A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy

Wood, Robert A.; Kim, Jennifer; Lindblad, Robert; Nadeau, Kari; Henning, Alice K.; Dawson, Peter; Plaut, Marshall; Sampson, Hugh A.

doi:10.1016/j.jaci.2015.10.005

Cited by 315 publications

(324 citation statements)

References 33 publications

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“…In a randomized, double-blind, placebo-controlled oral Immunotherapy trial with and without omalizumab, anti-IgE treatment significantly improves the safety profile of OIT. However, there was no evidence for a pro-tolerogenic effect (96). The induction of allergen-specific blocking antibodies of the IgG, in particular IgG4 antibodies, is considered to be one of the central mechanisms of allergen-specific immunotherapy.…”

Section: Oral and Sublingual Immunotherapy In Food Allergymentioning

confidence: 97%

Markers of tolerance development to food allergens

Ponce

Diesner

Szépfalusi

et al. 2016

Allergy

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IgE-mediated reactions to food allergens are the most common cause of anaphylaxis in childhood. Although allergies to cow's milk, egg, or soy proteins, in contrast to peanut and tree nut allergens, resolve within the first 6 years of life in up to 60% due to natural tolerance development, this process is not well understood. At present, there is no cure or treatment for food allergy that would result in an induction of tolerance to the symptom-eliciting food. Avoidance, providing an emergency plan and education, is the standard of treatment. Oral immunotherapeutic approaches have been proven reasonable efficacy; however, they are associated with high rates of side-effects and low numbers of patients achieving tolerance. Nevertheless, mechanisms that take place during oral immunotherapy may help to understand tolerance development. On the basis of these therapeutic interventions, events like loss of basophil activation and induction of regulatory lymphocyte subsets and of blocking antibodies have been described. Their functional importance at a clinical level, however, remains to be investigated in detail. Consequently, there is eminent need to understand the process of tolerance development to food allergens and define biomarkers to develop and monitor new treatment strategies for food allergy.IgE-mediated food allergy represents the most important cause of anaphylaxis in childhood. While milk and egg allergy are associated with a high rate of natural tolerance development within the first 6 years of life, this is less clear for other food allergies. Consequently, once it is communicated the diagnosis persists often lifelong severely impacting the quality of life of the patient and the environment despite the recommendation to reconsider clinical tolerance development from time to time.Currently, avoidance, providing an emergency plan and teaching, is the standard of treatment; however, there is no cure or treatment that has reached the level of recommendation to re-induce tolerance to the symptom-eliciting food. Tolerance assessment occurs either via oral food challenges or due to unintended exposure. Given the cost and time intensiveness of oral food challenges and its potential harmfulness, there is eminent need to understand the process of tolerance development and define markers thereof to develop and monitor new treatment strategies for food allergy. This review aimed to provide an overview on recent advances regarding markers and mechanisms of tolerance development to food allergens.Oral tolerance in the context of food allergy is considered to occur if the antigen/food can be ingested without problems despite prolonged periods of avoidance, while the status of desensitization is strictly dependent on regular ingestion of the respective food in order to confer protection from allergic reactions. Currently, there is no general consensus on the exact time frame of avoidance and re-exposure that would allow the usage of the terminus tolerance that is considered equivalent to cure in the context of or...

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Section: Oral and Sublingual Immunotherapy In Food Allergymentioning

confidence: 97%

Markers of tolerance development to food allergens

Ponce

Diesner

Szépfalusi

et al. 2016

Allergy

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“…In the first, Wood et al [67] studied the addition of omalizumab or placebo to open-label milk OIT. At the completion of treatment, 88.9% of the omalizumab-treated patients and 71.4% of the placebo-treated patients passed the 10-g "desensitization" OFC (P=.18).…”

Section: Adjunctive Therapiesmentioning

confidence: 99%

Oral Immunotherapy for Food Allergy

Wood

2017

J Investig Allergol Clin Immunol

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Food allergy is a potentially life-threatening condition with no approved therapies apart from avoidance and injectable epinephrine for treatment of acute allergic reactions. Oral immunotherapy (OIT) is an experimental treatment in which patients consume gradually increasing quantities of the food to which they are allergic in an attempt to induce some level of desensitization. While desensitization is possible in most patients, OIT carries significant risks for allergic reactions, and the ability to induce longer-term tolerance has not yet been established. This review focuses on selected studies of OIT for the treatment of common food allergies such as cow's milk, hen's egg, and peanut. Key words: Food allergy. Oral immunotherapy. Cow's milk. Hen's egg. Peanut. Desensitization. Tolerance. Sustained unresponsiveness. Skin prick test (SPT). Immunoglobulin E (IgE). Omalizumab. ResumenLa alergia alimentaria es una condición potencialmente mortal para la que no existen tratamientos aprobados, excepto la evitación y la epinefrina para tratar reacciones alérgicas graves. La inmunoterapia oral (OIT) es un tratamiento experimental en el cual los pacientes ingieren cantidades gradualmente crecientes del alimento al que son alérgicos, con el fin de inducir algún nivel de desensibilización. Si bien la desensibilización es posible en la mayoría de los pacientes, OIT conlleva riesgos importantes de reacciones alérgicas y la capacidad de inducir tolerancia a más largo plazo todavía no ha sido establecida. Este artículo de revisión se centra en una selección de estudios de OIT para el tratamiento de alergias a alimentos comunes, como son la leche de vaca, huevos de gallina y cacahuete. Palabras clave: Alergia alimentaria. Inmunoterapia oral. Leche de vaca. Huevo de gallina. Cacahuete. Desensibilización. Tolerancia. Falta de respuesta sostenida. Prick test. Inmunoglobulina. Omalizumab.

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“…We recently completed the first double-blind placebo-controlled (DBPC) trial of omalizumab in combination with OIT in patients with severe persistent cow's milk allergy. 4 Although no statistically significant benefit of omalizumab in promoting desensitization was detected compared to subjects receiving milk OIT (MOIT) alone, omalizumab-treated subjects exhibited highly significant improvements in nearly all safety parameters. 4 …”

Section: Introductionmentioning

confidence: 99%

Mechanistic correlates of clinical responses to omalizumab in the setting of oral immunotherapy for milk allergy

Frischmeyer‐Guerrerio

Masilamani

et al. 2017

Journal of Allergy and Clinical Immunology

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Background In our recent clinical trial, the addition of omalizumab to oral immunotherapy (OIT) for milk allergy improved safety but no significant clinical benefit was detected. Objective To investigate mechanisms by which omalizumab modulates immunity in the context of OIT, and to identify baseline biomarkers that predict subgroups of patients most likely to benefit from omalizumab. Methods Blood was obtained at baseline and multiple time-points during a placebo-controlled trial of OIT for milk allergy where subjects were randomized to receive omalizumab or placebo. Immunologic outcomes included measurement of basophil CD63 expression and histamine release (HR), and casein-specific CD4+ T regulatory (Treg) cell proliferation. Biomarkers were analyzed in relationship to measurements of safety and efficacy. Results Milk-induced basophil CD63 expression was transiently reduced in whole blood samples from both omalizumab and placebo subjects. However, IgE-dependent HR increased in washed cell preparations from omalizumab but not placebo subjects. No increase in Treg frequency was evident in either group. Subjects with lower rates of adverse reactions, regardless of arm, experienced better clinical outcomes. Pre-OIT basophil reactivity positively associated with occurrence of symptoms during OIT, while the baseline milk IgE/total IgE ratio correlated with the likelihood of achieving sustained unresponsiveness (SU). A combination of baseline basophil and serologic biomarkers defined a subset of patients where adjunctive therapy with omalizumab was associated with attainment of SU and a reduction in adverse reactions. Conclusions Combining omalizumab therapy with milk OIT led to distinct alterations in basophil reactivity but not T cell responses. Baseline biomarkers may identify subjects most likely to benefit from adjunctive therapy with omalizumab.

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A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy

Cited by 315 publications

References 33 publications

Markers of tolerance development to food allergens

Markers of tolerance development to food allergens

Oral Immunotherapy for Food Allergy

Mechanistic correlates of clinical responses to omalizumab in the setting of oral immunotherapy for milk allergy

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