Immunotherapy may increase the risk of allergic reactions.

By Jamie Ducharme
April 29, 2019
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In a new review published in the Lancet, researchers came to a disappointing conclusion about recent studies on treating peanut allergies. They found that treating children by exposing them to small amounts of peanuts, which has shown success in several studies, is actually associated with an increased risk of allergic reactions, including anaphylaxis.

This approach, called oral Immunotherapy, involves repeated controlled exposure to whatever is causing an allergic reaction — in this case peanut allergens — to retrain the immune system. Allergic reactions occur when the immune system treats benign substances, like certain foods, as if they were dangerous pathogens, like bacteria or viruses, and launches an inflammatory response. Immunotherapy is designed to teach the immune system to be less sensitive to the substances in question.

Multiple studies have found that oral immunotherapy — which involves feeding kids who are allergic to peanuts small amounts of peanut compounds — can help children tolerate the food. But according to the Lancet analysis, which examined 12 trials involving about 1,000 patients, those encouraging results may not translate to real protection over time. While people with peanut allergies had a 7% risk of experiencing anaphylaxis — a severe immune reaction in which blood pressure drops and the airways narrow, making breathing difficult — without oral immunotherapy, they had a 22% risk of having a bad reaction when they were taking these drugs, the paper says.

“The degree of desensitization [achieved in clinical trials] is incomplete. It’s not perfect,” says Dr. Derek Chu, an internal medicine physician and clinical immunology and allergy fellow at McMaster University in Canada. Everything from catching a common cold to taking drugs on an empty stomach can affect the way immunotherapies work, he says. “So many things can perturb it, break it or disturb it.”

That range in possible reactions is backed up by the variety of results from immunotherapy studies. Last November, a phase-three trial published in the New England Journal of Medicine found that an immunotherapy drug in development helped the majority of pediatric participants build immunity to peanut protein. The company developing the drug said it could be available as soon as this year, pending Food and Drug Administration (FDA) approval.

Another promising study, published in 2017, suggested that immunotherapy may be especially effective when combined with probiotics.

Chu — who, like an estimated 6 million people in Europe and North America, is allergic to peanuts — says it’s not totally clear why patients taking oral immunotherapies may be more susceptible to allergic reactions. It may be that people don’t follow drug regimens properly, he says, or it could be something about the drugs themselves. But his analysis found that people taking these therapies had a higher risk and frequency of allergic reactions than those taking a placebo or simply avoiding peanuts, regardless of when they started treatment, their age and their drug dose and duration.

Despite the disappointing results, the fundamental idea behind immunotherapy — building tolerance — has plenty of research behind it. Last month, the American Academy of Pediatrics issued new guidelines for parents hoping to prevent food allergies in their children. The new policies suggest that parents give children at high risk of developing peanut allergies peanut-containing foods as early as four to six months of age so they can start building immunity.

But people who have already developed peanut allergies currently don’t have many options, other than avoiding them completely. Chu says his findings should not be a condemnation of immunotherapy; they just show there’s a need for more research.

“This is really the first big crack at trying to treat peanut allergy, which is a fundamental milestone, and we should celebrate that,” he says. “But like anything else in medicine or technology or life, the first time you do something, it’s not necessarily going to be perfect.”

Chu says researchers should continue to fine-tune oral immunotherapy, but he says they should also look into other treatments and other delivery methods, including drugs given under the tongue, topically or by injection. Further, he says more research is needed to ensure that medications that look promising in the lab actually work well outside of it, especially since food allergies are growing more common. Until that work is done, he says, the scientific community should avoid over-hyping its preliminary results.

“Every time I eat, am I going to be safe?” he asks. “Sometimes, acting on a guess when you’re uncertain is more harmful than not acting at all.”

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