Today’s PAAD1 and its accompanying editorial2 will not affect how you provide anesthesia, pain management or critical care medicine. I just find the issue of peanut allergy enormously interesting and these articles provide a lot of insight into this issue. I don’t think I or my kids would have survived elementary school, summer camp, or birthday parties in today’s peanut avoidance culture. Peanut butter and jelly was my/their survival food and was my/their essential food group in brown bag lunches. I’m pretty sure this is true for many of you as well. Allergy is clearly not my area of expertise. Fortunately, my wife Dr. Pam Zeitlin, the chair of pediatrics at National Jewish Hospital does have this expertise and I asked her to assist in reviewing these articles. Myron Yaster MD
Original article
Sicherer SH, Bunyavanich S, Berin MC, Lo T, Groetch M, Schaible A, Perry SA, Wheatley LM, Fulkerson PC, Chang HL, Suárez-Fariñas M, Sampson HA, Wang J. Peanut Or al Immunotherapy in Children with High-Threshold Peanut Allergy. NEJM Evid. 2025 Mar;4(3):EVIDoa2400306. doi: 10.1056/EVIDoa2400306. Epub 2025 Feb 10. PMID: 39928078.
Editorial
Keet CA, Burks AW. To Eat or Not to Eat - Oral Immunotherapy for High-Threshold Peanut Allergy. NEJM Evid. 2025 Mar;4(3):EVIDe2400448. doi: 10.1056/EVIDe2400448. Epub 2025 Feb 25. PMID: 39998307.
“Peanut allergy affects approximately 2% of children in the United States and has significant negative effects on quality of life, mostly due to the burden of avoidance and the anxiety associated with the unpredictable risk of accidental exposures. Recently, treatment options for food allergies have rapidly expanded, with two products approved by the Food and Drug Administration: omalizumab (Palforzia), an immunoglobulin E blocker and a pharmaceutical grade peanut oral immunotherapy (P-OIT) n oral immunotherapy.”1,2
Essentially there are 2 groups of peanut allergic patients. Some who are very sensitive to peanut protein (low threshold) and those who have a high threshold (more peanut protein is required to trigger a reaction). After reading today’s articles, I (MY) was shocked at how little peanut protein could trigger a response in low threshold patients. Even In high threshold patients, “a challenge dose of between 443 mg of peanut protein (a little more than one peanut) and 5043 mg of peanut protein (about one and a half tablespoons of peanut butter) is enough to trigger a massive response.”1,2
Sicherer et al. in a prospective randomized controlled trial “using inexpensive home-measured peanut butter to assess the benefits of P-OIT in high threshold responder children who do not manifest symptoms of peanut allergy until they ingest more than the amount of such protein found the equivalent of one half of a single peanut.”1 They “randomly assigned (1:1) participants 4 to 14 years of age reacting to a challenge of between 443 mg and 5043 mg of peanut protein to peanut oral immunotherapy (P-OIT) using home-measured peanut butter versus peanut avoidance. The primary end point was the difference between groups in the proportion tolerating a two-dose-level increase or 9043 mg of peanut protein. For ingestion participants tolerating 9043 mg, sustained unresponsiveness (tolerance off treatment) was tested after 16 weeks of ad lib ingestion followed by 8 weeks of abstinence.”1
Ok, what did they find” “Of 73 participants, 38 were randomly assigned to P-OIT and 35 to avoidance. Thirty-two of 38 participants in the ingestion group (84.2%) and 30 of 35 in the avoidance group (85.7%) underwent the primary outcome food challenge. The primary analysis with prespecified multiple imputation for missing values showed 100% success for ingestion versus 21.0% for avoidance (between-group difference, 79.0 percentage points; 95% confidence interval [CI], 64.6 to 93.5; P<0.001). All 32 treated and 3 out of 30 avoiders (10%) tolerated 9043 mg. In the intention-to-treat analysis, sustained unresponsiveness occurred in 68.4% (26/38) on P-OIT versus 8.6% (3/35) tolerating 9043 mg among those avoiding (between-group difference, 59.9 percentage points; 95% CI, 42.4 to 77.3). No dosing reactions were greater than grade 1 severity, and no serious adverse events were reported.”1
Sicherer et al. concluded that “In this trial of P-OIT using store-bought, home-measured peanut versus peanut avoidance in high-threshold peanut allergy, those treated achieved significantly higher rates of desensitization with a durable response off treatment.”1 In simple English, this was an overwhelming success and those high threshold patients treated with peanut oral immunotherapy continued to have sustained unresponsiveness to peanut protein after the trial concluded.
In their editorial, Keet and Burks ask: “should allergists routinely assess threshold and offer OIT to high-threshold individuals? Would a simplified dosing regimen with even fewer or no dose escalations show similar benefits? Would it work in younger children”?2 We have an even more pressing question: Is it safe to conduct this therapy, unsupervised at home? Even in controlled hospital/outpatient settings catastrophic allergic reactions occur in peanut allergic patients when they are exposed to peanut protein.
I (PLZ) also wonder if children with peanut allergy could safely receive both omalizumab and oral immunotherapy. Omalizumab is an anti-IgE antibody that although not specific to peanut allergy, can reduce allergic reactions. Omalizumab is approved to reduce risk in accidental peanut exposure and only with peanut allergen avoidance. There is some evidence that combining omalizumab with oral immunotherapy to peanut can reduce the risk and severity of allergic reactions during the oral immunotherapy process.3,4 There is no cure for peanut allergy as yet. The decision to proceed with oral immunotherapy, omalizumab, or both, is still very much an individualized plan made in consultation between provider and family/patient.
Are the allergists in your practice incorporating this into their practice? Send your thoughts and comments to Myron who will post in a Friday Reader Response.
PS: The FDA has just approved a new nasal spray epinephrine (Neffy) to treat severe allergic reactions in kids ages 4 and up. This is the first emergency treatment that doesn’t use a needle. Neffy contains 2 milligrams (nasal epinephrine) and is the first needle-free option for older children and adults, while younger children under 33 pounds still have to use injection pens, which can be tricky to use and can cause delay and accidental injuries during emergencies.
Referemces
1. Sicherer SH, Bunyavanich S, Berin MC, et al. Peanut Oral Immunotherapy in Children with High-Threshold Peanut Allergy. NEJM Evid 2025;4(3):EVIDoa2400306. (In eng). DOI: 10.1056/EVIDoa2400306.
2. Keet CA, Burks AW. To Eat or Not to Eat - Oral Immunotherapy for High-Threshold Peanut Allergy. NEJM Evid 2025;4(3):EVIDe2400448. (In eng). DOI: 10.1056/EVIDe2400448.
3. MacGinnitie AJ, Rachid R, Gragg H, et al. Omalizumab facilitates rapid oral desensitization for peanut allergy. The Journal of allergy and clinical immunology 2017;139(3):873-881.e8. (In eng). DOI: 10.1016/j.jaci.2016.08.010.
4. Dantzer JA, Wood RA. Omalizumab as an adjuvant in food allergen immunotherapy. Curr Opin Allergy Clin Immunol 2021;21(3):278-285. (In eng). DOI: 10.1097/aci.0000000000000736.