Treatment With Fel d 1 Derived Synthetic Peptide Immune-Regulatory Epitopes Results In a Persistent Treatment Effect On Symptoms Of Cat Allergy 2 Years After Treatment With 4 Doses 4 Weeks Apart

Background: Previously, we identified a series of synthetic peptides from the major cat allergen Fel d 1 and showed these were safe and well-tolerated when administered to cat allergic subjects (Worm et al., JACI 2011). Cat-peptide antigen desensitisation (Cat-PAD), the first in a new class of Synthetic Peptide Immuno-Regulatory Epitopes (SPIREs), showed a persistent treatment effect one year after the start of treatment in an Environmental Exposure Chamber (EEC) model of cat allergy (Patel et al., JACI 2013).  In the current study, we evaluated the persistence of the treatment effect (tolerance) in the EEC model, two years after the start of treatment with 4 injections of Cat-PAD over a 12 week period.

Methods: In the original study 202 subjects were randomised to placebo, 8 x 3nmol Cat-PAD 2-weeks apart or 4 x 6nmol Cat-PAD 4-weeks apart; subjects attended EEC challenge at baseline and 18-22 weeks after the start of dosing. 89 subjects were enrolled into a follow-on study without further dosing and attended an EEC challenge at one year. Of these 50 subjects returned for a further follow-on study for EEC challenge 100-104 weeks after the start of treatment.  The EEC challenge consisted of 4 consecutive days of 3-hour allergen exposures (Fel d 1  approx. 50ng/m³ selected to be representative of the levels of allergen found in homes with a resident cat). 4 nasal symptoms and 4 ocular symptoms were scored every 30 minutes, each on a scale of 0-3, and combined to give a Total Rhinoconjunctivitis Symptom Score (TRSS) on a scale of 0-24.

Results: Treatment with 4 x 6nmol Cat-PAD showed a mean change in the TRSS score at the two year EEC visit of -5.87 versus a change of -2.02 on placebo with the treatment effect being greatest at the end of the challenge on Day 4 when the cumulative allergen load was highest (p < 0.05, Cat-PAD vs. placebo). The treatment effect at the one year visit to the EEC was recalculated for the subjects who participated in the two year follow up (Cat-PAD -7.15; placebo -2.99) demonstrating the treatment effect had been maintained at the same magnitude during the two year follow-up.

Conclusions: Treatment with 4 injections of Cat-PAD over a 12 week period showed a substantial reduction in subjects’ cat allergy symptom scores in the EEC model that persisted two years after the start of treatment. Cat-PAD is the first in a new class of SPIREs and is a potentially exciting new approach to treating cat allergy.