Dr. Hugh Sampson is one of the leaders in the food allergy field, and a student of history. He can cite that the first paper on on oral immunotherapy for food allergy was published in 1908, and that the strategy was largely abandoned until Italian researchers began working with it in the 1990s.
“One of my concerns has always been, why did people stop doing it?” says the director of the Jaffe Food Allergy Institute at New York’s Icahn School of Medicine at Mount Sinai. He knows of one potential answer: reactions.
The work on stinging insect allergy also looms large in Sampson’s thinking: For years, the extract for allergy shots to protect against wasp, hornet and other stingers was made by grinding up whole insects. “There was one lone voice who said: ‘But people are allergic to the venom, that’s what we ought to be using,’” he notes.
This led to a study that found, eureka, using venom extract prevented reactions in 96 percent of allergic patients. Meantime, the “whole body” extract proved no more effective than a placebo.
“They were giving something that was no better than injecting water,” says Sampson, who published an academic article in January 2013 warning the community of allergists not to rush OIT into their practices before it’s ready. “I just don’t want us to make a similar mistake with oral immunotherapy [for food].
We’ve got to do the studies right, we’ve got to make sure we’ve got the data right,” he told Allergic Living.
Since 2005, Sampson has been trying to get a different approach to food OIT off the ground. His idea was to combine the desensitization process with the injectable drug omalizumab – better known by the Xolair brand name. Xolair prevents or reduces reactions by neutralizing free-roaming IgE antibodies, the type of antibodies that set off allergic symptoms. In persistent asthma, the drug has shown largely favorable results.
For years, regulatory issues delayed Sampson’s use of this combined approach. Today, it is back on the drawing board, and Mount Sinai, Johns Hopkins and Stanford University researchers have 56 milk-allergic children enrolled in a significant study. Sampson says: “This is a placebo-controlled trial that should answer the question: ‘Does Xolair make a significant difference in the number of adverse reactions?’”
He explains that the drug doesn’t just reduce the IgE antibodies that attach to the mast cells involved in allergic reactions. It also should change the immune system’s overall response to the allergen. “Our hope is that we’ll be able to block the allergic reaction in favor of a more natural reaction seen in patients who aren’t allergic. This may possibly lead to tolerance.”
That, of course, is the big and complex issue. But Sampson’s team hopes to be able to soon answer the first question about reducing reactions. In safety trials with a few patients, conducted at Harvard and Stanford universities, there are already encouraging signs.
From his lab at Harvard, immunologist Dr. Dale Umetsu has become intrigued by the idea of a combination therapy with Xolair – both to decrease symptoms in patients as they go through desensitization, and also as a “rush” method for OIT, which is normally a long process with a high dropout rate.
“We think if you use Xolair with oral immunotherapy you can get to the high doses of the food allergen pretty quickly and minimize allergic reactions. Half of our patients have no reaction at all over the course of the desensitization,” he says of his team’s OIT trials that include Xolair injections at Boston Children’s Hospital, where he directs the asthma center.
Following three months of pre-treatment with Xolair, that’s just six weeks into combination oral immunotherapy for milk and eight weeks for peanut. (By comparison, the non-Xolair immunotherapy trials can run from six months to two years.)
“It just hastens the process,” agrees Dr. Kari Nadeau, an associate professor at the Stanford University School of Medicine who has collaborated on some of these small studies with Umetsu, whom she describes as a mentor. This spring, The New York Times Magazine featured the impressive results she has also been seeing with the combination therapy in children with multiple food allergies, setting the allergy world – both patients and professionals – abuzz.
“There’s so much excitement,” notes Nadeau, the director of the Stanford Alliance for Food Allergy Research. “People want something they can feel good about. They really want a cure.”
Next: More ideas – Chinese herbs and the peanut patch