What LEAP Meant for Food Allergy

Yes, some allergists took it upon themselves to begin introducing food allergens to high allergy-risk children at a young age. And it was a push against the guideline-directed and historically accepted practice of the oldest prevention known for food allergy: avoidance, avoidance, avoidance.

But what really changes patient care is proof. And when those allergists were proven right, it was by more than they could have even imagined.

It is fitting that, in the scope of discussing the greatest developments in US medicine this decade, the LEAP trial was published in February 2015, a near-perfect midpoint of the 2010s. The years prior to the reported outcomes of the early peanut introduction trial were highlighted by this slow shift from avoidance to exposure, oftentimes based on an academic hunch.

That’s how Tina Sindher, MD, clinical assistant professor at Stanford University, remembers that time. She was in fellowship training at the Children’s Hospital of Philadelphia (CHOP) in the mid-2010s, and though allergy risk prevention was the same then as it was during medical school and residency—avoidance, avoidance, avoidance—she saw her mentors begin to challenge that rule.

“What’s interesting is that, because I was in academia and I wasn’t practicing, it was something my mentors were already talking about,” Sindher told MD Magazine®. “They were thinking about it.”

Douglas Mack, MD, a pediatric allergist with McMaster University, was already into practice at the time. He recalled his home country Canada carrying dissenting guidelines written in 2013, that advised against avoidance. That ruling still stands out to him: there wasn’t concrete evidence supporting the change, but it was an accepted practice nonetheless.

He told MD Mag he had stopped advising parents with allergy-risk children to avoid the allergen long before the LEAP trial results were published on February 26, 2015.

A team of London-based investigators reported findings showing that just 1.9% of infants aged 4-11 months old with severe eczema, egg allergy, or both, who had consumed peanut protein regularly until 60 months of age, tested posted for peanut allergy.

Peanut allergy was prevalent in 13.7% of similar peanut allergy-risk infants who had avoided peanut protein for the same time period (P <.001). The absolute 11.8 percentage-point difference represented a relative reduction of 86.1% in peanut allergy prevalence among infants who consumed peanuts, versus those who had not.

Early, oral introduction of peanuts could actually prevent allergy development in high-risk infants, investigators concluded.

Mack pored through an embargoed copy of the study results days before their release. He was in disbelief.

“If you think about it, there’s very few public health interventions that’d reduce the risk of chronic disease by 80%. There’s very little that we do that has such a magnitude of effect for a concerning illness,” he told MD Mag. “It shattered every idea we had, and had a lot of intended and unintended consequences.”

Treatment guidelines essentially changed overnight. Sindher, herself a young mother at the time, saw an overflow of new referrals come in. Parents were panicked by the complete reversal of care. “Those with recent diagnoses believed they were to blame for their kids’ allergy occurring, because they didn’t expose them,” she explained.

Mack felt a sense of apology in the follow-up work those cases brought him. Parents with a 4-year-old just diagnosed with a peanut allergy, who had adhered to the avoidance mantra, were not as thrilled with the new findings.

But even those parents with the benefit of time have not been as receptive to the change in strategy, whether it be due to their own fear of exposing their high-risk child to a potential anaphylaxis trigger, or potential misinformation. Many specialists offer in-office allergen introduction care as means to assure safety to parents, but plenty other hurdles persist.

Parent precaution is also leading into a greater discussion of food allergy diagnosis and the merit of screening. Mack believes physicians took the LEAP findings to believe screening to identify high-risk patients prior to initiating early introduction—when in reality screening was only used to enroll the patient population.

He cited the work of colleagues like Marcus Shaker, MD, and Matthew Greenhawt, MD, who have shown the financial cost of applying pre-introduction screening to the peanut allergy population would be in the hundred millions. Some international guidelines, such as those practiced in Australia, emphasize an outright allergen introduction without screening. Mack suggested that may be the more practical strategy.

“We still have disagreement with how to implement this incredible, landmark study,” he said.

The whirlwind adoption of food introduction forced Sindher and colleagues to set “algorithms” of care and consistent messages for uncertain parents. And yet, she will go into 2020 knowing some parents will still practice old avoid, avoid, avoid.

There’s also little evidence early introduction can be applicable to children at high risk of other common allergens. Egg, the second-most common allergen behind cow’s milk, has been observed in about a half-dozen early introduction clinical trials, and lacks the standout data observed in LEAP, Mack noted.

But for all the questions raised by these findings, even more opportunities have been created. Next month, the US Food and Drug Administration (FDA) will rule on the Biologics License Application (BLA) for Aimmune Therapeutics’ investigative peanut oral immunotherapy AR101.

In September, the FDA Allergenic Products Advisory Community voted in favor of data from the phase 3 PALISADE trial, showing efficacy and safety of the product in reducing allergy incidence and reaction severity in patients aged 4-17. If AR101 is approved, it will be the first food allergy immunotherapy to be regulated in the US.

The FDA will also consider the BLA of once-daily epicutaneous peanut allergen skin patch Viaskin Peanut from DBV Technologies, currently scheduled for decision by August 2020. In 9 months, a field previously dormant of therapies could have competing products. “I used to get excited over a new nasal spray for rhinitis,” Mack joked.

Both immunotherapy options would have very clear limitations—namely, that their benefits are confined to continued patient desensitization. But their receiving a stamp from the FDA may give parents of patients the sense of treatment confidence they have been lacking&mdash;the same confidence gifted to physicians with the LEAP data.

“It was a big shift in the field, and now oral immunotherapy is being offered in private allergy practice,” Sindher said.

Plenty other advancements since 2010 have greatly benefitted allergic care—the introduction of new biologics, an improved understanding of the atopic march, potential food allergy vaccine mechanisms being assessed&mdash;but none have had the impact of the LEAP findings.

It may take another 10-15 years to come across as great of a clinical finding, Mack noted. And in the meantime, it’s helped to make the field all the more interesting.

“There’s so much about allergy we don’t understand,” Sindher said. “Each year we add a little more to the puzzle. But the LEAP trial was one of the most major pieces.”