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

• Published in: Journal of allergy and clinical immunology Vol. 129; no. 2; pp. 448 - 455.e5
• Main Authors: Keet, Corinne A., Frischmeyer-Guerrerio, Pamela A., Thyagarajan, Ananth, Schroeder, John T., Hamilton, Robert G., Boden, Stephen, Steele, Pamela, Driggers, Sarah, Burks, A. Wesley, Wood, Robert A.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.02.2012; Elsevier; Elsevier Limited
• Subjects: Administration, Oral; Administration, Sublingual; Adolescent; adverse effects; Allergic diseases; Allergies; Allergy and Immunology; Asthma; basophil; Basophils - immunology; Biological and medical sciences; Child; children; dairy protein; Desensitization, Immunologic; Digestive allergic diseases; Double-Blind Method; Drug dosages; FDA approval; Female; Food; Food allergies; Food allergy; Fundamental and applied biological sciences. Psychology; Fundamental immunology; histamine; Histamine - immunology; Humans; immunoglobulin E; Immunoglobulin E - blood; immunoglobulin G; Immunoglobulin G - blood; Immunopathology; Immunotherapy; Intracellular Signaling Peptides and Proteins - immunology; Male; mechanism of action; Medical sciences; Methods; Milk; milk allergy; Milk Hypersensitivity - blood; Milk Hypersensitivity - immunology; Milk Hypersensitivity - therapy; Milk Proteins - administration & dosage; non-specific protein-tyrosine kinase; Phosphoric Diester Hydrolases - immunology; Protein-Tyrosine Kinases - immunology; Proteins; Pyrophosphatases - immunology; Remission Induction; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; screening; Skin Tests; spontaneous histamine release; Syk Kinase; Tetraspanin 30 - immunology; titration; Food allergy; BEC; SLIT; Syk; IRR; spontaneous histamine release; CM; HR; basophil; PIPES; OFC; milk allergy; MFI; immunotherapy; OIT; SHR; DBPCFC; Cow’s milk; Piperazine-N,N′-bis(2-ethanesulfonic acid); Oral food challenge; Double-blind, placebo-controlled food challenge; Mean fluorescence intensity; Histamine release; Sublingual immunotherapy; Oral immunotherapy; Basophil-enriched mononuclear cell; Spleen tyrosine kinase; Incidence rate ratio; Immunopathology; Desensitization; Toxicity; Treatment efficiency; Spontaneous; Granulocyte; Oral administration; Sublingual administration; Basophil; Histamine; Immunology; Treatment; Immunotherapy; Digestive diseases
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2011.10.023

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 IgG4 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 IgG4 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.