Efficacy of 2 months of allergen-specific immunotherapy with Bet v 1–derived contiguous overlapping peptides in patients with allergic rhinoconjunctivitis: Results of a phase IIb study

• Published in: Journal of allergy and clinical immunology Vol. 138; no. 1; pp. 162 - 168
• Main Authors: Spertini, François, MD, DellaCorte, Gilles, MD, Kettner, Alexander, PhD, de Blay, Frédéric, MD, PhD, Jacobsen, Lars, PhD, Jutel, Marek, MD, Worm, Margitta, MD, Charlon, Vincent, PhD, Reymond, Christophe, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2016; Elsevier Limited
• Subjects: Adolescent; Adult; Allergen-specific immunotherapy; Allergens - administration & dosage; Allergens - immunology; Allergies; Allergy and Immunology; Aluminum; aluminum hydroxide; Antigens, Plant - administration & dosage; Antigens, Plant - immunology; Bet v 1; birch pollen allergy; clinical trial; Conjunctivitis, Allergic - immunology; Conjunctivitis, Allergic - physiopathology; Conjunctivitis, Allergic - therapy; contiguous overlapping peptides; desensitization; Desensitization, Immunologic - adverse effects; Desensitization, Immunologic - methods; Female; Humans; IgE; IgG4; Immunoglobulin E - immunology; Immunoglobulin G - immunology; Immunotherapy; Investigations; Male; Middle Aged; Otolaryngology; Peptides; Peptides - administration & dosage; Peptides - immunology; Quality of life; Respiratory Function Tests; Rhinitis, Allergic - immunology; Rhinitis, Allergic - physiopathology; Rhinitis, Allergic - therapy; synthetic peptides; Treatment Outcome; Young Adult; Poland; Denmark; Latvia; Sweden; Switzerland; RSMS; Nighttime nasal symptom score; Contiguous overlapping peptide; NNSS; WAO; IgE; LS; Confidence limit; mITT; World Allergy Organization; ANCOVA; Rhinoconjunctivitis symptom and medication score; aluminum hydroxide; Mini Rhinoconjunctivitis Quality-of-Life Questionnaire; contiguous overlapping peptides; Serious adverse event; birch pollen allergy; clinical trial; Rhinoconjunctivitis symptom score; AE; Analysis of covariance; COP; Modified intent-to-treat; Adverse event; IgG 4; CL; AIT; desensitization; RSS; Allergen-specific immunotherapy; Rhinoconjunctivitis medication score; SAE; Least squares; MiniRQLQ; synthetic peptides; RMS; Bet v 1; IgG4; IgG
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2016.02.044

Background An immunotherapy formulation consisting of 3 contiguous overlapping peptides (COPs) derived from Bet v 1, the major birch pollen allergen, showed good clinical tolerability in a previous phase I/IIa clinical trial. Objectives We sought to evaluate the efficacy and safety of allergen-specific immunotherapy using 2 dose regimens of Bet v 1 COPs versus placebo in subjects with birch pollen–induced allergic rhinoconjunctivitis. Methods A randomized, double-blind, placebo-controlled phase IIb clinical trial was performed to assess the efficacy of Bet v 1 COP immunotherapy during the 2013 birch pollen season. Before the season, Bet v 1 COPs (50 and 100 μg in aluminum hydroxide) or placebo (saline and aluminum hydroxide) were administered as 5 subcutaneous injections to 239 adults with allergic rhinoconjunctivitis to birch pollen. Bet v 1 COPs at 25 or 50 μg were administered on day 1, and 50 or 100 μg was administered on days 8, 15, 29, and 57, respectively. Patients were monitored for adverse events during the treatment period and assessed for combined rhinoconjunctivitis symptom and medication scores, as well as quality of life. Results Rhinoconjunctivitis symptom and medication scores improved in both Bet v 1 COP–treated groups, reaching statistical significance over placebo in the 50-μg group (least squares mean, −0.23; 26% improvement; P  = .015). Both active groups showed significant improvement in quality of life and nighttime nasal symptom scores, supporting the primary end point findings. Bet v 1 COP injections were well tolerated, with a higher frequency of systemic adverse events in the 100-μg group. Conclusion Two months of preseasonal immunotherapy with 3 COPs derived from Bet v 1 at a 50-μg dose showed promising efficacy, small risk for systemic reactions, and immunomodulatory changes in this single-season, dose-finding, phase IIb trial in patients allergic to birch pollen.