Methods: Initially 202 subjects were randomised to 4 x 6nmol Cat-PAD 4 weeks apart, 8 x 3nmol Cat-PAD 2 weeks apart, or placebo and 89 subjects were recruited into a 1 year follow-on study (Patel et al 2013). 50 subjects who completed the 1 year follow-on, were recruited into a 2 year follow-on study without further dosing. EEC challenges at Baseline, 20 weeks, 1 and 2 years consisted of 4 consecutive days of 3 hours (h) of allergen exposure with Fel d 1 levels of circa 50 ng/m3 (representative of levels in houses with an indoor cat). The 4 day challenge was designed to ensure late phase responses were present in the nasal airway. Subjects scored Running nose; Sneezing; Blocked nose; Itchy nose on a scale of 0-3 every 30 minutes during the EEC challenge. These scores were combined to give a Total Nasal Symptom Score (TNSS) on a scale of 0-12. A post-hoc analysis was performed to identify the peak TNSS on each challenge day.
Results: The least squares (LS) mean TNSS was significantly lower (p <0.05) for 4 x 6nmol Cat-PAD vs placebo at the following EEC challenge: Day 1 at 2h and 2.5h; Day 2 at 2h, 2.5h and 3h; Day 3 at 1h, 1.5h, 2h, 2.5h and 3h. On Day 4 of EEC Challenge, when the cumulative allergen challenge is greatest and late phase responses in the nose are likely to be maximal, LS mean TNSS was significantly lower for 4x6nmol Cat-PAD vs placebo at 2h (4.818 vs 7.762, p=0.0090), 2.5h (5.091 vs 7.667, p=0.0290) and 3h (4.818 vs 7.952, p=0.0080) time points.
Conclusions: Treatment with 4 injections of 6nmol Cat-PAD over 12 weeks showed a substantial reduction in subjects’ TNSS that persisted two years after starting treatment. The treatment effect is substantial under conditions where late phase responses are expected to be present in the nasal airway. Cat-PAD is the first in a new exciting class of SPIREs and may confer long-term disease modification in chronic nasal airway disease due to cat allergy.