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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01923779 NCT02292875.

Keywords: Allergic rhinoconjunctivitis; allergen challenge; allergic rhinitis; environmental exposure unit; grass; immunotherapy; peptide; synthetic peptide immunoregulatory epitope.