There are many clinical trials for OIT. Photo: Getty Recent headlines around the globe have proclaimed the results of an Australian study of a combination of oral immunotherapy and probiotics a “breakthrough” and a potential “cure” for peanut allergy.
But does the science live up to the breathtaking claim? No, it doesn’t, contend three Canadian food allergy researchers, whose own work includes immunotherapy (OIT) research.
After considering the results, this team of experts from McMaster University approached Allergic Living with counterpoints that they say set the record straight about the new Australian study, which was published in the August 2017 edition of The Lancet Child & Adolescent Health.
The Australian research, conducted by physicians from the Murdoch Childrens Research Institute, is a follow-up study that aimed to assess long-term results of a combination therapy. In this treatment, patients with peanut allergy underwent both standard OIT, which aims to desensitize those with peanut allergy through the consumption of specified doses of peanut, while they also took large doses of a probiotic culture (Lactobacillus rhamnosus). The combination therapy is called PPOIT.
Although the Canadian researchers find elements of the work interesting, they take big issue with statements such as the Institute’s news release heralding the new study as “the strongest evidence yet that a cure may be possible for peanut allergy.”
Allergy Experts’ Reality Check
Following is the reality check from Dr. Derek K. Chu, Dr. Manel Jordana and Dr. Susan Waserman.
Was true peanut tolerance found in study participants who had been allergic?
The Australian study examined patients 4 years after they had completed 18 months in a randomized controlled trial (the parent study) comparing a probiotic combined with peanut immunotherapy (PPOIT) versus placebo.
First, the claim that most patients treated with PPOIT achieved “long-lasting peanut tolerance,” in other words, were “cured,” is false. Patients who were supposedly “cured” had a very similar number of food-allergic reactions and skin prick test positivity to those who had never received any immunotherapy: 4 patients with PPOIT had 11 reactions whereas 6 patients treated with placebo had 9 reactions.
The average size of the skin prick wheal during testing was 8.1 mm +/- 7.7 mm in the PPOIT group, whereas it was 13.3 mm +/- 7.6 mm in the placebo group. Those values are not an important difference to patients or clinicians, and are of dubious statistical significance.
Did probiotics play a key role in the therapy?
The claim that probiotics were responsible for positive outcomes is unfounded. In the parent study, there were only 2 groups: those who received a combination of peanut and probiotics (PPOIT) versus those who received placebo. There was no group that received peanut without probiotics, or probiotics alone, to determine the contribution, if any, the probiotic made to any of the outcomes.
Therefore, from a scientific standpoint, no claims can be made about the long-term effects of 18 months of PPOIT over and above OIT that uses peanut alone.
Are this study’s findings a breakthrough?
It’s important to note that more than 10 previously published randomized studies of peanut immunotherapy have reported findings similar to the recent PPOIT study. On average in these clinical trials, about 80 percent of peanut-allergic patients who are given increasing amounts of peanut for approximately 18 months are able to ingest 5 grams of peanut in a single sitting without having an allergic reaction. This is a process called “desensitization”.
These previous studies have solidly established that patients must continue to eat their maintenance dose of peanuts to remain protected. Desensitization often disappears when patients stop eating peanuts regularly.
The new Australian PPOIT report simply replicates these findings: the researchers observed that a subset of patients (16 out of 31) who were desensitized to peanut in the parent study and who continued to eat peanuts on a regular basis remained, unsurprisingly, desensitized 4 years later. This hardly qualifies as a breakthrough.
Are there are other concerns about the study?
We also see major concerns about the design and conduct of the study, which limit the scientific validity of its findings. The patients in the latest PPOIT report were studied outside of a randomized clinical trial setting, which means the investigation no longer met the ‘gold standard’ method to demonstrate a treatment’s effectiveness. Indeed, at 4 years, the study was no longer randomized, blinded, balanced, or systematically conducted.
Further, standard eligibility for most peanut OIT trials is the confirmation of peanut allergy through an oral food challenge before being entered in the trial; the PPOIT study did not do this. This means some of those who entered the trial may not have even had peanut allergy in the first place. These and other limitations greatly reduce the credibility of the study’s findings.
Dr. Derek K. Chu, Dr. Manel Jordana and Dr. Susan Waserman. What’s the takeaway message here?
The PPOIT study is one of several trials aimed at developing a treatment for peanut allergy. The road towards developing transformative treatments for peanut allergy is a long one, and requires new insightful approaches by those committed to find them. Among other barriers to clinical application, peanut immunotherapy is associated with potential side effects, and a greater risk of reactions with “co-factors” such as exercise and infection.
So far, OIT has shown hope as a desensitization method to protect against accidental allergen consumption. Let it be clear – there is no peanut allergy cure, the problem is not yet solved.
Derek K. Chu, MD, PhD
Manel Jordana, MD, PhD
Susan Waserman, MD, MSc, FRCP(C)
McMaster University, Hamilton, Ontario, Canada
