A high-dose, depigmented polymerized birch pollen extract for subcutaneous allergen immunotherapy has a favourable efficacy/safety ratio

Abstract

Background: Subcutaneous allergen immunotherapy (SCIT) with depigmented, polymerized (DPP) birch pollen extract has been marketed at doses of up to 1000 DPP units/mL since 2001. We sought to determine the dose-dependent efficacy of a DPP birch pollen extract formulation in patients suffering from birch-pollen-induced allergic rhinitis or rhinoconjunctivitis with or without intermittent asthma.

Methods: A titrated conjunctival provocation test (CPT) was applied as a surrogate marker. This Phase II randomized, double-blind, parallel-group, dose-ranging clinical trial was performed at 39 centres in Germany, Lithuania and Poland. After randomization to four dose-level groups (100, 1000, 5000 and 10,000 DPP units/mL) and up-dosing, participants received maintenance SCIT with five monthly subcutaneous injections. The primary endpoint was the proportion of patients in whom a higher concentration of birch pollen (vs. baseline) was needed to elicit a positive CPT.

Results: Three hundred forty-three patients were included (mean (range) age: 42.6 (19-70)). The highest CPT responder rates were seen in the higher dose-level groups. In the intention-to-treat analysis, the difference between the 100 and 10,000 groups was statistically significant (p = 0.0118). Although the proportion of patients with ≥1 treatment-emergent adverse events increased with the dose, almost all these events were mild (65.6%) or moderate (18.5%).

Conclusion: Judging by the results of a CPT, the efficacy/safety ratio in SCIT appears to be favourable for a high-dose-level preparation of a DPP birch pollen extract.

Keywords: allergen immunotherapy; allergic rhinoconjunctivitis; birch pollen allergy; conjunctival provocation test.

FIGURE 1

The patient disposition. ITT, intention‐to‐treat; PP, per‐protocol. *more than 1 reason per patient possible, ^aincluding 3 patients classified as dropouts, ^bincluding 4 patients classified as dropouts, ^cincluding 2 patients classified as dropouts, ^dincluding 3 patients classified as dropouts.