A double-blind, placebo-controlled immunotherapy dose-response study with standardized cat extract

Abstract Background: Allergen immunotherapy with doses of cat extract containing approximately 15 μg of the major allergen, Fel d 1, have been proved clinically effective in several double-blind, placebo-controlled studies. However, the maintenance doses used in allergy practice in the United States are often considerably less than this proven dose. Objective: The purpose of this investigation was to determine whether maintenance immunotherapy with cat dander extract containing 0.6 μg or 3.0 μg of Fel d 1 was more effective than placebo and similar in efficacy to treatment with extracts containing 15.0 μg Fel d 1, immunologic parameters being used as the outcome. Methods: Twenty-eight cat-allergic patients were randomly entered, 7 in each group, into a double-blind, placebo-controlled comparison of the immunologic response to treatment with placebo or cat dander extract containing 0.6 μg, 3.0 μg, or 15.0 μg of Fel d 1. Maintenance doses were achieved in 8 visits over a period of 4 weeks through use of a cluster regimen; each subject then received 1 weekly maintenance injection before posttreatment measurements were made. The response to immunotherapy was assessed before immunotherapy and after the first weekly maintenance injection. Studies included responses to titrated skin prick tests to cat extract and an unrelated allergen and serum allergen-specific IgE and IgG 4 . Titrated nasal challenges were performed with cat extract; measurement of mRNA and secreted cytokines (IL-4, IL-5, and IFN-γ) was done at 6 hours. Serum cytokines (IL-4, IL-5, IFN-γ) were measured, and flow cytometric analysis of intracellular cytokines (IL-4, IL-5, IFN-γ) was performed. Cat allergen–stimulated lymphocyte proliferation was performed with measurement of cytokines in the supernatant (IL-4, IL-5, IFN-γ). Results: All 28 subjects completed the study. Significant and dose-dependent differences were encountered in the titrated skin prick tests ( P = .008), the cat-specific IgG 4 ( P = .01), and the reduction in CD4 + /IL-4 + PBMCs on flow cytometry ( P = .03). There were no significant differences between placebo and cat dander extract containing Fel d 1 0.6 μg. Both extracts containing 3.0 μg and 15.0 μg produced significant decreases in skin prick test sensitivity ( P = .02 and P = .002, respectively). The extracts containing 3.0 μg and 15.0 μg produced significant increases in cat-specific IgG 4 ( P = .01 and P = .006, respectively). Only the 15.0-μg-per-dose extract produced a significant reduction in the percent of CD4 + /IL-4 + PBMCs ( P = .003). Conclusion: In this double-blind, placebo-controlled study, a maintenance dose of cat dander extract containing 15.0 μg Fel d 1 produced the most consistent immunologic response. A dose of 3.0 μg reduced skin prick test sensitivity and increased cat-specific IgG 4 but did not reduce the circulating CD4 + /IL-4 + PBMCs, a change that is likely related to the clinically significant response to allergen immunotherapy. These findings suggest that a maintenance dose of 15.0 μg of Fel d 1 is most apt to be clinically effective for allergen immunotherapy. (J Allergy Clin Immunol 2003;111:155-61.)