Is Peanut Oral Immunotherapy Ready for Prime-Time?
Author: Derek Chu, MD, PhD
Royal College of Physicians and Surgeons of Canada-certified Internal Medicine Specialist
PGY5 Fellow in Clinical Immunology and Allergy in the Department of Medicine at McMaster University in Hamilton, Ontario, Canada
EAACI Research Methodology Board member
AAAAI Anaphylaxis and Food Allergy committees member.
Citation: Chu D. Commentary: is peanut oral immunotherapy ready for prime-time? [Published online May 30, 2019.]. Consultant360.
An estimated 5% of US adults and 8% of US children live with food allergies.1 Because there is currently no cure for food allergy, the standard-of-care approach for management is avoidance.1 In hopes of helping reduce the anxieties and burdens that often accompany avoidance, recent research has been geared towards examining the effects of peanut oral immunotherapy (OIT) as a means of treatment for peanut allergy.
The intent behind peanut OIT, which is experimental in its current state, is to reduce allergic and anaphylactic reactions by promoting desensitization to trace exposures of peanut.2 Although the approach is conceptually strong, in practice, the evidence shows some significant limitations to current forms of peanut OIT, according to the recent PACE study – a systematic review and analysis of randomized controlled trials (RCTs) that we recently published in The Lancet.3 Although we found that the rate of passing an in-office supervised food challenge was approximately 40% to 50% in the OIT group compared with 4% to 7% in the avoidance group, the data show that peanut OIT carries a risk for anaphylaxis of approximately 23% compared with 7% for avoidance.3 In combination, these data indicate that current forms of OIT can often achieve partial and variable desensitization to peanut, but that these results are traded off with a large increase in anaphylactic and allergic events compared with avoidance.3
Having a peanut allergy myself, I live in the same shoes as many other patients with peanut allergy. The vigilance required of individuals with peanut allergy can be burdensome, and oftentimes, peanut allergy can be accompanied by significant uncertainty, anxiety, concern, or frustration when it comes to avoiding the allergen in social situations and other aspects of daily life. For these reasons, the recent buzz and promise surrounding peanut OIT can be alluring. However, buzz and allure alone should not supersede the facts and critical considerations about peanut OIT.
First, peanut OIT is still in an experimental stage, as we have not worked out a number of very important kinks yet. To put this into context, there was a very prominent case just a few years ago in Japan where researchers conducted a randomized controlled trial (RCT) in a highly controlled setting for milk OIT.4 Unfortunately, a young child with milk allergy who was undergoing OIT in the trial took a previously tolerated dose of milk at home, had an anaphylactic reaction to the therapy, and sustained permanent brain damage as a result.4 As the physician and fiduciary for my patients, I want to use the best information possible to inform clinical decision-making and ensure my patients’ best interests are the focus when managing their food allergies.
Second, when patients present with food allergies, it is incumbent upon us as healthcare providers to obtain an accurate diagnosis and demystify for them the safest paths for living confidently with food allergy. We also need to connect patients with individualized, safe, effective, and proven management strategies.
It is important to note that the PACE study does not discount, condemn, or say that the whole concept of peanut OIT should be abandoned, as this is just the first iteration of experimental peanut OIT therapies. Big questions remain about how to improve peanut OIT, who the optimal candidates are, and practically, how to provide OIT or any new peanut allergy treatment safely en masse. Given that food allergy is a highly personal condition, there is a clear need to hear from the full spectrum of patient perspectives on what outcomes are valued in future treatments and what trade-offs are acceptable.
Until definitive evidence of the efficacy and safety of the next iteration of peanut allergy treatments emerges, there will continue to be bold, and often unsupported, claims by select practitioners. The unfortunate reality is that there is some predatory behavior out there targeting patients seeking help with managing food allergy. All stakeholders must demand that such bold claims meet the high standard of medicine to back them up through evidence from large, well-conducted randomized trials. If a fool-proof, highly effective new treatment exists, it should be easy to demonstrate its efficacy and safety in a clear and transparent way in an RCT.
PACE synthesized the worldwide experience of RCTs on peanut OIT, with over 12 different protocols tested in highly controlled settings by world experts who have dedicated their lives (and in many cases, holidays, evenings, and weekends) to finding a protocol that is both safe and effective and, in many cases, with no immediate or direct financial reward. PACE provides the best available information to date on peanut OIT and show significant limitations to current forms of peanut OIT. Please read the full paper available at The Lancet. We also provide an online interactive summary of findings here.
I encourage all who seek new options in food allergy management to participate in RCTs. Doing so has multiple benefits:
- Participants in RCTs have been consistently shown to fare better than those outside of RCTs, even if placed on placebo, because of the infrastructure, suport, and rigor, of well-conducted RCTs.
- The experience of patients in RCTs will not only benefit them, but the millions around the world with the same condition.
- Being part of a well-done RCT (which will, by necessity, include blinding and the principal investigator having no direct patient contact), means it removes conflict of interest and cost from the relationship between a patient and their healthcare provider, who is supposed to solely be their fiduciary.
Although further research and improvements in peanut OIT are needed, alternative immunotherapy approaches, as well as approaches that do not use immunotherapy at all, will likely comprise the next generation of approaches to managing peanut allergy. We should also not forget that significant improvements can be made with avoidance at multiple levels (government, regulatory, industry, etc.). Alternative immunotherapies could include subcutaneous immunotherapy, epicutaneous immunotherapy, sublingual immunotherapy, and potentially others. We need to invest in these approaches and broaden the discourse to include all individuals involved in the field of peanut allergy, including patients, caregivers, health care providers, researchers, policymakers, and funders. We all need to work together in order to curtail peanut allergy with proven treatments.
1. Sicherer SH, Sampson HA. Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2014;133(2):291-307.e5. https://doi.org/10.1016/j.jaci.2013.11.020.
2. The current state of oral immunotherapy (OIT) for the treatment of food allergy. American Academy of Allergy, Asthma, & Immunology. https://www.aaaai.org/conditions-and-treatments/library/allergy-library/oit. Page last reviewed February 6, 2019. Accessed May 14, 2019.
3. Chu DK, Wood RA, French S, et al. Oral immunotherapy for peanut allergy (PACE): a systematic review and meta-analysis of efficacy and safety [Published online April 25, 2019]. Lancet. https://doi.org/10.1016/S0140-6736(19)30420-9.
4. Bloom D. Study: nine children suffer severe symptoms in OIT trial. SnackSafely.com. https://snacksafely.com/2017/11/study-nine-children-suffer-severe-symptoms-in-oit-trial/. Published November 20, 2017. Accessed May 14, 2019.