Safety and tolerability of omalizumab in children with allergic (IgE-mediated) asthma.

OBJECTIVE: This pooled analysis assessed the safety of omalizumab in children with allergic (immunoglobulin E-mediated) asthma. STUDY DESIGN: Two double-blind, placebo-controlled studies in children (6 to < 12 years) with moderate-to-severe allergic asthma investigated the efficacy/safety of omalizumab. Children on optimized asthma care (inhaled corticosteroids ± other controller medications) were randomized (2:1) to omalizumab (75-375 mg sc, q2 or q4 wk) or placebo. Pooled safety findings from these trials are presented in this publication. RESULTS: The safety population included 926 children (omalizumab, n = 624; placebo, n = 302). Adverse events (AEs) were more frequently reported in the placebo (91.7%) than omalizumab (89.7%) group. The most common AEs were nasopharyngitis, upper respiratory tract infection and headache. Suspected treatment-related AEs included headache, erythema and urticaria; none of which were reported by ≥ 2% of patients receiving omalizumab. Serious AEs (SAEs) were reported by 3.4% and 6.6% of patients receiving omalizumab and placebo, respectively; the most common were appendicitis, pneumonia and bronchitis; no deaths were reported. CONCLUSIONS: Omalizumab has an acceptable safety profile, with a risk of AEs similar to placebo. This, combined with its efficacy profile, suggests that omalizumab may provide an additional asthma management option for children (6 to < 12 years) uncontrolled with current therapy that follows established guidelines.

Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma.

IgE plays an important role in allergic asthma. We hypothesized that reducing IgE in the airway mucosa would reduce airway inflammation. Forty-five patients with mild to moderate persistent asthma with sputum eosinophilia of 2% or more were treated with humanized monoclonal antibody against IgE (omalizumab) (n = 22) or placebo (n = 23) for 16 weeks. Outcomes included inflammatory cells in induced sputum and bronchial biopsies, and methacholine responsiveness. Treatment with omalizumab resulted in marked reduction of serum IgE and a reduction of IgE+ cells in the airway mucosa. The mean percentage sputum eosinophil count decreased significantly (p < 0.001) from 6.6 to 1.7% in the omalizumab group, a reduction significantly (p = 0.05) greater than with placebo (8.5 to 7.0%). This was associated with a significant reduction in tissue eosinophils; cells positive for the high-affinity Fc receptor for IgE; CD3+, CD4+, and CD8+ T lymphocytes; B lymphocytes; and cells staining for interleukin-4, but not with improvement in airway hyperresponsiveness to methacholine. This study shows antiinflammatory effects of omalizumab treatment and provides clues for mechanisms whereby omalizumab reduces asthma exacerbations and other asthma outcomes in more severe asthma. The lack of effect of omalizumab on methacholine responsiveness suggests that IgE or eosinophils may not be causally linked to airway hyperresponsiveness to methacholine in mild to moderate asthma.

Tolerability of retreatment with omalizumab, a recombinant humanized monoclonal anti-IgE antibody, during a second ragweed pollen season in patients with seasonal allergic rhinitis.

Two randomized, placebo-controlled, double-blind studies have shown clinical benefit with omalizumab (Xolair), a recombinant humanized monoclonal anti-immunoglobulin E (IgE) antibody, at a dose of 300 mg every 3 or 4 weeks in patients with seasonal allergic rhinitis. The present open-label, 12-week study was designed to assess the safety and tolerability of retreatment with omalizumab in 287 patients previously treated with this agent in one of the latter studies. Omalizumab, 300 mg, was administered subcutaneously every 4 weeks (three injections) to patients with IgE levels < or = 150 IU/mL (n = 182) and every 3 weeks (four injections) to patients with IgE levels > 150 IU/mL (n = 105) at screening before retreatment. Reported adverse events were monitored and blood samples were analyzed for laboratory safety (hematology and serum chemistry) and IgE levels. Urinalysis also was completed as part of the laboratory safety evaluation. The overall incidence and pattern of adverse events were similar to those reported in the primary study. There were no severe or serious adverse events related to omalizumab treatment and no anti-omalizumab antibodies were detected in any patient. Two patients withdrew from treatment because of adverse events (skin rash and nausea; facial erythema and edema) related to study treatment. Free IgE levels decreased to the levels associated with symptom reduction in the core study. In summary, retreatment during a second pollen season with omalizumab, 300 mg every 3 or 4 weeks, was well tolerated and was not associated with any significant immunologic reactions.

Omalizumab is effective in the long-term control of severe allergic asthma.

BACKGROUND: Previous reports show that addition of omalizumab to standard therapy reduces asthma exacerbations and simultaneously decreases use of inhaled corticosteroids (ICSs) and rescue medication in patients with allergic asthma. OBJECTIVE: To determine the effect of omalizumab on long-term disease control in patients with severe allergic asthma. METHODS: The present study concerns the 24-week, double-blind extension phase to a previous 28-week core study in which patients received subcutaneous omalizumab or matching placebo (at least 0.016 mg/kg/IgE [IU/mL] every 4 weeks) for 16 weeks in addition to their existing ICS therapy (beclomethasone dipropionate [BDP]; steroid-stable phase), followed by a 12-week phase in which controlled attempts were made to gradually reduce ICS therapy (steroid-reduction phase). During the extension phase patients were maintained on randomized treatment (omalizumab or placebo) and the lowest sustainable dose of BDP. The use of other asthma medications was permitted during the extension phase. Investigators were also allowed to switch patients from BDP to other ICS medications if considered necessary. RESULTS: A total of 460 patients (omalizumab, n = 245; placebo, n = 215) entered the extension phase. Overall, omalizumab-treated patients experienced significantly fewer exacerbations vs placebo during the extension phase (0.60 and 0.83 exacerbations per patient, respectively; P = 0.023), despite a sustained significant reduction in their use of ICS (mean BDP equivalent dose: omalizumab, 227 microg/d; placebo, 335 microg/d; P < 0.001). Treatment with omalizumab was well tolerated and the incidence of adverse events was similar in both treatment groups. CONCLUSIONS: These results indicate that omalizumab is effective in the long-term control of severe allergic asthma.

Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis.

BACKGROUND: Treatment with omalizumab, an anti-IgE antibody, improves symptoms and quality of life in patients with seasonal allergic rhinitis but has not previously been investigated in patients with perennial symptoms. OBJECTIVE: To investigate the efficacy, safety, and tolerability of omalizumab in the treatment of perennial allergic rhinitis (PAR). METHODS: Two hundred eighty-nine patients (aged 12 to 70 years) with moderate-to-severe symptomatic PAR were randomized to 16 weeks' double-blind subcutaneous treatment with either placebo (n = 145) or omalizumab (at least 0.016 mg/kg/IgE [IU/mL] per 4 weeks; n = 144). The primary efficacy variable was the mean daily nasal severity score, as determined from patient daily diary cards. Secondary efficacy variables included use of rescue antihistamine, rhinoconjunctivitis-specific quality of life (RQoL), and patients' evaluation of treatment efficacy. Safety and tolerability were evaluated from adverse event reports and laboratory safety parameters. RESULTS: Throughout 16 weeks of treatment, the mean daily nasal severity score was significantly lower in omalizumab-treated patients than with placebo (P < 0.001). The improvement in symptoms when taking omalizumab was paralleled by a reduction in use of rescue antihistamine (P < or = 0.005 overall) and improved RQoL relative to placebo. Patients' evaluation of treatment efficacy significantly favored omalizumab over placebo (P = 0.001). Omalizumab therapy was well tolerated. There were no safety concerns. CONCLUSIONS: Omalizumab was safe and well tolerated in the treatment of patients with PAR, providing effective control of symptoms and improved RQoL while simultaneously minimizing reliance on rescue antihistamines.

Evaluation of long-term safety of the anti-IgE antibody, omalizumab, in children with allergic asthma.

OBJECTIVE: To evaluate the long-term effects of the anti-IgE antibody omalizumab in children with asthma. METHODS: This was a 28-week, double-blind, randomized, placebo-controlled trial with a 24-week open-label extension. In the core trial 225 children (ages 6 to 12 years) with moderate-to-severe allergic asthma requiring inhaled beclomethasone dipropionate (BDP) received omalizumab every 2 or 4 weeks, and 109 received placebo. BDP dosage was stable for weeks 1 to 16, then reduced during weeks 17 to 24 using strict safety criteria. The lowest dose for optimal asthma control was maintained for 4 more weeks. During the 24-week extension, all patients (n = 309) received open-label omalizumab in addition to other asthma medications. One-year safety data were analyzed. RESULTS: The incidence of adverse events in patients treated with omalizumab for 52 weeks was similar to those treated for 28 weeks in the core trial, which was generally comparable with placebo. In the 52-week omalizumab group, upper respiratory tract infection and headache were the most frequently reported adverse events (47.1% and 42.7%, respectively). Eleven patients (4.9%) reported urticaria, which resolved spontaneously or with antihistamine, except for 1 patient who was discontinued because of severe urticaria. No anaphylactic reactions or adverse events suggestive of serum sickness or immune complex formation occurred. No anti-omalizumab antibodies were detected in any of the children. There is no evidence that new or more serious adverse events occur with long-term omalizumab treatment. CONCLUSIONS: Long-term treatment with omalizumab is safe and well tolerated in children with allergic asthma.

Omalizumab improves asthma-related quality of life in patients with severe allergic asthma.

BACKGROUND: We have previously shown that omalizumab, a recombinant humanized monoclonal anti-IgE antibody, reduces asthma exacerbations and decreases inhaled corticosteroid (ICS) requirement in patients with severe allergic asthma who were symptomatic despite moderate-to-high doses of ICSs. OBJECTIVE: The aim of the present study was to assess the effects of omalizumab on asthma-related quality of life (QOL). METHODS: These analyses were part of a multicenter, 52-week, randomized, double-blind, placebo-controlled study assessing the efficacy, safety, and tolerability of subcutaneous omalizumab (> or =0.016 mg/kg of IgE [in international unit per milliliter] per 4 weeks) in 525 adults with severe allergic asthma. A 16-week steroid-stable phase was followed by a 12-week steroid-reduction phase and a 24-week double-blind extension phase. The effect of treatment on asthma-related QOL was evaluated by using the Asthma Quality of Life Questionnaire (AQLQ) administered at baseline and at weeks 16, 28, and 52. RESULTS: The 2 treatment groups were comparable in terms of baseline AQLQ scores. At weeks 16, 28, and 52, omalizumab-treated patients demonstrated statistically significant improvements across all AQLQ domains, as well as in overall score. Moreover, a greater proportion of patients receiving omalizumab achieved a clinically meaningful improvement in asthma-related QOL during each phase of the study. Greater than 50% of both patients and investigators rated treatment similarly with omalizumab as excellent or good compared with less than 40% of placebo recipients. CONCLUSION: In patients requiring moderate-to-high doses of ICSs for severe allergic asthma, the measurably improved disease control afforded by add-on omalizumab therapy is paralleled by clinically meaningful improvements in asthma-related QOL.

Omalizumab improves asthma-related quality of life in children with allergic asthma.

BACKGROUND AND OBJECTIVE: Omalizumab is a recombinant, humanized, monoclonal anti-immunoglobulin E (IgE) antibody, developed for the treatment of IgE-mediated diseases. In children with allergic asthma, it was shown to reduce the requirement for inhaled corticosteroids while protecting against disease exacerbation. Here we report the effects of treatment with omalizumab on asthma-related quality of life (AQoL) in children with allergic asthma. METHODS: This evaluation was part of a previously reported 28-week, randomized, double-blind, placebo-controlled study to assess the efficacy, safety, and tolerability of omalizumab (at least 0.016 mg/kg/IgE [IU/mL] per 4 weeks) in children with allergic asthma who were well controlled on daily treatment with inhaled corticosteroids. Dosage of beclomethasone dipropionate was kept constant for 16 weeks (steroid-stable phase), then reduced over 8 weeks to the minimum effective dose (steroid-reduction phase). This dose was then maintained for the final 4 weeks. The Pediatric Asthma Quality of Life Questionnaire (PAQLQ) was administered at baseline, week 16, and week 28. RESULTS: Baseline demographics, PAQLQ scores, and other data were comparable for the 2 treatment groups. At the end of the steroid-reduction phase, patients in the omalizumab-treated group reported significant improvements in the "activities" and "symptoms" domain scores as well as overall AQoL compared with placebo. More patients in the omalizumab group achieved clinically relevant (> or =0.5) changes in PAQLQ scores during the course of the study, and this difference was significant for activities and overall AQoL. CONCLUSION: Omalizumab improves AQoL in children with allergic asthma.