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1.  Omalizumab for Chronic Urticaria: A Case Series and Overview of the Literature 
Case Reports in Dermatology  2012;4(1):19-26.
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.
doi:10.1159/000336205
PMCID: PMC3322628  PMID: 22493579
Omalizumab; Anti-IgE; Chronic urticaria; Biologics
2.  Omalizumab in recurring larynx angioedema: a case report 
Asia Pacific Allergy  2014;4(2):129-130.
Angioedema with swelling of larynx is a serious allergic reaction and can be life-threatening. It can occur after exposure to various triggers and usually it is very difficult for the patient and the doctor to find the trigger and maintain complete remission. In idiopathic recurring angioedema presenting with frequent attacks, prophylaxis with H1 antihistamines recommended. However, not all patients respond to antihistamines. Omalizumab is an anti-immunoglobulin (Ig)-E-Ig-G antibody approved for the treatment of asthma and also effective treatment in chronic spontaneous urticaria. We report a 47-year-old male patient with severe idiopathic angioedema controlled by corticosteroid and proggressed after discontining of corticosteroid because of its side effects. Omalizumab at a dose of 300 mg every 4 weeks was administrated and omalizumab provided a rapid clinical response after first injection. During the 4 months of omalizumab therapy, he had no further attacks and any other treatment needs. After 3 months of stopping omalizumab therapy, during the 4-week period he had two mild lip swelling in his lips that resolved with antihistamines.
doi:10.5415/apallergy.2014.4.2.129
PMCID: PMC4005344  PMID: 24809020
Omalizumab; Angioedema; Larynx
3.  275 Efficacy of Omalizumab in the Treatment of Urticaria-Vasculitis Associated to Churg-Strauss Syndrome: A Case Report 
The World Allergy Organization Journal  2012;5(Suppl 2):S106-S107.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1097/01.WOX.0000412032.39383.49
PMCID: PMC3513125
4.  Omalizumab vs. placebo in the management of chronic idiopathic urticaria: a systematic review 
Objectives
To examine the evidence derived from randomized controlled clinical trials on the efficacy and safety of omalizumab compared to placebo in controlling symptoms of chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU).
Data source
The electronic databases PubMed, Medline, EMBASE, Biomed Central, The Cochrane Central Register of Controlled Trials (CENTRAL), Wiley, OVID, and HighwirePress were reviewed. The date limit was set to May 31th, but it was extended to September 30th of 2014 due to a new publication. No language restriction was used. The articles included were randomized trials controlled with placebo in individuals older than 12 years diagnosed with CIU/CSU refractory to conventional treatment, the intervention being, omalizumab at different doses, and the comparison, placebo. The primary outcome was symptom improvement according to the weekly score of urticaria severity (UAS7), the itch severity score (ISS), the weekly score of number of urticarial lesions, the dermatology life quality index, and the chronic urticaria quality of life questionnaire (CU-QoL). Databases were searched using the following Mesh or EMTREE key words including as intervention “omalizumab” or “humanized monoclonal antibody,” compared to placebo and the disease of interest “urticaria” or “angioedema”. The title, abstract and article were reviewed by two independent investigators, according to the selection criteria in each of the databases. An assessment of the quality of the articles was performed according to the bias tool from the studies of the Cochrane Collaboration. Information such as author data, date of study, number of participants, interventions, dose and frequency of administration, comparison, time of follow-up, measurements of weekly score of urticaria activity, pruritus severity score, weekly urticarial lesions, percentage of angioedema and post-treatment change were extracted. Frequency of adverse events and the ones suspected to be caused by the intervention drug were included.
Results
770 records were identified in all databases described. 720 were eliminated for failing to meet the inclusion criteria in the first review or for duplicate records. 24 articles were reviewed by abstract, 18 additional articles were further removed, leaving 6 records for inclusion. An experimental study was excluded because it wasn’t randomized. Five studies were finally included, with 1117 patients, of these 831 received a dose of omalizumab of 75 mg (183 patients, 16.38%), 150 mg (163 patients, 14.59%), 300 mg (437 patients, 39.12%) or 600 mg (21 patients, 1.8%), as a single dose, or every 4 weeks until 24 weeks maximum. The average age was 42.07 years, predominantly female gender and white ethnicity. It was observed that the use of omalizumab 300 mg lowered the weekly scores of urticarial activity in 19.9 vs. 6.9 on placebo (p <0.01), 19 vs 8.5 and 20.7 vs 8.01 in three studies, the weekly ISS (−9.2 vs. - 3.5, p <0.001, −9.8 vs −5.1 p < 0.01, −8.6 vs −4.0 and −9.4 vs −3.63 p <0.001 in four studies), and the percentage of angioedema-free days (omalizumab 95.5% vs. placebo 89.2% p <0.001, and 91.95% vs. 88.1% p <0.001 in two of the studies respectively).
Limitations
The different doses used throughout the study, time of administration and follow-up periods ranged from single dose to monthly dose for 24 weeks. Therefore no meta-analysis of the review was conducted.
Conclusions and implications of the main findings
Despite the limitations, it is considered that omalizumab 300 mg is effective in treating chronic idiopathic urticaria refractory to H1 antihistamines. Further studies are required to determine the duration of effective treatment.
Registration number of the systematic review
CRD42014010029 (PROSPERO. International Prospective Register of Systematic Reviews).
doi:10.1186/s40413-014-0050-z
PMCID: PMC4280746  PMID: 25566332
Antibodies; Monoclonal; Humanized; Urticaria; Angioedema
5.  Treatment of Chronic Spontaneous Urticaria 
Chronic spontaneous urticaria is defined as persistent symptoms of urticaria for 6 weeks or more. It is associated with autoimmunity in approximately 45 percent of patients. Therapy is often difficult however the initial approach should employ high-dose non-sedating antihistamines; 4-6 tablets/day may be necessary. It has been shown that the response to 4 tablets/day exceeds 3, and exceeds 2, which exceeds 1. However the dose that corresponds to the maximal dose of first generation antihistamines (hydroxyzine, diphenhydramine) used previously, is 6/day. Yet over half the patients are refractory to antihistamines and other agents should be tried next. Whereas current guidelines (published) often add leukotriene antagonists and/or H2 receptor antogonists next, these are of little utility. Likewise drugs effective for urticarial vasculitis (colchicine, dapsone, sulfasalazine, hydroxychloroquine) are effective in a small percentage of patients and no study suggests that the response rate of any of them exceeds the 30% placebo responses seen in most double-blind, placebo controlled studies. The drugs that are effective for antihistamine-resistant chronic spontaneous urticaria are corticosteroids, cyclosporine, and Omalizumab. Use of steroids is limited by toxicity. If used at all, a dose of no more than 10 mg/day should be employed with a weekly reduction of 1 mg. The response rates to cyclosporine and Omalizumab are each close to 75%. Cyclosporine can be used effectively if care is taken to monitor blood pressure, urine protein, blood urea nitrogen, and creatinine, every 6 weeks. Omalizumab has the best profile in terms of efficacy/toxicity and, once approved by federal agencies for use in chronic spontaneous urticaria, a dramatic change in the treatment paradigm, whether associated with autoimmunity or not, is predicted. A phase 3 trial is currently in place. Refractoriness to both Omalizumab and cyclosporine is expected to be less than 5 percent of patients. Other agents, can then be tried.
doi:10.4168/aair.2012.4.6.326
PMCID: PMC3479225  PMID: 23115728
Urticaria; anti IgE receptor; antihistamine; cyclosporine; omalizumab
6.  Retrospective analysis of the efficacy of omalizumab in chronic refractory urticaria 
Allergy and Asthma Proceedings  2013;34(5):446-452.
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.
doi:10.2500/aap.2013.34.3694
PMCID: PMC3753597  PMID: 23998242
Age; ANA; antithyroid antibodies; autoimmune; CU Index; gender; high-dose antihistamine; IgE; omalizumab; urticaria
7.  Treatment of Severe Cold Contact Urticaria with Omalizumab: Case Reports 
Case Reports in Dermatology  2012;4(3):275-280.
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.
doi:10.1159/000346284
PMCID: PMC3551415  PMID: 23341807
Anti-immunoglobulin E; Cold contact urticaria; Omalizumab; Physical urticaria
8.  The role of omalizumab in the treatment of severe allergic asthma 
BACKGROUND:
A novel anti-immunoglobulin E (anti-IgE) therapy for asthma, omalizumab, has been approved for use in Canada.
OBJECTIVE:
To review the basic and clinical data for omalizumab, and to examine its possible role for asthma management in Canada.
METHODS:
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.
RESULTS:
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.
RECOMMENDATIONS:
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.
PMCID: PMC2806789  PMID: 16909166
Asthma severity; Atopy; IgE; Monoclonal antibodies
9.  269 Refractory Chronic Urticaria Treated with Omalizumab 
Background
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)
Object
Demonstrate Omalizumab's effectiveness in the treatment of Refractory Chronic Urticaria.
Methods
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.
Results
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.
Conclusions
Treatment with Omalizumab progressively decreases the severeness level on RCU, with a significant improvement on the patient's life quality.
doi:10.1097/01.WOX.0000412026.08889.ad
PMCID: PMC3513034
10.  Effectiveness of omalizumab in a patient with a life-threatening episode of bronchospasm and larynx angioedema after exposure to house dust 
Omalizumab is a monoclonal antibody against IgE, nowadays approved for the treatment of persistent severe (EU) or moderate-to severe (USA) IgE-mediated asthma but there is also some evidence (case reports and four published clinical trials) on the effectiveness of this medication in urticaria and angioedema. The case of a 42-year-old woman suffering from severe allergic asthma and severe chronic urticaria with concomitant angioedema is presented in the article. She had a life-threatening episode of bronchospasm and larynx edema after exposure to house dust recorded in her medical history. The patient did not respond to standard therapy. The improvement in asthma control and remission of chronic urticaria and angioedema was achieved after introducing the therapy with omalizumab.
doi:10.5114/pdia.2014.40659
PMCID: PMC3952055  PMID: 24683397
severe asthma; chronic urticaria; life-threatening angioedema; omalizumab
11.  T cell activity in successful treatment of chronic urticaria with omalizumab 
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.
doi:10.1186/1476-7961-9-11
PMCID: PMC3159131  PMID: 21791043
12.  Effects of Omalizumab Treatment in Patients With Refractory Chronic Urticaria 
Purpose
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.
Methods
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.
Results
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.
Conclusions
These findings suggest that omalizumab can be an effective and safe treatment in patients with refractory CU.
doi:10.4168/aair.2012.4.6.357
PMCID: PMC3479230  PMID: 23115733
Chronic urticaria; refractory; omalizumab
13.  Omalizumab, an anti-immunoglobulin E antibody: state of the art 
A large number of trials show that the anti-immunoglobulin (Ig) E antibody omalizumab is very effective in patients with severe allergic asthma. This is acknowledged in consensus documents. The drug also has a good safety profile and a pharmacoeconomic advantage due to a reduction in the number of hospitalizations for asthma attacks. In recent years, some studies have shown that omalizumab is effective also in nonallergic asthma. Effects on the complex signaling mechanisms leading to activation of effector cells and to mediator release may account for this outcome. Indeed, omalizumab has been reported to be effective in a number of IgE-mediated and non-IgE-mediated disorders. Concerning the former, clinical efficacy has been observed in rhinitis, allergic bronchopulmonary aspergillosis, latex allergy, atopic dermatitis, allergic urticaria, and anaphylaxis. In addition, omalizumab has been demonstrated to be able to prevent systemic reactions to allergen immunotherapy, thus enabling completion of treatment in patients who otherwise would have to stop it. Concerning non-IgE-mediated disorders, omalizumab has been reported to be effective in nasal polyposis, autoimmune urticaria, chronic idiopathic urticaria, physical urticaria, idiopathic angioedema, and mastocytosis. Current indications for treatment with omalizumab are confined to severe allergic asthma. Consequently, any other prescription can only be off-label. However, it is reasonable to expect that the use of omalizumab will be approved for particularly important indications, such as anaphylaxis, in the near future.
doi:10.2147/DDDT.S49409
PMCID: PMC3923619  PMID: 24532966
hypersensitivity; immunoglobulin E; anti-IgE; omalizumab; asthma; atopic dermatitis; anaphylaxis; urticaria; mastocytosis
14.  Omalizumab in Children 
Paediatric Drugs  2014;16(6):491-502.
Omalizumab is a recombinant humanized monoclonal antibody that reduces levels of circulating immunoglobulin E (IgE) and expression of IgE high-affinity receptors on mast cells and basophils, interrupting the subsequent allergic inflammatory cascade. Current indications for treatment with omalizumab in pediatric patients are clearly defined and are confined to moderate-to-severe uncontrolled allergic asthma and chronic spontaneous urticaria (CSU). Any other prescription can only be off label. Data available from clinical trials conducted in children suggest that omalizumab is clinically effective and generally well tolerated. Given its mechanism of action, recent reports have suggested its possible clinical use in other IgE-mediated disorders, such as allergic rhinitis, food allergy, and anaphylaxis. In recent years, several studies have also investigated the possible applications of omalizumab in a number of non IgE-mediated diseases. The aim of the present review is to assess all applications of omalizumab as therapy in the pediatric population. The approved indications—allergic asthma and CSU—are reviewed. Moreover, further potential applications of omalizumab are discussed in both IgE-mediated and non-IgE-mediated diseases.
doi:10.1007/s40272-014-0107-z
PMCID: PMC4250568  PMID: 25404353
15.  Efficacy and Safety of Omalizumab in Patients with Chronic Idiopathic/Spontaneous Urticaria Who Remain Symptomatic on H1 Antihistamines: A Randomized, Placebo-Controlled Study 
ASTERIA I was a 40-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous omalizumab as add-on therapy for 24 weeks in patients with chronic idiopathic urticaria/spontaneous urticaria (CIU/CSU) who remained symptomatic despite H1 antihistamine treatment at licensed doses. Patients aged 12–75 years with CIU/CSU who remained symptomatic despite treatment with approved doses of H1 antihistamines were randomized (1:1:1:1) in a double-blind manner to subcutaneous omalizumab 75 mg, 150 mg, or 300 mg or placebo every 4 weeks for 24 weeks followed by 16 weeks of follow-up. The primary end point was change from baseline in weekly itch severity score (ISS) at week 12. Among randomized patients (N=319: placebo n=80, omalizumab 75 mg n=78, 150 mg n=80, 300 mg n=81), 262 (82.1%) completed the study. Compared with placebo (n=80), mean weekly ISS was reduced from baseline to week 12 by an additional 2.96 points (95% confidence interval (CI): −4.71 to −1.21; P=0.0010), 2.95 points (95% CI: −4.72 to −1.18; P=0.0012), and 5.80 points (95% CI: −7.49 to −4.10; P<0.0001) in the omalizumab 75-mg (n=77), 150-mg (n=80), and 300-mg groups (n=81), respectively. The omalizumab 300-mg group met all nine secondary end points, including a significant decrease in the duration of time to reach minimally important difference response (⩾5-point decrease) in weekly ISS (P<0.0001) and higher percentages of patients with well-controlled symptoms (urticaria activity score over 7 days (UAS7) ⩽6: 51.9% vs. 11.3% P<0.0001) and complete response (UAS7=0: 35.8% vs. 8.8% P<0.0001) versus placebo. During the 24-week treatment period, 2 (2.9%), 3 (3.4%), 0, and 4 (5.0%) patients in the omalizumab 75-mg, 150-mg, 300-mg, and placebo groups, respectively, experienced a serious adverse event. Omalizumab 300 mg administered subcutaneously every 4 weeks reduced weekly ISS and other symptom scores versus placebo in CIU/CSU patients who remained symptomatic despite treatment with approved doses of H1 antihistamines.
doi:10.1038/jid.2014.306
PMCID: PMC4269803  PMID: 25046337
16.  An Overview of the Effects of anti-IgE Therapies 
Omalizumab, a humanized mAb that binds to the CH3 domain near the binding site for the high-affinity type-I IgE Fc receptors of human IgE, can neutralize free IgE and inhibit the IgE allergic pathway without sensitizing mast cells and basophils. We found that omalizumab in patients with severe persistent asthma (SPA) was an effective therapy for asthma and the following co-morbid conditions: chronic urticaria (CU), bee venom allergy, latex allergy, atopic dermatitis, food allergy and Samter’s syndrome. Information on the use of omalizumab in treatment of asthma and other allergic diseases has improved our understanding that treatment acts on many levels, including regulating levels of inflammatory proteins, including cytokines (copper-containing alpha- 2-glycoprotein, total antioxidant capacity, MDA, NO, H2O2, CXCL8, IL-10, TGF-β, GMCSF, IL-17, IL-1β), MPV, Hs-CRP, eosinophil cationic peptide, vitamin-D (25(OH)D), homocysteine (Hcy), OX-2, d- dimer, albumin, and sApo-2L. The decrease in Hcy concentrations and increase in 25(OH)D also support the existence of a vascular endothelial protection mechanism. Mediators and cells classically involved in pro-coagulant and anticoagulant pathways together play a role in SPA and CU pathophysiology and omalizumab effect.
The mechanism of action of omalizumab in the treatment of asthma is believed to be multifactorial, and includes effects mediated through altered production of redox metabolites, extrinsic coagulation pathway, oxidative markers-related mi RNA, TRAIL-related mi RNA, and regulation of production of known inflammatory proteins
doi:10.12659/MSM.890137
PMCID: PMC4181307  PMID: 25241913
Asthma; Anti-IgE; Omalizumab; Chronic Urticaria; Inflammatory Proteins
17.  Omalizumab in the management of patients with allergic (IgE-mediated) asthma 
Immunoglobulin E (IgE) is central to the pathophysiology of allergic asthma. Omalizumab, an anti-IgE monoclonal antibody, binds to the FcɛRI binding site on free IgE. As a result, circulating free IgE is reduced, IgE is prevented from attaching to mast cells and basophils, and FcɛRI receptor expression is down-regulated. The inflammatory response to allergens and the acute and chronic effector phases of allergic inflammation are thereby attenuated. In clinical trials in adults and adolescents, omalizumab reduced asthma exacerbations, severe asthma exacerbations, inhaled corticosteroid requirements, and emergency visits, as well as significantly improving asthma-related quality of life, morning peak expiratory flow and asthma symptom scores in patients with severe allergic (IgE-mediated) asthma. Results from clinical trials in children (<12 years) are consistent with those in the adult population. It is difficult to predict which patients will respond to omalizumab. Responders to omalizumab should be identified after a 16-week trial of therapy using the physician’s overall assessment. When treatment is targeted to these responders, omalizumab provides a cost-effective therapy for inadequately controlled severe allergic (IgE-mediated) asthma. Long-term therapy with omalizumab shows the potential for disease-modification in asthma. Ongoing studies are also evaluating the use of omalizumab in other non-asthma IgE-mediated conditions.
PMCID: PMC3048609  PMID: 21437144
omalizumab; IgE; allergic asthma
18.  Severe asthma and the omalizumab option 
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).
doi:10.1186/1476-7961-6-4
PMCID: PMC2478654  PMID: 18489791
19.  592 A Case of Multiple Simultaneous Urticarial Syndromes Refractory to Treatment 
Background
We report the case of a patient with 3 forms of physical urticaria and his response to treatment.
Methods
An atopic asthmatic 11 year old male was evaluated for a history of recurrent pruritus with a variable, erythematous rash unresponsive to therapy. Since the age of 5 years, he has experienced small red, raised, pinpoint, pruritic “bumps” over his entire body except the palms of his hands and soles of his feet. The duration of the lesions was generally 5 minutes to about 1 hour. They occurred with exercise, stress, cold air, and cold water. At the time of the evaluation, the patient was treated with oral levocetirizine 5 mg daily and hydroxyzine 50 mg at bedtime without resolution of symptoms.
Results
In clinic, the patient had a positive ice cube test, a positive dermatographia test and a negative warm test tube test. Methacholine and autologous sweat testing were declined. Otherwise he had a normal physical examination with a negative Darier sign. Laboratory studies did not reveal a disease process responsible for the urticaria. Based upon his historical symptoms and clinical findings, he was diagnosed with 3 distinct types of physical urticaria; cholinergic urticaria, cold urticaria and dermatographia. The dose of anti-histamine therapy was doubled and the patient returned to clinic in 4 weeks to report that his symptoms were slightly improved but had not resolved.
Conclusions
Physical urticarias are usually controlled by antihistamine therapy but refractory cases are not uncommon. This patient also has poorly controlled asthma for which he is scheduled to start omalizumab therapy upon turning 12 in 1 month. We will continue to follow this case to observe if omalizumab has an effect upon his urticarial symptoms.
doi:10.1097/01.WOX.0000411707.17504.ca
PMCID: PMC3513100
20.  281 Use of Monoclonal Antibody Omalizumab in the Treatment of Urticaria Chronic 
The World Allergy Organization Journal  2012;5(Suppl 2):S108-S109.
Background
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.
Method
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.
Results
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.
Conclusions
Omalizumab must be considered to be another therapeutic alternative in patients with idiopathic Urticaria.
doi:10.1097/01.WOX.0000412038.77501.a8
PMCID: PMC3513150
21.  Reduction in oral corticosteroid use in patients receiving omalizumab for allergic asthma in the real-world setting 
Background
Oral corticosteroids (OCS) are commonly administered in patients with severe persistent allergic asthma. Despite their efficacy, they are associated with a wide variety of adverse events. The eXpeRience registry was set up to investigate real-world outcomes among patients receiving omalizumab for the treatment of uncontrolled allergic asthma. Here, we present the effect of omalizumab treatment on OCS use.
Methods
eXpeRience was a 2-year, multinational, non-interventional, observational registry of patients receiving omalizumab for uncontrolled allergic asthma. OCS use (proportion of patients on maintenance OCS, mean total daily OCS dose and change in status of OCS therapy) was assessed at baseline, 16 weeks, and 8, 12, 18, and 24 months after the initiation of omalizumab. Response to omalizumab was assessed using the physician’s Global Evaluation of Treatment Effectiveness (GETE) at approximately Week 16. Safety data were also recorded.
Results
A total of 943 patients (mean age, 45 years; female, 64.9%) were enrolled in the registry, 263 of whom were receiving maintenance OCS at baseline. The proportion of patients taking maintenance OCS was markedly lower at Months 12 (16.1%) and 24 (14.2%) than at baseline (28.6%; intent-to-treat population). GETE status was determined in 915 patients receiving omalizumab: 64.2% were responders (excellent or good response), 30.7% were non-responders (moderate, poor or worsening response); 5.1% had no assessment. The frequency of serious adverse events was comparable to that seen in controlled trials of omalizumab.
Conclusions
Omalizumab use is associated with an OCS-sparing effect in patients with uncontrolled persistent allergic asthma in the real-world setting.
doi:10.1186/1710-1492-9-47
PMCID: PMC3879326  PMID: 24305549
Anti-immunoglobulin E; Oral corticosteroid use; Omalizumab; Registry; Uncontrolled persistent allergic asthma
22.  Omalizumab: the evidence for its place in the treatment of allergic asthma 
Core Evidence  2008;3(1):55-66.
Introduction:
Asthma is a chronic inflammatory airways disease associated with reversible airflow obstruction and bronchial hyperresponsiveness. Asthma is prevalent worldwide and results in significant morbidity, mortality, and healthcare costs, the majority of which arise from those with severe disease. Omalizumab is a monoclonal antibody to immunoglobulin E (IgE) that has been developed for the treatment of severe persistent allergic (IgE mediated) asthma.
Aims:
The aim of this review is to evaluate the available clinical evidence on omalizumab to determine the role it has to play in the treatment of persistent allergic asthma.
Evidence review:
There is clear evidence to show that omalizumab is effective in reducing the rate of asthma exacerbations, inhaled corticosteroid dose, and the need for rescue medication in patients with allergic asthma. Clinical data indicate beneficial effects on patient-reported symptoms and perceived quality of life, as well as a reduction in unscheduled healthcare visits. There is little evidence to suggest omalizumab may enhance lung function or reduce the requirement for oral corticosteroids. Omalizumab has a favorable safety profile, although anaphylaxis has occurred. A study in children showed similar results to those achieved in adults and adolescents, with fewer asthma exacerbations and school days missed. Omalizumab may be cost effective in patients when used as add-on therapy to inhaled corticosteroids and long-acting beta2 agonists (LABA).
Place in therapy:
Omalizumab is an effective add-on therapy to inhaled corticosteroids and LABAs in adults and adolescents with severe persistent allergic asthma. Currently there is insufficient evidence to support the use of omalizumab in children.
doi:10.3355/ce.2008.012
PMCID: PMC2899803  PMID: 20694084
allergic asthma; omalizumab; immunoglobulin E; evidence
23.  Omalizumab therapy in three patients with chronic autoimmune urticaria 
Annals of Saudi Medicine  2010;30(6):478-481.
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.
doi:10.4103/0256-4947.70567
PMCID: PMC2994167  PMID: 20864790
24.  Insights and advances in chronic urticaria: a Canadian perspective 
In the past few years there have been significant advances which have changed the face of chronic urticaria. In this review, we aim to update physicians about clinically relevant advances in the classification, diagnosis and management of chronic urticaria that have occurred in recent years. These include clarification of the terminology used to describe and classify urticaria. We also detail the development and validation of instruments to assess urticaria and understand the impairment on quality-of-life and the morbidity caused by this disease. Additionally, the approach to management of chronic urticaria now focuses on evidence-based use of non-impairing, non-sedating H1-antihistamines given initially in standard doses and if this is not effective, in up to 4-fold doses. For urticaria refractory to H1-antihistamines, omalizumab treatment has emerged as an effective, safe option.
doi:10.1186/s13223-015-0072-2
PMCID: PMC4336710
Chronic urticaria; Diagnosis; Classification; Management; Immunology; Antihistamines; Up-dosing; Omalizumab
25.  Leukotriene receptor antagonists for chronic urticaria: a systematic review 
A significant proportion of patients with chronic urticaria respond inadequately to first line treatment with antihistamines. Leukotreine receptor antagonists (LTRA) are also used for chronic urticaria, although firm recommendations on their use are lacking. We performed a systematic review of randomised trials to determine the role of LTRA in treatment of chronic urticaria. A search of PUBMED, EMBASE, SCOPUS, LILACS, the Cochrane Central Register of Controlled Trials, and the Web of Science for relevant randomized control trials or cross over studies yielded 10 eligible studies. The heterogeneity of trials were high, preventing valid meta-analysis of data. Most trials indicated that LTRA are not superior to placebo or antihistamine therapy, while combination therapy of LTRA and antihistamines appear to be more efficacious compared to antihistamine alone. The side effect profile and tolerability of this group of drugs is acceptable. The use of LTRA as monotherapy cannot be recommended. LTRA are effective add-on therapy to anti-histamines, and their use in patients responding poorly to antihistamines is justifiable. Further well designed randomized controlled trials with clear and standardized outcome measures are needed to determine the role of LTRA in chronic urticaria.
doi:10.1186/1710-1492-10-24
PMCID: PMC4016797  PMID: 24817895
Chronic urticaria; Leukotreine receptor antagonists; Leukotreine; Montelukast; Zafirlukast; Antihistamines

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