In search of general theories

What's next in food allergy immunotherapy?

02.04.2014 10:02

What's next in food allergy immunotherapy?

24.03.2014 22:15

 

Right now, food allergy management remains strict avoidance for routine practice, Robert Wood, MD, chief of allergy and immunology at Johns Hopkins Children's Center, told MedPage Today. But years of research are bringing oral immunotherapy closer, he noted.
 
"We're building on studies that we've done over the last 7 or 8 years," Wood, a leading figure in the NIH-funded Consortium for Food Allergy Research (CoFAR), explained. "Hopefully it improves ways of delivering immunotherapy to maximize both efficacy and safety."
 
Wood laid out six new frontiers for the field:
 
1. Immunotherapy Patches
 
Introducing the immune system to allergic triggers through the skin rather than orally has a potentially huge safety advantage.
 
Small, early-phase trials have shown few if any of the systemic adverse reactions that can happen with oral administration, requiring epinephrine in perhaps 12% of orally-treated children.
 
Two larger trials are underway in peanut allergy, one dubbed VIPES and another through CoFAR, both using higher doses than previously studied. Early phase research is also underway with milk and even aeroallergens.
 
"It's still going to be much safer," Wood said. "It's really because the amount of allergen that's being absorbed systemically is much lower" than with oral immunotherapy.
 
2. Baking Foods
 
Many kids allergic to milk or other foods are able to tolerate it if baked, which is thought to be because the immune system isn't sensitized to the different shape allergy-triggering proteins take when thoroughly heated.
 
And those kids who consumed baked versions of their allergy-causing food tended to overcome their allergy better, based on initial research, suggesting it acts as natural immunotherapy.
 
A head-to-head comparison of milk allergy oral immunotherapy against consumption of milk in baked foods for kids able to tolerate it is on the CoFAR docket this year, although initial results won't likely be seen until 2016.
 
"I think the immunotherapy will work better in terms of inducing more tolerance, but we have no idea. It's an open question," Wood said. "When Hugh Sampson and I wrote this protocol, we powered it to show a difference between the two groups. We came up with the same sample size but his power was in favor of baked egg and mine was in favor of oral immunotherapy."
 
3. Starting Early
 
Food allergy oral immunotherapy has been progressively working its way into younger age groups as safety has been established. Now Wood's group has started a trial testing the strategy for 1- to 3-year-olds.
 
"Starting early, when peanut allergy may not be quite so established in the immune system might work better," he explained. "We can't see a real age difference so far, but we do know that a food allergy like peanut is something that evolves over the first 5 years of life and becomes more and more established. It's possible that early intervention will have a better outcome."
 
4. Tackling Wheat Allergy
 
The first oral immunotherapy trial is now underway for wheat allergy, which Wood pointed out is an immunoglobulin-E-mediated severe anaphylactic allergic reaction different than Crohn's disease or gluten sensitivity.
 
Wheat allergy is fairly rare at a prevalence of about 0.5% but can be "every bit as severe as the worst peanut allergy" for kids who don't outgrow it early on, he noted.
 
"In a lot of ways, [wheat allergy] is a lot more dangerous," Wood told MedPage Today. "There's so much more wheat out in the world, out in the school."
 
5. Attacking Multiple Allergens at Once
 
While multiple aeroallergens have commonly been tackled simultaneously with sublingual immunotherapy, the same strategy is just getting underway in food allergy treatment.
 
The initial pilot trials treating up to five food allergies simultaneously with immunotherapy have recently reported results in adults and children.
 
"It's a really important idea because the majority of patients are allergic to more than one food," Wood noted. "Multiple foods would be ideal if we could do it safely."
 
Safety is the key issue, he said.
 
"Right now there's a lot of risk with doing a single food at a time, so it's unclear how much success we can have while still maintaining safety doing multiple foods."
 
6. Modified-Protein Immunotherapy
 
Another, albeit more distant, strategy aimed at safety is modifying how allergy-triggering food proteins are presented to the immune system.
 
The allergen could be hidden within nanoparticles to get it to the immune system without so much risk of systemic reaction or the offending protein could be modified (akin to the baking strategy) to reduce reaction risk.
 
Wood called his group's first such attempt with a recombinant peanut protein in humans a dismal failure.
 
"But that general idea of being able to modify the protein so you can give even much larger doses of the part you really need to build tolerance without the risk of reactions is something we would be hopeful for over the next 10 or 15 years," Wood told MedPage Today.