Sublingual Immunotherapy with House Dust Extract for House Dust-Mite Allergic Rhinitis in Children

Background: House dust extract is used in conventional immunotherapy for house dust-mite (HDM) allergic rhinitis in Japan. However, an alternative administration route is desired. The aims of the present double blind, placebo-controlled trial were to evaluate the therapeutic efficacy and safety of sublingual immunotherapy (SLIT) with house dust extract in pediatric patients with HDM allergic rhinitis. Methods: The study population comprised 31 subjects (21 males and 10 females) aged from 7 to 15 years old. Twenty patients (the active group) received house dust extract and 11 received placebo via sublingual administration. Extract or placebo (1 ml) was administered at 10-fold dilution once weekly for 40 weeks. During the study period, the subjects recorded their daily nasal symptoms and use (dose and frequency) of other medications in a nasal allergy diary. Results: The symptom scores in the active group began to decrease about 24 weeks after initiation of treatment and significant differences between the active and placebo groups were observed after 30 weeks. The average scores for the last four weeks of the study were significantly lower than those for the first four weeks in the active group but not in the placebo group. The only local adverse effect was a bitter taste reported by one patient. There were no other local or systemic adverse effects associated with SLIT. Conclusions: Our results suggest that SLIT with house dust extract for more than 30 weeks is safe and effective treatment for HDM allergic rhinitis in children

Long-term safety, efficacy, pharmacokinetics and pharmacodynamics of omalizumab in children with severe uncontrolled asthma

Background: Omalizumab is effective and well-tolerated in children with moderate to severe allergic asthma. However, the effects of long-term treatment with omalizumab in this population haven't been well investigated. The objective of this study is to evaluate the long-term safety, efficacy, pharmacokinetics and pharmacodynamics of omalizumab in children with uncontrolled severe asthma. Methods: Thirty-eight Japanese children (aged 7–16 years) who completed the 24-week treatment core study were included in an uncontrolled extension study, in which treatment with omalizumab continued until the pediatric indication was approved in Japan (ClinicalTrials.gov number: NCT01328886). Results: Thirty-five patients (92.1%) completed the extension study. The median exposure throughout the core and extension studies was 116.6 weeks (range, 46.9–151.1 weeks). The most common adverse events were nasopharyngitis, influenza, upper respiratory tract infection, and asthma. Serious adverse events developed in 10 patients (26.3%), but resolved completely with additional treatments. Incidence of adverse events didn't increase with extended exposure with omalizumab. Twenty-nine patients (76.3%) achieved completely- or well-controlled asthma compared with 9 patients (23.7%) at the start of the extension study. QOL scores, the rates (per year) of hospitalizations and ER visits were significantly improved compared with the baseline of the core study [39.0 vs 48.0 (median), p < 0.001 for QOL, 1.33 vs 0.16, p < 0.001 for hospitalization, 0.68 vs 0.15, p = 0.002 for ER visits]. Remarkably, the mean total IgE level showed a decreasing trend while exposure to omalizumab remained at steady-state. Conclusions: Long-term treatment with omalizumab is well-tolerated and effective in children with uncontrolled severe allergic asthma. No new safety findings were identified

Omalizumab in Japanese children with severe allergic asthma uncontrolled with standard therapy

AbstractBackgroundOmalizumab has demonstrated clinical benefits in children with moderate to severe allergic asthma. However, no studies have been performed in Japanese asthmatic children. The aim of this study was to evaluate the efficacy including free IgE suppression and safety of omalizumab in Japanese children with severe allergic asthma. The primary objective was to examine whether omalizumab decreases serum free IgE levels to less than 25 ng/ml (target level of suppression).MethodsThirty-eight Japanese children (6–15 years) with uncontrolled severe allergic asthma despite inhaled corticosteroids (>200 μg/day fluticasone propionate or equivalent) and two or more controller therapies received add-on treatment with omalizumab in a 24-week, multicenter, uncontrolled, open-label study.ResultsThe geometric mean serum free IgE level at 24 weeks was 15.6 ng/mL. Compared with baseline, total asthma symptom scores, daily activity scores and nocturnal sleep scores at 24 weeks were significantly improved. The rates of asthma exacerbation and hospitalization due to asthma were reduced by 69.2% and 78.2%, respectively (p < 0.001), versus baseline. Quality-of-life scores were also significantly improved (p < 0.001). In addition, 11 (28.9%) patients reduced the dose of any asthma controller medications. Thirty-six (94.7%) patients experienced at least one adverse event during the treatment period. All adverse events were mild or moderate in severity and no new safety concerns were detected. No patients discontinued the study.ConclusionsIn Japanese children with severe allergic asthma, omalizumab decreased free IgE levels to less than 25 ng/mL. Omalizumab improved asthma control and was well-tolerated, as well

Desensitization to a whole egg by rush oral immunotherapy improves the quality of life of guardians: A multicenter, randomized, parallel-group, delayed-start design study

Background: Patients with food allergies and their families have a significantly reduced health-related quality of life (QOL). Methods: We performed a multicenter, randomized, parallel-group, delayed-start design study to clarify the efficacy and safety of rush oral immunotherapy (rOIT) and its impact on the participants' daily life and their guardians (UMIN000003943).Forty-five participants were randomly divided into an early-start group and a late-start group. The early-start group received rOIT for 3 months, while the late-start group continued the egg elimination diet (control). In the next stage, both groups received OIT until all participants had finished 12 months of maintenance OIT. Results: The ratio of the participants in whom an increase of the TD was achieved in the first stage was significantly higher in the early-start group (87.0%), than in the late-start group (22.7%). The QOL of the guardians in the early-start group significantly improved after the first stage (65.2%), in comparison to the late-start group (31.8%). During 12 months of rOIT, the serum ovomucoid-specific IgE levels, the percentage of CD203c+ basophils upon stimulation with egg white, and the wheal size to egg white were decreased, while the serum ovomucoid-specific IgG4 levels were increased. However, approximately 80% of the participants in the early-start group showed an allergic reaction during the first stage of the study, whereas none of the patients in the late-start group experienced an allergic reaction. Conclusions: rOIT induced desensitization to egg and thus improved the QOL of guardians; however, the participants experienced frequent allergic reactions due to the treatment. Keywords: Desensitization, Food allergy, Guardians, Oral immunotherapy, Quality of lif