Grass pollen allergy immunotherapy(Stallergenes Greer Ltd.)

In Europe, allergen extracts are standardized based on skin prick wheal size in 20–30 allergic subjects. To understand the biological activity of clinically effective Sublingual immunotherapy, we used this method to determine the biological activity of solution and tablet Timothy grass pollen (TIM) extracts, compared to an FDA‐approved extract (Reference) of 10 000 BAU/ml. Blinded, quadruplicate skin prick tests with concentrate and three serial half‐log dilutions allowed the construction of a semilogarithmic regression line per extract. Bioequivalent allergy units (BAU) values were obtained from the comparison with reference. Extracts and dilutions showed a neat linear dose response (all: R2 > 0.98) in 33 rhinitis patients. Relative potencies: Staloral® 12 000 BAU/ml, Soluprick® 10 300 BAU/ml, Oralair® 8200 BAU, and Grazax® 6200 BAU. Even though all extract concentrates differed in wheal size (P = 0.01–0.001), Grazax® producing a 25% smaller wheal size than Oralair®, and the biological activity of these clinically effective TIM tablets led in the same range (6200–8200 BAU; 0.92–1.23 cm2). SLIT dose‐finding studies for other pollens might start with allergen extracts producing 1.1 cm2 wheal surface.

Allergoids are chemically modified allergen extracts administered to reduce allergenicity and to maintain immunogenicity. Oralair® (the 5‐grass tablet) is a sublingual native grass allergen tablet for pre‐ and co‐seasonal treatment. Based on a literature review, meta‐analysis, and cost‐effectiveness analysis the relative effects and costs of the 5‐grass tablet versus a mix of subcutaneous allergoid compounds for grass pollen allergic rhinoconjunctivitis were assessed.

A Markov model with a time horizon of nine years was used to assess the costs and effects of three‐year immunotherapy treatment. Relative efficacy expressed as standardized mean differences was estimated using an indirect comparison on symptom scores extracted from available clinical trials. The Rhinitis Symptom Utility Index (RSUI) was applied as a proxy to estimate utility values for symptom scores. Drug acquisition and other medical costs were derived from published sources as well as estimates for resource use, immunotherapy persistence, and occurrence of asthma. The analysis was executed from the German payer's perspective, which includes payments of the Statutory Health Insurance (SHI) and additional payments by insurants. Comprehensive deterministic and probabilistic sensitivity analyses and different scenarios were performed to test the uncertainty concerning the incremental model outcomes.

The applied model predicted a cost‐utility ratio of the 5‐grass tablet versus a market mix of injectable allergoid products of € 12,593 per QALY in the base case analysis. Predicted incremental costs and QALYs were € 458 (95% confidence interval, CI: € 220; € 739) and 0.036 (95% CI: 0.002; 0.078), respectively. Compared to the allergoid mix the probability of the 5‐grass tablet being the most cost‐effective treatment option was predicted to be 76% at a willingness‐to‐pay threshold of € 20,000. The results were most sensitive to changes in efficacy estimates, duration of the pollen season, and immunotherapy persistence rates.

This analysis suggests the sublingual native 5‐grass tablet to be cost‐effective relative to a mix of subcutaneous allergoid compounds. The robustness of these statements has been confirmed in extensive sensitivity and scenario analyses.