Anti-IgE Antibody Therapy for Japanese Cedar Pollinosis: Omalizumab Update

Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollens is a substantial problem in Japan. Omalizumab, a novel humanized monoclonal anti-immunoglobulin E (IgE) antibody, has already been proven to reduce symptoms associated with SAR. To investigate the safety and efficacy of omalizumab in the treatment of patients with Japanese cedar pollen-induced SAR compared to placebo or anti-allergic drug, two randomized, double-blind studies were conducted in Japan. Omalizumab (150, 225, 300, or 375 mg) or placebo was administered subcutaneously every 2 or 4 weeks based on serum total IgE and body weight at baseline. IPD was administered 300 mg per day through the season. Primary and all secondary efficacy variable scores were significantly lower in the omalizumab group than in the placebo group (P < .01) and IPD, Th2 cytokine inhibitor group (P < .01). Omalizumab was effective and safe in the treatment of SAR induced by Japanese cedar pollens. And the methods of increasing effects by combining omalizumab with antibody-specific immunotherapy are being considered. These strategy is more effective than immune-therapy alone

Omalizumab is Effective and Safe in the Treatment of Japanese Cedar Pollen-induced Seasonal Allergic Rhinitis

Background: Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollen is a substantial problem in Japan. Omalizumab, a novel humanized monoclonal anti-immunoglobulin E (IgE) antibody, has already been proven to reduce symptoms associated with SAR. We investigated the safety and efficacy of omalizumab in the treatment of patients with Japanese cedar pollen-induced SAR compared to placebo. Methods: A randomized, placebo-controlled, double-blind study was conducted in 100 Japanese patients with a history of moderate-to-severe SAR induced by Japanese cedar pollens. Omalizumab (150, 225, 300, or 375 mg) or placebo was administered subcutaneously every 2 or 4 weeks based on serum total IgE and body weight at baseline. The primary efficacy variable was the mean of daily nasal symptom medication scores (sum of the daily nasal symptom severity score and daily nasal rescue medication score) during the treatment period. Secondary efficacy variables included the daily ocular symptom medication score and related variables. Results: Primary and all secondary efficacy variable scores were significantly lower in the omalizumab group than in the placebo group (P < .01). Serum free IgE levels markedly decreased in the omalizumab group and were associated with clinical efficacy. The overall incidence of injection site reactions was higher in the omalizumab group than in the placebo group; however, the adverse reaction profile was similar between the two groups when excluding injection site reactions. No anti-omalizumab antibodies were detected. Conclusions: Omalizumab was effective and safe in the treatment of SAR induced by Japanese cedar pollen

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