title: Fel d 1-derived synthetic peptide immuno-regulatory epitopes show a long-term treatment effect in cat allergic subjects.
abstract: BACKGROUND
  Cat-PAD, the first in a new class of synthetic peptide immuno-regulatory epitopes (SPIREs), was shown to significantly improve rhinoconjunctivitis symptoms in subjects with cat allergy up to 1 year after the start of a short course of treatment.
  
  
  OBJECTIVE
  To evaluate the long-term effects of Cat-PAD on rhinoconjunctivitis symptoms following standardized allergen challenge 2 years after treatment.
  
  
  METHODS
  In a randomized, double-blind, placebo-controlled, parallel group study, subjects were exposed to cat allergen in an environmental exposure chamber (EEC) before and after treatment with two regimens of Cat-PAD (either eight doses of 3 nmol or four doses of 6 nmol) given intradermally over a 3-month period. In this follow-up study, changes from baseline in rhinoconjunctivitis symptoms were reassessed 2 years after the start of treatment.
  
  
  RESULTS
  The primary endpoint showed a mean reduction in total rhinoconjunctivitis symptom scores of 3.85 units in the 4 × 6 nmol Cat-PAD group compared to placebo 2 years after the start of treatment (P = 0.13), and this difference was statistically significant in the secondary endpoint at the end of day 4 when the cumulative allergen challenge was greatest (P = 0.02). Consistent reductions in nasal symptoms of between 2 and 3 units were observed for 4 × 6 nmol Cat-PAD compared to placebo between the 2 and 3 h time points on days 1-4 of EEC challenge at 2 years (P < 0.05). The 8 × 3 nmol dose did not show a meaningful effect in this study.
  
  
  CONCLUSIONS
  A persistent, clinically meaningful reduction in rhinoconjunctivitis symptoms was observed on EEC challenge 2 years after the start of a short course of treatment with 4 × 6 nmol Cat-PAD. This study is the first to provide evidence of a long-term therapeutic effect with this new class of SPIREs.
authors.affiliation: Cetero Research, Mississauga, ON, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Couroux
authors.affiliation: Cetero Research, Mississauga, ON, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Patel
authors.affiliation: Adiga Life Sciences Inc., Hamilton, ON, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Armstrong
authors.affiliation: Clinical Immunology & Allergy and Respirology Divisions, Department of Medicine and Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Larché
authors.affiliation: Circassia Limited, Oxford, UK.
authors.forename: R P
authors.initials: RP
authors.lastname: Hafner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D002415:Cats; D003233:Conjunctivitis, Allergic / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D003888:Desensitization, Immunologic / Q000009:adverse effects; D000939:Epitopes / Q000008:administration & dosage* / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000276:immunology*; D065631:Rhinitis, Allergic / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000485:Allergens; D000939:Epitopes; D006023:Glycoproteins; D010455:Peptides; C059296:Fel d 1 protein, Felis domesticus
keywords: Fel d 1; SPIREs; T-cell epitopes; allergic rhinitis; allergic rhinoconjunctivitis; cat allergy; immune tolerance; immunotherapy; persistence