As it stands in 2019, the treatment of food allergies in Australia is allergen avoidance and the use of ‘rescue’ medication (adrenaline auto-injector, AAI) when required.

 

There is so much public interest and demand for an effective treatment of the allergy itself, rather than just the symptoms.  Parents worry about accidental exposure, we want to do SOMETHING positive to move our child towards a safer future- something other than pure avoidance.

 

I have a friend who has taken their child to the US to participate in oral immunotherapy- desperate to give their child a measure of protection after episodes of anaphylaxis from accidental exposure to peanut butter residue on playground equipment.

 

So what is out there in Australia, where are we at in terms of finding a ‘cure’ for food allergy?

 

Australia has been called ‘the food allergy capital of the world’.  10% of 1-year-olds will have a food allergy, with 4-8% of school-age children and 2% of adults living with food allergies in Australia.

 

There has been a four-fold increase in Anaphylaxis admissions from 1998-2012 (Mullins 2018).

 

We have introduced measures/guidelines aiming to reduce the incidence of food allergy (new cases)- such as the early introduction of allergens in line with the LEAP study & the EAT study results.

 

But we do not yet have a standard treatment for those who have already developed food allergies- other than allergen avoidance and AAI.

 

Given our understanding that food allergies are caused by an abnormal immune system response to ingestion of a food, it makes sense that a lot of the work on treatments of food allergy focuses on altering the way the immune system deals with the allergen (aka immunotherapy).

 

There are two main goals/outcomes used to evaluate the outcomes of food allergy treatment trials:

 

Desensitation: An increase in the threshold at which a patient reacts, but only while they have ongoing exposure to the food (maintenance dosing).

 

Tolerance/sustained unresponsiveness: the long-lasting ability to eat the food without reaction even when no longer regularly consuming the allergen.

 

Immunotherapy involves exposing the immune system to the allergen, usually in increasing doses, trying to ‘retrain’ or re-programme the immune response.

 

Immunotherapy can be ‘delivered’ in a variety of ways:

 

Oral immunotherapy (OIT)

The allergen is ingested in increasing doses.  Generally, it is felt that the allergen needs to be exposed orally (ie it needs to be eaten/drunk in its natural form, not taken via capsule etc).

 

Oral Immunotherapy plus ‘adjuvant’.

In this situation, the allergen is administered with an ‘adjuvant’ (an agent that modifies/enhances the effect of the allergen).

 

There are various adjuvants currently being used in clinical trials in Australia.  These include:

  • Probiotics
  • Short chain fatty acids- butyrate
  • Immunomodulatory drugs- eg omalizumab- an immune-suppressing drug that targets IgE
  • Changing the protein- eg boiled peanuts vs raw/roasted

 

Sublingual Immunotherapy (SLIT)

In SLIT, the allergen is given as a droplet that is held under the tongue for 1-2 mins before being swallowed.

 

Epicutaneous Immunotherapy (EPIT)

In this form of treatment, the allergen is delivered using ‘patches’.  The patch, impregnated with the allergen (at this stage peanut or milk) is placed on the skin.  It allows absorption of the allergen across the skin where it can then come into contact with the immune system.

 

Subcutaneous Immunotherapy (SCIT)

SCIT is currently used for environmental allergens (eg insect stings).  It involves the injection of the allergen under the skin.

 

Vaccines.

Recent Phase I study results were released for a peanut allergy vaccine.  The vaccine was shown to be tolerated. It is thought that the vaccine ‘redirects’ the immune system.  Research is ongoing.

 

For the purposes of this discussion, I‘m going to focus more on Oral immunotherapy and EPIT as these seem to be the areas of most interest in recent discussions.

 

Oral Immunotherapy.

OIT has been shown in both individual studies and ‘grouped’ studies (meta-analysis) to be effective in inducing desensitisation in food allergy patients.

 

OIT alone- peanuts:

ARA101 (PALISADE group).

This study, published in the New England Journal of Medicine, had 551 participants who were allocated either to placebo or treatment with an escalating dose of peanut protein over a 12 month period.

At the conclusion of the study, an oral food challenge was performed which showed 67% of those in the active treatment arm, vs 4% of those receiving placebo could tolerate 600mg peanut protein (about 2 peanuts) without dose-limiting symptoms.

 

OIT with adjuvant.

It seems that combining the allergen with an adjuvant (eg probiotic, short chain fatty acid) increases its effectiveness.

 

Peanut + probiotic

PPOIT (Tang 2013) was a randomised trial of peanut + probiotic administration in children allergic to peanuts.  The initial study had 62 children participating and showed that 82% of children receiving the active treatment developed sustained unresponsiveness vs 4% of those receiving placebo.  

 

OIT + omalizumab

Omalizumab (Nadaeu 2011) is an immune-suppressing drug that targets IgE.

Studies have shown that the addition of omalizumab allowed more rapid dose escalations, but there was no difference in the rate of tolerance in the placebo vs trial group at the end of the study.

 

EPIT- Epicutaneous Immunotherapy

EPIT is delivered by way of a small patch (similar to a nicotine replacement therapy patch) that is applied to the skin and changed daily.

In most study protocols, there is an initial doing/observation period following by dose escalations to the point of wearing the patch 24 hrs per day indefinitely.  It seems to be well tolerated, and investigators did show a difference in rates of desensitisation (35.5% vs 13.6%) in treatment vs placebo groups.  It does not seem to be as effective as OIT, but does have a better side effect profile.

 

But what does that all mean??

So all of that information is great and all, but what is the human side of all of this?

 

Oral Immunotherapy is a big undertaking.  At the moment it is not available in Australia outside of clinical trials.  This means people are travelling overseas with their children to enrol in centres that offer OIT at great cost and disruption to families.

 

Allergy and Anaphylaxis Australia has identified OIT as a priority, recognising that people are calling for more active options to help their children.

 

Looking at Instagram accounts of overseas clinics, they say OIT ‘sets children free’.  And there are some really positive stories being shared, which gives a lot of hope.

 

But it is also a really hard road for many.

 

There are physical restrictions- multiple clinic visits, doses must be taken with food, there is a 2 hour period of physical inactivity/observation after each dose.  Some kids report not feeling well while going through the process.

 

And there are significantly higher rates of reactions, including anaphylaxis when going through OIT.

 

The biggest problem being faced at the moment is that if the outcome of OIT is only ‘desensitsation’, that protection is variable and temporary- once the child stops ‘dosing’ they revert to reacting to even small amounts of the food.  There is not yet long term data on how to maintain a level of protection. Children who are desensitised still need to avoid the allergen and carry their EpiPens. The desensitisation gives them a degree of protection against accidental exposure- ie it raises their threshold for reaction.

 

Even while in a state of desensitisation, if the child has asthma, a viral infection, in older/adolescent patients at the time of menstruation, or undertakes strenuous exercise around the time of eating, their reactivity is higher- they are more likely to have anaphylactic reactions to previous tolerated ‘doses’ of their allergen.

 

So as with anything, it’s a cost-benefit analysis.

 

Is going through something strenuous and expensive worth that outcome for your family?

 

It’s also why we need to get really good clinical trial information before ‘unleashing’ this treatment widely.  

 

Researchers are working on determining the ‘best’ adjuvant, the safest and most effective dosing protocol and means of delivery. They are finding different age groups react differently to the same therapeutic regimen, and we need long term data on the ‘maintenance’ phase of treatment.

 

All these questions need to be answered and it is why there is so much research being directed towards it currently.

 

Peanuts are still the allergen that Caleb reacts most to on skin prick testing.  I have seen him have anaphylaxis to accidental exposure to a very small amount of residue.  

Any additional protection I can give would be amazing.  But I also want robust evidence and safety data. I want experienced centres with reputable specialists and clear protocols.  

 

Which means, for now, I wait.  I continue with avoidance and carrying EpiPens.  I advocate far and wide for his safety and inclusion and keep in regular contact with our immunologist so that when things do become available in his age group, we can get on board if it’s the right thing for us.

 

Bibliography.

The Murdoch Children’s Research Institute website was accessed.

#oralimmunotherapy on Instagram was searched to find some real-life experiences reported by families going through OIT.

The American Academy of Asthma, Allergy and Immunology Website:  The current state of oral immunotherapy for the treatment of food allergies.  https://www.aaaai.org/conditions-and-treatments/library/allergy-library/oit

AR101 Oral Immunotherapy for Peanut Allergy, N Engl J Med 2018; 379:1991-2001

Beyer K.  A European Perspective on immunotherapy for food allergy.  Clinical Reviews in Allergy and Immunology. March 2012

Canani RB, Costanzo MD, Leone L, Pedata M, Meli R, Calignano A. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol. 2011;17(12):1519–1528.

Du Toit G., Roberts G., Sayre P.H., Bahnson H.T., Radulovic S., Santos A.F. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372:803–813.

Esposito S, Isidori C, Pacitto A, Salvatori C, Sensi L, Frati Fm Di Cara G, Marucci F.  Epicutaneous immunotherapy in rhino-conjunctivitis and food allergies: a review of the literature.  Journal of Translational Medicine201816:329

Feuille E, Nowak-Wegrzyn A. Allergen-Specific Immunotherapies for Food Allergy. Allergy Asthma Immunol Res. 2018;10(3):189–206. doi:10.4168/aair.2018.10.3.189

Mullins RJ . Paediatric food allergy trends in a community‐based specialist allergy practice, 1995‐2006. Med J Aust 2007; 186: 618–21.

Nadeau KC, Schneider LC, Hoyte L, Borras I, Umetsu DT  Rapid oral desensitization in combination with omalizumab therapy in patients with cow’s milk allergy.  J Allergy Clin Immunol. 2011 Jun; 127(6):1622-4

Perkin MR, Logan K, Marrs T, et al. Enquiring About Tolerance (EAT) study: Feasibility of an early allergenic food introduction regimen. J Allergy Clin Immunol. 2016;137(5):1477–1486.e8. doi:10.1016/j.jaci.2015.12.1322

Tang ML , Martino DJ . Oral immunotherapy and tolerance induction in childhood. Pediatr Allergy Immunol 2013; 24: 512–20.

Tang ML , Ponsonby AL , Orsini F , Tey D, Robinson M , Su EL et al. Administration of a probiotic with peanut oral immunotherapy: a randomized trial. J Allergy Clin Immunol 2015; 135: 737–44.e8.

Wasserman R, Jones D, Windom H.  Oral Immunotherapy for food allergy. The FAST perspective.  Annals of Asthma, Immunology and allergy.  Sept 2018, Vol 121 Issue 3, pp 272-275