"A tough nut cracked? Scientists discover new treatment for peanut allergy sufferers," is the punning headline in The Independent. It comes from research that suggests that exposing children with a peanut allergy to trace elements of peanuts boosts their tolerance to the nut.
The children, aged 7 to 16 years, were randomly divided into two groups, with one group given gradually increasing doses of peanut flour, eating up to 800mg daily, and the other group given standard care.
The study found that after six months 84-91% of the children given peanut flour could safely tolerate 800mg of peanut protein – equivalent to five peanuts, and at least 25 times as much as they could tolerate before treatment. Children in the control group could not tolerate peanuts at all.
The concept of gradually introducing allergic substances is nothing new. "Immunotherapy" has been used for many years, but previous attempts to treat peanut allergy with injections (the usual form of the therapy) were unsuccessful.
This new approach is promising but, as the researchers note, it is unclear how long the children's tolerance to peanuts will last and whether they will need top-up treatments.
Still, the results are encouraging and are likely to lead to further investigation into oral immunotherapy for peanut allergies, and possibly other food allergies.
Where did the story come from?
The study was carried out by researchers from Cambridge University Hospitals NHS Foundation Trust and was funded by the Medical Research Council. Two of the authors have a patent application that covers the dosing protocol described in the study.
It was published in the peer-reviewed medical journal, The Lancet.
Not surprisingly, this story was widely covered in the media. The Independent described the desensitisation programme as a "revolutionary new therapy" and The Daily Telegraph called it a "breakthrough treatment", while the Daily Express talked of a "cure".
While the results of this trial are very promising, such reports are potentially misleading. Further research is required before any such treatment is approved, a process that may take several years.
Even if this approach continues to be successful in wider populations, it is unlikely to amount to a "cure" where a person with a peanut allergy can happily scoff a bag of peanuts. Hopefully, we can expect that therapy will reduce the risk of a severe allergic reaction if a person inadvertently eats food containing small amounts of peanuts.
What kind of research was this?
This was a randomised controlled crossover trial that examined peanut oral immunotherapy (OIT) in children with peanut allergies. Immunotherapy is a treatment strategy that aims to modulate the immune system so that it desensitises it when exposed to the substance that normally causes the allergic response (the allergen). Immunotherapy, most often given by injection, has been developed for other allergies, such as bee sting allergies.
A randomised controlled trial, in which participants are randomised to receive either the active treatment or to be in a control group, is the best type of research to determine the effectiveness of a treatment.
In a crossover trial, participants in both arms of a study receive a sequence of different treatments. In this case the control group was offered OIT during a second phase of the trial.
The researchers point out that peanut allergy is the most common cause of severe and sometimes fatal allergic reactions to food. Immunotherapy injections have been tried for peanut allergy, but were associated with severe adverse reactions.
An earlier smaller phase I study by the researchers found that OIT is safe. The researchers say their aim was to study whether it would also be effective in children.
What did the research involve?
The researchers randomly assigned a group of children with peanut allergy to either gradually increasing doses of peanut protein (OIT) or control (avoiding peanuts) for 26 weeks and then retested their peanut allergy. In phase II of the study, the control group was given the OIT treatment.
The researchers enrolled 104 children aged 7 to 16 years with suspected peanut allergy referred from allergy clinics and a national patient support group. Peanut allergy was diagnosed or confirmed by a skin prick test and a peanut "challenge" (a double-blind placebo-controlled food challenge). In this test the child is tested for a reaction to peanuts under medical supervision, with neither participants nor staff knowing whether they are given the real allergen or a placebo.
During the first phase of the trial, which lasted 26 weeks, the OIT group were given gradually escalating daily doses of peanut flour, which was mixed into their ordinary food.
The children began on a daily dose of 2mg of peanut protein. If they showed no reaction, this amount was doubled every two to three weeks until the children reached a "maintenance dose" of 800mg daily (the highest amount of protein used in a previous pilot study).
While each increase in dose took place at the research centre, the same dose was then given at home. The children were asked to complete symptom diaries and were also provided with adrenaline auto-injections to use in case of a severe allergic reaction.
In a second phase of the trial, children in the control group were offered peanut OIT.
At the end of six months, all the children had another peanut "challenge" assessment with a dose of 1,400mg of peanut protein.
Researchers also looked at the proportion of participants who tolerated daily consumption of 800mg of protein during the 26 weeks, and the proportion of the control group who were desensitised or tolerated 800mg during the second phase of the trial.
They assessed the maximum amount of peanut protein that was tolerated after OIT without any adverse effects, the number and type of adverse events, and changes in the quality of life scores, as measured by a validated questionnaire.
At the end of the study the children were encouraged to continue eating 800mg of peanut protein each day.
What were the basic results?
Ninety-nine children took part in the trial (five of the original 104 did not react during their first peanut "challenge").
The researchers found that:
- 62% of children in the OIT group had become desensitised to peanuts at six months, compared with none in the control group.
- 84% (95% confidence interval [CI] 70-93) of the OIT group tolerated daily consumption of 800mg protein (equivalent to roughly five peanuts).
- The average increase in the maximum amount of daily peanut tolerated after OIT was 1,345mg, an increase of more than 25 times the original amount they could tolerate.
- After the second phase in which the control group were offered OIT, 54% tolerated a 1,400mg peanut "challenge" (equivalent to roughly 10 peanuts) and 91% tolerated a daily ingestion of 800mg protein.
- The children reported a better quality of life after OIT.
- Side effects after OIT were mostly mild. Gastrointestinal symptoms were the most common (31 participants with nausea, 31 with vomiting, and one with diarrhoea), followed by oral itching (affecting 76 children after 6.3% of doses) and wheeze (affecting 21 children after 0.41% of doses).
- One child needed an adrenaline injection on two occasions.
How did the researchers interpret the results?
The researchers say that further trials are needed in different populations, but the study shows that peanut immunotherapy is effective and has few concerning side effects in this age group.
In an accompanying press release, Dr Pamela Ewan, co-author and head of the allergy department at Cambridge University Hospitals, said: "This large study is the first of its kind in the world to have had such a positive outcome, and is an important advance in peanut allergy research.
"However, further studies in wider populations are needed," she continued. "It is important to note that OIT is not a treatment people should try on their own and should only be done by medical professionals in specialist settings."
This well-conducted study has shown that children with peanut allergy can be treated successfully with immunotherapy.
The main aim of these treatments is to avoid severe allergic reactions if the child accidentally eats peanuts. An important issue not addressed by the study is how long the effects of the immunotherapy might last, and whether the positive effects might lead to a false sense of security.
Studies are needed to determine how long and how frequently maintenance immunotherapy doses need to continue to be given to maintain peanut tolerance in these children.
Studies will also be needed to determine whether a similar treatment can work in:
- adults with peanut allergies
- people with allergies to other nuts or foodstuffs
These findings are likely to bring hope to parents of children with peanut allergies. However, it is vital that they do not attempt to replicate this treatment at home.
All of the tolerance tests and dose increases during treatment were carried out in a research facility. The children were under medical supervision, so they could receive specialist medical treatment immediately if they experienced a severe allergic reaction (anaphylaxis). Severe allergic reactions can be fatal if not treated immediately.
It is likely that the encouraging results of this study will now lead to a phase III trial, which involves a much larger population and usually lasts for a few years.
If such a trial proves successful, oral immunotherapy may then be offered at NHS allergy clinics.