SCIT with a high-dose house dust mite allergoid is well tolerated: safety data from pooled clinical trials and more than 10 years of daily practice analyzed in different subgroups.

BACKGROUND: Efficacy of house dust mite (HDM) allergen immunotherapy (AIT) in allergic rhinitis and controlled allergic asthma has been documented in controlled trials with adults and children. However, tolerability comparing clinical development and post marketing data, particularly in different subgroups, is missing. METHODS: We performed an analysis of pooled safety data for subcutaneous AIT (SCIT) with a high-dose house dust mite allergoid from 6 randomized, controlled trials (RCT) in HDM allergic respiratory disease (ARD) and of post marketing safety data from more than 10 years including different subgroups (age, gender, asthma status). RESULTS: In all, 500 patients with ARD were treated in RCTs: 279 received the marketed dose of 1800 protein nitrogen units (PNU) high-dose HDM allergoid AIT (214 double-blind placebo controlled [HDM-DBPC], 65 children/adolescents usual care controlled [HDM-RCT(UC)]), and 221 placebo (PL). 38.8% adverse events (AEs) were observed with 1800 PNU in HDM-DBPC (31.2% PL, 35.5% HDM-ALL [1800 PNU]); the difference was primarily because of local reactions; there was no difference in systemic reactions (10.9% PL, 11.2% HDM-DBPC, 11.2% HDM-ALL); one out of 279 high-dose HDM allergoid-treated patients had a serious adverse event (SAE).Children (n = 39)/adolescents (n = 26) had fewer related AEs and local reactions compared to adults; systemic reactions: children 12.8%, adults 11.2% adolescents 7.7%. Females had slightly more AEs. Treatment was well tolerated in asthmatic patients (n = 267; GINA I n = 32, II n = 104, III n = 17, 114 no classification).In more than 10 years more than 100,000 patients were treated with high-dose HDM allergoid (1800 PNU) under daily practice conditions. Adverse drug reactions (ADRs) were reported in 0.5% of patients. 94.6% of these ADRs were expected. CONCLUSION: SCIT with the marketed dose of high-dose HDM allergoid was well tolerated in clinical development and in daily practice. There was no increased risk for the investigated patient subgroups. Tolerability was comparable to HDM sublingual immunotherapy (SLIT) tablets.

Patients' compliance with different administration routes for allergen immunotherapy in Germany.

BACKGROUND: Allergen immunotherapy (AIT) is the practice of administering gradually increasing quantities of an allergen extract to an allergic subject to ameliorate the symptoms associated with the subsequent exposure to the causative allergen. It is the only treatment that may alter the natural course of allergic diseases. According to AIT guidelines and summary of product characteristics (SmPCs), the treatment should be carried out for at least 3 years. It is controversially discussed whether subcutaneous or sublingual administration routes cause higher patients' compliance. METHODS: German sales data for different preparations of the allergen manufacturer Allergopharma GmbH & Co. KG were retrospectively evaluated for 5 consecutive years, based on prescriptions per patient: pollen sublingual immunotherapy (SLIT) and high-dose hypoallergenic (allergoid) or unmodified depot pollen and mite preparations for subcutaneous immunotherapy (SCIT). To identify patients' compliance, "completed treatment years" were determined. A completed treatment year was defined by the required number of prescribed allergen preparations according to the recommended dosage scheme given in the respective SmPCs. RESULTS: Prescription data of 85,241 patients receiving pollen or mite SCIT and 706 patients receiving pollen SLIT were included in this analysis. Patients' compliance for at least 3 treatment years with high-dose hypoallergenic pollen SCIT was higher when administered perennially (60%) compared to preseasonally (27%). Prescriptions for at least 3 years were received from 42% of patients with pollen SCIT and from 45% of patients with mite SCIT. Compliance with SLIT was lowest with only 16% of patients receiving prescriptions for at least 3 treatment years. Children and adolescents were more compliant than adults, independent of whether they received SLIT or SCIT. CONCLUSION: In general, patients' compliance with SCIT using high-dose hypoallergenic or unmodified depot preparations was higher than with pollen SLIT. Perennial application of SCIT seems to increase compliance in comparison to the preseasonal application. Children and adolescents were most compliant, independent of the preparation applied.

Influence of subcutaneous specific immunotherapy on drug costs in children suffering from allergic asthma.

BACKGROUND: Subcutaneous specific immunotherapy (SCIT) is an effective treatment attenuating the progression of allergic asthma. To date, there is a lack of studies investigating the economic consequences of SCIT on health care expenditures. METHODS: A health-economic piggy-back analysis of SCIT was conducted based on a RCT that enrolled 65 children and adolescents with allergic asthma. Patients were allocated into two groups: A group receiving SCIT with a high-dose hypoallergenic house dust mite preparation plus asthma medication and a control group receiving only asthma medication. For both groups asthma control was achieved before the start of the SCIT treatment and was maintained during the study. Both, costs and cost-effectiveness of SCIT with the high-dose hypoallergenic house dust mite preparation were investigated based on total medication costs, incremental medication costs and treatment effects (measured as lung function), respectively. A bootstrap analysis was performed to validate the results. RESULTS: A steady decline in medication costs could be observed in the SCIT group one year after treatment start compared to the control group. This cost trend became statistically significant 3 years after SCIT started. The calculated potential savings in the SCIT group correlated with an improved lung function. The distribution of the bootstrap results revealed that the probability of SCIT having a superior effectiveness compared to the control group is around 90%. CONCLUSION: SCIT with a high-dose hypoallergenic preparation received by children and adolescents suffering from mite induced allergic asthma reduces the allergic medication intake and has cost-saving effects. Additional costs associated with SCIT may be completely compensated by drug cost savings 4 years after end of SCIT. Additionally, SCIT is superior compared to routine care as measured by the lung function that improved in SCIT-treated patients. TRIAL REGISTRATION: (EudraCT no. 2004 - 003892 - 35).