Peanut Oral Immunotherapy With or Without H1 and H2 Antihistamine Premedication for Peanut Allergy (PISCES): A Placebo-Controlled Randomized Clinical Trial.

BACKGROUND: Current forms of peanut oral immunotherapy (OIT) are associated with side effects, and there is a lack of evidence addressing how to mitigate them. OBJECTIVE: To determine whether premedication with desloratadine and ranitidine results in fewer side effects during peanut OIT/desensitization. METHODS: A total of 43 patients with peanut allergy (mean age, 7.6 ± 2.1 years, 37% females, 63% males, baseline eliciting dose, 33 ± 26 mg) were randomized to OIT with or without concomitant H1 and H2 antihistamine blockade, or double-placebo. Patients, study staff/investigators, and statisticians were blinded. The primary outcomes were the frequency and severity of OIT-induced adverse events. The secondary outcomes were quality of life and eliciting doses to blinded food challenge. RESULTS: Adverse reactions occurred more in the OIT groups compared with the double-placebo group (OIT with antihistamines vs double-placebo hazard ratio, 3.75 [95% CI, 2.79-4.72]; OIT with placebo antihistamines vs double-placebo, hazard ratio, 4.62 [95% CI, 3.61-5.62]). Patients given antihistamines cotreatment with OIT had a similar risk of adverse events compared with those who did not use antihistamines with OIT (hazard ratio, 1.23 [95% CI, 0.49-1.97]). OIT with and without antihistamines accelerated the incidence rate of adverse events compared with double-placebo (4.8 and 6.4 events per patient vs 3.5 per patient, incidence rate ratio, 2.49 [95% CI, 1.36-4.56] and 2.04 [95% CI, 1.01-4.15], respectively). Antihistamines pretreatment modestly reduced the frequency of moderate to severe adverse reactions among OIT-treated groups (1.9 per patient vs 4.2 per patient, incidence rate ratio, 0.46 [95% CI, 0.24-0.89]), primarily urticaria (0.6 vs 2.1 per patient) followed by abdominal pain (2.6 vs 4.2 per patient), but increased neuropsychiatric adverse events (primarily tiredness and sedation, 2.3 vs 0.7 per patient). Eliciting doses after treatment were similar in all groups. Quality of life improved similarly regardless of treatment with peanut OIT or placebo OIT. CONCLUSIONS: Peanut OIT with antihistamines modestly reduce the skin and gastrointestinal components of the high incidence of adverse reactions during OIT, and there are no clear differences in improvement in quality of life whether treated with OIT, OIT with antihistamines, or placebo OIT despite OIT being effective in inducing desensitization. Safer food allergy treatment approaches that importantly improve quality of life need to be proved in future robust randomized trials.

Peanut allergy: Beyond the oral immunotherapy plateau.

BACKGROUND: There are a lack of disease-modifying treatments for peanut allergy, which is lifelong in most instances. Oral immunotherapy has remained at the forefront of prospective treatments, though its efficacy is consistently undermined by the risk of adverse reactions and meager sustained effects. AIM: This review discusses the current state of oral immunotherapy, its strengths and limitations, and the future of therapeutics for the treatment of peanut allergy. CONCLUSION: The persistence of peanut allergy is currently attributed to reservoirs of peanut-specific memory B cells and Th2 cells, though the cellular and molecular interplay that facilitates the replenishment of peanut-specific IgE remains elusive. Uncovering these events will prove critical for identification of novel targets as we forge ahead to a new age of peanut allergy treatment with biotherapeutics.

Interrupting reactivation of immunologic memory diverts the allergic response and prevents anaphylaxis.

BACKGROUND: IgE production against innocuous food antigens can result in anaphylaxis, a severe life-threatening consequence of allergic reactions. The maintenance of IgE immunity is primarily facilitated by IgG+ memory B cells, as IgE+ memory B cells and IgE+ plasma cells are extremely scarce and short-lived, respectively. OBJECTIVE: Our aim was to investigate the critical requirements for an IgE recall response in peanut allergy. METHODS: We used a novel human PBMC culture platform, a mouse model of peanut allergy, and various experimental readouts to assess the IgE recall response in the presence and absence of IL-4Rα blockade. RESULTS: In human PBMCs, we have demonstrated that blockade of IL-4/IL-13 signaling aborted IgE production after activation of a recall response and skewed the cytokine response away from a dominant type 2 signature. TH2A cells, identified by single-cell RNA sequencing, expanded with peanut stimulation and maintained their pathogenic phenotype in spite of IL-4Rα blockade. In mice with allergy, anti-IL-4Rα provided long-lasting suppression of the IgE recall response beyond antibody treatment and fully protected against anaphylaxis. CONCLUSION: The findings reported here advance our understanding of events mediating the regeneration of IgE in food allergy.

The Initiation of Th2 Immunity Towards Food Allergens.

In contrast with Th1 immune responses against pathogenic viruses and bacteria, the incipient events that generate Th2 responses remain less understood. One difficulty in the identification of universal operating principles stems from the diversity of entities against which cellular and molecular Th2 responses are produced. Such responses are launched against harmful macroscopic parasites and noxious substances, such as venoms, but also against largely innocuous allergens. This suggests that the established understanding about sense and recognition applied to Th1 responses may not be translatable to Th2 responses. This review will discuss processes and signals known to occur in Th2 responses, particularly in the context of food allergy. We propose that perturbations of homeostasis at barrier sites induced by external or internal subverters, which can activate or lower the threshold activation of the immune system, are the major requirement for allergic sensitization. Innate signals produced in the tissue under these conditions equip dendritic cells with a program that forms an adaptive Th2 response.