Spotlight on Omalizumab in Allergic Asthma

Omalizumab (Xolair) is a humanized monoclonal antibody used in the treatment of adolescent and adult patients with moderate to severe allergic asthma inadequately controlled with inhaled corticosteroids (ICS). It selectively binds to circulating immunoglobulin E (IgE) and, thereby, prevents binding of IgE to mast cells and other effector cells. Without surface-bound IgE, these cells are unable to recognize allergens, thus preventing cellular activation by antigens and the subsequent allergic/asthmatic symptoms. Omalizumab decreases free serum IgE levels in a dose-dependent manner, reduces IgE receptor density on effector cells, and significantly improves airway inflammation parameters.Omalizumab is slowly absorbed after subcutaneous administration, and mean elimination half-life is 26 days, thus allowing infrequent administration of the drug. Omalizumab dosage is determined by bodyweight and pretreatment serum total IgE levels. Patients treated with subcutaneous omalizumab in clinical trials received a dosage that was approximately equal to 0.016 mg/kg/IgE (IU/mL) per 4 weeks. Thus, patients received 150 or 300 mg every 4 weeks, or 225, 300, or 375 mg every 2 weeks.In adults and adolescents (> or = 12 years of age) with moderate to severe allergic asthma, subcutaneous administration of omalizumab as add-on therapy with ICS improved the number of asthma exacerbations, rescue medication use, asthma symptom scores, and quality-of-life (QOL) scores compared with placebo during 28- and 32-week double-blind trials. In addition, concomitant ICS use was significantly decreased in patients receiving omalizumab, and in the two largest double-blind trials approximately 40% of omalizumab recipients completely withdrew from ICS therapy while maintaining effective asthma control. In general, results of extension studies showed that the beneficial effects of omalizumab were maintained over a total period of 52 weeks. Omalizumab was well tolerated as add-on therapy with ICS during treatment for up to 52 weeks. Common adverse events in clinical trials included injection site reaction, viral infection, upper respiratory tract infection, sinusitis, headache, and pharyngitis, although the incidence of adverse events with omalizumab was similar to that with placebo.In conclusion, omalizumab, as add-on therapy with ICS, is an effective and well tolerated agent for the treatment of moderate to severe allergic asthma in adolescents and adults. In addition to its symptomatic and QOL benefits, omalizumab therapy allows ICS dosage reduction or discontinuation of ICS in many patients. Comparisons of omalizumab with other asthma therapies have yet to be conducted; however, clinical efficacy and tolerability data indicate that omalizumab is a valuable option in the treatment of allergic asthma.     

Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE

BACKGROUND: Patients with severe persistent asthma who are inadequately controlled despite Global Initiative for Asthma (GINA) 2002 step 4 therapy are a challenging population with significant unmet medical need. We determined the effect of omalizumab on clinically significant asthma exacerbations (requiring systemic corticosteroids) in the first omalizumab study to exclusively enrol patients from this difficult-to-treat patient population. METHODS: Following a run-in phase, patients (12-75 years) inadequately controlled despite therapy with high-dose inhaled corticosteroids (ICS) and long-acting beta(2)-agonists (LABA) with reduced lung function and a recent history of clinically significant exacerbations were randomized to receive omalizumab or placebo for 28 weeks in a double-blind, parallel-group, multicentre study. RESULTS: A total of 419 patients were included in the efficacy analyses. The clinically significant asthma exacerbation rate (primary efficacy variable), adjusted for an observed relevant imbalance in history of clinically significant asthma exacerbations, was 0.68 with omalizumab and 0.91 with placebo (26% reduction) during the 28-week treatment phase (P = 0.042). Without adjustment, a similar magnitude of effect was seen (19% reduction), but this did not reach statistical significance. Omalizumab significantly reduced severe asthma exacerbation rate (0.24 vs 0.48, P = 0.002) and emergency visit rate (0.24 vs 0.43, P = 0.038). Omalizumab significantly improved asthma-related quality of life, morning peak expiratory flow and asthma symptom scores. The incidence of adverse events was similar between treatment groups. CONCLUSIONS: In patients with inadequately controlled severe persistent asthma, despite high-dose ICS and LABA therapy, and often additional therapy, omalizumab significantly reduced the rate of clinically significant asthma exacerbations, severe exacerbations and emergency visits. Omalizumab is effective and should be considered as add-on therapy for patients with inadequately controlled severe persistent asthma who have a significant unmet need despite best available therapy.     

Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with concomitant allergic asthma and persistent allergic rhinitis: SOLAR

BACKGROUND: Anti-IgE therapy could be particularly beneficial for patients with concomitant disease as it targets a common factor in both diseases. The aim of this study was to evaluate the efficacy and safety of omalizumab in patients with concomitant moderate-to-severe asthma and persistent allergic rhinitis. METHODS: This multicentre, randomized, double-blind, parallel-group, placebo-controlled trial evaluated the safety and efficacy of omalizumab. A total of 405 patients (12-74 years) with a stable treatment (>/= 400 microg budesonide Turbuhaler) and >/= 2 unscheduled medical visits for asthma during the past year or >/= 3 during the past 2 years were enrolled. Patients received omalizumab (>/= 0.016 mg/kg/IgE [IU/ml] per 4 weeks) or placebo for 28 weeks. RESULTS: Fewer patients treated with omalizumab experienced asthma exacerbations (20.6%) than placebo-treated patients (30.1%), P = 0.02. A clinically significant (>/= 1.0 point) improvement in both Asthma Quality of Life Questionnaire and Rhinitis Quality of Life Questionnaire occurred in 57.7% of omalizumab patients compared with 40.6% of placebo patients (P < 0.001). Omalizumab reduced Wasserfallen symptom scores for asthma (P = 0.023), rhinitis (P < 0.001) and the composite asthma/rhinitis scores (P < 0.001) compared with placebo. Serious adverse events were observed in 1.4% of omalizumab-treated patients and 1.5% of placebo-treated patients. CONCLUSION: Omalizumab is well tolerated and effective in preventing asthma exacerbations and improving quality of life in patients with concomitant asthma and persistent allergic rhinitis.     

An evaluation of the cost-effectiveness of omalizumab for the treatment of severe allergic asthma

Omalizumab is the first licensed anti-immunoglobulin (Ig) E antibody shown to be effective for treatment of allergic (IgE-mediated) asthma. Recent international guidelines recommend omalizumab as add-on treatment to fixed dose inhaled corticosteroid (ICS) and long-acting β₂-agonist (LABA) combination therapy. However, omalizumab is more expensive than other current asthma treatments and health and reimbursement authorities are increasingly demanding evidence of economic benefit to support pricing and formulary listing. The aims of this article are to (i) summarize data on the human and economic burden of severe asthma, (ii) summarize the efficacy data obtained for omalizumab in clinical trials in patients with inadequately controlled severe persistent allergic asthma despite high-dose ICS plus a LABA, and (iii) discuss the cost-effectiveness evidence published for omalizumab in this patient population. A wealth of evidence exists highlighting that the health, economic and societal burden of asthma is considerable and is highly skewed towards patients with severe asthma, particularly when asthma is inadequately controlled. Omalizumab is clinically beneficial in patients with severe persistent allergic asthma despite high-dose ICS plus a LABA, particularly in a subgroup of patients who respond to therapy. In patients who respond to therapy, the cost-effectiveness of omalizumab compares well with other biologic treatments for chronic illness.     

Monoclonal anti-IgE antibody: a novel therapy for allergic airways disease.

LEARNING OBJECTIVES: To familiarize the practitioner with a novel (monoclonal anti-immunoglobulin [Ig]E antibody) form of therapy for allergic airways disease. To understand the relevance of IgE as a therapeutic target. To appreciate the concepts behind the design of the molecule. To learn how anti-IgE was used in clinical trials. To anticipate the likely effects (efficacy and safety) in clinical use in patients with allergic asthma and with allergic rhinitis. To characterize the types of patients who might benefit from this therapy. DATA SOURCES: Published data for preclinical and clinical studies. RESULTS: Omalizumab is a nonimmunogenic, nonanaphylactogenic monoclonal anti-IgE antibody. In clinical use, omalizumab reduces levels of serum-free IgE. Given subcutaneously in patients with moderate-severe allergic asthma, omalizumab reduced exacerbations compared with placebo, and at the same time it allowed inhaled corticosteroids to be reduced or withdrawn. In patients with allergic rhinitis, omalizumab reduced the severity of symptoms and rescue antihistamine usage versus placebo. In both settings, quality of life was improved with active treatment relative to placebo. The drug seems safe and well tolerated. CONCLUSION: As the first clinical anti-IgE agent, omalizumab is an interesting new addition to the currently available therapies for allergic airways disease. The benefits demonstrated underline the importance of IgE in these conditions. The use of anti-IgE in other IgE-mediated allergic diseases warrants further research.     

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, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma

BACKGROUND: A recombinant humanized anti-IgE mAb, omalizumab, forms complexes with free IgE, blocking its interaction with mast cells and basophils; as a consequence, it might be effective in the treatment of asthma. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of omalizumab in the treatment of inhaled corticosteroid-dependent asthma. METHODS: In this phase III, double-blinded, placebo-controlled trial, 525 subjects with severe allergic asthma requiring daily inhaled corticosteroids were randomized to receive placebo or omalizumab subcutaneously every 2 or 4 weeks, depending on baseline IgE level and body weight. Inhaled corticosteroid doses were kept stable over the initial 16 weeks of treatment and tapered during a further 12-week treatment period. RESULTS: Omalizumab treatment resulted in significantly fewer asthma exacerbations per subject and in lower percentages of subjects experiencing an exacerbation than placebo treatment during the stable steroid phase (0.28 vs 0.54 [P =.006] and 14.6% vs 23.3% [P =.009], respectively) and during the steroid reduction phase (0.39 vs 0.66 [P =.003] and 21.3% vs 32.3% [P =.004], respectively). Beclomethasone dipropionate reduction was significantly greater with omalizumab treatment than with placebo (median 75% vs 50% [P <.001]), and beclomethasone dipropionate discontinuation was more likely with omalizumab (39.6% vs 19.1% [P <.001]). Improvements in asthma symptoms and pulmonary function occurred along with a reduction in rescue beta-agonist use. Omalizumab was well tolerated, with an adverse-events profile similar to that of placebo. CONCLUSION: The addition of omalizumab to standard asthma therapy reduces asthma exacerbations and decreases inhaled corticosteroid and rescue medication use.     

The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma

BACKGROUND: Patients with severe persistent asthma who are inadequately controlled despite treatment according to current asthma management guidelines have a significant unmet medical need. Such patients are at high risk of serious exacerbations and asthma-related mortality. METHODS: Here, we pooled data from seven studies to determine the effect of omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, on asthma exacerbations in patients with severe persistent asthma. Omalizumab was added to current asthma therapy and compared with placebo (in five double-blind studies) or with current asthma therapy alone (in two open-label studies). The studies included 4308 patients (2511 treated with omalizumab), 93% of whom had severe persistent asthma according to the Global Initiative for Asthma (GINA) 2002 classification. Using the Poisson regression model, results were calculated as the ratio of treatment effect (omalizumab : control) on the standardized exacerbation rate per year. RESULTS: Omalizumab significantly reduced the rate of asthma exacerbations by 38% (P < 0.0001 vs control) and the rate of total emergency visits by 47% (P < 0.0001 vs control). Analysis of demographic subgroups showed that the efficacy of omalizumab on asthma exacerbations was unaffected by patient age, gender, baseline serum IgE (split by median) or by 2- or 4-weekly dosing schedule, although benefit in absolute terms appeared to be greatest in patients with more severe asthma, defined by a lower value of percentage predicted forced expiratory volume in 1 s (FEV(1)) at baseline. CONCLUSIONS: These results suggest that omalizumab may fulfil an important need in patients with severe persistent asthma, many of whom are not adequately controlled on current therapy.     

‘Real‐life’ effectiveness studies of omalizumab in adult patients with severe allergic asthma: systematic review

We reviewed 24 ‘real‐life’ effectiveness studies of omalizumab in the treatment of severe allergic asthma that included 4117 unique patients from 32 countries with significant heterogeneity in patients, clinicians and settings. The evidence underscores the short‐ and long‐term benefit of anti‐IgE therapy in terms of the following: improving lung function; achieving asthma control and reducing symptomatology, severe exacerbations and associated work/school days lost; reducing healthcare resource utilizations, in particular hospitalizations, hospital lengths of stay and accident specialist or emergency department visits; reducing or discontinuing other asthma medications; and improving quality of life – thus confirming, complementing and extending evidence from randomized trials. Thus, omalizumab therapy is associated with signal improvements across the full objective and subjective burden of illness chain of severe allergic asthma. Benefits of omalizumab may extend up to 2–4 years, and the majority of omalizumab‐treated patients may benefit for many years. Omalizumab has positive short‐ and long‐term safety profiles similar to what is known from randomized clinical trials. Initiated patients should be monitored for treatment response at 16 weeks. Those showing positive response at that time are highly likely to show sustained treatment response and benefit in terms of clinical, quality of life and health resource utilization outcomes.     

Impact of omalizumab on quality-of-life outcomes in patients with moderate-to-severe allergic asthma.

BACKGROUND: Moderate-to-severe allergic asthma has a substantial impact on patients' quality of life (QOL). Despite care consistent with treatment guidelines, many patients with moderate-to-severe asthma still experience variability in asthma control, signaling an unmet need within this population. Omalizumab has recently demonstrated clinical efficacy and safety in treating IgE-mediated asthma. OBJECTIVE: To summarize asthma-related QOL outcomes associated with omalizumab therapy in moderate-to-severe allergic asthma. METHODS: A systematic review and meta-analysis of asthma-related QOL on data from published clinical trials and unpublished clinical study reports were conducted on omalizumab. The Juniper Asthma Quality of Life Questionnaire (AQLQ) measured asthma-related QOL. RESULTS: Statistically significant results for asthma-related QOL end points consistently favored omalizumab over placebo. Moderate to large effect sizes in the omalizumab groups were observed across the clinical trials and during study extension phases. A meta-analysis indicated a 1.6- to 2-fold increase in moderate (> or = 1 point) and a 1.8- to 2.1-fold increase in large (> or = 1.5 point) improvements in AQLQ overall scores in the omalizumab-treated group compared with placebo during the steroid-stabilization and steroid-reduction phases of the trials. CONCLUSIONS: Significant differences and large effect sizes favoring omalizumab were observed despite the control group receiving active, guideline-consistent treatment. The meta-analysis findings demonstrate that omalizumab treatment provides QOL benefits in patients with moderate-to-severe allergic asthma.     

Anti-immunoglobulin E treatment with omalizumab in allergic diseases: an update on anti-inflammatory activity and clinical efficacy

Omalizumab is a humanized monoclonal anti-IgE antibody developed for the treatment of allergic disease, with established efficacy in patients with moderate-to-severe allergic asthma and in patients with intermittent (seasonal) and persistent (perennial) allergic rhinitis (AR). Omalizumab is known to result in a marked reduction in serum levels of free IgE and down-regulation of IgE receptors on circulating basophils. Recent work has shed further light on its mechanism of action, showing significant and profound reductions in tissue (nasal and bronchial) eosinophils and in bronchial IgE+ cells (mast cells), as well as T cells and B cells. Omalizumab treatment was also shown to be associated with down-regulation of IgE receptors on circulating (precursor) dendritic cells, suggesting that blocking IgE may inhibit more chronic aspects of allergic inflammation involving T cell activation. Further work with omalizumab demonstrated it to have important benefits in patients with poorly controlled asthma despite high-dose inhaled corticosteroid therapy, and analysis of clinical data suggests that the patients who are the best 'responders' to anti-IgE treatment are those with asthma at the more severe end of the spectrum. Notably, systemic anti-IgE therapy with omalizumab has been shown to improve symptoms, quality of life and disease control (asthma exacerbations) in patients with concomitant asthma and persistent AR. These impressive clinical data and the studies elucidating the anti-inflammatory profile of omalizumab also serve to emphasize the fundamental importance of IgE in the pathogenesis of allergic diseases.     

Add-on omalizumab improves day-to-day symptoms in inadequately controlled severe persistent allergic asthma

Background:  Omalizumab is efficacious in the treatment of moderate-to-severe and severe persistent allergic (immunoglobulin E-mediated) asthma, reducing exacerbations, emergency visits and improving quality of life (QoL). However, as exacerbations are relatively infrequent, assessment of efficacy on day-to-day symptoms is warranted.
Aims:  To investigate the effect of add-on omalizumab on day-to-day symptoms, and how they correlate with QoL in severe persistent asthma.
Methods:  The correlation between asthma symptom scores and QoL [Asthma Quality of Life Questionnaire (AQLQ)] was assessed. Symptom-free days (total symptom score = 0) and symptom-controlled days (definition 1: total symptom score ≤1; and definition 2: morning peak expiratory flow ≥90% of baseline, daytime asthma score ≤1 and night-time asthma score = 0) were compared between the omalizumab-treated group, omalizumab responders and placebo.
Results:  Four hundred and nineteen patients (omalizumab, n  = 209; placebo, n  = 210) were included in the efficacy analyses, and 61% (118/195) of patients with response data were classified as responders. Total symptom score strongly correlated with AQLQ overall and symptom scores and individual domains. AQLQ overall score correlated well with symptom scores. Responders had significantly more symptom-free days than the omalizumab-treated and placebo groups (45.8%, 37.2% and 22.6% respectively), and more symptom-controlled days (definition 1: 56.1%, 47.9% and 35.3%, respectively, and definition 2: 50.8%, 43.9% and 28.0%, respectively).
Conclusions:  In patients with inadequately controlled severe persistent asthma, day-to-day symptoms correlate well with QoL. Add-on omalizumab significantly improves day-to-day symptoms compared with placebo. Further improvement in responders confirms the physician's assessment as a response measure.     

Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma

BACKGROUND: Patients with severe asthma are often inadequately controlled on existing anti-asthma therapy, constituting an unmet clinical need. OBJECTIVE: This randomized, double-blind, placebo-controlled trial evaluated the ability of omalizumab, a humanized monoclonal anti-IgE antibody, to improve disease control sufficiently to enable inhaled corticosteroid reduction in patients with severe allergic asthma. METHODS: After a run-in period when an optimized fluticasone dose (> or =1000 microg/day) was received for 4 weeks, patients were randomized to receive subcutaneous omalizumab [minimum 0.016 mg/kg/IgE (IU/mL) per 4 weeks; n=126] or matching placebo (n=120) at intervals of 2 or 4 weeks. The study comprised a 16-week add-on phase of treatment followed by a 16-week fluticasone-reduction phase. Short-/long-acting beta(2)-agonists were allowed as needed. RESULTS: Median reductions in fluticasone dose were significantly greater with omalizumab than placebo: 60% vs. 50% (P=0.003). Some 73.8% and 50.8% of patients, respectively, achieved a > or =50% dose reduction (P=0.001). Fluticasone dose reduction to < or =500 microg/day occurred in 60.3% of omalizumab recipients vs. 45.8% of placebo-treated patients (P=0.026). Through both phases, omalizumab reduced rescue medication requirements, improved asthma symptoms and asthma-related quality of life compared to placebo. CONCLUSION: Omalizumab treatment improves asthma control in severely allergic asthmatics, reducing inhaled corticosteroid requirements without worsening of symptom control or increase in rescue medication use.     

Short- and long-term real-world effectiveness of omalizumab in severe allergic asthma: systematic review of 42 studies published 2008-2018

Introduction: Omalizumab is a recombinant monoclonal anti-IgE antibody approved in the US as add-on treatment in moderate-to-severe allergic asthma (in severe allergic asthma [SAA] in Europe). A 2016 review of 24 real-world effectiveness studies in SAA published between 2008–2015 concluded that omalizumab was associated with significant improvements in objective and subjective outcomes with benefits extending beyond 2 years. Several new real-world studies have been published since, bringing the total to 42 studies.

Areas covered: This systematic review of 42 studies published since 2008 updates and extends the 2016 review on the real-word evidence on omalizumab in SAA. It offers greater granularity as to time windows within which outcomes are reported and includes studies extending well beyond 4 years post omalizumab initiation.

Expert commentary: This review firmly establishes the short-term effectiveness of omalizumab in adolescent and adult patients with SAA at 1 year, and provides strong evidence of long-term effectiveness up to 4 years and emergent evidence of effectiveness beyond 4 years. In the aggregate, these 42 studies underscore the long-term effectiveness of omalizumab in terms of: reducing exacerbations and symptoms, achieving asthma control, improving lung function, enhancing quality of life, decreasing emergency department visits and hospitalizations, and promoting concomitant medication-sparing.     

Omalizumab therapy for children and adolescents with severe allergic asthma

Omalizumab, a therapeutic humanized monoclonal antibody specific for human IgE, was introduced in clinical practice more than a decade ago as an add-on therapy for moderate-to-severe allergic asthma in patients aged ≥12 years. Omalizumab has been demonstrated to be effective in adults with uncontrolled persistent asthma, with an excellent safety profile. In simple terms, omalizumab works by inhibiting the allergic cascade, that is, by neutralization of the circulating free IgE. This leads to reduction in the quantity of cell-bound IgE, downregulation of high-affinity IgE receptors, and, eventually, prevention of mediator release from effector cells. Evidence is far less abundant on the role of omalizumab in pediatric asthma. Although efficacy and safety of omalizumab in children and adolescents with uncontrolled, persistent allergic asthma has been recognized as well, further studies are needed to clarify a number of open questions in this specific patient population.     

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.     

The anti-inflammatory effects of omalizumab confirm the central role of IgE in allergic inflammation

Anti-IgE therapy with omalizumab reduces serum levels of free IgE and downregulates expression of IgE receptors (Fc epsilonRI) on mast cells and basophils. In the airways of patients with mild allergic asthma, omalizumab reduces Fc epsilonRI+ and IgE+ cells and causes a profound reduction in tissue eosinophilia, together with reductions in submucosal T-cell and B-cell numbers. In patients with seasonal allergic rhinitis, omalizumab inhibits the allergen-induced seasonal increases in circulating and tissue eosinophils. Omalizumab decreases Fc epsilonRI expression on circulating dendritic cells, which might lead to a reduction in allergen presentation, T(H)2 cell activation, and proliferation. As a systemic anti-IgE agent, omalizumab has demonstrated clinical efficacy in patients with moderate and severe allergic asthma and in those with seasonal and perennial allergic rhinitis, as well as in patients with concomitant allergic asthma and allergic rhinitis. The anti-inflammatory effects of omalizumab at different sites of allergic inflammation and the clinical benefits of anti-IgE therapy in patients with allergic asthma and allergic rhinitis emphasize the fundamental importance of IgE in allergic inflammation.     

Omalizumab in allergic diseases, a recent review

Omalizumab is a biological engineered molecule, targeting the Cepsilon3 domain of the IgE molecule. It binds with free IgE and prevents free IgE from attaching to high-affinity IgE receptor (FcepsilonRI) on effector cells such as mast cells, basophils and also on dendritic cells. The result is a blocking of mediator release from these cells and the inhibition of antigen presentation by dendritic cells. In addition, omalizumab downregulates FcepsilonRI expression on these effector cells. Omalizumab prevents early and late phase allergic reactions of skin and lungs. Omalizumab has been investigated extensively in moderate-to-severe asthma in adults and children. It effectively reduces rates of asthma exacerbation, emergency visits for asthma and hospital admissions among these patients. Currently, omalizumab is primarily indicated for patients, age 6 years and over, with moderate to severe asthma (GINA step 4). Omalizumab was investigated in patients with seasonal allergic rhinitis (to ragweed, birch and grass pollens) and has been found to improve rhinitis symptoms and to reduce medication use among these patients. Administered together with allergen immunotherapy, omalizumab reduced incidence of side effects and rates of anaphylaxis from allergen immunotherapy. Omalizumab has been investigated in the treatment of food allergy, atopic dermatitis and urticaria. Despite benefits observed from these initial trials, it further deserves investigations to clarify optimal conditions for use in these conditions. Side effects from omalizumab were few, however, it requires careful considerations in administration of this agent. An observational period (up to 2 hours after the first three doses) and the availability of auto-injectable epinephrine are recommended. Pharmacoeconomics of omalizumab is briefly reviewed. Omalizumab represents a major breakthrough of translational medicine in allergy.     

Safety and tolerability of omalizumab

Background Omalizumab (Xolair^®) is a recombinant humanized monoclonal anti-IgE antibody with proven efficacy in patients with moderate-to-severe and severe persistent allergic (IgE-mediated) asthma.
Objective To review clinical study data to assess the safety profile of omalizumab.
Methods We analysed the safety of omalizumab using data from completed clinical studies (up to 1 year) involving more than 7500 patients with asthma, rhinitis or related conditions and up to 4 years in one study of patients with severe allergic asthma, as well as post-marketing safety data. Analysis focuses on the risk of immune-system effects, hypersensitivity reactions, malignant neoplasia, parasitic infections and thrombocytopenia.
Results Omalizumab exhibited a good safety and tolerability profile that was maintained up to 4 years in one study. The incidence of anaphylaxis was 0.14% in omalizumab-treated patients and 0.07% in control patients. No omalizumab-treated patient developed measurable anti-omalizumab antibodies. Post-marketing, based on estimated exposure of 57 300 patients (June 2003–December 2006), the frequency of anaphylaxis attributed to omalizumab use was estimated to be at least 0.2% of patients. Current clinical trial data do not support an increased risk of malignant neoplasia or thrombocytopenia with omalizumab.
Conclusion Data indicate that the proven efficacy of add-on omalizumab in patients with moderate-to-severe or severe allergic asthma is accompanied by a favourable safety and tolerability profile.     

Omalizumab,a recombinant humanized anti-IgE antibody,reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma

BACKGROUND: Prevention of serious asthma exacerbations is an important therapeutic goal in patients with asthma. OBJECTIVE: The purpose of this study was to investigate the effect of omalizumab (Xolair), a recombinant humanized monoclonal anti-IgE antibody, on the rate of serious exacerbations during long-term therapy. METHODS: A pooled analysis was completed of 3 multicenter, randomized, double-blind, placebo-controlled phase III studies with omalizumab in adults/adolescents aged > or =12 years (n = 1071) and in children aged 6 to 12 years (n = 334) who required treatment with inhaled corticosteroids for allergic asthma. Rates of serious asthma exacerbations were computed and compared between omalizumab- and placebo-treated patients. Serious exacerbations were those leading to unscheduled outpatient visits, emergency room treatment, or hospitalization during 1 year of treatment. RESULTS: In all, 767 patients were treated with omalizumab (at least 0.016 mg/kg/IgE [IU/mL], administered subcutaneously every 4 weeks). Another 638 patients were treated with placebo. The rate of unscheduled, asthma-related outpatient visits was lower for the omalizumab-treated patients than for the placebo-treated patients (rate ratio [95% CI], 0.60 [0.44, 0.81]; P <.01), as were asthma-related emergency room visits (rate ratio [95% CI], 0.47 [0.24, 1.01]; P =.05). Importantly, hospitalizations for asthma were markedly reduced in patients receiving omalizumab (rate ratio [95% CI], 0.08 [0.00, 0.25]; P <.01). CONCLUSION: Omalizumab reduces the rate of serious asthma exacerbations and the need for unscheduled outpatient visits, emergency room treatment, and hospitalization in patients with moderate-to-severe allergic asthma.