are not always a sign of intestinal damage. Consequently, routine biopsies after one to two years on the gluten-free diet or biopsies based on evaluation of risk of intestinal damage are two potential strategies for the high volume of celiac disease patients that will need to be assessed, according to the article. One goal would be minimizing the number of patients whose celiac disease is incorrectly categorized as uncomplicated thus making them ineligible for new drugs.
With evaluation of damage to the intestine anticipated to be more frequent, the authors call for the development and use of new tests to monitor celiac disease severity without the need for an invasive procedure such as endoscopy and biopsy.
While more sophisticated tools for judging the level of immune reaction in those who have celiac disease are being investigated, they have not been established through clinical trials and are not being used in patient care in celiac disease. These need more study and to be introduced into everyday work ups, the authors wrote.
Genetic testing may also play an increased role since several drugs in development target only those who have the most common celiac gene, HLA-DQ2.5.
Regulation and health care coverage
FDA regulations will shape the way patients are treated for celiac disease across the globe as new treatments are approved and made available, says the paper, which notes that globally, drug developers focus on the FDA when launching new drugs. Regulators in other countries then review the same data on drug safety and effectiveness. One potential barrier is that health insurance companies in the U.S. and government agencies in countries with socialized healthcare may be unwilling to offer coverage for new medications as they compare the cost-benefit of a new drug to the gluten-free diet, which is paid for by patients themselves in many places.
Confirming who has celiac disease
The gluten-free diet is followed by a mix of patients, from those with celiac disease confirmed through a biopsy to those who put themselves on the diet without a diagnosis because it resolved their symptoms.
A potential major challenge to the introduction of new drugs to treat celiac disease will be confirming whether those on the gluten-free diet truly have celiac disease, according to the authors. “Misdiagnosis may affect as many as 40 percent of patients on a lifelong gluten-free diet believing they have medically diagnosed celiac disease,” they wrote.
Estimates of how many celiac disease patients have the intestinal damage that is likely to be tied to eligibility for new drugs vary from 8 to 40% in one study, but improved methods for assessing damage suggest that up to 60% of patients on a well-controlled gluten-free diet have damage, the article says. Meanwhile, FDA draft guidelines for approval of drugs to be used with the gluten-free diet emphasize that a drug must result in improvement in both intestinal health and symptoms.
When new drugs to treat celiac disease become available, careful medical review of a patients’ diagnosis is likely to be needed as large numbers of patients likely have a “doubtful diagnosis” of celiac disease, the paper says. If that’s the case, currently the only way to confirm celiac disease is a gluten challenge followed by an endoscopy and biopsy. For those who truly have celiac disease, persistent symptoms and intestinal damage despite a strict gluten-free diet will need to be verified by a dietitian’s review of the diet and potentially an endoscopy, as well.
The authors also raise concern that both those with confirmed celiac disease and those who initiated a gluten-free diet on their own do not regularly see a doctor for celiac disease management and might not be aware of newly available drugs. Likewise, primary care doctors and even some gastroenterologists also might not know about treatments. The authors say education campaigns targeted at patients and physicians will be critical for raising awareness.
Children and new treatments
There will be unique barriers to using a drug to treat children with celiac disease even after a medication is approved for adults, the article notes. However, the challenges of a gluten-free diet are significant for children.
Children can struggle with fitting in while following a special diet, as well as keeping to the diet as strictly as needed. Social isolation and a lack of support put a strain on children and their families, the paper says.
Data from clinical trials for drugs for adults are challenging to apply to children because children vary in size, absorption and drug metabolism as they grow. However, there are specific concerns about involving children in clinical trials.
Factors that need to be taken into consideration in clinical trials involving children include the impact of a gluten challenge on growth, minimizing invasive procedures and formulating child-friendly drugs. However, the option to take a drug along with the gluten-free diet or in place of it could fill a major gap in treatment for children, the authors write.
What the future holds
“In the future, the first question for physicians considering newly approved pharmaceutical treatments for their patients with celiac disease will be whether their patient has a solid diagnosis,” the paper concludes.
Further, the expected arrival of new drugs for celiac disease will be “transformative for patients on the gluten-free diet, and their physicians, dietitians, endoscopy centers and clinical laboratories.”
Support groups
There are a number of support groups for caregivers and patients with celiac disease. Reach out to your gastroenterologist, dietitian, local hospital or community center for more details.
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Written by
Amy Ratner
Director of Scientific Affairs
Beyond Celiac
