By Dr. Paul Ehrlich
Within days of publication of a study [“Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase-2 randomized controlled trial”)] by Katherine Anagnostou, PhD, from the Department of Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom, and her colleagues, in the preeminent British medical journal, The Lancet, the American press is buzzing with talk about the possibility of treating peanut allergy with oral immunotherapy (OIT). What is it about the Brits? Research is ongoing in the US, but it rarely rises to this level of attention. Call it the Downton Abbey Effect. Let’s face it—Dallas doesn’t have the appeal it used to, but when the British do an epic about old money and class, people talk. Dr. Anagnostou says, “To our knowledge, our findings provide the first well controlled and accurate estimate of the effect size, benefits, and risks of desensitisation with peanut OIT.”
My own experience with British medicine goes back about 40 years when I was doing a pediatric fellowship. I spent 6 months at the foremost children’s hospital in London, Great Ormond Street Hospital, formerly known as the Hospital for Sick Children. The head of the department was the Royal Pediatrician (“Give the Princess two baby aspirin and call me in the morning, Your Majesty.”) The staff was continually complaining about the crowded conditions, but when I asked if they could move to available space two blocks away adjacent to St. George Garden where the kids could be taken outside for fresh air, I was told, “We know that’s what you do in America, doctor, but if we did that we could no longer be called Great Ormond Street.” Treatment be damned; let’s protect the brand!
Inevitably, when a study gets the attention this one has gotten, the way it is interpreted for the public ranges from the thoughtful to the misleading. On the thoughtful side of the ledger, Jane Brody in the New York Times places it in a much wider context. On the other side, Time used a headline that reflected a kind of dismissiveness and incomprehension that I would have hoped we were past: “Cure Your Kids’ Peanut Allergies by Feeding Them Peanuts.” However, that misleading headline has now been changed to something more innocuous, no doubt because peanut allergy families let them know.
The publication has had some novel ripple effects. We have heard from social media sources that food-allergy-mom email boxes and Facebook walls are being flooded by friends and relatives with news reports of this study. Having spent years trying to educate their social and family circles on the seriousness of this epidemic, they are being told that a “cure” exists and they had better get with the program. The message to these people should be, “it’s not that easy, so back off.”
So what are the takeaways from this article? For the moment I will defer to Dr. Matthew J. Greenhawt of the University of Michigan, who analyzes it in the same issue of The Lancet. Echoing Dr. Anagnostou, he is impressed by the sample size, the coherence of the protocol, the large percentage of effective desensitization, and the reporting of immunological changes. “Compared with control participants, those completing OIT had a significant 25-fold increase of their no observed adverse effect level over baseline, and their caregivers had a significant improvement in quality of life. Adverse effects were mild.”
He contrasts this with other papers: “Previous studies have concluded that OIT can safely produce desensitization to peanut and other allergens among selected, but not all, participants. These studies have significant methodological concerns, including small sample sizes, selection bias (involving referral center populations of older children without past severe reactions and with motivated caregivers), and lack of control groups or pre-OIT challenge to confirm that the patient still has persistent allergy.”
Good as this study may be, however, it does highlight the frustration felt on both ends of the stethoscope. Haven’t we been here before? After a decade of OIT trials in the US, we still seem to be stuck on the first rung of the ladder. My friend Dr. Renata Engler has said, “Most money goes into confirming what we already know instead of focusing on the gaps where we could add information.” At least in this case it was British taxpayers who were picking up the tab.
I have some questions of my own. For one, the sample was defined by age—7-16—and was almost evenly divided by sex, but not by other factors. This makes sense as a starting point but what will happen when more studies are opened up to a more heterogeneous sample? Will these percentages hold up? For another thing, just 2% of subjects in the active group and 4% of the control group had a baseline history of grade 4—worst-case—adverse reactions on the WHO scale. Over 90% of the active group had grade 1 and 2. I don’t do OIT in my practice, but as I think about my peanut allergy patients, I know that many with this level of allergy are managing quite well without undertaking the level of commitment and inconvenience that OIT would entail. I also noticed that one patient was withdrawn from the study because in his parents’ opinion, his allergy was too mild to participate.
Given the number of complicating factors left out of news reports of just this study, like its authors and Dr. Greenhawt, I am convinced that OIT is a work in progress.
Photograph from www.geograph.org.uk/
I watch the studies with interest but agree there are too many factors to take into consideration. I wonder just how many of those in the trials are simply “aging out of their allergies,” and how many are dealing with an intolerance rather than anaphylactic severe allergies. Are those with asthma and eczema in these studies? Would the study show truer results if the test subjects were adults who undergo OIT? For now, I will let those willing be the guinea pigs. I find the side effects and (in my opinion) lack of evidence of long term success to simply not be worth the risk for us. Thanks for always providing a voice of reason among the din!
Thank you for delving deeper into the issue. My friends and family were excited by the idea of a simple “cure” for my child, and while I wish it was as simple as the headlines made it seem, I know that it’s much more complex, and may not be right for every child.
I appreciate this observation: “Haven’t we been here before? After a decade of OIT trials in the US, we still seem to be stuck on the first rung of the ladder.” As a parent following these studies for years, I am very frustrated. Researchers need to collaborate on large, long-term studies designed to lead to decisive conclusions and recommendations. Anything less is a waste of time and money at this point — we already know OIT pretty much works for some subset of patients for some period of time given some level of maintenance dose.
“The message to these people should be, “it’s not that easy, so back off.” I am in complete agreement. It was not easy for us. In fact, it was one of the most anxiety filled summer of our lives. While we know that OIT works (and is a smooth process for many), there are those for whom it does not work. The path to decipher that it does not work is time consuming, anxiety filled, physically challenging and possibly life threatening. When the treatment is worse than the disease, it’s time to stop. But how do we know the patients for whom OIT will work or not work? We don’t. How do we know if or when to stop treatment if there are symptoms? That is another gray area. Bottom line is that this is a complex treatment that is being over-simplified in the media.
I have felt this way about many food allergy studies. The trials generally exclude those with asthma (or sometimes just uncontrolled asthma) or those who have had a life-threatening reaction in the recent past, but those are the ones that need treatment the most. However, I can completely understand parents not wanting to enroll their exceptionally sensitive children in clinical trials, due to the risks.
I agree that this is a very complicated matter and that there are no simple treatment options on the table, at this time.