High‐ and low‐dose oral immunotherapy similarly suppress pro‐allergic cytokines and basophil activation in young children

Kulis, Michael D.; Yue, Xianchang; Guo, Rishu; Zhang, Huamei; Orgel, Kelly; Ye, Ping; Li, Quefeng; Liu, Yutong; Kim, Edwin; Burks, A. Wesley; Vickery, Brian P.

doi:10.1111/cea.13256

Cited by 51 publications

(56 citation statements)

References 27 publications

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“…Levels of CD203c expression in basophils after anti-IgE, IL-3, or peanut stimulation were also similar between the 3 treatment arms at baseline ( Fig E1, C). Consistent with previous OIT studies of peanut allergy, 7,18,[25][26][27] our OIT protocol significantly decreased peanut-induced %CD63 high basophils as early as week 12 of the OIT build-up phase (Fig 1, A). Upregulation of CD63 in basophils was suppressed during the OIT maintenance phase from weeks 52 to 104.…”

Section: Peanut Oit Suppresses Basophil Activation and Reduces Peanutsupporting

confidence: 90%

“…21,22 Some studies have suggested that BATs are more reliable than skin prick tests and sIgE levels in differentiating food allergy from tolerance in children. 32,34 Although suppression of basophil activation by immunotherapy has been demonstrated in food allergy to egg, 37 milk, 38 and peanut, 7,8,18,[25][26][27]39,40 only a few studies have examined the association of basophil activation with treatment outcomes. 18,26,27,37,40,41 Our analysis of BAT results obtained for more than 2 years in the POISED study shows that basophil activation remains suppressed even after 13 weeks off active OIT, and that sustained protection is associated with lower levels of basophil activation by peanut before, during, and after OIT.…”

Section: Discussionmentioning

confidence: 99%

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Sustained successful peanut oral immunotherapy associated with low basophil activation and peanut-specific IgE

Tsai

Mukai

Chinthrajah

et al. 2020

Journal of Allergy and Clinical Immunology

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Section: Peanut Oit Suppresses Basophil Activation and Reduces Peanutsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Sustained successful peanut oral immunotherapy associated with low basophil activation and peanut-specific IgE

Tsai

Mukai

Chinthrajah

et al. 2020

Journal of Allergy and Clinical Immunology

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“…Unexpectedly, the SU rate did not differ significantly by peanut OIT dose (ITT: 71% high dose, 85% low dose). Mechanistic studies supported this finding with decreases in basophil reactivity, peanut SPT, and pn‐sIgE, and T H 2 cytokines (IL‐5, IL‐13, IL‐9) demonstrated across all subjects but with no difference between high‐ and low‐dose OIT subjects . Safety, on the other hand, did appear to favor the lower dose.…”

Section: Peanut Oitmentioning

confidence: 69%

Food allergy immunotherapy: Oral immunotherapy and epicutaneous immunotherapy

Kim

Burks

2020

Allergy

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IgE-mediated food allergy remains a significant and growing problem across the globe.Of the various treatment modalities, oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) have been the best studied. Across various studies of OIT for egg, milk, and peanut allergy, strong levels of desensitization have been shown. With egg and peanut OIT, a limited remission, or sustained unresponsiveness (SU), has further been demonstrated. These advances have been further validated by successful phase 2 and phase 3 studies of peanut OIT. EPIT, using daily administrations of a proprietary patch, demonstrated efficacy as well as safety and tolerability in parallel phase 2 studies; however, its phase 3 study did not meet its primary efficacy outcome. Despite its good track record of desensitization, the safety and tolerability of OIT has remained a question. EPIT, on the other hand, has proven safe and tolerable; however, the adequacy of its desensitization has remained to be determined. As OIT and EPIT continue their march toward regulatory review, optimizations for immunotherapy and novel therapies continue to be developed providing hope for food allergy patients everywhere. K E Y W O R D Sdesensitization, epicutaneous immunotherapy, food allergy, oral immunotherapy, sustained unresponsiveness

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“…We considered that low dose and high dose did not differ in the effect of rush OIT for severe milk allergy. Kulis et al [8] reported no significant differences in proallergic cytokines, including IL-5, IL-13, and IL-9, T cells, or basophils between low-and high-dose peanut OIT. Yanagida et al [5] reported that the effect of increasing the threshold was observed by continuing a maximum of 3 mL of milk OIT in children severely allergic to milk.…”

Section: Discussion/conclusionmentioning

confidence: 98%

Single-Center Noninferiority Randomized Trial on the Efficacy and Safety of Low- and High-Dose Rush Oral Milk Immunotherapy for Severe Milk Allergy

Takaoka

Yajima²,

Ito

et al. 2020

Int Arch Allergy Immunol

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Introduction: Oral immunotherapy (OIT) has been reported to be effective but associated with a risk of severe symptoms. Thus, an OIT method with decreased risk is required. Objectives: We aimed to evaluate the efficacy and safety of lowand high-dose OIT regimens in children with severe milk allergy. Methods: Overall, 33 participants (median age, 9 years; median final dose of the milk oral food challenge [OFC], 2 mL) were included. The participants were randomly assigned to groups that received either a low (20 mL; n = 19) or high (100 mL; n = 14) maintenance target dose of OIT. The dose was gradually increased to the target dose in the rush escalation phase and was then maintained daily at home. The primary endpoint was the final OFC dose at 6 months of OIT. Adverse events during OIT were evaluated. Results: The final OFC dose after OIT was significantly higher than that before OIT in both groups (low-dose, p = 0.000; high-dose, p = 0.006), but there was no significant difference in the final OFC dose between the 2 groups (p = 0.767). In the maintenance phase, the high-dose group had significantly more severe symptoms than did the low-dose group (0.5%, 11/2,355 total intake events vs. 0.1%, 4/3,230 total intake events; p = 0.018). Conclusions: An equally increased dose effect was observed for maintenance OIT doses of 20 and 100 mL in children with severe milk allergy. The risk of severe symptoms in the maintenance phase was lower in the low-dose group. A low-dose OIT regimen is recommended for severe milk allergy.

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High‐ and low‐dose oral immunotherapy similarly suppress pro‐allergic cytokines and basophil activation in young children

Abstract: Peanut OIT leads to decreases in pro-allergic cytokines, including IL-5, IL-13, and IL-9 and decreased basophil activation. No differences in T cell or basophil responses were found between subjects on low or high-dose maintenance OIT, which has implications for clinical dosing strategies.

Cited by 51 publications

References 27 publications

Sustained successful peanut oral immunotherapy associated with low basophil activation and peanut-specific IgE

Sustained successful peanut oral immunotherapy associated with low basophil activation and peanut-specific IgE

Food allergy immunotherapy: Oral immunotherapy and epicutaneous immunotherapy

Single-Center Noninferiority Randomized Trial on the Efficacy and Safety of Low- and High-Dose Rush Oral Milk Immunotherapy for Severe Milk Allergy

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