Passive Prophylactic Administration with a Single Dose of Anti–Fel d 1 Monoclonal Antibodies REGN1908–1909 in Cat Allergen–induced Allergic Rhinitis: A Randomized, Double-Blind, Placebo-controlled Clinical Trial
Open Access
- 1 July 2021
- journal article
- research article
- Published by American Thoracic Society in American Journal of Respiratory and Critical Care Medicine
- Vol. 204 (1), 23-33
- https://doi.org/10.1164/rccm.202011-4107oc
Abstract
Rationale: Sensitization to Fel d 1 (Felis domesticus allergen 1) contributes to persistent allergic rhinitis and asthma. Existing treatment options for cat allergy, including allergen immunotherapy, are only moderately effective, and allergen immunotherapy has limited use because of safety concerns. Objectives: To explore the relationship among the pharmacokinetic, clinical, and immunological effects of anti-Fel d 1 monoclonal antibodies (REGN1908-1909) in patients after treatment. Methods: Patients received REGN1908-1909 (n = 36) or a placebo (n = 37) in a phase 1b study. Fel d 1-induced basophil and IgE-facilitated allergen binding responses were evaluated at baseline and Days 8, 29, and 85. Cytokine and chemokine concentrations in nasal fluids were measured, and REGN1908-1909 inhibition of allergen-IgE binding in patient serum was evaluated. Measurements and Main Results: Peak serum drug concentrations were concordant with maximal observed clinical response. The anti-Fel d 1 IgE/cat dander IgE ratio in pretreatment serum correlated with Total Nasal Symptom Score improvement. The allergen-neutralizing capacity of REGN1908-1909 was observed in serum and nasal fluid and was detected in an inhibition assay. Type 2 cytokines (IL-4, IL-5, and IL-13) and chemokines (CCL17/TARC, CCL5/RANTES [regulated upon activation, normal T-cell expressed and secreted]) in nasal fluid were inhibited in REGN1908-1909-treated patients compared with placebo (P < 0.05 for all); IL-13 and IL-5 concentrations correlated with Total Nasal Symptom Score improvement. Ex vivo assays demonstrated that REGN1908 and REGN1909 combined were more potent than each alone for inhibiting Fc epsilon RI- and Fc epsilon RII (CD23)-mediated allergic responses and subsequent T-cell activation. Conclusions: A single, passive-dose administration of Fel d 1-neutralizing IgG antibodies improved nasal symptoms in catallergic patients and was underscored by suppression of Fc epsilon RI-, Fc epsilon RII-, and T-helper cell type 2-mediated allergic responses.Keywords
This publication has 48 references indexed in Scilit:
- Systemic reactions associated with subcutaneous allergen immunotherapy: timing and risk assessmentAnnals of Allergy, Asthma & Immunology, 2011
- Burden of allergic rhinitis: Results from the Pediatric Allergies in America surveyJournal of Allergy and Clinical Immunology, 2009
- A follow-up study of immunotherapy-treated birch-allergic patients: effect on the expression of chemokines in the nasal mucosaClinical & Experimental Allergy, 2008
- The IgE-facilitated allergen binding (FAB) assay: Validation of a novel flow-cytometric based method for the detection of inhibitory antibody responsesJournal of Immunological Methods, 2006
- Allergen-specific immunotherapy with recombinant grass pollen allergensJournal of Allergy and Clinical Immunology, 2005
- Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivityJournal of Allergy and Clinical Immunology, 2005
- IL-13 induces eosinophil recruitment into the lung by an IL-5– and eotaxin-dependent mechanismJournal of Allergy and Clinical Immunology, 2001
- Symptom control in patients with hay fever in UK general practice: how well are we doing and is there a need for allergen immunotherapy?Clinical & Experimental Allergy, 1998
- Relationship between facilitated allergen presentation and the presence of allergen-specific IgE in serum of atopic patientsClinical and Experimental Immunology, 1995
- Immunotherapy with cat- and dog-dander extracts: IV. Effects of 2 years of treatmentJournal of Allergy and Clinical Immunology, 1989