The Safety and Efficacy of Sublingual and Oral Immunotherapy for Milk Allergy

Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 11/2011; 129(2):448-55, 455.e1-5. DOI: 10.1016/j.jaci.2011.10.023
Source: PubMed


Oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) are potential therapies for food allergy, but the optimal method of administration, mechanism of action, and duration of response remain unknown.
We sought to explore the safety and efficacy of OIT and SLIT for the treatment of cow's milk (CM) allergy.
We randomized children with CM allergy to SLIT alone or SLIT followed by OIT. After screening double-blind, placebo-controlled food challenges and initial SLIT escalation, subjects either continued SLIT escalation to 7 mg daily or began OIT to either 1000 mg (the OITB group) or 2000 mg (the OITA group) of milk protein. They were challenged with 8 g of milk protein after 12 and 60 weeks of maintenance. If they passed the 60-week challenge, therapy was withdrawn, with challenges repeated 1 and 6 weeks later. Mechanistic correlates included end point titration skin prick testing and measurement of CM-specific IgE and IgG(4) levels, basophil histamine release, constitutive CD63 expression, CD203c expression, and intracellular spleen tyrosine kinase levels.
Thirty subjects with CM allergy aged 6 to 17 years were enrolled. After therapy, 1 of 10 subjects in the SLIT group, 6 of 10 subjects in the SLIT/OITB group, and 8 of 10 subjects in the OITA group passed the 8-g challenge (P = .002, SLIT vs OIT). After avoidance, 6 of 15 subjects (3 of 6 subjects in the OITB group and 3 of 8 subjects in the OITA group) regained reactivity, 2 after only 1 week. Although the overall reaction rate was similar, systemic reactions were more common during OIT than during SLIT. By the end of therapy, titrated CM skin prick test results and CD63 and CD203c expression decreased and CM-specific IgG(4) levels increased in all groups, whereas CM-specific IgE and spontaneous histamine release values decreased in only the OIT group.
OIT was more efficacious for desensitization to CM than SLIT alone but was accompanied by more systemic side effects. Clinical desensitization was lost in some cases within 1 week off therapy.

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Available from: Corinne A Keet, Oct 05, 2015
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    • "These current types of experimental treatments need to be tested for optimization in safety, efficacy, and length of time [26-34]. Safety is of critical importance at all phases of any protocol (initial dose escalation day, dose escalation, and maintenance phases) and allergic reactions while on OIT remain an important feature in long-term follow-up studies and in determining the overall success of food allergen immunotherapy [35]. However, one major limitation to the clinical application of current protocols is their use in participants with more than one food allergy, which would require multiple sequential rounds of immunotherapy over many years. "
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    ABSTRACT: Up to 30% of patients with food allergies have clinical reactivity to more than one food allergen. Although there is currently no cure, oral immunotherapy (OIT) is under investigation. Pilot data have shown that omalizumab may hasten the ability to tolerate over 4 g of food allergen protein. To evaluate the safety and dose tolerability of a Phase 1 Single Site OIT protocol using omalizumab to allow for a faster and safe desensitization to multiple foods simultaneously. Participants with multiple food allergies received OIT for up to 5 allergens simultaneously with omalizumab (rush mOIT). Omalizumab was administered for 8 weeks prior to and 8 weeks following the initiation of a rush mOIT schedule. Home reactions were recorded with diaries. Twenty-five (25) participants were enrolled in the protocol (median age 7 years). For each included food, participants had failed an initial double-blind placebo-controlled food challenge at a protein dose of 100 mg or less. After pre-treatment with omalizumab, 19 participants tolerated all 6 steps of the initial escalation day (up to 1250 mg of combined food proteins), requiring minimal or no rescue therapy. The remaining 6 were started on their highest tolerated dose as their initial daily home doses. Participants reported 401 reactions per 7,530 home doses (5.3%) with a median of 3.2 reactions per 100 doses. Ninety-four percent (94%) of reactions were mild. There was one severe reaction. Participants reached their maintenance dose of 4,000 mg protein per allergen at a median of 18 weeks. These phase 1 data demonstrate that rush OIT to multiple foods with 16 weeks of treatment with omalizumab could allow for a fast desensitization in subjects with multiple food allergies. Phase 2 randomized controlled trials are needed to better define safety and efficacy parameters of multi OIT experimental treatments with and without omalizumab.
    Allergy Asthma and Clinical Immunology 02/2014; 10(1):7. DOI:10.1186/1710-1492-10-7 · 2.03 Impact Factor
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    • "A recent open-label randomized study done by Keet et al.,36 compared the efficacy and safety of SLIT and OIT. 30 patients with IgE-mediated cow's milk allergy, aged 6 to 17 years, were randomly assigned to SLIT alone or to SLIT followed by OIT. "
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    ABSTRACT: Food allergy has increased dramatically in prevalence over the past decade in westernized countries, and is now a major public health problem. Unfortunately for patients with food allergy, there is no effective therapy beyond food allergen avoidance, and rapid medical treatment for accidental exposures. Recently, oral immunotherapy (OIT) has been investigated as a treatment for this problem. In this review, we will discuss the progress in developing OIT for food allergy, including a novel approach utilizing Xolair (anti-IgE monoclonal antibody, omalizumab) in combination with OIT. This combination may enhance both the safety and efficacy of oral immunotherapy, and could lead to a widely available and safe therapy for food allergy.
    Allergy, asthma & immunology research 01/2013; 5(1):3-15. DOI:10.4168/aair.2013.5.1.3 · 2.43 Impact Factor
    • "D'autres ont employé la voie épicutanée à l'aide de patch-tests aux aliments [10] [11]. Dans certaines études la voie sublinguale est suivie par une ITO ou même comparée à l'ITO [12] [13] [14] [15]. Une étude récente utilise un traitement par omalizumab avant et pendant l'ITO [16] "
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    ABSTRACT: In this review of immunotherapy for food allergies, we propose to consider the principles and then to describe the main research results, considering the methods used to treat allergy to milk, egg and peanut. We will describe new approaches, e.g., the use of cooked milk and egg, and emphasize the importance of personalizing the protocol for induction of tolerance as used by specialists in food allergy in children.
    Revue Française d'Allergologie 01/2013; 53(1):20–31. DOI:10.1016/j.reval.2012.11.008 · 0.25 Impact Factor
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