Use Of Omalizumab Research Articles

Omalizumab no Tratamento do Penfigóide Bolhoso - O Estado da Arte

Introdução: Assistiu-se recentemente a um avanço significativo no conhecimento da fisiopatologia do penfigóide bolhoso, tendo sido demonstrado o papel patogénico dos auto-anticorpos anti-BP180 do subtipo IgE. O presente trabalho pretende explicitar os mecanismos patogénicos dos auto-anticorpos IgE no penfigóide bolhoso e discutir os dados publicados relativos à utilização clínica de omalizumab no seu tratamento.Material e Métodos: Revisão de artigos em revistas com indexação na Medline/PubMed usando como termos de pesquisa “omalizumab bullous pemphigoid”.Resultados: São revistas e discutidas 9 publicações, bem como como artigos relacionados, quando considerado pertinente. Na maioria dos casos, o omalizumab revelou-se um fármaco eficaz em seguro, sendo utilizado mais frequentemente como adjuvante a outras terapêuticas imunossupressoras. O papel de biomarcadores como IgE total ou contagem de eosinófilos na seleção de doentes ou monitorização do tratamento é ainda desconhecido.Conclusões: A utilização de omalizumab no tratamento do penfigóide bolhoso é sustentada pela patogenicidade conhecida dos auto-anticorpos IgE específicos. A experiência clínica publicada é escassa, apontando o omalizumab como uma opção segura e eficaz no penfigóide bolhoso resistente à corticoterapia/imunossupressão. Por não condicionar imunossupressão, poderá constituir uma opção valiosa no tratamento do penfigóide bolhoso. São necessários estudos prospetivos aleatorizados, particularmente se comparativos com prednisolona oral em monoterapia.

Omalizumab (anti-IgE) therapy in the asthma–COPD overlap syndrome (ACOS) and its effects on circulating cytokine levels

Context: The term “asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome” (ACOS) has been applied to the condition, in which a person has clinical features of both asthma and COPD.Methods: The patients (N = 10) were presented to our clinic with low lung function, limited reversibility of airway obstruction, hyperinflation, abnormal body composition, dyspnea and episodic wheezing. Based on the clinical and laboratory findings, the patients were diagnosed with ACOS. Patients’ serum IL-2 (sIL-2), sIL-4 sIL-6, sIL-10, sIL-17, sTNF-α and sIFN-γ levels were investigated as an apoptotic marker and a marker for inflammation.Results: Having undergone omalizumab treatment and a long-term (12 months) later, patients had a decreased IgE, fractional exhaled nitric oxide concentrations (FENO), eosinophil, neutrophils, macrophages, eosinophil cationic peptide (ECP) and sIL-4 levels.Conclusion: To our knowledge, this is the first documentation of omalizumab use in ACOS. We demonstrated decreased IL-4, allergic pulmonary symptoms (dyspnea, wheezing, bronchial hyper responsiveness) and migraine attacks in the patients.

A retrospective medical chart review of the use of omalizumab in chronic idiopathic urticaria

A retrospective medical chart review of the use of omalizumab in chronic idiopathic urticaria

The Use of Omalizumab in Thetreatment of Nasal Polyps

The Use of Omalizumab in Thetreatment of Nasal Polyps

Immunogenicity of a peptide-based anti-IgE conjugate vaccine in non-human primates.

The anti‐human immunoglobulin E (IgE) monoclonal antibody, omalizumab (Xolair®, Genentech, South San Fransisco, CA), is effective in the treatment of poorly controlled moderate to severe allergic asthma and chronic idiopathic urticaria. It acts by specifically binding to the constant domain (Cϵ3) of free human IgE in the blood and interstitial fluid. Although efficacious, use of omalizumab is limited due to restrictions on patient weight and pre‐existing IgE levels, and frequent dosing (q2–4 weeks). A vaccine inducing anti‐IgE antibodies has the potential for similar clinical benefits with less frequent dosing and relatively lower cost of goods. We developed a vaccine containing two IgE peptide‐conjugates targeting the Cϵ3 domain of human IgE. As part of preclinical evaluation of the vaccine to optimize formulation and dose prior to initiating clinical studies, we evaluated the vaccine in non‐human primates, and demonstrate the induction of anti‐peptide antibodies that can bind to conformationally intact human IgE and are capable, at least in some animals, of substantial lowering circulating IgE levels.

Efficacious Use of Omalizumab in the Treatment of Cystic Fibrosis

Efficacious Use of Omalizumab in the Treatment of Cystic Fibrosis

Consensus-based approach for severe paediatric asthma in routine clinical practice

Abstract Introduction Accurate identification of paediatric patients with severe asthma is essential for an adequate management of the disease. However, criteria for defining severe asthma and recommendations for control vary among different guidelines. Material and methods An online survey was conducted to explore expert opinions about the definition and management of severe paediatric asthma. To reach a consensus agreement, a modified Delphi technique was used, and practice guidelines were prepared after the analysis of the results. Results Eleven paediatric pulmonologists and allergists with wide expertise in severe asthma responded to the survey. Consensus was reached in 50 out of 65 questions (76.92%). It was considered that a patient has severe asthma if during the previous year they had required 2 or more cycles of oral steroids, required daily treatment with medium doses of inhaled corticosteroids (with other controller medication) or high doses (with or without other controller medication), did not respond to optimised conventional treatment, or if the disease threatened the life of the patient or seriously impaired their quality of life. The definition of severe asthma may also include patients who justifiably use health resources on a regular basis, or have psychosocial or environmental factors impeding control. For monitoring, the use of questionnaires designed specifically for paediatric population, such as CAN or ACT, is recommended. As regards treatment, the use of omalizumab should be considered prior to the use of oral corticosteroids. Conclusions This paper provides consensus recommendations that may be useful in the management of severe paediatric asthma.

Effectiveness of omalizumab in a patient with severe asthma and atopic dermatitis

The anti-IgE antibody omalizumab is currently indicated in severe asthma not controlled by standard drug therapy. Recently, new indications for omalizumab were suggested, which include atopic dermatitis (AD), a skin disorder characterized by elevated levels of IgE. We report the case of a 39-year old woman with severe asthma and severe AD, both resistant to conventional drug treatment. The patient had a IgE level of 1304 kU/L, which exceeded the recommended maximum level for treating asthma with omalizumab (stated in 700 Ku/L) but was far lower than previously reported in cases of AD treated with anti-IgE. The treatment consisted of a dose of omalizumab 375 mg every two weeks, and induced a rapid improvement of asthma, with no need of other drugs after three months, along with a progressive decline of severity of AD, which after five months was completely cured. These findings suggest the usefulness of omalizumab in patients with concomitant severe asthma and AD, also considering the pharmaco-economic balance obtained by withdrawing the multiple drugs used to treat both diseases.

Position statement for the use of omalizumab in the management of chronic spontaneous urticaria in Indian patients.

Chronic spontaneous urticaria (CSU) affects 1% of the world population and also their quality of life, and 50% of these patients are refractory to H1-antihistamines. Omalizumab is a humanized monoclonal anti-IgE antibody that binds with free IgE antibodies and reduces the circulating levels of free IgE. This reduction in free IgE prevents mast-cell degranulation. The EAACI/GA2LEN/EDF/WAO guidelines recommend omalizumab as the third-line of therapy as an add-on to antihistamines. The recommended dose of omalizumab is 300 mg, 4 weekly in the management of CSU refractory to standard of care with H1-antihistamines in adults and adolescents ≥12 years of age. In some patients, a dose of 150 mg may be acceptable. Omalizumab has a good safety profile. However, due to the biologic nature of the drug, all patients administered omalizumab must be observed for 2 h after administration for anaphylactoid reactions. There have been no studies on the effect of impaired renal or hepatic function on the pharmacokinetics of omalizumab. While no particular dose adjustment is recommended, omalizumab should be administered with caution in these patients.

IgE-Related Chronic Diseases and Anti-IgE-Based Treatments.

IgE is an immunoglobulin that plays a central role in acute allergic reactions and chronic inflammatory allergic diseases. The development of a drug able to neutralize this antibody represents a breakthrough in the treatment of inflammatory pathologies with a probable allergic basis. This review focuses on IgE-related chronic diseases, such as allergic asthma and chronic urticaria (CU), and on the role of the anti-IgE monoclonal antibody, omalizumab, in their treatment. We also assess the off-label use of omalizumab for other pathologies associated with IgE and report the latest findings concerning this drug and other new related drugs. To date, omalizumab has only been approved for severe allergic asthma and unresponsive chronic urticaria treatments. In allergic asthma, omalizumab has demonstrated its efficacy in reducing the dose of inhaled corticosteroids required by patients, decreasing the number of asthma exacerbations, and limiting the effect on airway remodeling. In CU, omalizumab treatment rapidly improves symptoms and in some cases achieves complete disease remission. In systemic mastocytosis, omalizumab also improves symptoms and its prophylactic use to prevent anaphylactic reactions has also been discussed. In other pathologies such as atopic dermatitis, food allergy, allergic rhinitis, nasal polyposis, and keratoconjunctivitis, omalizumab significantly improves clinical manifestations. Omalizumab acts in two ways: by sequestering free IgE and by accelerating the dissociation of the IgE-Fcε receptor I complex.

Postural tremor due to use of omalizumab

Postural tremor due to use of omalizumab

Beyond Psoriasis: Novel Uses for Biologic Response Modifiers in Pediatric Dermatology.

Dermatologists have witnessed the increasing availability of novel biologic response modifiers for the treatment of inflammatory and autoimmune diseases in recent years. The most common dermatologic indication for the use of biologic response modifiers in adults is psoriasis, but the U.S. Food and Drug Administration has not approved any of these agents for use in any dermatologic disease in children with the exception of omalizumab, and as such, use in this population is considered off-label. In this review, we focus on the use of these agents in children to treat inflammatory skin diseases other than psoriasis, including atopic dermatitis, hidradenitis suppurativa, pemphigus vulgaris, bullous pemphigoid, and toxic epidermal necrolysis, with an emphasis on the use of etanercept, infliximab, rituximab, omalizumab, and ustekinumab. By highlighting novel uses of these agents, particularly for the treatment of dermatologic conditions for which optimal therapies are yet to be established, we hope to raise awareness of the potential use of this class of medications to treat inflammatory skin diseases in children.

Current and emerging treatments for severe asthma.

Severe asthma, which is poorly controlled despite the elimination of modifiable factors and the correct use of standard therapy, accounts only for 5% of people with asthma but it contributes to approximately 50% of the economic costs of asthma. Because of this unmet need, novel therapies have been developed for optimal treatment of these patients. The use of tiotropium, omalizumab, mepolizumab and thermoplasty in well-selected patients provides better control and most importantly a reduction in asthma exacerbations.

Consenso para el abordaje del asma grave pediátrica en la práctica clínica habitual

IntroductionAccurate identification of paediatric patients with severe asthma is essential for an adequate management of the disease. However, criteria for defining severe asthma and recommendations for control vary among different guidelines. Material and methodsAn online survey was conducted to explore expert opinions about the definition and management of severe paediatric asthma. To reach a consensus agreement, a modified Delphi technique was used, and practice guidelines were prepared after the analysis of the results. ResultsEleven paediatric chest disease physicians and allergy specialists with wide expertise in severe asthma responded to the survey. Consensus was reached in 50 out of 65 questions (76.92%). It was considered that a patient has severe asthma if during the previous year they have required 2 or more cycles of oral steroids, required daily treatment with medium doses of inhaled corticosteroids (with other controller medication) or high doses (with or without other controller medication), did not respond to optimised conventional treatment, or if the disease threatened the life of the patient or seriously impairs their quality of life. The definition of severe asthma may also include patients who justifiably use health resources on a regular basis, or have psychosocial or environmental factors impeding control. For monitoring, the use of questionnaires designed specifically for paediatric population, such as CAN or ACT, is recommended. As regards treatment, the use of omalizumab should be considered prior to the use of oral corticosteroids. ConclusionsThis paper provides consensus recommendations that may be useful in the management of severe paediatric asthma.

Successful treatment of occupational delayed pressure urticaria and angioedema with omalizumab

Physical urticarias are present in approximately 17% of patients with chronic urticaria. 1 Most of the time delayed pressure urticaria and angioedema are associated with chronic spontaneous urticaria. This type of physical urticaria is usually nonpruritic, causes pressure-induced pain and burning 4 to 6 hours after exposure, and causes significant impairment in quality of life. It is a lymphocyte inflammatory condition associated with increased skin expression of tumor necrosis factor a and interleukin 3. 2 Constitutional symptoms may be present, such as fever, malaise, myalgias, arthralgias, and headaches. Laboratory analysis may reveal acute episodes of leukocytosis with a shift to the left and elevated erythrocyte sedimentation rate and C-reactive protein level, which are biomarkers of the ongoing inflammatory process. Histamine1 and histamine2 antihistamines are not typically helpful, and oral corticosteroids usually work very well. 3,4 Dapsone can be a corticosteroid-sparing alternative. 5 Rarely has the use of omalizumab been reported to completely control delayed pressure urticaria and angioedema 6,7 because this condition is usually managed with daily corticosteroid administration. Omalizumab-depleting free circulating IgE reduces the ability of mast cells to express inflammatory processes mediated by the release of vasoactive substances present in the cytoplasmatic granules and also stabilizes the mast cell with the downregulation of the highaffinity IgE receptors. 8 In this letter, we present the successful

A 12½-year journey of a patient with Samter triad syndrome and sporadic omalizumab use

A 12½-year journey of a patient with Samter triad syndrome and sporadic omalizumab use

Evaluation of IgE Antibodies to Omalizumab (Xolair®) and Their Potential Correlation to Anaphylaxis

Omalizumab (Xolair®) is a recombinant humanized monoclonal antibody that selectively binds to human immunoglobulin E (IgE). Omalizumab is used to treat IgE-mediated diseases such as chronic idiopathic urticaria (CIU) and moderate to severe allergic asthma. In pre-marketing clinical trials in patients with asthma, anaphylaxis was reported in 3 of 3,507 (0.1%) patients. In post-marketing spontaneous reports, the frequency of anaphylaxis attributed to omalizumab use was estimated to be at least 0.2% of patients based on an estimated exposure of about 57,300 patients from June 2003 through December 2006. To better understand the risk of anaphylaxis in patients with allergic asthma receiving omalizumab, a post-marketing pharmacosurveillance study was initiated in 2009. As part of this study, an assay was developed to detect antibodies of IgE isotype to omalizumab. Serum samples from patients in the study were evaluated using this assay. Our results indicated that there was no observable correlation between either anaphylaxis or skin test reactivity and the presence of antibodies of IgE isotype to omalizumab. Here, we discuss the development of this assay as well as the results of the immunogenicity assessment.

Anti‐IgE for chronic urticaria – are children little adults after all?

Omalizumab is a recombinant monoclonal antibody, targeting the epsilon 3 domain of free serum IgE antibodies, and thus preventing their attachment to the cognate high-affinity receptor on mast cells and reducing the number of cell-bound receptors. It represents the first ‘biological’ that has been studied in allergy and was registered several years ago for the treatment of severe allergic asthma in adults and children by the FDA and the EMA. About one year ago, omalizumab was registered for adult patients with chronic spontaneous urticaria – with or without angioedema – which is insufficiently controlled by standard treatment, including high-dose antihistamines. During the last years, international guidelines have profoundly changed our therapeutic approaches to chronic urticarial patients in which, instead of a previously recommended combination treatment with different histamine receptor antagonists, an increase of non-sedating H-1 receptor antagonists of the second generation up to a quadruple dose of the standard recommended regimen is now the general rule (1,2,3,4). These new recommendations have led to a remarkable improvement of response rates seen in urticarial patients; however, by far not all adult patients with chronic spontaneous urticaria are sufficiently controlled even by high doses of antihistamines. The application of omalizumab as a third-line option has demonstrated an unexpected additional benefit and leads to a complete relief of symptom in almost all treated patients. All three of the pivotal phase III studies in adults have led to a recommended dose of 300 mg omalizumab in 4 weeks, which differs from dose regimens for allergic asthma, where the patient's body weight and the total serum IgE levels determine the omalizumab dose. It seems that with the novel treatment option the vast majority of all adult patients with chronic spontaneous urticaria are adequately controlled without major safety problems, which is a remarkable step forward in the long-term treatment of urticaria. The problems of chronic urticaria in childhood seem to be inadequately perceived, which may be due to its low prevalence compared to adults. Until recently, the natural course of CU has not really been studied in large cohorts of children. A recent prospective study from Thailand suggests that chronic urticaria in children has a more favorable outcome than in adults, with a remission rate of 18.5% after one year and 54% after 3 years 5. Like adults, more than 30% of the children with a chronic spontaneous urticaria were found to have autoantibodies to the alpha subunit of the high-affinity IgE receptor (Fc-epsilon-R 1) and/or anti-IgE antibodies. The presence of these autoantibodies may be screened for by performing the autologous serum skin test (ASST). Up to now, the intervention with the recombinant monoclonal antibody omalizumab has been studied in childhood only for severe asthma as well as in rhinitis. In most parts of the world, it is registered for the treatment of uncontrolled severe asthma after the age of six. A systematic review on the use of omalizumab in children, which appears in this issue, indicates that the addition of omalizumab in patients with uncontrolled allergic asthma can be considered as effective and safe 6. Up to now, there is not a single randomized controlled trial in children with urticaria. Therefore, the different case reports presented in this issue reporting a beneficial effect in refractory solar urticaria, and in spontaneous and physical urticaria are very encouraging and of high interest (7,8,9). Although very severe clinical cases of uncontrollable chronic urticaria compared to adults seem to be rare and the outcome may be more favorable in childhood, the information presented here strongly suggests that the pathophysiologic mechanism leading to chronic urticaria in childhood may be similar. It appears that the time has come to ask for randomized controlled trials with omalizumab and possibly other biologics for an apparently forgotten disorder in childhood which may deserve more attention and consideration than given in the past.

Systematic review on the use of omalizumab for the treatment of asthmatic children and adolescents.

There are less data on omalizumab treatment in pediatric asthma than in adult population. Thus, to establish the efficacy and safety of subcutaneous omalizumab as an add-on therapy, a systematic review of placebo-controlled studies was performed. Primary outcome was the frequency of asthma exacerbations. Secondary outcomes included spirometric measures, rescue medication use, asthma symptoms, health-related quality of life, and adverse events. Three randomized controlled trials (1381 participants) fulfilled the selection criteria. During the stable phase, omalizumab decreased the number of patients with at least one significant asthma exacerbation (26.7% vs. 40.6%, NNTB = 7, 95% CI, 5, 11). The predefined post hoc subgroup analysis showed that duration of treatment did not influence this result. During the steroid reduction phase, omalizumab reduced the number of patients with at least one exacerbation (RR = 0.48, 95% CI, 0.38, 0.61; NNTB = 6, 95% CI, 4, 8) and also the mean number of asthma exacerbations per patient (MD = -0.44, 95% CI, -0.72, -0.17) when compared to placebo. The frequency of serious adverse events was similar between omalizumab (5.2%) and placebo (5.6%), and there were no evidence of increased risk of hypersensitivity reactions, nor malignant neoplasms. Data indicate that the efficacy of an add-on omalizumab in patients with moderate-to-severe allergic asthma uncontrolled with recommended inhaled steroid treatment is accompanied by an acceptable safety profile.

Real-life efficacy and safety of omalizumab in Portuguese patients with persistent uncontrolled asthma

IntroductionThe real life effectiveness, safety and the use of omalizumab for Portuguese patients with uncontrolled persistent allergic asthma are not sufficiently well known. The objective of this report was to make an evaluation, in a post-marketing, non-interventional, observational registry, of the Portuguese population included in the eXpeRience study. MethodsThe methods used in this report are the same as the global eXpeRience ones, applied to a Portuguese sub-population. Patients with uncontrolled allergic asthma who had started omalizumab within the previous 15 weeks were enrolled and received omalizumab add-on therapy for 24 months. The physicians’ global evaluation of treatment effectiveness (GETE), asthma symptoms and control (ACT score), quality of life (mini-AQLQ score), exacerbations, and serious adverse events (SAE) were reported. ResultsOf the 943 patients recruited in the eXpeRience registry, 62 patients were from Portugal. 62.1% of them were observed to be responders with good/excellent GETE assessment at Week 16. Clinically meaningful improvements in asthma control (ACT score) and quality of life (mini-AQLQ score) were observed with omalizumab therapy at Months 12 (mean change: +7.7 [n=35]; +2.1 [n=20], respectively) and 24 (mean change: +7.0 [n=26]; +2.7 [n=13], respectively). Asthma symptoms and rescue medication usage were reduced to ≤1 day/week at Month 24 from a baseline of ≥3.5 days/week. The proportion of patients with no clinically significant exacerbations increased from 6.5% during pre-treatment (n=62) to 50% at Month 12 (n=54) and 60% at Month 24 (n=45). ConclusionThe findings from the Portugal subpopulation of eXpeRience registry confirm that omalizumab add-on therapy is efficacious and well tolerated in the management of uncontrolled persistent allergic asthma. Another pertinent issue is the fact that the Portuguese subpopulation response is similar to the international population average of the study.