Clinical Efficacy of One Short Course of Mannan-Conjugated Birch Pollen Allergoid Immunotherapy: A Comparative Evaluation After Prior Placebo Treatment

<b>Background/Objectives</b>: Allergen immunotherapy (AIT) with chemically modified allergoids represents a promising approach for the treatment of allergic rhinoconjunctivitis. This post hoc analysis investigated the clinical efficacy of a mannan-conjugated birch pollen allergoid (T502) by comparing outcomes in patients who received placebo in one pollen season and active treatment in the following year. <b>Methods</b>: Data were derived from four randomized clinical trials (EudraCT Numbers: 2018-002522-23, 2020-004126-32, 2021-002252-36, and 2022-004082-20) conducted over four consecutive years. Two independent patient groups were analyzed, with each group receiving placebo in the first year and subcutaneous T502 (10,000 mTU/mL) in the subsequent year. Daily symptom score (dSS), daily medication score (dMS), and combined symptom and medication score (CSMS) were assessed during the birch pollen season in April of each year. <b>Results</b>: In the first comparison between placebo in 2020 and an early treatment start in January 2021, treatment with T502 led to a 43.79% reduction in dSS (<i>p</i> ≤ 0.0001), a 71.43% reduction in dMS (<i>p</i> ≤ 0.001), and a 42.1% reduction in CSMS (<i>p</i> ≤ 0.001), all statistically significant. In the second comparison between placebo in 2022 and a late treatment start in March 2023, the reduction in dMS was 74.47% (<i>p</i> ≤ 0.001), whereas reductions in dSS (1.47%, <i>p</i> = 0.898) and CSMS (20.3%, <i>p</i> = 0.057) were not statistically significant. <b>Conclusions</b>: Subcutaneous immunotherapy (SCIT) with T502 significantly reduces allergic symptoms and medication use, particularly when all injections are completed before the onset of the birch pollen season in April. These findings highlight both the clinical value of T502 and the importance of optimized treatment timing.