Red Flag Over Long-term Efficacy of Oral Immunotherapy

SAN ANTONIO, Texas — After oral immunotherapy for milk allergy, the initial benefits sometimes wear off and reactions can return more aggressively than before, according to the first long-term follow-up of children.

"We had a high degree of optimism," senior investigator Robert Wood, MD, director of pediatric allergy and immunology at Johns Hopkins University in Baltimore, Maryland, told reporters attending a news conference. "I'm not saying we've lost that optimism, but it has certainly been tempered by looking at where these kids stand 3 to 5 years out."

The study results were presented here at American Academy of Allergy, Asthma & Immunology 2013 Annual Meeting by lead investigator Corinne Keet, MD, also from Johns Hopkins University. "These results underline the fact that oral immunotherapy for food allergy is not yet ready for clinical practice," she said. Moving forward, long-term follow-up of oral immunotherapy will be essential, she noted.

Oral immunotherapy for food allergy is not yet ready for clinical practice.

Dr. Wood told Medscape Medical News that despite initial excitement in the field, the findings are discouraging because they suggest that treatment cessation might not be an option for some patients.

"Some of them probably do require consistent lifetime exposure to stay protected," he said. "We've worried that a patient may leave a study with a false sense of security.... Some of the more dramatic failures were kids that looked like absolute successes at the end of the study."

The investigators followed 32 children from 2 previous randomized trials (J Allergy Clin Immunol. 2008;122:1154-1560 and 2012;129:448-455). After those children completed their initial oral immunotherapy for milk and passed an oral food challenge for milk protein, they were sent home with instructions to continue consumption.

A median of 4.5 years after the start of their therapy and 3 to 15 months after treatment cessation, the investigators questioned the children about their milk consumption and symptoms, and tested their blood for milk-specific immunoglobulin (Ig)E and IgG4.

They found that only 19% of children were consuming uncooked cow's milk in an unrestricted fashion; 31% had restricted their intake, but consumed at least 1 serving per day.

Table. Milk Consumption After Immunotherapy Cessation

Milk Consumption	Patients (%)
Unrestricted	19
≥1 uncooked serving/d	31
<1 uncooked serving/d	28
Only minimal or baked	6
None	16

"Soroughly 50% of subjects were consuming at least 1 serving per day," said Dr. Keet. However, the symptoms reported were disappointing, she noted.

"We initially thought that most subjects were doing quite well after these milk oral immunotherapy studies, but we found that 3 to 5 years after their desensitization, only 25% are consuming milk without symptoms at all," Dr. Keet said.

Table. Symptoms After Milk Consumption

Symptoms	Patients (%)
None	25
Occasional	22
Frequent and predictable	38
No milk consumption	16

Atotal of 31% of children reported a systemic reaction to milk consumption, and 19% had used at least 1 dose of epinephrine.

"We initially thought that with continued milk consumption, subjects would have fewer and fewer symptoms, but we found that some subjects became far more reactive than they had been early in therapy," Dr. Keet explained.

This is still a potentially dangerous therapy.

Session moderator Stacie Jones, MD, told Medscape Medical News that "this is still a potentially dangerous therapy."

"It's great that we are seeing these very exciting clinical results in oral immunotherapy — particularly for egg, milk, and peanut — early on," said Dr. Jones, who is from the Arkansas Children's Hospital in Little Rock. "But the warning is that these effects may not be long lasting."

Asked why he thinks the initial benefits of oral immunotherapy can wear off, Dr. Wood said that many patients continue to avoid milk, even if they have passed an oral milk challenge test. With continued avoidance, symptoms can recur, he noted.

"Everyone left the protocol on an individually prescribed dose of milk," Dr. Wood explained. However, "kids who are allergic to food don't tend to like that food.... The main thing I've come to believe is that they self-restricted because they didn't like the side effects, so they were not as protected as we believed."

The presenters have disclosed no relevant financial relationships.

American Academy of Allergy, Asthma & Immunology (AAAAI) 2013 Annual Meeting: Abstract 467. Presented February 24, 2013.