Dose-response relationship of a new Timothy grass pollen allergoid in comparison to a 6-grass pollen allergoid Condensed title for a running head : Dose-response relationship of a Timothy grass pollen allergoid

Background: Subcutaneous allergen immunotherapy with grass pollen allergoids has been proven to be effective and safe in the treatment of patients with allergic rhinoconjunctivitis. Based on the extensive cross-reactivity among Pooideae species, it has been suggested that grass pollen extracts could be prepared from a single species, rather than from a multiple species mixture. Objective: To find the optimal dose of a Phleum pratense allergoid preparation and compare its efficacy and safety to a 6-grass pollen allergoid preparation. Methods: In this double-blind, placebo-controlled study (EudraCT: 2011-000674-58), 3 doses of Phleum pratense allergoid (1800 Therapeutic Units (TU), standard dose 6000 TU, and 18000 TU) were compared with placebo and the marketed 6-grass pollen allergoid (6000 TU). In a preseasonal dosing regimen, 102 patients were randomized to 5 treatment groups and received 9 subcutaneous injections. The primary efficacy endpoint was the change in wheal size (late phase reaction, LPR) in response to the intracutaneous testing (ICT) before and after treatment, comparing the active allergoids to placebo. Secondary outcomes were the change in Total Nasal Symptom Score (TNSS) assessed in the allergen exposure chamber (AEC), the changes in Phleum pratense-serum specific IgG4, and the incidence of adverse events (AEs). Results: All 3 doses of the Phleum pratense and the 6-grass pollen allergoid preparations were significantly superior to placebo for the primary outcome, whereas there were no significant differences in the change in TNSS. Compared to the standard dose, the high dose of Phleum pratense did not produce any additional significant benefit, but showed a slight increase in AEs. Yet this increase in AEs was lower than for the 6-grass pollen preparation. Conclusions & Clinical Relevance: The standard dose of the new Phleum pratense allergoid was comparable to the marketed 6-grass pollen preparation at equal dose for the parameters measured.