There is limited research and funding for allergies and anaphylaxis in Australia. However the current research is of critical importance as it has already begun research studies that are looking for a better understanding of why allergies are on the rise. Importantly, Australian researchers are sharing some information with international researchers in the study of allergies and anaphylaxis.
This chapter outlines research currently being undertaken in Australia relating to allergies and immunology as well as research partnerships with other countries. The current status of oral immunotherapy for allergies both in Australia and overseas is discussed, as well as new medications and alternative therapies.
Research in Australia
Research into allergy includes not just the search for a cure or harm minimisation for allergy sufferers but the research into the causes of allergies and the cause of the sharp rise in childhood allergies which has occurred in the last twenty years.
The Australian Society of Clinical Immunology and Allergy (ASCIA) stated that there is a strong need to increase the understanding of the underlying causes of allergic disease, as this will lead to improved treatments.
The Department of Health is committed to health and medical research and has several funding models which provide opportunities for research into both risk factors and treatments for allergies.
The Department of Health’s Medical Research Future Fund (MRFF) is an endowment fund to provide sustainable funding for medical research in the medium and longer term. It has provided $437,000 to the University of Western Australia for a research project into what dietary factors increase the risk for children developing food allergies.
Professor Brandon Murphy, the Chief Medical Officer of the Department of Health, said that one of the core areas of the MRFF is translational research and clinical trials.
The Biomedical Translation Fund (BTF) is a for-profit venture capital fund which matches funding to Australian biomedical start-ups that have secured private capital investment. So far, it has invested in two companies focused on allergies and anaphylaxis:
ProTA Therapeutics Pty Ltd has received $10 million for development of a new treatment into food allergies in children and adults; and
Aravax Pty Ltd has received $5.59 million for research into a new type of peptide immunotherapy to treat peanut allergy.
The National Health and Medical Research Council (NHMRC) have also provided a grant of $6 million to the Murdoch Children’s Research Institute (MCRI) for food allergy research.
Ms Carolina Valerio, a clinical research nurse at the Children’s Hospital at Westmead, noted in her submission that no allergy specific research received a grant from the NHMRC in the most recent round of funding. The Children’s Hospital at Westmead had previously received a grant to undertake research into oral immunotherapy. Due to a lack of funding, this hospital‘s Chair of Allergy and Clinical Immunology position is vacant and cannot be filled.
Ms Valerio also said private funding from charities is highly competitive and the amounts awarded are often insufficient to fund complete research studies. She has undertaken the task of fundraising for her department and describes it as ‘an additional full time, unpaid job’.
Dr Melanie Wong, at the Children’s Hospital at Westmead, stated there is active research into allergies being undertaken in Victoria, Western Australia, New South Wales and South Australia. All of these research groups require support and funding in order to translate their findings into clinical practice.
One of the leading research facilities in Australia in the area of food allergy research is the Centre for Food Allergy Research (CFAR). CFAR was established in 2013 as a collaboration of researchers and clinicians in Australia, funded by the NHMRC. It is currently supported by a NHMRC Centre of Research Excellence (CRE) grant which will expire in 2022.
Dr Catherine Hornung of CFAR stated that most of CFAR’s individual trials are funded through grants and CFAR provides funding for some of its PhD and postdoctoral researchers.
Dr Hornung went on to say that CFAR would like more funding to employ experts in health economics and implementation evaluation experts in order to ensure the outcomes of their research are able to be implemented effectively at a policy level.
Without funding for CFAR, the framework that it provides for research collaboration would be lost, as well as the ability of researchers to speak to other leading medical experts and allergy patient advocacy organisations, such as ASCIA and Allergy and Anaphylaxis Australia (A&AA).
Dr Hornung stated ‘we feel very strongly that we need to continue to have that framework to pull all the researchers together so that there is one body to look to for this kind of expertise.’
Since 2015, ausEE Inc., a patient support and advocacy organisation for sufferers of Eosinophilic Gastrointestinal Disorder (EGID), has contributed almost $100,000 to research into the treatment and diagnosis of EGID. They note this is a relatively small amount raised from donations from supporters and would like the MRFF to prioritise more research into EGID in the future.
The Australian College of Nursing (ACN) stated there has not been a significant increase in allergy research funding since 2015. It said ‘there is a need for a great deal more research funding to identify the multifaceted underlying causes of allergy and anaphylaxis so that consistent, evidence-based management and treatment strategies can be developed.’
In one submission, the author stated they would like to see a balance of funding for research into prevention of further allergies and treatments for current allergy sufferers.
Currently, most allergen trials offered in Australia are into peanut allergy exclusively.
Dr Kristin Perrett, Chief Investigator for CFAR, gave evidence that CFAR’s ‘next step’ would be the establishment of a food allergy clinical trial program which has the potential to be world leading. She stressed that this kind of research must be completed in a clinical setting to optimise patient safety.
Dr Perrett is currently involved in a peanut patch immunotherapy trial through the Royal Children’s Hospital in Melbourne with Professor Mimi Tang. This trial has expanded from peanuts to researching egg and milk allergy. Professor Robyn O’Hehir is conducting allergy research with peptides at the Royal Prince Alfred Hospital in Sydney.
CFAR has conducted research into infant feeding which has led to significant changes in infant feeding guidelines. These new guidelines recommend earlier introduction of allergenic foods such as peanuts, eggs and dairy to infants, rather than avoiding them, which had been the previous recommendation.
Ms Victoria Soriano, a PhD candidate at CFAR, has continued researching the impacts of this change to infant feeding guidelines. Her study looks at whether parents are following the new guidelines and has shown that allergenic foods such as peanuts and eggs are being introduced within the first year of life to children.
Ms Soriano said that the outcome of the research into infant feeding guidelines will inform future research no matter what the outcome of the study is. If her study finds that earlier introduction of allergenic food does reduce childhood allergy then this will lead to a larger push for education of the new infant feeding guidelines. If there is no change to the prevalence of food allergy then CFAR’s researchers will know to focus on other risk factors for the development of childhood allergies.
Dr Rachel Peters, from CFAR, stated that as of November 2019, there was a trial underway to determine if supplementing infants with vitamin D can prevent food allergy.
Dr Peters said that there are trials looking into preventing eczema by improving the skin barrier and trials into allergen exposure at different sites in Australia. There are also trials ongoing looking into the rise of food allergies in Australia which will report ‘in the next couple of years’.
Dr Perrett of CFAR stated that there are large gaps in Australia regarding research as well as surveillance. Increasing surveillance and reporting of allergies from state-based registries could lead to a better understanding of risk factors, prevalence, diagnosis and management of food allergies. She said further that, with sustained funding, CFAR has the ability to play a role in not only filling these gaps but also producing world leading research.
Dr Wong, from the Children’s Hospital at Westmead, gave evidence that there is more research needed in Australia and that many clinical services in public hospitals had a strong interest in performing some of this research. However, due to the high level of need for clinical immunology and allergy services there is no time to perform this clinical research.
The Molecular Allergy Research Laboratory at James Cook University is funded by the NHMRC. It has performed research into proteomics, molecular biology, bioinformatics and clinical immunology as they relate to allergic diseases. Its work has improved the understanding of the mechanism of allergic reactions as well as furthering information on the prevalence of allergies in Australia and Asia.
Members of the Australian organisation TiARA (Tick Induced Allergies Research and Awareness) were the first researchers to find the link between tick bites and mammalian meat allergy (MMA) as well as doing research into the prevention of MMA through proper tick removal practices. A TiARA member also performed research into the use of personal repellents in order to prevent tick bites and MMA.
At the Royal Adelaide Hospital there is a clinical trial into Jack Jumper Ant venom immunotherapy made with new adjuvants with an aim to reduce the amount of venom required for the therapy. Ants must be ‘milked’ for venom to be used in immunotherapy which is a highly time consuming and labour intensive.
The Allergy Research Group at the Queensland University of Technology (QUT) identified that there are many opportunities for research into allergic rhinitis comorbid with seasonal asthma. The Allergy Research Group stated that based on small-scale research, patients who have received grass pollen allergen immunotherapy for allergic rhinitis have a reduced reaction to thunderstorm asthma. Further funding for research is needed to expand on these findings as well as other factors which may influence the development of allergic rhinitis.
The Allergy Research Group at QUT is also part of the AusPollen Aerobiology Collaboration Network. This group has implemented a pollen monitoring network across Australia through the contributions of researchers at numerous universities. The AusPollen partnership is funded by the NHMRC until mid-2020 and is seeking to apply for further funding to continue its work into the future.
There is limited funding for pollen collection around Australia. Professor Janet Davies, Head of the Allergy Research Group at the School of Biomedical Sciences and Institute of Health and Medical Innovation at the Queensland University of Technology stated that Australia has only 25 pollen monitoring stations compared to Europe’s 600 stations and 87 stations in the United States. She said further that the technology to monitor pollen in Australia is antiquated and highly labour intensive and that there is a strong need for innovation in this area in Australia.
One submission suggested that pollen counts should be conducted earlier in the year than October in order to reduce the risks of allergies and improve asthma management.
Dr Prathyusha Sanagavarapu is performing research at Western Sydney University into the mental health and wellbeing of parents and their allergy suffering children, in particular during the transition to school.
The Committee received evidence from patients, the parents of patients and prospective subjects of research trials. Parents and patients had a high level of interest in participating in research trials for food allergy but often found it difficult to find information about trials or found the trials too restrictive to take part in.
Mrs Linda Norwood stated she chose for her son to take part in a peanut immunotherapy patch trial as it appeared to be the only choice for him available in Australia. Another factor in confirming this decision for her was that only 30 per cent of participants would be given placebos, which would increase her son’s chance of getting an active dose of the treatment. She noted that taking part in a research trial restricted other treatment options, such as undertaking food challenges for her son’s other allergies, and highlighted the increasing incidence of patients on the trial having anaphylactic episodes during treatment.
Mrs Norwood also noted that, if given the opportunity to take part in a trial where there was no placebo option, she would find that a more attractive option.
Mrs Maria Stipic had similar sentiments. She was considering enrolling her three-year-old child in a trial in Melbourne, and the time commitment plus the distance she lived from the hospital made this a large commitment. She also stated that she would be much more likely to take part in a trial that had no placebo.
Several submitters commented they would like information about clinical trials and different treatment options to be more readily available.
One submitter noted that they had learned about current treatment options and research trials from being a member of patient advocacy groups like A&AA rather than from their allergist.
Another person stated that they have closely followed available research trials in Australia since 2015 but have been frustrated by appropriate trials being in different states or their children not being in the age bracket required.
One submitter suggested they would like to see more research into ‘environmental changes and medical advances and how these may be affecting our bodies in an adverse way.’ They also said that often research into allergies has a siloed approach and lacks a broader vision.
Peak body perspectives on the future of research
The National Allergy Strategy (NAS) stated that it would like to see more research into the services and resources required by allergy sufferers in order to increase safety and make the anxiety felt by allergy sufferers more manageable.
The peak organisation for allergy patients, A&AA provided a list of areas they would like to see further research into:
the psychosocial aspects of severe allergy, recovery from a life threatening events of anaphylaxis, and other quality of life matters;
the risk of allergic or anaphylactic reactions from touch, smell or airborne ingestion;
the gaps in care and support for families after a fatal allergic reaction;
improved diagnostic tools and prediction markers for the severity of anaphylaxis, including research into why some allergy sufferers grow out of their allergies and others do not;
the number of doses of adrenaline required during an anaphylactic episode as well as the stability of adrenaline auto injectors above 25 degrees Celsius (manufacturer warnings indicate adrenaline auto-injectors should be kept between 15–25 degrees Celsius);
the prevalence, diagnosis and current treatment options for non IgE mediated food allergy;
patient management of atopic dermatitis and allergic rhinitis, including patient compliance with treatment regimens;
the relationship between tick bites and mammalian meat allergy (MMA), including the prevalence of MMA in Australia; and
prevalence data on all allergic disease states in Australia.
Overseas research and collaboration
Dr Perrett of CFAR stated they have close working relationships with researchers in the United Kingdom and the United States of America. She said:
These people regularly come to our strategic update days where we bring the collaboration together to inform best practice on what's happening around the world. We're setting up some very key links with people in terms of trials and trial design to think about embedding treatment into routine care.
Dr Perrett also said CFAR was looking to apply for funding from the MRFF or other sources in order to work closely with overseas research centres which are currently doing treatment trials and bring that knowledge to Australian clinical care.
Oral immunotherapy (OIT) in Australia
Oral immunotherapy (OIT) treatments for severe allergies was a frequently raised topic in submissions.
Food Allergy Goals stated that ‘OIT involves planned and managed incremental exposure to known allergens under controlled conditions over many months to provoke desensitisation.’
This treatment has been offered through clinical trials and research projects overseas for a number of years and in many cases seems to have significantly lowered the risk of severe anaphylaxis in highly sensitive patients.
OIT can be done in two ways:
Food immunotherapy, where small portions of food as used to desensitise the patient; or
Pharmacological immunotherapy, where the allergen is presented to the body through a pharmaceutical, such as a patch or pill.
Immunotherapy for venom anaphylaxis (venom immunotherapy or VIT) operates on a similar principal to OIT, with treatment being increased doses of insect venom in order to create tolerance. OIT for Jack Jumper Ant is currently being run in Tasmania, Victoria and South Australia.
Consideration of OIT in Australia (Medical specialist perspectives)
Most of the evidence received by the Committee was concerned with limited or no access to food based oral immunotherapy in Australia. Unless otherwise stated, the term oral immunotherapy or OIT will refer to food oral immunotherapy.
ASCIA submitted that OIT is currently only available in clinical research settings, though the field is expanding rapidly. Overseas, OIT is often a part of clinical care for allergy sufferers and many Australian families have relocated to countries where OIT is offered clinically in order to have access to this treatment.
ASCIA stressed the need for OIT to be performed safely and responsibly and the importance of quality, peer reviewed research before OIT is rolled out at a clinical level in Australia. It also stated that it would be impossible to meet demand for OIT in Australia due to the lack of an MBS item number for food allergen challenges.
ASCIA also stated that OIT does not provide a cure for allergies for most patients and side effects include possible anaphylaxis. As such, ‘further assessment of safety, patient selection and appropriate use in Australia is required.’
The NAS described OIT as a ‘promising strategy’ for the management of allergy and reduction of the risk of anaphylaxis leading to improved quality of life for many allergy sufferers. It echoed ASCIA’s concerns however, about the risks of side effects from the therapy and the importance of expert supervision. It stated that more research into this area is need in Australia and that individuals should be aware of the risks before undertaking such a course of treatment.
A&AA submitted that there were three times more anaphylactic reactions for patients undergoing OIT than for patients avoiding the allergen.
ausEE Inc., a patient advocacy group for sufferers of Eosinophilic Oesophagitis, is supportive of OIT but would like patients to be aware that developing Eosinophilic Oesophagitis can be a side effect of undergoing OIT. They stated that potential patients should be aware of the risks of development Eosinophilic Oesophagitis during OIT and clinicians should investigate gastrointestinal symptoms of patients through the course of the treatment.
A&AA stated that any patient seeking to undergo OIT should first undertake a food challenge in order to determine if they are truly allergic to the food. It went on to say that waitlists for food challenges in Australian hospitals were already very long and that any treatment program not offering a cure should not be allowed to further worsen these waiting times.
A&AA continued by stating that it believes OIT requires more research and a standardised treatment regimen, but it is supportive of expediting current research and overseas treatment regimens so they can be made available in Australia.
Dr Kirsten Perrett of CFAR stated that OIT leads to desensitisation to the treated allergen in the majority of children and adults who undertake OIT, but there are significant safety concerns. She did not believe that OIT was ready to be offered clinically in Australia.
Dr Perrett stated further that the desensitisation caused by OIT was a temporary state that could be affected by changes in the patient’s immune system. The risk of an anaphylactic reaction while on OIT could be affected by having a fever or infection, menstruation, or simply having a higher body temperature due to exercise. While a small minority of children and adults who undertook OIT entered a long term remission in their allergy, this group of people are by far the minority.
Although it was too early to offer OIT in a clinical setting in Australia, Dr Perrett stated that it would be appropriate to offer OIT in a trial scenario where it could be closely monitored, supervised and evaluated. Such a trial scenario would not be limited in the way a typical clinical trial is limited and would be offered through hospitals to any patient who wanted to go through the process.
When asked how this process would differ from a clinical care rollout if it was offered to every allergy patient and not restricted, Dr Perrett answered that there would be research into the results, enhanced monitoring, follow-up, and rigorous supervision of the process of the treatment. She stressed there are too many unknowns to offer OIT in a clinical setting at this stage.
Dr Dean Tey, a paediatric immunologist appearing in a private capacity, stated that Australian families should not have to travel overseas in order to access OIT, but stated the importance of administering this new treatment with clinical oversight and research so that therapies can be refined and made safer.
Dr Tey said further that there were ethical concerns with OIT. Is it ethical to ask an OIT patient to stop eating their allergen for two months and then eat it to see if their allergic unresponsiveness was permanent, putting the patient at risk for a dangerous anaphylactic response? He went on to say that when dealing with anaphylaxis, there is a need for a high level of certainty before declaring remission and more long term research is required.
Dr Perrett of CFAR set out three main barriers to the implementation of OIT in Australia:
Access: any clinical implementation of OIT would have access issues, as allergy clinics in Australia are already overwhelmed by demand and struggle to provide current treatments, such as food challenges. Any trial of OIT would need to be separately funded from current allergy clinics.
Efficacy: there are still many unknowns with OIT, such as the correct amount to ‘updose’ the allergen while undergoing treatment, correct maintenance doses, what foods can be treated concurrently, and whether new adjuvants provide benefits to the treatment.
Safety: recent research published in the Lancet has shown the risk of anaphylaxis is three times more likely while a patient is undergoing OIT.
Support for OIT in Australia (Patient/parent perspectives)
The Committee received a lot of evidence from parents and patient advocacy groups calling for an immediate introduction of OIT in Australia.
Mrs Melissa Mooney of Food Allergy Goals commented that a systemic implementation of OIT, rather than the ad hoc development that has occurred in the United States, would be preferable in Australia.
Mrs Mooney gave evidence that there is a lack of balance in the discussion surrounding OIT in Australia. She contrasted articles published in the Lancet medical journal that were highly critical of OIT with the experiences of patients and their families who have undergone OIT in the United States and had found it highly successful. She emphasised that OIT was not a treatment for everyone but considering its success stories it needed to be explored in Australia.
Mrs Simone Albert, of Food Allergy Goals, whose son had also underdone OIT overseas for four allergens, stated that OIT is a robust treatment that requires a large time commitment and is not for everybody. Prospective patients in Australia would need informed consent, particularly around the psychological aspects involved. She further described the treatment as arduous for the patient but fairly simple in administration.
Mrs Albert went on to say that since her son had completed the initial OIT regimen and was now in maintenance he had not had an anaphylactic reaction. Previous to OIT, he had averaged one anaphylactic episode a year.
Dr Emily Amos reinforced the view that OIT had to be a personal decision for the patient and their family. Dr Amos stated that undergoing OIT for her daughter would not be right for her family due to distance from a large hospital and other factors, but might be something she considers in the future.
Mrs Melissa Mooney of Food Allergy Goals said that due to the probable lengthy time before the pharmaceutical immunotherapy being trialled in Australia was available to the public, there was a generation of children who would miss out on this treatment option. As such, it was important to give food based OIT thorough consideration as a treatment option.
Mrs Mooney said further that this generation of allergy children are approaching adolescence, ‘heading into what is the most dangerous phase’ and that this generation needed treatment options like OIT.
Mrs Mooney stated that education about the severity of side effects would be very important for patients starting on an OIT protocol, and that the high incidence of side effects for patients undergoing OIT was sometimes used to scare people away from the treatment, but increased levels of education and support would allay those fears.
Mrs Simone Albert gave evidence that, after undergoing OIT, many of the issues around labelling and traces of food present in packaged food are no longer an issue for her family due to her son’s desensitisation. She also said that some people have improved asthma and allergic rhinitis symptoms after undergoing OIT and that research has shown that IgE levels have decreased following OIT treatment.
Another submission stated that there is anecdotal evidence that patients in maintenance post OIT have reduced asthma symptoms and are also less likely to get colds and flu, with leads to improvements in school attendance for children. There are also less tangible benefits, like improvement in confidence and other psychological benefits.
Mrs Mooney suggested that funding for the rollout of OIT would decrease the burden on the hospital system for providing oral food challenges and care for people during and after anaphylactic episodes.
Mrs Mooney added that undergoing OIT is particularly attractive for patients who have multiple severe allergies, frequently experience anaphylaxis and have a significantly affected quality of life.
Mrs Mooney also gave evidence about taking part CFAR’s roundtable on OIT, stating that although there was movement in the right direction, the possibility of OIT being trialled in Australia still seemed far away. Funding and certainty of patient outcomes seemed to be barriers to medical professionals accepting OIT as a treatment option.
The Committee received numerous submissions from patients and their families requesting that oral immunotherapy be made available in Australia or that more funding for research into this therapy be made available for trials.
Some submitters expressed frustration at how OIT was available in Singapore and the United States but not available in Australia, saying the cost was prohibitive for them to undertake the therapy overseas.
Other people were more sceptical about OIT. One submission noted that the desensitisation of OIT would only work up to a point and that in some patients it can increase the risk of anaphylaxis. They suggested that better education about the topic would ‘help bring a sense of security and power rather than the current feeling of panic among allergy sufferers that there is help available and we are being denied it.’
Mrs Carolina Valerio said one of her major concerns with her child undergoing OIT was the risk of developing eosinophilic oesophagitis (EoE) during or after treatment. She advocated for more research both into OIT and EoE, as EoE is a poorly understood disease.
Another submission to the inquiry had the opposite view. The submitter stated they would happily take the risk of an ‘additional [anaphylactic] reaction or two´ if their son was able to freely eat their allergen after the treatment.
Ms Maria Stipic wrote in her submission that although there is a strong research emphasis on finding a cure for allergies in Australia, most parents who consider OIT for their children view it as a treatment. Reducing the risk of an anaphylactic reaction in severely allergic individuals already provides a great improvement in quality of life.
Current practice and research
The Committee also received evidence about the state of current research into OIT in Australia, including some doctors currently practicing this therapy.
Ms Maria Said, Chief Executive Officer of A&AA said she was aware of three to four doctors who were providing OIT outside of a research setting. She gave evidence of one health professional that has no training in allergy or immunology providing OIT to patients. She emphasised that A&AA liked to work alongside ASCIA and follow their recommendations around research and emerging treatments. A&AA is also concerned by the lack of long term research into the effects of OIT on patients.
Immunotherapy for non-food allergies is already offered at a clinical level in Australia. Dr Suzan Bekir, Clinical Director of the Australian Allergy Centre stated that non-food immunotherapy is currently being offered for dust mites and grass pollen allergies.
Professor Robyn O’Hehir of Alfred Health said she is currently working on research into peanut peptide oral immunotherapy but stressed the need to go through the full regulatory process as patient safety was a high concern. She also stated that peanut OIT is a practiced globally but is a research tool in Australia.
Dr Joanne Smart at the Royal Children’s Hospital in Melbourne said that OIT will be available in Australia in the future but the issue will be resourcing, as current allergy and immunology clinics already struggle to keep up with the needs of the community.
This view was echoed by Professor Michael Gold, from the Women’s and Children’s Hospital in Adelaide, who said that food OIT would ‘create a huge demand and burden on the public system.’
Aside from doing research into food based OIT, CFAR is also doing research into immunotherapy using novel adjuvants, peptide vaccines and other pharmaceuticals which are currently being trialled and may have longer term effects for patients.
Dr Perrett discussed with the Committee trials examined in the Lancet all involved older children and adults:
… there has been a large meta-analysis done recently and published in The Lancet of 12 studies of food oral immunotherapy trials. That has shown serious concerns with adverse events in terms of a three-times increased risk of having anaphylaxis while you are on oral immunotherapy than if you avoid the food. At the moment those trials are done on older children and adults.
What we are looking at is a model of a pragmatic trial done with a younger age group where we believe oral immunotherapy can harness the modulation of the immune system at a younger age. Pragmatic trials in this type of way have been done in Canada and they show a far better efficacy in terms of desensitisation, fewer side effects and a better safety profile for that younger age group.
However, any trials into OIT would have to be publicly funded, as the nature of food immunotherapy means there is no pharmaceutical product which a company could invest in by funding research.
Mrs Melissa Mooney of Food Allergy Goals gave evidence that a group of Canadian doctors doing an OIT trial with preschool aged children had provided ‘much more balanced’ view of OIT versus pure avoidance:
Allergists and the medical community as a whole must stop confusing parents with endless mixed messages about OIT both within and outside of research. The fact is, many allergists are already offering OIT outside of research. In our current era of basing medical treatment decisions on a comparison of risks versus benefits, there is simply no one-size-fits-all approach.
…telling parents of children with peanut allergy that avoidance is the only option outside research fails to take into account the negative long-term consequences of avoidance—such as poor quality of life, social isolation and anxiety.
Several submissions to the inquiry mentioned the probiotic and peanut allergy OIT research undertaken at the Murdoch Children’s Research Institute (MCRI) in Melbourne, requesting that this research get funding and the results be expedited.
Another submitter asked that the MCRI probiotic and peanut OIT research and the Westmead Children’s Hospital peanut OIT trial be expanded to include other major allergens, including tree nuts.
One submission expressed frustration at the time required for the MCRI’s study to become a viable treatment as part of clinical practice, noting that there is evidence OIT is more effective in children. The submitter had concerns by the time the therapy was generally available it was would be too late for any treatment to be effective on their son.
Overseas oral immunotherapy (OIT)
The Committee received a large amount of evidence from families who had travelled overseas, primarily to the United States, to receive OIT.
Mrs Linda Norwood gave evidence of her son receiving OIT for peanut and cashew allergies in the United States over a period of two years. As a result of this treatment, he can now eat two peanuts and two cashews a day, compared to previously where he had an anaphylactic reaction to traces of nuts in a hot chocolate drink. This has led to significant improvements in the family’s quality of life, reducing stress and anxiety around eating and travel.
In her submission Mrs Norwood said:
Our son is so much safer now, and his food options have really increased. Although he can’t eat handfuls of his allergens, he can eat foods with cross contamination and traces. He doesn’t react on contact any more. He loves trying all the new foods that were off limits before. He can join in birthdays and other celebrations without needing to bring his own food. Eating out and travelling are much more relaxing and enjoyable experiences for the whole family. Although he is still considered allergic and needs to carry Epipens, his life is much freer now because his tolerance to his allergens is so much higher. He is less likely to have a severe reaction to accidental exposure. His quality of life and anxiety around food has greatly improved since the treatment.
Mrs Albert of Food Allergy Goals confirmed that OIT has been practiced for over ten years in both a private and public setting in the United States. As well as being offered in some hospitals in the United States, it is also offered in children’s hospitals in Singapore, Canada, Hong Kong, and other places. OIT is also offered in a research setting in the United Kingdom, but is still open to the public.
Mrs Catherine Sly, a parent of a child who had undergone OIT, said that the way OIT is offered can vary. Some people go through the process faster, moving to larger doses of the allergen at a quicker pace and complete the treatment in only a few months. Others need more time between doses and have a more difficult experience, experiencing mild allergic reactions like mouth tingling and stomach pain. Mrs Sly reported that her daughter’s doctor had given 4,000 up-doses in his practice and has never had to use an EpiPen for an anaphylactic reaction.
Mrs Sly said she would have preferred to undergo OIT in Australia and that pursuing the treatment overseas has been difficult in many ways. In Australia they would have had family and community support and would not have had to split their family between two countries. Despite these difficulties, she described OIT as life changing for their daughter; stating she could now go to birthday parties and eat the cake, enjoys pizza and chocolate and was generally happier and less anxious. Her daughter’s immunotherapy maintenance is done through peanuts bought from supermarkets.
Mrs Norwood said that part of what caused her to look into OIT overseas was that several allergies could be treated concurrently. In Australia, her son had taken part in the Westmead Children’s Hospital peanut patch immunotherapy trial and found improvement in his peanut allergy however, ‘having done just the peanut trial but still being allergic to other allergens didn't change our life as much as the oral immunotherapy did.’
Mrs Mooney of Food Allergy Goals said that Canada was a good example of allergy parents and doctors working together to make OIT available. In Quebec, a doctor wanted to expand his current trials on OIT and asked parents to help him fundraise with the aim of having the provincial government match their donations. The parents group raised $750,000 which was then matched by the Quebec government and allowed the expanded trial to start.
The doctor in charge of the pilot is working with the Canadian Society of Allergy and Clinical Immunology to create protocols for clinical use with a view to a national rollout of OIT in Canada. Mrs Mooney stated this process, involving government, doctors, patient groups and professional peak bodies, is an example of how OIT could be implemented in Australia.
Dr Dean Tey noted that OIT had about an 80 per cent success rate for desensitisation towards the allergen. There is roughly a 10 to 20 per cent dropout rate in OIT trials for patients who found the therapy too taxing or had bad anaphylactic reactions during treatment. Rates for sustained unresponsiveness or remission of the allergy are much lower, between 50 and 80 per cent depending on the trial and the allergen being treated.
Dr Tey also said that the national guidelines for allergy in Australia and the United States of America both state that OIT should not be practiced clinically outside of research setting. There is less clarity about the practice in Europe and Japan. However, he is not aware of Australian families travelling to Japan or Europe to access OIT, only the United States.
The Committee received several submissions from parents of children with severe allergies asking why OIT was not available in Australia and referencing success stories they had read online about undergoing OIT. Many people stated they would like OIT made available in Australia. There were also several submissions from families planning to make the trip to the United States for treatment in the near future.
One submission stated the family had already travelled to the United Stated for sublingual immunotherapy (SLIT) for their daughter which had been successful in reducing her allergies. That family is now planning to make another trip to the United States for OIT to treat her remaining anaphylactic allergy.
Mrs Simone Albert also gave evidence about choosing to undergo OIT for her son in America. Her son had severe allergies to dairy, egg, wheat, rye, peanuts, and other allergens, leading the family to make the decision to undergo OIT. They documented this process through their Facebook page Oliver’s Choice in the hopes it would encourage Australian medical bodies to introduce the treatment in Australia.
One submitter wrote that they explored undergoing OIT in Singapore for their daughter but chose not to due to the risks and high costs of undergoing overseas treatment.
Ms Kym Banjac gave evidence about her plans to relocate to the United States for a year for her daughter Mila’s OIT treatment. She emphasised that despite the risks of increased anaphylaxis, she still wants to undergo OIT, saying:
Because we no longer want our allergy children, our non-allergy siblings and ourselves to live in fear every single day. And believe me, we do. I do. My husband does. My boys do. We are terrified that the next mistake might take Mila’s life. And there is no respite from that stress. It is with us 24 hours a day, every day of our lives.
Ms Emily Marney wrote from the United States where her son Angus was undergoing OIT for dairy and peanut allergy. She has already seen improvements in his reactions to dairy and peanuts and feels that the OIT treatment is safer than food challenges offered in Australian hospitals. In order to afford to travel to the US for treatment the family created a Go Fund Me crowdfunding page, held community events and had donation tins in local shops and restaurants. She describes the decision to undertake OIT as an ‘investment into Angus’ future allowing him the freedom to choose any career, go on school camps, sleepovers and live a life free of anxiety and food aversions.’
Support for dupilumab
The Committee received a large amount of evidence about the new medication dupilumab (trade name Dupixent), a monoclonal antibody injection typically used to treat severe eczema.
Dupilumab is administered by injection and is approved for prescription for people aged 12 and over with a cost of $1,600 a month. This therapy has been on the publicly funded health system in the United Kingdom since 2018.
The Department of Health confirmed that Sanofi, the manufacturer of dupilumab, had applied to Pharmaceutical Benefits Advisory Committee (PBAC) for listing of the therapy on the Pharmaceutical Benefits Scheme (PBS) in July 2018 and July 2019. Although PBAC acknowledged the clinical need for treatments for moderate to severe eczema, it did not recommend dupilumab for listing at those meetings.
Professor Constance Katelaris at Campbelltown Hospital stated that dupilumab has ‘astounding’ trial data and a very good safety profile. It also has less harmful side effects than the immunosuppressant agents which are typically prescribed to treat severe eczema.
Professor Katelaris said she had been able to access dupilumab for 12 patients. All have reported excellent results, describing it as ‘life changing.’ Three of her patients have reported one side effect, worsening ocular allergy, but have been able to control it working with ophthalmologists. Even those patients who experienced this side effect would not stop treatment as it has been so effective.
Professor Katelaris did concede that the treatment of eczema with dupilumab is expensive with ongoing fortnightly injections costing $800 or $900. However, in contrast, other eczema treatments such as cyclosporine or methotrexate, have severe side effects, including hypertension, renal disease and the possibility of developing cancer.
Many eczema sufferers and their families wrote to the Committee urging for the PBAC to list dupilumab on the PBS. Many noted the high cost of the therapy and that they would not be able to afford it without it being listed on the PBS.
Mrs Funk of Eczema Support Australia reported that she had heard from members of her organisation that dupulimab had reduced their symptoms by 90 to 100 per cent. The first person she met who was on the drug ‘was bouncing off the walls with joy and wanting to shout from the rooftops.’ Another of her members whose eczema had previously been treated with chemotherapy drugs and had to stop due to organ failure was now on dupilumab and his only side effect was dry eye.
Mrs Funk also said a change.org petition had attracted three thousand signatures asking for dupilumab to be added to the PBS. Many of the comments under this petition noted the suffering of people with severe eczema and desperation they feel without this medication.
One person who was undergoing dupilumab treatment wrote saying that their productivity has doubled since starting receiving the injections. Their sleep has improved due to the reduction of eczema on their scalp, they take less time off work, and can perform more everyday tasks like driving and cleaning.
Sanofi made a further application for to PBAC to list dupilumab on the PBS which was considered in PBAC’s March 2020 meeting. In that meeting the PBAC ‘…recommended the listing of dupilumab for the treatment of patients aged 12 years and older with severe atopic dermatitis who are inadequately controlled on topical therapies.’
Other emerging therapies
The Committee received evidence about some other emerging therapies in Australia.
One submitter mentioned being treated by the emerging therapy omalizumab (trade name Xolair), which was added to the PBS last year. Omalizumab is used to treat severe allergic asthma and is a monoclonal antibody therapy, similar to dupilumab. The author of the submission had previously been given the medication under compassionate supply from the manufacturer but has developed an allergy to the medication and can no longer take it. While they were able to take omalizumab, the author found it an excellent treatment.
Another submitter noted they were pleased omalizumab had been added to the PBS. They stated ‘biologicals’ (drugs like omalizumab and dupilumab) are expensive for the Government to subsidize but are preferable to the long term side effects of the corticosteroids or chemotherapy drugs which are currently prescribed for severe allergic conditions.
The biopharmaceutical company Sanofi stated that ‘identifying specific and effective biologic treatments continues to be an area of unmet need for patients.’ It has investigated a number of research strategies but has found that modifying immune dysregulation has been most successful.
New technologies have also been developed for venom immunotherapy. Clinical trials are currently undergoing in South Australia and Tasmania by the Australian biotechnology company Vaxine Pty Ltd to see if the adjuvant Advax™ can increase the efficacy of current desensitisation therapies for ant bites and bee stings. This trial has struggled to attract funding from the NHMRC and other Australian funding agencies however.
Alternative medicines and therapies
The Committee received evidence about alternative medicines and therapies practiced by allergy patients. Alternative medicines or therapies, sometimes referred to as complementary medicines, are medical products containing ingredients such as vitamins, minerals, herbs, nutritional supplements, aromatherapy preparations and homeopathic medicine. These products are regulated in Australia under the Therapeutic Goods Act 1989 (Cth).
Therapeutic devices (defined as a device used to diagnose, prevent, monitor, treat or alleviate an injury, disease or disability) can be registered on the Australian Register of Therapeutic Goods (ARTG) in Australia if the company submits an application to the Therapeutic Goods Administration (TGA). Depending on the risk level of the device, the TGA may assess the application before registering the device on the ARTG.
The TGA stated that it is aware of allergy testing devices which are not listed on the ARTG. These include Vega (electro-diagnosis) testing, Kinesiology, Iridology, VoiceBio, the Alcat, and Cytotoxic testing (Bryan’s Test). There are also several allergy remedies available commercially based on ‘tradition of use’ such as traditional Chinese medicine, homeopathic remedies and aromatherapy.
In order to prevent and address medical devices or medicines being inappropriately promoted to consumers (such as making claims of treating or curing allergies when there is no proof of this) the TGA has several measures in place. These include a complaints process, random or targeted post-market review, advertising requirements, and sanctions (e.g. directions, infringement notices, and civil or criminal penalties) for companies that continue with non-compliant advertising.
Ms Loretta Marron, Chief Executive Officer of Friends of Science in Medicine, said that the use alternative therapies in the place of conventional medicine can harm patients in three ways: financial harm to the patient, harm to them from disappointment when the treatment doesn’t work, and harm from the delay of diagnosis and proper treatment.
The Department of Health noted that it ‘is aware of a number of non-validated diagnostic and treatment approaches being used by some health practitioners to diagnose and manage allergies’. If a health practitioner is found to be practicing medicine in an unsafe way there are regulatory measures, professional codes of conduct and associated compliance actions which protect the public.
The NAS stated that allergy patients often seek alternative health practitioners in cases where there are delays in access to care or when treatment options are limited. The non-validated testing and treatment options offered by many alternative practitioners can be expensive as well as unsafe through the use of overly restrictive elimination diets.
Dr Brynn Wainstein, President of ASCIA, said that use of alternative therapies can increase the costs and burdens to the Australian health care system:
Incorrect diagnosis and management can lead to higher needs for patients once they do get access to an allergy specialist, requiring more appointments and lengthening waiting lists overall.
Dr Wainstein said he is aware of many cases where the initial consultation between a patient and an allergy specialist is spent undoing harm from previously given incorrect advice and diagnosis. There are also cases of mild allergic disease, such as mild eczema or hay fever, which have been poorly treated and become serious ongoing problems requiring specialist treatment from an allergist or immunologist: ‘The result of this is that inappropriate healthcare encounters make the bottlenecks for access to allergy services worse rather than better.’
Dr Preeti Joshi, Co-chair of the NAS, reinforced Dr Wainstein’s comments, saying that parents of children with severe allergies sometimes turn to alternative medicine due to long waiting times to see specialists. This is why organisations like NAS and ASCIA are looking into shared care models of medical practice, particularly in rural areas, in an attempt to alleviate long waiting times.
Dr Joshi said further that there currently are alternative medical practices operating without any specialist input that claim to be ‘allergy centres’, charging patients large amounts of money for treatment. In some cases these clinics are staffed by GPs.
Dr Emily Amos, a GP and parent of children with allergies, wrote that she understands the desperation of parents who seek alternative therapies for their severely allergic children, noting that ‘desperation will breed misinformation.’ She said that the remedy for this is better access to reliable and sympathetic information from reputable sources. She referenced ASICA’s website and factsheets, as well as the A&AA Facebook group as excellent sources of up to date information and support groups for parents of children with allergies.
Dr Merryn Netting, a paediatric dietician specialising in allergy, wrote that consumers who seek alternative medical treatment are sometimes referred for non-validated food allergy testing, such as IgG testing (as opposed to the standard IgE testing) which is expensive and often results in unnecessary food restrictions. She is particularly concerned about the use of broad exclusion diets in children as it may result in the development of more serious allergies and anaphylaxis and in some cases can lead to malnutrition.
One submitter said that after their son started displaying allergy symptoms they were put on the waiting list, which was 18 months long, to see a public paediatric immunologist. Their GP would not provide skin prick testing to determine allergens so the family turned to a kinesiologist who used ‘muscle impulse testing’ to diagnose their son’s allergies. The family also paid for IgG blood testing which showed their son was allergic to multiple foods. The family used this information as a guide until they were able to get reliable testing done through a specialist. The submitter stated however they are aware of many people who rely on IgG blood testing and eliminate food groups from their child’s diet based on its results.
A child care sector worker said they are aware of parents taking their children to companies which will provide diagnoses of allergies and supporting letters to them without any testing or follow up of the child’s medical concerns. Parents are self-diagnosing their children and then finding a company that will provide documentation for the food they would like to exclude from their child’s diet. The submission said there needs to be higher standards for companies providing medical testing to the public.
The Allergy Medical Group noted that it has seen a growth of alternative practitioners offering kinesiology, vega testing, acupressure, homeopathy and crystal therapy among others to treat allergies, usually costing patients between one and two thousand dollars per treatment. It was also aware of mainstream medical practitioners offering IgG testing despite it being ‘useless in the context of allergy.’
Professor Peter Smith, Director of the Allergy Medical Group, suggested that alternative practitioners who misrepresent their treatments should be pursued by health authorities.
Professor Smith also said that part of the decision by a patient to seek alternative therapies was often due to waiting times to see medical specialists. ‘If somebody has got a six to twelve or eighteen month wait, they're going to go and look elsewhere where people make promises to help them.’
The ACN highlighted that misdiagnosis and over diagnosis of allergies is a significant problem in the community which often leads to unnecessary exclusion diets. They are aware of allergy testing being done through hair sample and blood tests by naturopaths and other alternative practitioners and the high costs charged by these providers.
Another submitter stated that social media patient support forums on Facebook often have people promoting alternative medical treatment as well as special diets and foods for the treatment of allergies and eczema. Misinformation is also common, as well as people encouraging others to cease prescribed treatments such as cortisone creams. The author has also witnessed businesses promoting cosmetic products to allergy and eczema sufferers which have not been assessed by the TGA.
This view was echoed by A&AA, stating that social media platforms like Facebook can be highly useful forums for support and for allergy sufferers to benefit from the experiences of others. However, if poorly managed these groups can be sources of misinformation which can lead to poor and even dangerous outcomes for followers.
The ACN drew parallels between allergy patients seeking alternative therapies and the increasing phenomenon of vaccine hesitancy and rejection. They said:
The World Health Organisation has found that decisions to refuse vaccination despite its availability are highly contextual and that health provider recommendations are effective in overcoming that hesitancy because health workers remain the most trusted advisor and influencer of vaccination decisions.
The ACN wrote that increasing the involvement of nurses in allergy treatment and management would be a key strategy to reducing the uptake of alternative diagnosis and treatments.
ausEE Inc. highlighted that sufferers of EGID and EoE may seek alternative treatments due to a lack of a reliable test that determines what foods may trigger their disease, as well as the limited availability of medications to treat their EOE. As well as this, due to the relative rarity of EoE and lack of knowledge about it amongst many medical practitioners, some EoE sufferers may resort to alternative therapies to manage their EoE symptoms which have not been identified by mainstream medicine. ausEE Inc. states that some of their members have found alternative therapies beneficial while other have found the treatments expensive and the advice conflicting and in some cases even dangerous.
Ms Amanda Lennestaal, a parent of a child with FPIES, wrote in her submission that parents of children with FPIES sometimes seek treatment outside of mainstream medicine. She said that although many children outgrow FPIES, the stress and difficulty of caring for a child with this condition makes many parents susceptible to alternative treatments that promise a cure. She knows of parents who have spent large amounts of money on iridology, skin prick testing and hair analysis in order to diagnose their child. Others have turned to essential oils or nutrition products sold through direct sales methods. Many turn to these methods due to the lack of care they have received in the public healthcare system.
Coeliac Australia wrote that self-diagnosis and alternative therapies used without mainstream testing and oversight are a problem in Australia. The prevalence of coeliac disease in Australia is approximately 1.4 per cent; however studies from the CSIRO in 2016 found that 12.1 per cent of Australians avoid wheat and/or gluten. This not only results in an unnecessarily restricted diet but adds to the perception that gluten intolerance is a lifestyle choice rather than a serious medical condition.
The Committee received submissions from allergy sufferers who are using alternative treatments. One submission from a woman suffering from mammalian meat allergy said she is seeing a naturopath as there were no other options for treatment and she is on a waiting list to get into a clinic. Another submission said they would trial kinesiology for their child and that they ‘have seen energy work assist others with allergies.’
The Friends of Science in Medicine, a group that supports evidence-based medicine, noted that there are many natural therapies using ‘biofeedback’ or ‘electro-diagnosis’ devices which are listed with the TGA, despite having little scientific evidence to back their claims. Some of these devices claim to assist in the treatment of allergies and anaphylaxis.
The TGA reviewed bio-resonance and bio-feedback devices in order to verify these devices’ therapeutic claims were supported by scientific evidence. This lead to the cancellation of 15 devices from the ARTG, either through sponsors withdrawing their support for the device or by the TGA itself.
The removal of devices from the ARTG does not however prevent practitioners from selling these devices or using them during patient consultations as long they do not make claims regarding these devices’ therapeutic efficacy.
The TGA also stated that it ‘intends to escalate its regulatory response where necessary to address ongoing noncompliant advertising. This may include the use of official warnings, directions notices and infringement notices as appropriate.’
The Committee is pleased to see the research being done by CFAR, hospitals, universities, and other research organisations and notes the cutting edge research being done in the area of allergies. Despite this, the Committee is concerned that the NHMRC did not award any specific funding for allergy related research in the 2019 funding round and that there has not been a significant increase in allergy funding since 2015. It is also concerned that the funding for CFAR does not extend past 2022.
The presence of a placebo in clinical and research trials can be a disincentive, particularly to parents who are considering placing their children in research trials. The Committee shares these concerns and would like to see a larger number of trials offered which have no placebo, similar to the model used for vaccine trials.
The Committee believes there is merit in funding clinical allergen trials into allergens other than peanut allergy in Australia.
The Committee also suggests that ASCIA promote currently available trials on their website to ensure there is public knowledge of current trials.
The Committee was very interested in the large amount of evidence it received about food based oral immunotherapy. It was concerned by the amount of people who are going to the United States of America and elsewhere to receive this treatment, often at great personal and financial expense.
The Committee notes that there is a large gap between the experiences of people who have undergone food based OIT overseas and the views of the Australian medical specialist community who would like there to be more study of this therapy before any sort of clinical roll-out. The Committee recognises and appreciates the views of both sides in this issue; the frustration of parents of allergic children whose lives are highly affected by these allergies and the desire of the scientific community for evidence-based research and the absolute priority of patient safety and efficacy.
The Committee is particularly concerned about the current generation of children with severe allergy as they enter adolescence, a time when young people are exposed to new, less controllable environments, when there is less parental supervision, and when people are more likely to engage in risk taking behaviour.
Despite this, the Committee is also aware that OIT is a relatively new treatment and there are still many unknowns about this therapy. The Committee would like to see research undertaken into the long term prognosis of people who have undergone OIT and the chances of remission for allergy sufferers. It would also like to see research done into side effects of OIT, such as the risk of developing eosinophilic oesophagitis or anaphylaxis during treatment.
On a more practical level, the Committee is also concerned by how a rollout of OIT would be facilitated in Australia and how this would impact on existing allergy and immunology services with current high demand and long waiting lists. The Committee has received evidence throughout the inquiry about long waiting times to see allergists and immunologists for initial appointments as well as for existing allergy treatments such as food challenges. Although some people giving evidence believed OIT could be rolled out through clinical hospital based practice, the Committee is not convinced this is realistic or practical due to workforce and funding issues.
The Committee received numerous submissions requesting that the new biological therapy dupilumab be listed on the PBS and was very moved by the suffering of people who live with severe eczema.
The Committee was pleased to find out that the PBAC had decided to recommend dupilumab for listing on the PBS in its March 2020 meeting.
There is clear evidence that people who suffer from allergies and anaphylaxis and other allergic diseases such as eczema or allergic rhinitis are particularly susceptible to the promises of alternative therapy providers due to long waiting times to see allergy specialists and the often limited nature of treatments available.
The Committee sympathises with people who seek alternative treatments, especially those who feel they have no other choice due to long waiting times or a lack of understanding from practitioners who may be unfamiliar with rarer allergenic diseases such as eosinophilic oesophagitis or FPIES. The Committee also recognises that alternative medicine and therapies can play a role in health care when used alongside conventional medicine.
Despite this, the Committee is very concerned by the proliferation of unscientific cures and advice on social media platforms in particular, as well as the proliferation of IgG allergy testing offered by alternative practitioners which can have limited diagnostic validity.
The exclusive use of alternative therapies can lead to more pressure on existing resources when people do see an allergy specialist as patients who have previously seen alternative practitioners can have higher needs, require more education, or may have conditions exacerbated by postponing conventional treatments.
The Committee agrees with the Australian College of Nurses that an increased role of nurses in allergy care, particularly in cases where access to specialists is limited, may assist in reducing uptake of alternative therapies.
The Committee was pleased to hear that 15 bio-resonance devices had been de-listed from the ARTG though is concerned about the proliferation of similar non-scientific therapeutics which still exist on the market.
The Committee recommends that the Australian Government give consideration of how best to increase the utilisation of nurses and allied health care workers to support the care of patients with allergic disease.
The Committee recommends that the Therapeutic Goods Administration and any other relevant authorities, such as the Australian Competition and Consumer Commission (ACCC) conduct an independent, evidence-based review into all therapeutic goods, services, or devices which claim to diagnose or treat allergies.
Mr Trent Zimmerman MP