Background: There is still great need to develop new strategies to improve the efficacy of allergen immunotherapies with optimal safety standards for patients. A new promising approach is to couple allergoids to mannan. The objective of this phase IIa/IIb study was to identify the optimal dose of mannan-conjugated birch pollen allergoids for the short-course treatment of birch pollen-induced allergic rhinoconjunctivitis.Methods: For this prospective, randomized, double-blind, placebo-controlled, dose-finding study, 246 birch pollen-allergic adults received 0.5 mL placebo or 1000, 3000 or 10,000 mTU/mL of mannan-conjugated birch pollen allergoids at five pre-seasonal visits. Efficacy was assessed by comparing allergic rhinoconjunctivitis symptoms and use of anti-allergic medication during the peak of the birch pollen season 2020. Immunologic, tolerability and safety effects were also analysed.Results: The highest dose of mannan-conjugated birch pollen allergoids reduced the combined symptom and medication score during the peak birch pollen season by a median of 24.7% compared to placebo. The production of Bet v 1 specific IgG4 significantly increased in a dose-dependent manner (3.6- and 4.5-fold) in the 3000 and 10,000 mTU/mL groups. The Bet v 1 specific IgE/IgG4 ratio was also strongly reduced (up to -70%). No fatalities nor serious adverse events were reported, and no adrenaline was used. In total, four systemic reactions occurred (two grade I and two grade II).Conclusion: All doses of mannan-conjugated birch pollen allergoids can be considered as safe. Since the application of 10,000 mTU/mL resulted in the highest efficacy, this dose qualifies for further investigation.

Background: Subcutaneous immunotherapy has emerged as an effective option for treating allergic diseases. Here, we assessed the clinical impact of the mannan‐conjugated birch pollen polymerized allergoid T502 in birch pollen‐induced allergic rhinoconjunctivitis. Methods: In this prospective, randomized, double‐blind placebo‐controlled phase III trial, 298 birch pollen–allergic adult patients were treated across 28 trial sites in Germany. Patients received either placebo or 23,000 mTU T502 subcutaneously over five pre‐seasonal visits. Efficacy was assessed by comparing the combined symptom and medication score (CSMS) between placebo and T502 during the peak birch pollen season 2022. Safety, tolerability and immunologic effects were also analyzed. Results: During the peak birch pollen season, the median CSMS of the T502 group was reduced by 33% ( p = 0.002) compared to placebo. The median daily symptom score and daily medication score were reduced by 30.4% ( p < 0.001) and 56.3% ( p = 0.045), respectively. Health related quality of life improved as reflected by reduction of RQLQ values by 31.5% ( p < 0.0001). Production of Bet v 1 sIgG4 and Bet v 1 sIgG increased up to 6.2‐fold and 3‐fold respectively in the T502 group ( p < 0.0001). The sIgE/sIgG4 ratio was strongly reduced in the T502 group at V7 (−62.9%, p < 0.0001). No fatalities nor serious adverse events were reported. In total, 16 systemic allergic reactions occurred (Grade I/II). Conclusions: Treatment with T502 significantly reduced symptoms and medication need in rhinoconjunctivitis patients. The treatment is well tolerated and safe.

Background: Rhinosinusitis is commonly treated with decongestants, analgesics, and local corticosteroids. Phytotherapeutics are also utilised for symptomatic relief, including cineole, the main component of eucalyptus oil. Methods: The current non-interventional, anonymised survey investigated quality of life in participants with rhinosinusitis (with or without additional symptoms of bronchitis) via the German version of a validated quality of life questionnaire (RhinoQol). Overall, 310 subjects administered a cineole preparation (Sinolpan) and 40 subjects applying nasal decongestant were recruited in German pharmacies. Results: Significant improvements in frequency (64.0%), bothersomeness (52.1%), and impact (53.9%) of rhinosinusitis symptoms were reported upon treatment with cineole over a mean treatment period of seven days (p < 0.001 each). The overall treatment efficacy of cineole was evaluated as good or very good by 90.0% of the participants, and the quality of life during work or leisure time improved upon treatment. Six (non-serious) possibly related side effects were reported in four participants who were administered cineole. The tolerability of the treatment was assessed as good or very good by 93.9% of the participants. Conclusions: Cineole can be considered as a safe and well-tolerated rhinosinusitis treatment conferring a clear improvement in quality of life outcomes.

Background: Mannan‐conjugated allergoids represent an effective option for treating allergic diseases. This study evaluated the clinical impact of the mannan‐conjugated, polymerised birch pollen allergoid EP‐088_T502 in patients with birch pollen‐induced allergic rhinoconjunctivitis over 3 years. Methods: Following up to a double‐blind, placebo‐controlled dose‐finding study, in this open, long‐term extension study, 154 birch pollen‐allergic patients were enrolled in Germany. Patients were treated with a cumulative dose of 48,000 mTU EP‐088_T502 administered subcutaneously over five pre‐seasonal visits in each of the two treatment years (2021, 2022) with a subsequent follow‐up year in 2023. The primary efficacy endpoint was the combined symptom and medication score (CSMS) during the peak birch pollen season, which was compared with the CSMS of the placebo group during the peak pollen season of 2020. Safety, tolerability, and immunogenicity were also analysed. Results: Compared to the placebo group of the preceding study, median CSMS during the peak birch pollen seasons showed reductions of 47.5% in 2021 ( p < 0.001), 51.8% in 2022 ( p < 0.001), and 36.5% in 2023 ( p < 0.001). Median daily symptom scores were reduced by 40.7% in 2021 ( p < 0.001), 40.7% in 2022 ( p < 0.001), and 25.6% in 2023 ( p < 0.010). Median daily medication scores reached 0.07 in 2021 and 0.04 in 2022 ( p < 0.001) and were reduced by 65.9% in 2023 ( p < 0.003). Immunological responses showed a 4.82‐fold increase in Bet v1 sIgG4 ( p = 0.001) and a marked decrease (−65.5%, p = 0.001) in the sIgE/sIgG4 ratio after the first treatment phase. EP‐088_T502 demonstrated good safety and tolerability, with only six mild to moderate systemic allergic reactions (Grade I/II). No epinephrine was used. Conclusion: In this open‐label study, two consecutive years of pre‐seasonal short‐course allergen immunotherapy (AIT) with EP‐088_T502 markedly reduced symptoms and medication need in patients with birch pollen‐induced rhinoconjunctivitis. Persistent therapeutic effects observed during the follow‐up year, although limited by attrition of the study population, suggest sustained clinical improvement and indicate the potential disease‐modifying impact of this treatment regimen.

Background/Objectives: Allergen immunotherapy (AIT) is the only disease-modifying treatment for grass pollen allergy. However, the proportion of patients interested in AIT who meet guideline-defined eligibility criteria remains unclear. This study aimed to characterise symptom burden, medication use, and AIT eligibility in adult patients with grass pollen allergy during the peak pollen season. Methods: In this multicentre, prospective, non-interventional epidemiological study, 479 adults with confirmed grass pollen allergy recorded daily nasal, ocular, and systemic symptoms, as well as anti-allergic medication use, via a validated electronic diary (CCC STUDY Diary) over a 30-day period in June/July 2025. A combined symptom-medication score (CSMS) was calculated daily, with a predefined threshold of ≥1.5 indicating clinically relevant symptom severity and potential eligibility for AIT. Both additive and weighted calculation approaches for CSMS and the daily medication score (dMS) were evaluated to assess methodological robustness and reproducibility. Results: The mean additive CSMS was 2.14, indicating moderate symptom burden. Overall, 63.3% of participants exceeded the CSMS threshold of 1.5 and were considered eligible for AIT. Sensitivity analyses demonstrated excellent concordance between additive and weighted CSMS/dMS calculations (Spearman’s ρ >0.98; p<0.001), and Bland–Altman analysis confirmed minimal bias (0.157) and narrow limits of agreement. Asthma was reported as a comorbidity in 36% of patients, generally associated with mild to moderate daily respiratory symptoms. Limitations included the self-reported nature of the data and a slightly reduced sample size; however, the results are representative of adult patients seeking care in specialised allergy centres in Germany. Conclusions: The CSMS also in its additive and therefore modernized form is a reliable, reproducible, and clinically meaningful tool for quantifying symptom severity and identifying patients suitable for AIT. Approximately two-thirds of adults interested in grass pollen AIT exhibited moderate to severe symptoms and were eligible for treatment according to current guideline recommendations.

Background/Objectives: The guideline on allergen-specific immunotherapy of the European Academy of Allergy and Clinical Immunology recommends subcutaneous allergen-specific immunotherapy for the treatment of allergic rhinitis in children and adults with moderate to severe symptoms. The five years cohort study described below was designed in 2020 to demonstrate non-inferiority in terms of safety, tolerability and efficacy in a paediatric population compared with adult patients treated with microcrystalline tyrosine-adsorbed allergoids for their tree and grass pollen allergy in a perennial setting. Here, we present the preliminary findings from the first year. Methods: The Combined Symptom and Medication Score was chosen as the primary endpoint of this therapy. Secondary endpoints include the Rhinoconjunctivitis Quality of Life Questionnaire, the retrospective Rhinoconjunctivitis score, the Asthma Control Test and the Rhinitis Control Test, as well as an analysis of adverse drug reactions. Results: A total number of 320 patients were enrolled into this study, with 129 of these patients in the age group between 5 and 17 years and 191 patients in the adult age group. Mean Combined Symptom and Medication Score values did not differ significantly between minors and adults in the first pollen season after treatment induction. The retrospective score showed a strong and significant reduction in rhinoconjunctivitis and asthma symptoms. Treatment was well tolerated, with more than 80% of patients reporting no adverse drug reactions. Conclusions: The validity of this study approach of a cohort study has been confirmed by this first interim analysis for the initial course of therapy in the first year.