Oral and Sublingual Immunotherapy for Food allergy
Dr. Wesley Burks discussed Oral and Sublingual Immunotherapy for Food allergy.
We need to decide on the ultimate goal of OIT - is it desensitization or tolerance?
In oral immunotherapy (OIT), we take the protein powder of the food and ingest it. In SLIT, we take the extract of the protein and drop it under tongue.
Paradigm of food immunotherapy trials - build up phase, maintenance phase and ongoing challenges to assess desensitization.
After 1 year of peanut OIT, there is a definite difference in desensitization/ threshold for reactivity between the active arm and placebo. If you stop OIT though, what is the evidence for tolerance? How long does the benefit of treatment persist? Still not fully elucidated.
In egg OIT studies, approximately 30 to 55% demonstrated "sustained unresponsiveness" off OIT, depending on duration of OIT. For the peanut OIT studies, treatment successes generally had lower sizes of SPT at baseline. Similarly, the lower the baseline PN sIgE, the higher likelihood of continuing to pass oral challenges after treatment with OIT.
In conclusion, OIT produces allergic side effects, but does result in an increased threshold of reactivity - not clear if tolerance develops. An upcoming study funded by Immune tolerance network will hopefully help with some of the unanswered questions in OIT.
8 foods cause 90% of food allergies (click to enlarge the image). The likelihood of a negative oral food challenge is shown in relation to the respective values of skin prick test (SPT) and serum IgE (sIgE).
Future approaches in the treatment of food allergy
Dr Hugh Sampson discussed Future approaches in the treatment of food allergy.
Future ideas include heat denatured food proteins, recombinant proteins, epicutaneous IT, peptide-based IT, LAMP-Vax-food DNA therapy.
Heat and processing changes the conformation of some epitopes and renders the protein non-reactive. 76% of kids with milk allergy tolerated baked milk. Heat-denatured milk therapy should lead to tolerance in about 70% of children. Baked milk and egg need to be tried in all milk and egg allergic children; OIT gives most robust desensitization. Boiled milk is not heat-treated enough to denature the milk protein - it really needs 1hr at 350 F, at least. There is not yet a good commercial assay for the sequential epitopes to determine who is most likely to fail baked challenges.
Recombinant proteins substitute a single amino acid within the epitopes for Ara H 1,2 and 3 - in a mouse model this looked promising. CoFAR study - Phase I safety study of the recombinant peanut vaccine - 5 of 10 subjects developed mild to moderate anaphylaxis - so it’s a “no go”.
Epicutaneous IT, e.g., Viaskin peanut - contains 100 mcg of protein in a disc applied to the back or arm depending on age of subject. Viaskin results are more impressive in kids under age of 12, but they are only getting desensitization to equivalent of 1 peanut/day. VIPES trial looked at an epicutaneous dose of 1000 mcg, preliminary results suggest best results in younger children. Epicutaneous IT is showing promise but he would like to see a more robust desensitization response.
Peptide based immunotherapy only delivers the T-cell specific epitopes and decreases (in theory) risk of IgE cross linking and adverse effects. Mouse studies of peptide immunotherapy based on Ara H 2 look quite promising. Mouse studies of LAMP-VAX Peanut are also looking promising. LAMP-Vax for Japanese Red Cedar has translated well to humans, so perhaps peanut therapies will be successful - it is still too soon to know.
Nanoparticle encapsulated peanut protein for SLIT and OIT also being investigated - still in mouse models only but treated mice did well.
TLR conjugate proteins are being considered because they activate immune system and allow much lower doses of Ag (think MPL grass IT studies). Other TLR4 agonists include glucopyranosyl lipid A - fully synthetic ligand - in Phase I trials.
What about other tree pollen influences on Ara h8? Oak definitely does along with Alder - so it is not always birch responsible for cross reactivity with peanut. In child eating peanut without difficulty, with a positive skin test or Ara h 2, the worst thing you can do is take it out of their diet. The entire panel agrees that if there is any doubt, you should do an oral challenge, so you can know for sure and not give inappropriate advice.
Omalizumab can reduce rates of adverse reactions to OIT by 70%, compared to placebo. OIT with duplimumab (anti IL-4R) is in planning stages.
Dr Burks reminded audience of the importance of cofactors for reactions to food - exercise, viral illness, NSAIDs can increase risk of reactions to OIT. Unexpected anaphylaxis to OIT doses on maintenance is usually due to fever, exercise, menses, other co-factors. Unfortunately, we can't predict for whom these co-factors will be important and for whom they won't matter.
Remember EVERYONE reacts at some point to OIT - it's not a benign therapy and requires commitment of patient and parent.
Desensitization effects of OIT is real, but should anyone define that as a cure? It is if you never stop the treatment… The idea that we have solved food allergy with these treatments is premature.
If kids are going to develop EoE as a consequence of OIT treatment, we usually see it in first weeks/months, not later.
This is a Twitter summary from 2014 #ACAAI meeting. The post is a part of series. See the rest here: http://allergynotes.blogspot.com/search/label/ACAAI
The Twitter summary was made possible by @DrAnneEllis and @MatthewBowdish
Several allergists did a great job posting updates from the 2014 meeting of the #ACAAI. I used the website “All My Tweets” to review the tweets. For comparison, here are the tweets from previous #ACAAI meetings (scroll down the page for the past years): http://allergynotes.blogspot.com/search/label/ACAAI