Safety and tolerability of omalizumab (Xolair), a recombinant humanized monoclonal anti-IgE antibody.

Omalizumab (Xolair) is a humanized monoclonal antibody designed to bind specifically to immunoglobulin (Ig)E. It is indicated in the United States for the treatment of adolescent and adult patients (>or=12 yr) with moderate-to-severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen, and whose symptoms are inadequately controlled with inhaled corticosteroids. Omalizumab was evaluated in an extensive clinical development program that included 12 controlled phase IIB/III clinical trials with more than 5,243 patients who were appropriate for inclusion in the safety analysis (all ages in all controlled studies). In these studies, omalizumab had an adverse event profile comparable to that of the control group (i.e., placebo or standard therapy). Data presented in this article supports omalizumab as a safe and well-tolerated agent for the treatment of IgE-mediated asthma.

Exhaled nitric oxide in children with asthma receiving Xolair (omalizumab), a monoclonal anti-immunoglobulin E antibody.

OBJECTIVE: To evaluate the effect of a humanized monoclonal antibody to immunoglobulin E, omalizumab (Xolair, Novartis Pharmaceuticals, East Hanover, NJ; Genentech Inc, South San Francisco, CA), on airway inflammation in asthma, as indicated by the fractional concentration of exhaled nitric oxide (FE(NO)), a noninvasive marker of airway inflammation. Xolair was approved recently by the US Food and Drug Administration for moderate-to-severe allergic asthma in adolescents and adults. STUDY DESIGN: As an addendum at 2 sites to a randomized, multicenter double-blind, placebo-controlled trial, FE(NO) was assessed in children with allergic asthma over 1 year. There were 3 consecutive study periods: 1) stable dosing of inhaled beclomethasone dipropionate (BDP) when the dose was optimized (period of 16 weeks); 2) inhaled steroid-reduction phase (period of 12 weeks), during which BDP was tapered if subjects remained stable; and 3) open-label extension phase, during which subjects receiving placebo were switched to active omalizumab (period of 24 weeks). The primary outcome was area under the FE(NO) versus time curve (AUC) for adjusted FE(NO), defined as the ratio of FE(NO) at each time point compared with the value at baseline. RESULTS: Twenty-nine subjects participated and were randomized to omalizumab (n = 18) and placebo (n = 11) treatment groups in a 2:1 ratio dictated by the main study. There was a significant difference for age, resulting in a difference in absolute forced expiratory volume in 1 second but no difference in asthma severity based on the forced expiratory volume in 1 second percentage predicted. Baseline BDP dose was comparable between groups, as were baseline values of mean FE(NO) (active: 38.6 +/- 25.6 ppb; placebo: 52.7 +/- 52.9 ppb). The degree of BDP dose reduction during the steroid-reduction and open-label phases was equivalent between the omalizumab and placebo-treated groups; subjects in the omalizumab- and placebo-treated groups had reduced their BDP dose by an average of 51% and 60%, respectively, at the end of the steroid-reduction phase and by 68% and 94%, respectively, by the end of the open-label period. In the active and placebo groups, 44% and 27% and 75% and 73% of subjects had stopped use of inhaled corticosteroids at the end of the steroid-reduction and open-label phases, respectively. There was no significant difference between the active and placebo groups during the steroid-stable phase for AUC of adjusted nitric oxide (1.31 +/- 1.511 vs 1.45 +/- 0.736). However, during the steroid-reduction phase, the variability of adjusted FE(NO) in the placebo-treated group was greater than that of the omalizumab-treated group at most visits, with a significant difference between groups for AUC of adjusted nitric oxide (0.88 +/- 0.69 vs 1.65 +/- 1.06). FE(NO) fell from 82.1 +/- 55.6 ppm at the end of the steroid-reduction phase to 33.3 +/- 21.6 ppb at the end of the open-label period in the placebo group who were placed on active omalizumab. This decrease occurred while the mean dose of BDP remained very low. Analysis of FE(NO) over 52 weeks of omalizumab treatment in the active group demonstrated that there was a significant reduction from baseline to the end of the open-label period (41.9 +/- 29.0 to 18.0 +/- 21.8 ppb) despite a high degree of steroid reduction. CONCLUSION: In this preliminary study based on FE(NO), a noninvasive marker of airway inflammation, treatment with omalizumab may inhibit airway inflammation during steroid reduction in children with allergic asthma. The degree of inhibition of FE(NO) was similar to that seen for inhaled corticosteroids alone, suggesting an antiinflammatory action for this novel therapeutic agent in asthma. This is in keeping with recent evidence that omalizumab inhibits eosinophilic inflammation in induced sputum and endobronchial tissue.

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.

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.