Development of cockroach immunotherapy by the Inner-City Asthma Consortium

Abstract

Background: Cockroach allergy is a key contributor to asthma morbidity in children living in urban environments.

Objective: We sought to document immune responses to cockroach allergen and provide direction for the development of immunotherapy for cockroach allergy.

Methods: Four pilot studies were conducted: (1) an open-label study to assess the safety of cockroach sublingual immunotherapy (SLIT) in adults and children; (2) a randomized, double-blind biomarker study of cockroach SLIT versus placebo in adults; (3) a randomized, double-blind biomarker study of 2 doses of cockroach SLIT versus placebo in children; and (4) an open-label safety and biomarker study of cockroach subcutaneous immunotherapy (SCIT) in adults.

Results: The adult SLIT trial (n = 54; age, 18-54 years) found a significantly greater increase in cockroach-specific IgE levels between the active and placebo groups (geometric mean ratio, 1.92; P < .0001) and a trend toward increased cockroach-specific IgG4 levels in actively treated subjects (P = .09) but no evidence of functional blocking antibody response. The pediatric SLIT trial (n = 99; age, 5-17 years) found significant differences in IgE, IgG, and IgG4 responses between both active groups and the placebo group but no consistent differences between the high- and low-dose groups. In the SCIT study the treatment resulted in significant changes from baseline in cockroach IgE, IgG4, and blocking antibody levels. The safety profile of cockroach immunotherapy was reassuring in all studies.

Conclusions: The administration of cockroach allergen by means of SCIT is immunologically more active than SLIT, especially with regard to IgG4 levels and blocking antibody responses. No safety concerns were raised in any age group. These pilot studies suggest that immunotherapy with cockroach allergen is more likely to be effective with SCIT.

Keywords: Cockroach; immunotherapy; inner city asthma; subcutaneous immunotherapy; sublingual immunotherapy.

Conflict of interest statement

Disclosure of potential conflict of interest: R. A. Wood has consultant arrangements with the Asthma and Allergy Foundation of America, is employed by Johns Hopkins University, has received grants from the National Institutes of Health (NIH), and receives royalties from UpToDate. E. C. Matsui, G. Hershey, and G. T. O’Connor have received grants from the NIH. R. Gruchalla has received a grant and travel support from the National Institute of Allergy and Infectious Disease (NIAID) and has consultant arrangements with the US Food and Drug Administration. A. H. Liu is on the Data Monitoring Committee for a large clinical trial for GlaxoSmithKline, has consultant arrangements with DBV, and has received speakers’ honoraria from Merck. J. A. Pongracic has received a grant, travel support, and payment for writing and reviewing the manuscript from the University of Wisconsin and is employed by the Pediatric Faculty Foundation of the Ann & Robert H. Lurie Children’s Hospital of Chicago. E. Zoratti has received a grant and travel support from the NIAID. M. Granada has received a grant from the NIH and has received payment for lectures from Forest Labs. S. R. Durham has consultant arrangements from Stallergenes, Circassia, Merck, and ALK-Abelló; has received grants from Novartis, Stallergenes, and Letti; has received payment for lectures from Merck Sharp and Dohme; and has received payment for manuscript preparation from ALK-Abelló. W. W. Busse has received grants from the NIH/NIAID and the National Heart, Lung, and Blood Institute; is a board member for Merck; has consultant arrangements with Amgen, Novartis, GlaxoSmithKline, MedImmune, and Genentech; is on the data monitoring boards for Boston Scientific and Genentech; is on the study oversight committee for ICON; and receives royalties from Elsevier. The rest of authors declare that they have no relevant conflicts of interest.

Published by Mosby, Inc.

Figures

FIG. 1

IgE and IgG4 levels and blocking antibody activity responses by study group. Average* biomarker levels by treatment arm in BioCSI (total n = 54, column 1), BioCSI2 (n = 89, column 2), and SCITCO (n = 10, column 3). Treatment effects for BioCSI and BioCSI2 are detailed in Table I. All 3 biomarkers showed significant change from baseline during the 6-month treatment period in SCITCO. *Geometric means are plotted for IgE and IgG4 levels and arithmetic means for blocking antibody activity.