The safety and efficacy of sublingual and oral immunotherapy for milk allergy

Corinne Keet, Pamela A. Frischmeyer-Guerrerio, Ananth Thyagarajan, John Thomas Schroeder, Robert G Hamilton, Stephen Boden, Pamela Steele, Sarah Driggers, A. Wesley Burks, Robert A Wood

Research output: Contribution to journalArticle

Abstract

Background: 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. Objective: We sought to explore the safety and efficacy of OIT and SLIT for the treatment of cow's milk (CM) allergy. Methods: 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 If they passed the 60-week challenge, therapy was withdrawn, with challenges repeated 1 and 6 weeks later.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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
JournalThe Journal of Allergy and Clinical Immunology
Volume129
Issue number2
DOIs
StatePublished - Feb 2012

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Sublingual Immunotherapy
Milk Hypersensitivity
Immunotherapy
Safety
Milk
Milk Proteins
Histamine Release
Skin Test End-Point Titration
Immunoglobulin E
Therapeutics
Immunoglobulin G
Food Hypersensitivity
Basophils
Skin Tests

Keywords

  • basophil
  • Food allergy
  • immunotherapy
  • milk allergy
  • spontaneous histamine release

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The safety and efficacy of sublingual and oral immunotherapy for milk allergy. / Keet, Corinne; Frischmeyer-Guerrerio, Pamela A.; Thyagarajan, Ananth; Schroeder, John Thomas; Hamilton, Robert G; Boden, Stephen; Steele, Pamela; Driggers, Sarah; Burks, A. Wesley; Wood, Robert A.

In: The Journal of Allergy and Clinical Immunology, Vol. 129, No. 2, 02.2012.

Research output: Contribution to journalArticle

Keet, Corinne ; Frischmeyer-Guerrerio, Pamela A. ; Thyagarajan, Ananth ; Schroeder, John Thomas ; Hamilton, Robert G ; Boden, Stephen ; Steele, Pamela ; Driggers, Sarah ; Burks, A. Wesley ; Wood, Robert A. / The safety and efficacy of sublingual and oral immunotherapy for milk allergy. In: The Journal of Allergy and Clinical Immunology. 2012 ; Vol. 129, No. 2.
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AU - Thyagarajan, Ananth

AU - Schroeder, John Thomas

AU - Hamilton, Robert G

AU - Boden, Stephen

AU - Steele, Pamela

AU - Driggers, Sarah

AU - Burks, A. Wesley

AU - Wood, Robert A

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N2 - Background: 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. Objective: We sought to explore the safety and efficacy of OIT and SLIT for the treatment of cow's milk (CM) allergy. Methods: 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. Results: 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. Conclusion: 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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