Even when oral immunotherapy for peanut allergy appears to work when tested in the doctor’s office, it may significantly increase allergic and anaphylactic reactions outside the clinic, a new study finds.

After pooling the results of 12 clinical trials that included a total of more than 1,000 patients, researchers found that compared with avoiding peanut exposure and placebo treatments, oral immunotherapies were associated with three times the risk of anaphylaxis and nearly twice the number of serious adverse events, according to the study published in The Lancet.

“The premise of the studies was based on the assumption that if you can eat peanut in the clinic you will be desensitized and that will translate into desensitization everywhere else,” said the study’s lead author, Dr. Derek Chu, a fellow in clinical immunology and allergy at McMaster University in Hamilton, Ontario. “But assumptions don’t always turn out to be true.”

Part of the problem is that testing in a medical clinic is a controlled environment. A child on oral immunotherapy might be able to ingest a bit of peanut without any issues in the clinic, but when they are at home taking their daily dose of “medicine,” other factors such as having a cold, exercising or even menstruation can affect the way the body interacts with therapy, Chu said.

The researchers analyzed 12 studies on peanut oral immunotherapy, involving 1,041 patients whose average age was 8.7 years. Three of the trials included in the new study had not been published. When the patients from all 12 trials were pooled in a single analysis, some disturbing trends popped out.

Higher risk at home

The risk of anaphylaxis among children receiving oral immunotherapy turned out to be more than three times higher than in kids avoiding the allergen or treated with placebo medication. Children on immunotherapy were two times more likely to use epinephrine, compared to children on a placebo or completely avoiding peanuts.

Oral immunotherapy was also associated with a higher risk of serious adverse events and allergic reactions such as vomiting, upper respiratory tract reactions, and swelling.

Even with the possible risk of anaphylaxis at home, the treatment may be still be worthwhile for parents and children who are afraid of accidental exposure to peanuts, said Dr. Bruce J. Lanser, an assistant professor of pediatrics and director of the Pediatric Food Allergy Program at National Jewish Health. Because the therapy may raise their sensitivity threshold, coming in contact with a bit of peanut will be less likely to trigger anaphylaxis, Lanser said.

For others, the side effects of the daily dose might not be worth it, said Dr. Scott Sicherer, a professor of pediatrics and director of the Jaffe Food Allergy Institute at the Icahn School of Medicine at Mount Sinai in New York and author of “Food Allergies: A Complete Guide to Eating When Your Life Depends on it.”

“If your main hope is to raise your threshold, then this might be the right match for you," Sicherer said. "But if your main goal is not to have any reactions, then maybe not.”

The results highlight a flaw in how researchers have been evaluating the success or failure of oral immunotherapy, Chu said. In the trials, treatment is considered to be successful if the child can consume a bit of peanut in the clinic.

But that's not what many parents and children care most about — prevention of life-threatening reactions, Chu said.

Chu and his colleagues aren’t suggesting that patients not try oral immunotherapy. Rather, the researchers would like to see future trials designed to examine how the therapies work in the real world.