Persistence of the clinical effect of grass allergen peptide immunotherapy after the second and third grass pollen seasons.

BACKGROUND: Grass allergen peptides are in development for the treatment of grass pollen-induced allergic rhinoconjunctivitis. A previous randomized, placebo-controlled study demonstrated that grass allergen peptides significantly improved total rhinoconjunctivitis symptom scores (TRSSs) after posttreatment challenge (PTC) to rye grass in an environmental exposure unit after 1 intervening grass pollen season (GPS1). OBJECTIVE: We sought to evaluate the efficacy/safety of 4 dosing regimens of grass allergen peptides after a second (GPS2) and third (GPS3) intervening GPS in the environmental exposure unit. METHODS: Eligible subjects who were randomized in the parent study (GPS1) during the first year of recruitment were invited to participate in GPS2 and GPS3, which took place 1 and 2 years after treatment cessation, respectively. Participants were not treated further, and both participants and study personnel remained blinded. The primary efficacy end point was the change in mean TRSS (reported every 30 minutes) from GPS1 baseline to the follow-up PTC calculated across all time points over days 2 to 4 for GPS2 and across hours 1 to 3 over days 2 to 4 for GPS3. Secondary efficacy end points and safety were also assessed. RESULTS: One hundred twenty-two and 85 participants were enrolled in GPS2 and GPS3, respectively. A numerically greater, but not statistically significant improvement from baseline in mean TRSS at PTC was observed in the group receiving one 6-nmol intradermal injection every 2 weeks for 14 weeks group compared with the placebo at GPS2 (-6.0 vs -3.6, P = .0535) and GPS3 (-6.2 vs -3.6, P = .1128). Similar findings were observed for the group receiving one 6-nmol intradermal injection every 2 weeks for 14 weeks at GPS3 (-6.4 vs -3.6, P = .0759). No adverse safety signals were detected. CONCLUSION: Treatment with grass allergen peptides led to an improvement in allergic rhinoconjunctivitis symptoms after 3 intervening GPSs, corresponding to up to 2 years off treatment.

Treatment with grass allergen peptides improves symptoms of grass pollen-induced allergic rhinoconjunctivitis.

BACKGROUND: Synthetic peptide immunoregulatory epitopes are a new class of immunotherapy to treat allergic rhinoconjunctivitis (ARC). Grass allergen peptides, comprising 7 synthetic T-cell epitopes derived from Cyn d 1, Lol p 5, Dac g 5, Hol l 5, and Phl p 5, is investigated for treatment of grass pollen-induced ARC. OBJECTIVE: We sought to evaluate the efficacy, safety, and tolerability of intradermally administered grass allergen peptides. METHODS: A multicenter, randomized, double-blind, placebo-controlled study evaluated 3 regimens of grass allergen peptides versus placebo in patients with grass pollen-induced allergy (18-65 years). After a 4-day baseline challenge to rye grass in the environmental exposure unit (EEU), subjects were randomized to receive grass allergen peptides at 6 nmol at 2-week intervals for a total of 8 doses (8x6Q2W), grass allergen peptides at 12 nmol at 4-week intervals for a total of 4 doses (4x12Q4W), or grass allergen peptides at 12 nmol at 2-week intervals for a total of 8 doses (8x12Q2W) or placebo and treated before the grass pollen season. The primary efficacy end point was change from baseline in total rhinoconjunctivitis symptom score across days 2 to 4 of a 4-day posttreatment challenge (PTC) in the EEU after the grass pollen season. Secondary efficacy end points and safety were also assessed. RESULTS: Two hundred eighty-two subjects were randomized. Significantly greater improvement (reduction of total rhinoconjunctivitis symptom score from baseline to PTC) occurred across days 2 to 4 with grass allergen peptide 8x6Q2W versus placebo (-5.4 vs -3.8, respectively; P = .0346). Greater improvement at PTC also occurred for grass allergen peptide 8x6Q2W versus placebo (P = .0403) in patients with more symptomatic ARC. No safety signals were detected. CONCLUSION: Grass allergen peptide 8x6Q2W significantly improved ARC symptoms after rye grass allergen challenge in an EEU with an acceptable safety profile.

Comparative efficacy of cetirizine and fexofenadine for seasonal allergic rhinitis, 5-12 hours postdose, in the environmental exposure unit.

In a previous study, cetirizine and fexofenadine similarly relieved seasonal allergic rhinitis symptoms in the first 5 hours, but cetirizine was more effective at 21-24 hours postdose. This randomized, double-blind, placebo-controlled study compared the response to treatment between 5 and 12 hours. Eligible ragweed allergic subjects were exposed to pollen in the Environmental Exposure Unit and randomized (n = 599) to a single dose of cetirizine, 10 mg; fexofenadine, 180 mg; or placebo (2.5:2.5:1). The primary efficacy end point was the change from baseline in total symptom severity complex (TSSC) score at 12 hours postdose. TSSC score was the sum of self-rated scores (0 = absent to 3 = severe) for runny nose, sneezing, itchy nose/palate/throat, and itchy/watery eyes, recorded half-hourly. Mean baseline TSSC scores were similar: 9.2, cetirizine and fexofenadine; 8.9, placebo. Reductions in TSSC scores from baseline were 4.3 at 12 hours and 5.0 overall (i.e., average over 5-12 hours postdose) for cetirizine and 3.4 and 4.4, respectively, for fexofenadine. Cetirizine produced a 26% greater reduction in TSSC at 12 hours (p = 0.001) and 14% greater reduction in TSSC overall (p = 0.006) compared with fexofenadine. Cetirizine and fexofenadine reduced TSSC scores (p < 0.001) and individual symptoms (p < 0.05) more than placebo. However, cetirizine was more effective than fexofenadine (p < 0.05) for runny nose and sneezing (12 hours and overall), itchy/watery eyes (12 hours), and itchy nose/throat/palate (overall). Incidence of treatment-emergent adverse events and somnolence were similar among groups: cetirizine, 25.3 and 0.8%, respectively; fexofenadine, 29.6 and 0%, respectively; placebo, 35.0 and 0%, respectively. In conclusion, cetirizine produced greater relief of seasonal allergic rhinitis symptoms than fexofenadine at 12 hours postdose and over the 5- to 12-hour postdose period.