TY - JOUR
T1 - The safety and efficacy of sublingual and oral immunotherapy for milk allergy
AU - Keet, Corinne A.
AU - Frischmeyer-Guerrerio, Pamela A.
AU - Thyagarajan, Ananth
AU - Schroeder, John T.
AU - Hamilton, Robert G.
AU - Boden, Stephen
AU - Steele, Pamela
AU - Driggers, Sarah
AU - Burks, A. Wesley
AU - Wood, Robert A.
N1 - Funding Information:
Supported by National Institutes of Health (NIH) training grants 5T32-AI07007 and 5T32–AI007062–3 , NIH grant R21AI079853 (to J.T.S), NIH grant K23AI091869 (to P.A.F.-G.), a Johns Hopkins Clinician Scientist Award (to P.A.F.-G.), and the Eudowood foundation . The study described was also made possible in part by grant numbers 1KL2RR025006-01, UL1RR025005, and UL1RR024128 from the National Center for Research Resources (NCRR) , a component of the NIH, and the NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NCRR or NIH. Information on the NCRR is available at http://www.ncrr.nih.gov/ . Information on Re-engineering the Clinical Research Enterprise can be obtained from http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp . Greer Laboratories (Lenoir, NC) provided the study material. S. B. is supported by the US Air Force . The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Air Force, the Department of Defense or the US Government.
PY - 2012/2
Y1 - 2012/2
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 If they passed the 60-week challenge, therapy was withdrawn, with challenges repeated 1 and 6 weeks later.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 IgG4 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 IgG4 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.
AB - 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 IgG4 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 IgG4 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.
KW - Food allergy
KW - basophil
KW - immunotherapy
KW - milk allergy
KW - spontaneous histamine release
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U2 - 10.1016/j.jaci.2011.10.023
DO - 10.1016/j.jaci.2011.10.023
M3 - Article
C2 - 22130425
AN - SCOPUS:84856493828
SN - 0091-6749
VL - 129
SP - 448-455.e5
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 2
ER -