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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. [ABSTRACT FROM AUTHOR]

Background: The European Academy of Allergy and Clinical Immunology recommended the Combined Symptom and Medication Score (CSMS) as primary endpoint in clinical trials on allergen‐specific immunotherapy (AIT) in allergic rhinoconjunctivitis. Here, the correlation between the CSMS and the validated standardised Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)), Rhinitis Control Assessment Test (RCAT) and Visual Analogue Scale (VAS) was analysed. Methods: Two prospective, multicentre, non‐interventional studies on tree pollen, grass pollen and house dust mite allergic patients were performed. The first study comprised 167 patients receiving AIT (AIT population), and the second included 56 patients treated with symptomatic medication only (control population). For up to two seasons (pollen)/exposure periods (house dust mites), participants documented their symptoms and medication intake in a CSMS diary, including VAS. In addition, the standardised RQLQ(S) and the RCAT were completed during study visits. Results: Comparison between CSMS and RQLQ(S) revealed a positive correlation in the AIT population (r = 0.426) and in the control population (r = 0.569). For CSMS and RCAT, a negative correlation with r = −0.409 (AIT) and r = −0.547 (control) was shown. Positive correlation between CSMS and VAS was also demonstrated with r = 0.585 (AIT) and r = 0.563 (control). Conclusion: These results support the assumption that the CSMS correlates with quality of life, symptom severity and symptom control on the one hand, while the moderate strength of correlations on the other hand mirrors distinctions of the CSMS compared to the assessments used here. [ABSTRACT FROM AUTHOR]

Background: The World Allergy Organization and the European Academy of Allergy and Clinical Immunology recommend to perform product‐specific meta‐analyses for allergen‐specific immunotherapies because of the high degree of heterogeneity between individual products. This meta‐analysis evaluates the efficacy and safety of Glutaraldehyde‐modified and MCT® (MicroCrystalline Tyrosine)‐adsorbed allergoids (MATA). Methods: The databases MEDLINE, LILACS, embase, LIVIVO, Web of Science and Google (Scholar) were searched for publications on MATA up to June 2019. Primary endpoint was the combined symptom and medication score (CSMS). Secondary endpoints were single scores, immunogenicity and improvement of allergic condition. Secondary safety endpoints were the occurrence of side effects. A random effects model was applied with (standardized) mean differences ([S]MDs) including confidence intervals (CI). Heterogeneity was analyzed using the I2 index and publication bias using Egger's test and Funnel plots. Subgroups were analyzed regarding age and asthma status. Results: Eight randomized double‐blind placebo‐controlled trials were selected for efficacy and 43 publications for safety analysis. In total, 4531 patients were included in this analysis including eight studies containing data on children and adolescents. AIT with MATA significantly reduced allergic symptoms and medication use with a SMD for CSMS of −0.8 (CI: −1.24, −0.36) in comparison to placebo. Heterogeneity was moderate between the studies. The total symptom score (−1.2 [CI: −2.11, −0.29]) and the total medication score (−2.2 [CI: −3.65, −0.74]) were also significantly reduced after MATA treatment. Patient's condition improved significantly after treatment with MATA, with an odds ratio of 3.05 (CI: 1.90, 4.90) when compared to placebo. The proportion of patients, who developed side effects was 38% (CI: 19%, 57%). No serious side effects occurred. Safety in the subgroups of asthmatic patients, children and adolescents did not differ from the overall patient population. Conclusions: This meta‐analysis reveals a large body of evidence from publications investigating MATA. MATA significantly improved allergic symptoms and reduced the use of anti‐allergic medication in comparison to placebo, with an excellent safety profile. Especially for children and asthmatic patients, the use of MATAs can be considered as safe, because the safety profiles in these groups did not differ from the total patient population. [ABSTRACT FROM AUTHOR]

One patient experienced aggravated rhinoconjunctivitis symptoms because of increasing pollen load at the onset of the season and hence discontinued AIT at day 8. In this first-in-patient study, we demonstrate that the administration of a carbamylated monomeric tree pollen allergoid escalated to a maximal daily dose of 50 000 UA is safe and well tolerated in patients with birch pollen-induced allergic rhinoconjunctivitis. In conclusion, this early phase clinical dose escalation study has successfully demonstrated the safety and feasibility of this sublingual allergen immunotherapy with the carbamylated monomeric tree pollen allergoid up to a dose of 50 000 UA per day. [Extracted from the article]

Background Methods Results Conclusions 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.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.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).Treatment with T502 significantly reduced symptoms and medication need in rhinoconjunctivitis patients. The treatment is well tolerated and safe. [ABSTRACT FROM AUTHOR]

Background: Double-blind, placebo-controlled trials (DBPCTs) have confirmed the efficacy of allergen-specific immunotherapy (AIT) with depigmented-polymerized allergen extracts (DPAEs). This systematic review evaluates the efficacy of AIT using different allergens in different severity stages of rhinoconjunctivitis with or without asthma in the pollen studies and asthma and rhinitis in the house dust mite studies in comparison to placebo. Methods: We used MEDLINE, Embase, CENTRAL and LILACS databases to review DBPCTs published until July 2016. The combined symptom and medication score (cSMS) served as primary endpoint. The total rhinoconjunctivitis symptom score (RCSS) and total score in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were secondary efficacy endpoints. Solicited local and systemic adverse events were secondary safety endpoints. We assumed a random effects model with standardized mean differences (SMDs) or mean differences as summary statistics. In a subgroup analysis, we classified the studies following the GINA (Global Initiative for Asthma) and ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines for rhinoconjunctivitis and asthma severity. Results: Six DBPCTs in pollen and 2 trials in house dust mites (HDM) were selected. Patients (N = 915) with intermittent or mild persistent asthma were included in 3 (37.5%) and 5 (62.5%) trials, respectively. Two (25%) HDM studies included patients with moderate persistent asthma, 4 trials patients with moderate-to-severe rhinoconjunctivitis. Treatment periods ranged from 12 to 24 months. AIT with DPAEs yielded significantly lower cSMS (SMD: 1.9, 95% CI: 0.9–2.8) and RQLQ (SMD: 0.3, 95% CI: 0.1–0.5) values than did placebo. An exploratory analysis of cSMS and RCSS suggested that the efficacy of AIT treatment with DPAEs was higher in trials including patients with more severe rhinoconjunctivitis and asthma. A publication bias was not detected. Heterogeneity between individual studies was explained by differences in severity. Patients receiving DPAEs did not experience a significantly higher risk of local (OR: 1.55, 95% CI: 0.86–2.79) or systemic reactions (OR: 1.94, 95% CI: 0.98–3.84). Conclusions: Compared to placebo, AIT with DPAEs is effective in patients with pollen- or HDM-induced rhinoconjunctivitis with or without allergic asthma and improves health-related quality of life. It does not differ significantly in safety and tolerability. [ABSTRACT FROM AUTHOR]

Background: Clinical practice needs a common parameter that can provide an early, reliable estimation of the outcome of sublingual immunotherapy (SLIT) in an upcoming pollen season. We investigated whether the conjunctival provocation test (CPT) can predict the beneficial outcome of SLIT in patients with allergic rhinoconjunctivitis after 4 weeks of treatment. Methods: We conducted two separate prospective, randomized, double-blind, placebo-controlled, multicenter trials. Adults 18–75 years of age received placebo or SLIT tablets containing tree or grass pollen allergoids and underwent CPTs. Participants receiving SLIT were divided into two groups (reactive, nonreactive) according to their CPT reactions after 4 weeks of treatment. These two groups were compared with regard to clinical outcome parameters (total combined score, rhinoconjunctivitis total symptom score, total rescue medication score, well days) assessed during the pollen season for the 14-day (tree) or 30-day (tree/grass) peaks and for the entire 60-day seasons. Participants' global evaluations of therapy after completing treatment were also compared. Results: The tree pollen trial randomized 188 participants; 182 participants were evaluable, 76 of whom received SLIT and were suitable for this post hoc analysis. The grass pollen trial included 90 participants; 82 participants were evaluable, 44 of whom underwent SLIT. Comparing SLIT participants who reacted to the CPT after 4 weeks (tree: 77.6%; grass: 79.5%) with those who ceased to show a reaction (tree: 22.4%; grass: 20.5%) (tree: P = 0.0001; grass: P = 0.003), the total combined score for the 14-day (P = 0.017) and 30-day peaks (P = 0.042) as well as the rhinoconjunctivitis total symptom score assessed for the 14-day peak (P = 0.024) were significantly lower in the nonreactive group of the tree pollen trial. In the grass pollen trial, the nonreactive group rated their SLIT treatment significantly better (P = 0.019). Conclusions: Using clinically meaningful outcome parameters during the pollen season, both trials independently led to similar results when comparing participants' reactions to the CPT 4 weeks after beginning SLIT. These results suggest that CPT allows an early estimation of allergic rhinoconjunctivitis symptoms before an upcoming season. Thus, the CPT can be used as a valuable parameter to predict the beneficial outcome of ongoing SLIT. Trial registration: Both trials registered with the Medical Ethics Committee of the North Rhine Medical Council (EudraCT numbers 2012-004916-79 (grass pollen trial) and 2013-002129-43 (tree pollen trial)) and the German Federal Ministry of Health (Paul-Ehrlich-Institut). [ABSTRACT FROM AUTHOR]