The use of omalizumab in allergen immunotherapy

Although omalizumab (anti‐IgE) is currently only approved for the treatment of asthma and chronic idiopathic urticaria, it has also been studied as an off‐label treatment for numerous allergic conditions, including use as an adjunct to allergen immunotherapy in the treatment of allergic rhinitis, asthma, venom hypersensitivity and food allergy. We conducted a review of publications involving the use of omalizumab with allergen immunotherapy, by searching PubMed with key search terms of “omalizumab” and “immunotherapy.” Omalizumab has been used in combination with inhalant allergen immunotherapy for the treatment of seasonal allergic rhinitis and comorbid asthma. While there have been no randomized controlled trials evaluating the addition of omalizumab to venom IT, several case reports and small patient series have been published on the use of omalizumab with venom IT. Omalizumab has been used in conjunction with oral immunotherapy for the treatment of milk, peanut and egg, as well as other foods in multi‐allergen protocols. In conclusion, omalizumab used in conjunction with immunotherapy has shown promising results, especially in the reduction of adverse reactions. At this stage, larger, randomized, placebo‐controlled trials are needed to better identify those patients who would benefit the most from the addition of omalizumab to immunotherapy, as well as optimal dosing strategies and duration of treatment.     

Omalizumab

Omalizumab, a monoclonal antibody that targets circulating IgE, is approved as add-on therapy for adult and adolescent patients with severe allergic asthma in the EU and moderate to severe allergic asthma in the US. Several randomized, double-blind trials have demonstrated the therapeutic efficacy of subcutaneously administered omalizumab as add-on therapy in patients with allergic asthma. The INNOVATE study included only patients with severe persistent disease, and omalizumab was associated with a statistically significant relative reduction of 26% in the rate of clinically significant asthma exacerbations (primary endpoint) compared with placebo (after adjustment for an imbalance in the exacerbation history at baseline). Results for a number of secondary outcomes also significantly favored omalizumab over placebo. Two large studies in patients with moderate to severe allergic asthma showed that, compared with placebo, omalizumab was associated with statistically significant relative reductions of 41-58% in the mean number of asthma exacerbations (primary endpoint) during the trial. Omalizumab also significantly reduced asthma symptom scores and the use of inhaled corticosteroids and rescue medication. Moreover, all of these trials showed that omalizumab was associated with clinically and statistically significant improvements from baseline in overall asthma-related quality of life.In general, omalizumab was well tolerated in clinical trials. Most adverse events were mild or moderate in severity and occurred at a similar frequency among omalizumab and placebo recipients. Injection-site reactions were the most commonly reported adverse events in clinical trials with omalizumab. Although rare, anaphylactic reactions have occurred following administration of omalizumab, and appropriate precautions should be taken.Results of several large randomized trials, therefore, have established omalizumab as an effective and well tolerated agent for use as add-on therapy in patients with severe persistent allergic asthma (EU labeling) or those with moderate to severe disease (US labeling). In addition, international treatment guidelines acknowledge the importance of omalizumab as a treatment option in these difficult-to-treat patient populations.     

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.     

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.     

Targeted therapy for allergic asthma: predicting and evaluating response to omalizumab

Evaluation of: Bousquet J, Rabe K, Humbert M et al. Predicting and evaluating response to omalizumab in patients with severe allergic asthma. Respir. Med. 101(7), 1483–1492 (2007).

Among new asthma therapies, omalizumab is the only monoclonal antibody that has been proven to be effective and safe in treating severe, inadequately controlled asthma. Nevertheless, it has been pointed out that not all patients respond to it. This paper analyzes the results of a recent study that was aimed at achieving a more accurate evaluation of the response to omalizumab in patients with severe allergic asthma, by identifying possible pretreatment characteristics that can be predictive of a better and superior response to omalizumab. The results established that it is difficult to predict which patients will gain most benefit from treatment, according to pretreatment baseline characteristics.     

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.     

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.     

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.     

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.     

Effects of omalizumab on markers of inflammation in patients with allergic asthma

Asthma is a chronic inflammatory disease of the airways in which immunoglobulin E (IgE) plays a key role by activating a variety of inflammatory cells through interactions with FcɛRI and FcɛRII receptors. The role of IgE in allergic inflammation provided the rationale for developing omalizumab, a humanized monoclonal anti-IgE antibody, for patients with moderate-to-severe or severe allergic asthma. The reductions in circulating levels of IgE resulting from omalizumab treatment leads to reductions in FcɛRI expression on mast cells, basophils and dendritic cells. This combined effect results in attenuation of several markers of inflammation, including peripheral and bronchial tissue eosinophilia and levels of granulocyte macrophage colony stimulating factor, interleukin (IL)-2, IL-4, IL-5 and IL-13. By blocking IgE binding to its receptors and diminishing dendritic cell FcɛRI receptor expression, omalizumab may also reduce allergen presentation to T cells and the production of Th2 cytokines. The anti-inflammatory effects of omalizumab may, therefore, explain the reductions in asthma exacerbations and symptoms seen in clinical trials in patients with moderate-to-severe or severe, persistent, inadequately controlled allergic asthma.     

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.     

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.     

Cost-effectiveness of omalizumab in patients with severe persistent allergic asthma

BACKGROUND: The health, economic and societal burden of asthma is considerable, and is greatest in patients with severe asthma, particularly when inadequately controlled. Real-life studies that assess the effectiveness of treatment are of particular interest. METHODS: We determined the incremental cost-effectiveness ratio (ICER) of adding omalizumab to standard therapy using data from the real-life 1-year randomized open-label study (ETOPA) and using Canada as a reference country. Only patients receiving high-dose ICS plus LABA were included in the analysis, reflecting the EU label for omalizumab. Costs and quality-adjusted life years (QALYs) gained were used to calculate the ICER for omalizumab (cost/QALY). Probabilistic sensitivity analysis was performed to determine the 95% confidence interval and one-sided sensitivity analyses were performed. RESULTS: The base case lifetime analysis of standard therapy vs standard therapy plus add-on omalizumab for the first 5 years, gave an ICER of 31,209 Euro. Probabilistic sensitivity analysis indicated that the 95% confidence interval around the ICER was 27,739-40,840 Euro. The ICER range for one-way sensitivity analyses was 23,762 Euro without discounting to 66,443 Euro without inclusion of asthma-related mortality. CONCLUSIONS: This study demonstrates that add-on omalizumab therapy is cost-effective in patients with severe persistent allergic asthma.     

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.     

Omalizumab therapy: patients who achieve greatest benefit for their asthma experience greatest benefit for rhinitis

Background:  Asthma and rhinitis are considered components of a single IgE-mediated inflammatory disorder. However, despite being shown to often co-exist, they are typically treated as independent conditions. Omalizumab, an anti-IgE antibody, has proven effective in the treatment of both asthma and rhinitis.
Aims:  To examine whether a response to omalizumab in terms of asthma control predicts a higher likelihood of rhinitis response in patients with concomitant allergic asthma and rhinitis.
Methods:  This post hoc analysis was conducted on efficacy results from the SOLAR trial in which patients with moderate-to-severe asthma and rhinitis were randomized to receive omalizumab or placebo for 28 weeks. Patients were classified as asthma responders based on the physician's overall assessment (complete control or marked improvement in a five-level evaluation). Rhinitis responders were identified using the Rhinitis Quality of Life Questionnaire (RQLQ) questionnaire (≥ 1.0 point improvement in overall score).
Results:  Data were available for 207 omalizumab-treated patients and 192 placebo patients. According to the physicians overall assessment, 123 (59.4%) of omalizumab-treated patients were asthma responders, with the likelihood of a rhinitis response significantly ( P   <  0.001) greater in these patients than in the placebo group. The odds ratio for rhinitis response in omalizumab-treated asthma responders vs nonresponders was 3.56 (95% CI: 1.94–6.54).
Conclusions:  A response in terms of asthma following omalizumab therapy is associated with a significantly increased probability of improvement in rhinitis.     

Improvement of asthma control with omalizumab in 2 obese pediatric asthma patients.

BACKGROUND: Dosing of the anti-IgE antibody (omalizumab) in the treatment of allergic asthma depends on serum IgE concentration and body weight. It is unclear whether omalizumab is therapeutically effective in obese patients with difficult-to-control asthma whose body weights fall outside dosing guidelines. OBJECTIVE: To report the efficacy of omalizumab in 2 obese pediatric patients with severe persistent asthma whose high body weights placed them outside current dosing guidelines. METHODS: Omalizumab was given at maximum doses to both patients. Standard asthma therapy was continued throughout the treatment period. Multiple parameters of asthma disease activity were followed at every health encounter for approximately 1 year during and before omalizumab treatment. These parameters included asthma disease severity and activity, pulmonary functions, daily inhaled corticosteroid requirements, systemic steroid rescue, and urgent care and emergency department visits and hospitalizations. RESULTS: While receiving omalizumab, both patients had improvements in asthma disease activity and reduction in systemic steroid requirements. One patient required fewer daily inhaled corticosteroids and achieved total asthma control. CONCLUSION: Patients with difficult-to-treat asthma may benefit from receiving omalizumab even if they fall outside current dosing guidelines because of high body weight.     

Cost-effectiveness analysis of omalizumab in adults and adolescents with moderate-to-severe allergic asthma

BACKGROUND: Omalizumab can reduce hospitalization and emergency department visits and improve quality of life in patients with moderate-to-severe, suboptimally controlled allergic asthma. Given the high cost and modest efficacy of this agent, it is not clear that it is cost-effective if given to a broad population with asthma. OBJECTIVE: The purpose of this study was to evaluate the cost-effectiveness of omalizumab in adults and adolescents with moderate-to-severe allergic asthma. METHODS: A retrospective economic analysis was performed to determine the cost-effectiveness of omalizumab using 52-week data from 2 randomized controlled clinical trials in adults and adolescents with moderate-to-severe allergic asthma. The analysis was conducted from a third-party payer's perspective, and only direct costs were considered. RESULTS: The incremental cost-effectiveness ratios showed that the cost to achieve an additional successfully controlled day was $523, and the daily cost to achieve at least a 0.5-point increase in Asthma Quality of Life Questionnaire score was $378 in 2003 dollars. CONCLUSION: From a pharmacoeconomic standpoint, omalizumab would be better used in allergic asthmatic patients with poorly controlled symptoms despite maximal therapy, given the high cost and modest efficacy of this agent. It could be cost saving if given to nonsmoking patients who are hospitalized 5 or more times or 20 days or longer per year despite maximal asthma therapy.     

Relationship between pretreatment specific IgE and the response to omalizumab therapy

Background:  Omalizumab, an anti-IgE antibody, has proven efficacy in patients with moderate-to-severe and severe persistent allergic (IgE-mediated) asthma. While previous analyses have had some limited success in predicting which patients will gain greatest benefit based on pretreatment baseline characteristics, it remains important to try to improve this predictability.
Methods:  Following a run-in phase, patients (12–75 years) inadequately controlled despite current therapy were randomized to receive omalizumab or placebo for 28 weeks in a double-blind, parallel-group, multicenter study (INNOVATE). Univariate analyses were performed to assess whether pretreatment specific IgE serum levels and related variables could be identified that were predictive of a response to omalizumab patients ( n  = 337) enrolled in INNOVATE. Response was measured via variables including exacerbations, QoL, FEV₁ and physicians' overall assessment.
Results:  A total of 305 patients (90.5%) were sensitive to more than one allergen and the majority of patients were positive to D1 Dermatophagoides pteronyssinus and D2 Dermatophagoides farinae . Patients with relatively high values of D1 or D2, but with these making a relatively low contribution to total specific IgE load, appeared to attain most benefit from omalizumab. However, no consistent predictive effect for omalizumab response was observed either for total specific IgE or levels of IgEs specific for individual allergens.
Conclusions:  Based on these data, pretreatment allergen-specific IgE levels do not provide any better prediction of response to treatment as compared with pretreatment total IgE. At present, the most reliable method of identifying patients who respond to omalizumab treatment remains a physician's assessment.     

Airway inflammation and eotaxin in exhaled breath condensate of patients with severe persistent allergic asthma during omalizumab therapy

PurposeThe central role of IgE in allergic inflammation in asthma has provided a rationale for the development of omalizumab, the humanized monoclonal anti-IgE antibody. The aim of the study was to determine the effect of omalizumab treatment on changes in airway inflammatory process and eotaxin in exhaled breath condensate in patients with persistent severe allergic asthma.Material and MethodsThe study was performed on a group of 19 patients with severe persistent allergic asthma treated with conventional therapy (according to GINA 2006) and with or without omalizumab (9 vs 10 patients). Eotaxin in exhaled breath condensate, exhaled nitric oxide, blood eosinophil count and serum ECP were measured before and after 16 weeks of therapy.ResultsIn the group treated with omalizumab, a statistically significant decrease in the concentrations of eotaxin in EBC, FENO, serum ECP, and blood eosinophil count after 16 weeks of treatment was observed. Statistically significant correlations were revealed between the decrease in eotaxin and the decrease in FENO, serum ECP and blood eosinophil count after omalizumab therapy.ConclusionsDownregulation of eotaxin expression in the airways through limitation of eosinophilic inflammation could be essential in the beneficial effect of anti-IgE therapy with omalizumab in asthma patients.