Omalizumab is a recombinant humanized monoclonal antibody that blocks the high-affinity Fc receptor of IgE. Omalizumab has been approved for the treatment of moderate to severe asthma; however, there is currently more and more data showing promising results in the management also of chronic urticaria. We present a case series of 19 patients with chronic urticaria treated in a university department with omalizumab and give an overview of the existing literature comprising an additional 59 cases as well as a total of 139 patients enrolled in two randomized controlled trials comparing omalizumab with placebo. The collective evidence points to omalizumab as a safe and effective treatment option for patients with chronic urticaria who do not sufficiently respond to standard therapy as recommended by existing guidelines.
Omalizumab; Anti-IgE; Chronic urticaria; Biologics
Chronic urticaria (CU) is a common and debilitating disease, and the need for effective treatment has increased. Omalizumab may be an alternative regimen in patients with CU who do not respond to conventional treatments. The aim of this study is to investigate the efficacy and to observe the clinical results of omlizumab in patients with refractory CU.
We conducted a retrospective analysis of 26 patients with refractory CU who were treated with omalizumab. Omalizumab was administered every 2 or 4 weeks, depending on body weight and the total serum IgE level, for 24 weeks.
Fourteen patients (53.8%) achieved remission after the treatment; they had a significantly higher prevalence of personal (P=0.033) and family history of allergic diseases (P=0.002) than those who did not achieve remission. During omalizumab treatment, the urticaria activity score declined significantly (12.11±1.97 to 2.7±4.23; P=0.001) and the CU-quality of life score improved significantly (34.65±13.58 to 60.88±11.11; P=0.004). There were significant decreases in the use of systemic steroids (42.3%-11.5%; P=0.027) and immunomodulators (65.4%-19.2%; P=0.002). The dose of antihistamines required to control CU also decreased significantly (215.66±70.06 to 60.85±70.53 mg/week of loratadine equivalents; P<0.001). No serious adverse event was noted.
These findings suggest that omalizumab can be an effective and safe treatment in patients with refractory CU.
Chronic urticaria; refractory; omalizumab
Omalizumab has been shown to be effective in chronic urticaria (CU) patients in numerous reports. However, it remains unknown whether there are specific phenotypes of CU that are more responsive to omalizumab therapy. We sought to identify CU phenotypes responsive to treatment with omalizumab by characterizing patients and their response patterns. A retrospective chart review analysis of refractory CU patients unresponsive to high-dose H1-blockers and immunomodulators and subsequently treated with omalizumab at the University of Wisconsin Allergy Clinic was performed with particular focus on their autoimmune characteristics, response to therapy, and dosing parameters. We analyzed 19 refractory CU patients (16 patients failed or had toxic side effects to immunomodulators) treated with omalizumab with an overall response rate of 89% (17/19). Of these 19 patients, 9 patients (47%) had a complete response, 8 patients (42%) had a partial response, and 2 patients (11%) had no response. In comparing the response patterns to omalizumab, we found no statistically significant differences among “autoimmune positive” versus “autoimmune negative” patients. No statistically significant differences in responses were observed when comparing demographic parameters including age, gender, IgE levels, or dosing regimen. Our study shows that omalizumab has robust efficacy in refractory CU patients regardless of their autoimmune status, age, gender, IgE levels, or dosing protocol.
Age; ANA; antithyroid antibodies; autoimmune; CU Index; gender; high-dose antihistamine; IgE; omalizumab; urticaria
Omalizumab, a humanized monoclonal anti-IgE antibody has the potential to alter allergen processing. Recently, it has been postulated the assessment of PHA-stimulated adenosine triphosphate (ATP) activity as maker of CD4+ T cells activity in peripheral blood cells. We present the case report of a 35-year-old woman with a history of chronic idiopathic urticaria and angioedema of 8 years of development with poor response to treatment. The patient was partially controlled with cyclosporine at doses of 100 mg/12 h. However, she was still developing hives daily. Finally treatment with omalizumab was started at dose of 300 mg every 2 weeks. The patient experienced a decrease in urticarial lesions 2 days after starting therapy. We also evaluated the effects of omalizumab therapy on the activity of peripheral blood CD4+ T cells from the patient, in order to determine the potential modification of anti-IgE therapy on the process of antigen presentation-recognition. Activity of CD4+ cells by ATP release was clearly increased demonstrating an enlarged CD4 activity. Omalizumab may be useful in the treatment of severe chronic urticaria. ATP activity of peripheral blood CD4+ T cells might be a non-subjective method to assess Omalizumab activity.
Chronic idiopathic urticaria is a condition that is often controllable with antihistamine therapy. However, some patients have disease burden that is difficult to manage, non-responsive to antihistamines and often requires immunosuppressive medications such as corticosteroids or cyclosporine. We present here a study that demonstrates the effectiveness of omalizumab in treating this condition and the temporal relationship between improvement and down regulation of the high affinity IgE receptor (FcεRI). For this, blood samples were obtained from a symptomatic patient before each treatment and processed for flow cytometric analysis of FcεRI levels on the surface of blood basophils. Down regulation of FcεRI was observed in association with significant clinical improvement and discontinuation of immunosuppressive medications.
We report 2 patients with cold urticaria with different response to treatment with omalizumab (Xolair®). Cold contact urticaria (CCU) is a common subtype of physical urticaria. It is characterized by the development of wheal and/or angioedema within minutes after cold contact. Clinical manifestation of CCU can range from mild, localized whealing to life-threatening anaphylactic shock reactions. Omalizumab has been described to be useful in cases of chronic urticaria and may be an interesting option for treatment of CCU. We describe one patient with significant and long-lasting improvement of symptoms and one without any improvement after anti-immunoglobulin E therapy. In our case reports, we want to highlight that there is still a small group of patients without benefit from omalizumab treatment. It is necessary to identify this minor subgroup of patients where omalizumab does not represent an effective treatment possibility.
Anti-immunoglobulin E; Cold contact urticaria; Omalizumab; Physical urticaria
Chronic urticaria (CU) is a common disorder characterized by recurrent episodes of urticaria pruritic erythematous lesions, associated with angioedema1. It affects 0.1% of the population, it is estimated that approximately 15 to 25% of the population will have hives at some point in their lives.2 About 80% of UC patients are diagnosed as idiopathic chronic urticaria and that no cause is identified, 3 experiencing deterioration in their quality of life affecting your work, social relationships, schemes requiring multiple medications and doses higher than usual. This study proposes Omalizumab (anti-IgE humanized antibody) as a treatment for Refractory Chronic Urticaria (RCU)
Demonstrate Omalizumab's effectiveness in the treatment of Refractory Chronic Urticaria.
A clinical study, was carried out to evaluate the effectiveness of the Omalizumab's treatment on RCU diagnosed patient, including male and female patients ages 12 to 50 diagnosed with RCU, with Scorad higher tan 30 points. We made a questionnaire to know about the patient's family background, skin symptoms beginning, administration of drugs such sistemic steroids, inmunosupresors, calceurine inhibitors, presence of inmunotherapy and age of start. Omalizumab was administered on doses according patient's weight and IgE levels, bimonthly or monthly according to treatment guides. Severeness level was calculated with scorad every 1 month, with IgE seric level measurement and life quality questionnaire.
5 patients diagnosed with RCU were included in the group of Omalizumab and 5 patients in the control group (placebo). All patients were female. A gradual decrease on the life quality score and in Score, with a significant P under 0.05 was observed on all patients treated with omalizumab compared with patient in the group with placebo.
Treatment with Omalizumab progressively decreases the severeness level on RCU, with a significant improvement on the patient's life quality.
Churg-Strauss Syndrome (CCS) is a rare systemic necrotizing small vessel vasculitis associated with bronchial asthma, peripheral blood eosinophilia and eosinophilic lung infiltration. Skin changes compatible with vasculitis are present in about 75% of patients. Previous reports suggest that patients with CSS can be treated with anti-IgE (omalizumab) in addition to conventional therapy to achieve asthma control. Here we report the efficacy of a 6-month treatment with omalizumab in a patient with CSS characterized by severe asthma and urticarial vasculitis.
A 44 year old Caucasian female with a 5 year history of severe asthma, chronic urticaria and mild eosinophilia (1100/μL) was evaluated for possible CSS. Total serum IgE was 662 KU/l with positive skin prick tests for dust mites. Bronchial asthma was not controlled and FEV1 was 60% despite treatment with budesonide (640 mcg/die) and formoterol (18 mcg/die). Diffuse and confluent urticarial rash occurred in the last 6 months before evaluation and responded neither to prednisone (10 mg/die) and rupatadin (10 mg/die) nor to immunosuppressive agents (cyclosporin 200 mg/die or azathioprin 100 mg/die). The patient was treated, as add-on therapy, with omalizumab (300 mg s.c. every 2 weeks) accordingly to total IgE and weight parameters reported in the drug information leaflet.
After 6 months of treatment the patient reported a significant improvement in asthma control with 50% reduction of nocturnal awakenings and asthma exacerbations and a major FEV1 improvement (101% at 16 weeks and 103% at 24 weeks). Eosinophil count was reduced to 600/μL. A 75% reduction of oral prednisone was registered after 8 weeks of treatment. Importantly, urticarial lesions disappeared after the first injection of omalizumab. Omalizumab injections were well tolerated and no adverse event was recorded.
This case suggests that omalizumab can be beneficial and safe in patients affected by CSS with severe asthma and urticarial vasculitis. In addition to its effect on serum IgE, efficacy of omalizumab in CSS may be related to an inhibitory effect on blood eosinophilia.
The chronic Urticaria is a real problem of health and a frequent problem in the consultation of the allergist, which the treatment is not to satisfactory. Some Urticaria can be for autoimmunity where the antibody involved is IgE. Omalizumab is an monoclonal antibody against the C3 domain of the epsilon heavy chain of the antibody IgE (domain C3 of the IgE), involved, in allergic problems, which has proved a great utility in asthma off difficult control.
Five patients of both genders were studied aged between 30 and 45 years, carriers of chronic Urticaria at least of ten years duration. Theirs control was not satisfactory, with the treatment habitual. They were not used glucocorticoids. The clinical evaluation and test of laboratory stated Chronic Urticaria idiopathic. The total IgE was below 100 U. I. The monoclonal antibody Omalizumab applying it for 6 month accorded to habitual schedule.
According to dose schedule monoclonal antibody Omalizumab apply the antibody to them, calculating the dose habitual schedule applying for 6 month. According to dose schedule the monoclonal antibody Omalizumab apply to them, it applying for 6 month.
All the patient improved their Urticaria between weeks 3 and fort of application of the drug, getting the control of the symptoms between the month 2 and 3 in the 5 patients, without requiring other drugs for their control, and remained asymptomatic for 3 and forth months discontinuity the product up to 6 months, not reactivity the Urticaria, the older case takes now 1 year without activity of his disease.
Omalizumab must be considered to be another therapeutic alternative in patients with idiopathic Urticaria.
Chronic urticaria is a common skin disease. In about 45% of patients the cause is an autoantibody directed at the α-subunit of the high-affinity IgE receptor (chronic autoimmune urticaria; CAU). Omalizumab is a monoclonal anti-IgE antibody that has a proven role in the treatment of various allergic diseases. We gave omalizumab once every month for 16 weeks to three patients that were refractory to standard treatment, including high doses of antihistamines, leukotriene receptor antagonist, and corticosteroid. There was dramatic improvement in the primary efficacy variable—the change in mean urticaria activity score (UAS) from baseline (i.e., the average over the first 4-week period before omalizumab) to the final 4-week period of omalizumab treatment. There was improvement in the secondary efficacy variables, which included change from baseline in interference with sleep, interference with daily activities, daily diary record of urticaria signs and symptoms based on a scoring system, and rescue medication use. These improvements persisted for 12 weeks after discontinuation of the drug. Omalizumab may have a role in treating refractory cases of CAU.
This guideline is a result of a consensus reached during the 19th Asian-Australasian Regional Conference of Dermatology by the Asian Academy of Dermatology and Venereology Study Group in collaboration with the League of Asian Dermatological Societies in 2010. Urticaria has a profound impact on the quality of life in Asia and the need for effective treatment is required. In line with the EAACI/GA2LEN/EDF/WAO guideline for the management of urticaria the recommended first-line treatment is new generation, non-sedating H1-antihistamines. If standard dosing is ineffective, increasing the dosage up to four-fold is recommended. For patients who do not respond to a four-fold increase in dosage of non-sedating H1-antihistamines, it is recommended that therapies such as H2-antihistamine, leukotriene antagonist, and cyclosporine A should be added to the antihistamine treatment. In the choice of second-line treatment, both their costs and risk/benefit profiles are the most important considerations.
Asia; Consensus; Guideline; Wheal; Treatment; Urticaria
Controlled trials have demonstrated the efficacy of antihistamines in the treatment of chronic idiopathic urticaria. Second-generation antihistamines are recommended as first-line therapy for chronic idiopathic urticaria. The purpose of this study was to determine the effect of desloratadine, a newer, nonsedating, second-generation antihistamine, on symptoms of chronic idiopathic urticaria, disease severity, and quality of life (QoL).
In an open-label, observational, multicenter study, 348 subjects with chronic idiopathic urticaria were given 5 mg of desloratadine once daily for 2 weeks. Outcome measures included change from baseline at Day 14 using the Aerius Quality of Life Questionnaire (AEQLQ); change from baseline in pruritus score, number and maximum size of hives, sleep quality, and activity impairment; and subjects' response to therapy.
Desloratadine significantly decreased subjects' overall condition and symptom scores from baseline to Day 14 (2.19 ± [SD] 0.66 and 1.14 ± 0.89, respectively; P < 0.0001). Desloratadine treatment significantly improved all 10 AEQLQ domain scores from baseline to Day 7 and Day 14 (P < 0.0001). Sleep disturbance scores decreased 40% from baseline to Day 7 (1.42 ± 1.03 to 0.85 ± 0.89, respectively), and interference with daily outdoor activity scores showed a 41% decrease from baseline to Day 7 (1.11 ± 0.98 to 0.66 ± 0.90) (P < 0.0001 for both). There were significant reductions in itching, size of hives, and hive score at both Days 7 and 14. Treatment resulted in moderate, marked, or complete relief of symptoms in 76.2% of subjects. Desloratadine was well tolerated, with no adverse events reported.
In an open-label, observational study, desloratadine 5 mg once daily significantly decreased symptoms of chronic idiopathic urticaria and improved subject QoL.
Chronic Idiopathic Urticaria; Desloratadine; Quality of Life
This consensus statement was developed by Special Interest Group – Urticaria (IADVL). Urticaria, a heterogeneous group of diseases, often cannot be recognized by its morphology. Due to non-specific and non-affordable diagnosis, management of urticaria, especially chronic urticaria, is very challenging. This guideline includes definition, causes, classification and management of urticaria. Urticaria has a profound impact on the quality of life and causes immense distress to patients, necessitating effective treatment. One approach to manage urticaria is identification and elimination of the underlying cause(s) and/or eliciting trigger(s), while the second one is treatment aimed at providing symptomatic relief. This guideline recommends use of second-generation non-sedating H1 antihistamines as the first-line treatment. The dose can be increased up to four times to meet the expected results. In case patients still do not respond, appropriate treatment options can be selected depending on the cost.
Chronic urticaria; consensus statement; definition; treatment; urticaria
Vasculitic urticaria (UV) is a condition characterized by hives lasting more than 24 hours, itchy and burning with residual hyperpigmentation. Histopathology is characterized by leukocytoclastic vasculitis, perivascular infiltrate and fibrin deposits. The incidence is approximately 2%, prevalence in women (5:1). The treatment includes steroids, immunosuppressants, and has suggested the use of monoclonal antibodies. We report a patient treated with omalizumab.
Female 51 years old, his mother died of complications from Lupus Erythematosus (SLE). 10 years ago was diagnosed with SLE by criteria haematological and immunological joints treated with azathioprine, chloroquine and deflazacort, with control of lupus, immunosuppressive suspended and continuing low-dose steroids. Have hives as secondary reaction to netilmicin and penicillin. Two years ago shows like lesions papules and burning and itching rash on chest and limbs, with no peeling hyperpigmented macules, managed with systemic steroids (prednisone) and antihistamines, with a decrease of the same but has l month after similar injuries, and macula, adjust the dose of steroid 1 mg/kg with a decrease in events with exacerbations and remissions, until 3 months course again with increasing symptoms with erythematous, violaceous, painful to the touch did not disappear in extremities lower, upper abdomen and chest, with no improvement after systemic steroids, antihistamines, and immunosuppressants, laboratories report 4.600 leukocytes, eosinophils 100/mcl, 90.1 mgU/dl C3, C4 8.6 mg/dL of 169 I U IgE/mL, leukocytoclastic vasculitis biopsy reports, deciding Omalizumab use was calculated based on weight and IgE, showing significant improvement with disappearance of the lesions, without pain or itching with hives.
Gradual decrease was observed of Score of 6 to 1 and score-related quality of of life with a 84.37 to 42.36 CUQ2oL after 3 applications, with a significant P by comparing the results and statistical analysis.
We conclude that Omalizumab may be useful in the treatment of vasculitic urticaria, although it requires clinical trials that include a greater number of patients and be compared with conventional treatment.
A novel anti-immunoglobulin E (anti-IgE) therapy for asthma, omalizumab, has been approved for use in Canada.
To review the basic and clinical data for omalizumab, and to examine its possible role for asthma management in Canada.
A literature search from 1960 to 2006 was conducted in MEDLINE to identify studies of omalizumab. In addition, abstracts from recent respiratory and allergy scientific meetings were sought, and any unpublished data were requested from the manufacturer. A consensus panel of respiratory and allergy specialists reviewed and summarized the data, and derived a set of recommendations for omalizumab use.
Omalizumab is a humanized monoclonal antibody designed to bind to the C epsilon 3 domain of the IgE molecule, forming soluble immune complexes that are cleared by the reticuloendothelial system. Subcutaneous injections, given at two- or fourweek intervals at the recommended dose, result in a rapid decrease in free circulating IgE levels. In two phase III clinical trials of 1405 adult and adolescent patients with moderate to severe asthma maintained on moderate doses of inhaled corticosteroids (ICS), omalizumab reduced exacerbation rates compared with placebo, and was associated with improved symptoms and a greater corticosteroid-sparing effect. In a trial of 419 patients with severe disease that was uncontrolled despite the use of high-dose ICS and concurrent long-acting beta2-agonists, severe exacerbations were 50% less frequent in omalizumab-treated patients than in control subjects. Retrospective analyses have identified the characteristics of patients most likely to respond to omalizumab treatment.
Omalizumab may be considered as a potential adjunctive therapy in atopic patients with severe asthma uncontrolled by conventional therapy with optimal doses of ICS and appropriate adjunctive therapy (eg, long-acting beta2-agonists). Typically, patients are identified by the need for frequent short course or continuous oral corticosteroids. Therapy should be initiated only after review by a specialist to confirm the diagnosis and that conventional therapy is optimal.
Asthma severity; Atopy; IgE; Monoclonal antibodies
Omalizumab has demonstrated efficacy among patients with moderate to severe persistent allergic asthma, whose symptoms are inadequately controlled with other controller agents. This therapy is generally well tolerated, but there are some safety considerations, the most important of which is the rare, but potentially life-threatening, occurrence of omalizumab-associated anaphylaxis.
In Canada, data from the manufacturer of omalizumab indicate that the frequency of anaphylaxis attributed to Xolair in post-marketing use is approximately 0.2%. Other researchers, including the American Omalizumab Joint Task Force (OJTF), have suggested a lower overall frequency of 0.09%.
This paper provides a summary of the epidemiologic research carried out to date and presents a concise, practical set of recommendations for the prevention, monitoring and management of omalizumab-associated anaphylaxis. Prevention tips include advice on patient education measures, concomitant medications and optimal administration. For the first three injections, the recommendation is to monitor in clinic for two hours after the omalizumab injection; for subsequent injections, the monitoring period should be 30 minutes or an appropriate time agreed upon by the individual patient and healthcare professional.
In the event that a patient does experience omalizumab-associated anaphylaxis, the paper provides recommendations for handling the situation in-clinic and recommendations on how to counsel patients to recognize the potential signs and symptoms in the community and react appropriately.
IgE antibodies are a pivotal factor in pathophysiology of allergic diseases, and the possibility of reducing their level by anti-IgE has long been envisioned. Following several attempts, an effective biologic agent was obtained with the recombinant humanized mono-clonal antibody (rhuMAb)-E25, known as omalizumab. A number of controlled clinical trials demonstrated its efficacy and safety in the treatment of severe allergic asthma uncontrolled by standard drug treatment with maximal recommended doses, and treatment with omalizumab is currently included in international guidelines on asthma management. Other studies reported a clear effectiveness also in allergic rhinitis, but the cost of the anti-IgE treatment suggests its use in patients with rhinitis concomitant with asthma. Other indications to be further investigated are skin disorders such as atopic dermatitis and IgE-mediated urticaria, as well as adverse reactions to foods, with a particularly important role in preventing food-induced anaphylaxis. Finally, there are data indicating the usefulness of omalizumab when used in combination with allergen specific immunotherapy, in terms of reducing the adverse reactions to treatment and increasing the clinical efficacy.
IgE; anti-IgE; omalizumab; allergic asthma; allergic rhinitis; atopic dermatitis; food allergy; allergen immunotherapy
Atopic diseases and asthma are increasing at a remarkable rate on a global scale. It is now well recognized that asthma is a chronic inflammatory disease of the airways. The inflammatory process in many patients is driven by an immunoglobulin E (IgE)-dependent process. Mast cell activation and release of mediators, in response to allergen and IgE, results in a cascade response, culminating in B lymphocyte, T lymphocyte, eosinophil, fibroblast, smooth muscle cell and endothelial activation. This complex cellular interaction, release of cytokines, chemokines and growth factors and inflammatory remodeling of the airways leads to chronic asthma. A subset of patients develops severe airway disease which can be extremely morbid and even fatal. While many treatments are available for asthma, it is still a chronic and incurable disease, characterized by exacerbation, hospitalizations and associated adverse effects of medications. Omalizumab is a new option for chronic asthma that acts by binding to and inhibiting the effects of IgE, thereby interfering with one aspect of the asthma cascade reviewed earlier. This is a humanized monoclonal antibody against IgE that has been shown to have many beneficial effects in asthma. Use of omalizumab may be influenced by the cost of the medication and some reported adverse effects including the rare possibility of anaphylaxis. When used in selected cases and carefully, omalizumab provides a very important tool in disease management. It has been shown to have additional effects in urticaria, angioedema, latex allergy and food allergy, but the data is limited and the indications far from clear. In addition to decreasing exacerbations, it has a steroid sparing role and hence may decrease adverse effects in some patients on high-dose glucocorticoids. Studies have shown improvement in quality of life measures in asthma following the administration of omalizumab, but the effects on pulmonary function are surprisingly small, suggesting a disconnect between pulmonary function, exacerbations and quality of life. Anaphylaxis may occur rarely with this agent and appropriate precautions have been recommended by the Food and Drug Administration (FDA). As currently practiced and as suggested by the new asthma guidelines, this biological agent is indicated in moderate or severe persistent allergic asthma (steps 5 and 6).
Omalizumab, a humanized monoclonal antibody that binds circulating IgE antibody, is a treatment option for patients with moderate to severe allergic asthma whose asthma is poorly controlled with inhaled corticosteroids and inhaled long-acting β2 agonist bronchodilators. This review considers the mechanism of action, pharmacokinetics, efficacy, safety and place in management of omalizumab in asthma and focuses particularly on key articles published over the last three years. Omalizumab reduces IgE mediated airway inflammation and its effect on airway remodeling is under investigation. Recent long-term clinical trials confirm the benefits of omalizumab in reducing exacerbations and symptoms in adults and in children with moderate to severe allergic asthma. No clinical or immunological factor consistently predicts a good therapeutic response to omalizumab in allergic asthma. In responders, the duration of treatment is unclear. The main adverse effect of omalizumab is anaphylaxis, although this occurs infrequently. Preliminary data from a five-year safety study has raised concerns about increased cardiovascular events and a final report is awaited. Clinical trials are in progress to determine whether omalizumab has efficacy in the treatment of non-allergic asthma.
IgE; severe asthma; allergic asthma; omalizumab
Atopic dermatitis (AD) is a chronic cutaneous inflammatory disease. Various categories of therapeutic medications are used for treating AD. Omalizumab is a monoclonal anti-IgE antibody that binds to IgE molecules at the high-affinity receptor (FcεRI) binding site. Therefore, omalizumab can be used as a potential new systemic treatment agent for recalcitrant AD patients with elevated IgE levels. A 34-year-old man had been treated for AD with several topical and oral agents. However, he was refractory to these therapies and his serum IgE levels were very high. We treated him with omalizumab. After 8 months of the treatment, his symptoms were notably improved and the SCORAD index was decreased. Thus, we report on the first case of recalcitrant AD that was successfully treated with omalizumab in Korea.
Atopic dermatitis; Biologies; Omalizumab
Current therapy for allergic bronchopulmonary aspergillosis (ABPA) uses oral corticosteroids, exposing patients to the adverse effects of these agents. There are reports of the steroid-sparing effect of anti-IgE therapy with omalizumab for ABPA in patients with cystic fibrosis (CF), but there is little information on its efficacy against ABPA in patients with bronchial asthma without CF.
To examine the effects of omalizumab, measured by asthma control, blood eosinophilia, total serum immunoglobulin E (IgE), oral corticosteroid requirements, and forced expiratory volume spirometry in patients with ABPA and bronchial asthma.
A retrospective review of charts from 2004–2006 of patients treated with omalizumab at an academic allergy and immunology practice in the Bronx, New York were examined for systemic steroid and rescue inhaler usage, serum immunoglobulin E levels, blood eosinophil counts, and asthma symptoms, as measured by the Asthma Control Test (ACT).
A total of 21 charts were screened for the diagnosis of ABPA and bronchial asthma. Four patients with ABPA were identified; two of these patients were male. The median monthly systemic corticosteroid use at 6 months and 12 months decreased from baseline usage. Total serum IgE decreased in all patients at 12 months of therapy. Pre-bronchodilator forced expiratory vital capacity at one second (FEV1) was variable at 1 year of treatment. There was an improvement in Asthma Control Test (ACT) symptom scores for both daytime and nighttime symptoms.
Treatment with omalizumab creates a steroid-sparing effect, reduces systemic inflammatory markers, and results in improvement in ACT scores in patients with ABPA.
allergic bronchopulmonary aspergillosis; omalizumab; asthma
Research has underscored the effects of exposure and sensitization to allergens on the severity of asthma in inner-city children. It has also revealed the limitations of environmental remediation and guidelines-based therapy in achieving greater disease control.
We enrolled inner-city children, adolescents, and young adults with persistent asthma in a randomized, double-blind, placebo-controlled, parallel-group trial at multiple centers to assess the effectiveness of omalizumab, as compared with placebo, when added to guidelines-based therapy. The trial was conducted for 60 weeks, and the primary outcome was symptoms of asthma.
Among 419 participants who underwent randomization (at which point 73% had moderate or severe disease), omalizumab as compared with placebo significantly reduced the number of days with asthma symptoms, from 1.96 to 1.48 days per 2-week interval, a 24.5% decrease (P<0.001). Similarly, omalizumab significantly reduced the proportion of participants who had one or more exacerbations from 48.8 to 30.3% (P<0.001). Improvements occurred with omalizumab despite reductions in the use of inhaled glucocorticoids and long-acting beta-agonists.
When added to a regimen of guidelines-based therapy for inner-city children, adolescents, and young adults, omalizumab further improved asthma control, nearly eliminated seasonal peaks in exacerbations, and reduced the need for other medications to control asthma. (Funded by the National Institute of Allergy and Infectious Diseases and Novartis; ClinicalTrials.gov number, NCT00377572.)
Omalizumab is a recombinant DNA-derived humanized immunoglobulin G (IgG) anti-IgE monoclonal antibody approved for use in patients with allergic asthma. However, it is not approved for allergic bronchopulmonary aspergillosis (ABPA). Conflicting reports exist about the effects of omalizumab on ABPA in patients with cystic fibrosis (CF). We report 2 patients with CF treated with omalizumab, in whom frequency of ABPA exacerbations was markedly reduced with treatment. Additionally, hospitalizations were reduced from 5 per year to once in 18 months in the first patient and from twice to once per year in the second patient. Free IgE decreased by 87.9% after 6 months of therapy in the first patient and by 95.6% after 7 months of therapy in the second patient. Neither of the two patients had evidence of asthma. Omalizumab may be useful in treating ABPA in patients with CF, and including free IgE in monitoring the response to therapy will be helpful.
Allergic bronchopulmonary aspergillosis; cystic fibrosis; free IgE; omalizumab