Humanized Monoclonal anti-IgE Antibody Research Articles

GA2LEN ANACARE consensus statement: Potential of omalizumab in food allergy management.

Immunoglobulin E (IgE)-mediated food allergies are the most common type of food allergy, often causing rapid symptoms after exposure to allergens posing a serious health risk and a high impact on patient's and caregiver's quality of life. Omalizumab, a humanized anti-IgE monoclonal antibody, reduces allergic reactions by binding to circulating IgE. Omalizumab has been successfully used in allergic asthma, chronic rhinosinusitis with nasal polyps, and chronic urticaria, and was recently approved for treating IgE-mediated food allergies by the US Food and Drug Administration (FDA). This GA2LEN ANACARE Consensus Statement presents our position on the use of omalizumab for treating IgE-mediated food allergies, based on a systematic review and meta-analysis, experience with use for other conditions, and expert consensus achieved via an eDelphi process. Following publication of the recent OUtMATCH study (stage 1) results and subsequent FDA approval, we propose that there is now sufficient evidence to recommend omalizumab as the only drug currently available that can mechanistically reduce IgE-mediated food allergic reactions. We acknowledge that the evidence does not reach the highest level of evidence which would be needed for a guideline recommendation.

Eliminating drug target interference with specific antibody or its F(ab')2 fragment in the bridging immunogenicity assay.

Background: DB-1003 is a humanized anti-IgE monoclonal antibody with higher affinity than omalizumab. In the affinity capture elution (ACE)-based bridging electrochemiluminescent immunoassay (ECLIA) for antibodies to DB-1003, monkey serum IgE caused false-positive results. Materials & methods: The target-specific antibody or its F(ab')2 fragment was used to mitigate drug target interference in an ACE-based bridging ECLIA for the detection of anti-DB-1003 antibodies. Results: The sensitivity of the developed assay was at least 100ng/ml. When the anti-drug antibody concentration was 250ng/ml, the assay tolerated at least 20.0μg/ml of the monkey IgE. Conclusion: Incorporating the target-specific antibody or its F(ab')2 fragment can overcome the interference from monkey serum IgE in ACE-based bridging ECLIA for anti-DB-1003 antibody detection.

Biologics in allergic rhinitis.

This paper aims to review biologics in allergic rhinitis (AR). Biologic agents of Omalizumab, Dupilumab, Mepolizumab, Reslizumab, and Benralizumab are reviewed in detail. The search is performed in "Pubmed," "Google," Google Scholar" and EBSCO Academic Search Ultimate (EKUAL) database of Kırıkkale University Library from 2021 to 2000, and randomized and/or placebo-controlled studies, review papers, meta-analysis, and reports are taken into consideration. The search was performed with the keywords of "allergic rhinitis," "biologics," "biologic agents," "Omalizumab," "Dupilumab," "Mepolizumab," "Reslizumab," "Benralizumab," "Anti IgE," "Anti-IL-4/IL-13", "Anti IL-5". Search is also performed in the "U.S. Food and Drug Administration" (FDA) and "European Medicines Agency" (EMA) web systems. Biological agents such as monoclonal antibodies (MAb) in treatment are called biological therapy or biotherapy. Omalizumab is a humanized Anti-IgE monoclonal antibody. Omalizumab treatment improved the Daily Nasal Rescue Medication Score (DNSSS) and decreased the use of antiallergic drugs in seasonal and perennial AR and rhino-conjunctivitis. Omalizumab is also used in specific immunotherapy patients with allergic rhinitis and reduced allergic reactions associated with allergen immunotherapy, such as anaphylaxis. Dupilumab is an Anti-IL-4/IL-13 biologic agent. Dupilumab treatment significantly improved sino-nasal Outcome Test (SNOT-22) total scores in perennial allergic rhinitis. Anti-IL-5 monoclonal antibodies of Mepolizumab, Reslizumab Benralizumab reduce the number of eosinophils in the blood and tissue, corticosteroid addiction and asthma attacks are reduced, and their use in the treatment of severe eosinophilic asthma has been approved. Biologics, especially Omalizumab, and Dupilumab, may be used more in allergic rhinitis.

Hematopoietic stem cell transplantation in patient with DOCK8 deficiency: Ukrainian experience

Dedicator of Cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency that exemplifies the broad clinical features of primary immunodeficiencies (PIDs), extending beyond recurrent infections including atopy, autoimmunity, and cancer. Purpose - to describe the natural course of hyper-IgE syndrome (HIES) disease in an 8-year-old boy and his path to diagnosis, as well as our first local history of conservative treatment for 6 months. In particular, we describe the effectiveness of omalizumab, and the application of allogeneic hematopoietic stem cell transplantation with follow-up. Clinical case. The 8-year-old boy presented with severe eczema and an involvement of the whole surface of the body. Infectious syndrome manifested from the age of 4 months in a form of recurrent respiratory infections. Over the next few years, the child suffered from life-threatening infections with high serum IgE (>3000 IU/ml). The examination revealed a cushingoid constitution, flat-valgus feet, and dysmorphic features. Therefore, HIES was suspected. Genetic studies have confirmed the diagnosis by detecting a pathogenic homozygous mutation in the DOCK8 gene (Deletion Exons 2-46). We decided to use a humanized monoclonal anti-IgE antibody (off-label) to control the skin syndrome rather than systemic steroids. A significant improvement in skin condition, a decrease in eosinophils, and IgE were observed. Allogeneic stem cell transplantation of hematopoietic cells (HSCT) derived from peripheral blood of an human leukocyte antigen (HLA) - identical sibling donor was performed. The donor had a pathogenic mutation identical to the recipient in the DOCK8 gene but in a heterozygous state. Our data and treatment approach may be clinically useful as a diagnostic and treatment approach to HIES. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies No conflict of interests was declared by the authors.

Comparison of Omalizumab Treatment Response in Patients with Chronic Spontaneous Urticaria and Symptomatic Dermographism: A Single-Center Retrospective Study

Introduction: Omalizumab is a humanized anti-IgE monoclonal antibody, which is effective in the treatment in patients with chronic spontaneous urticaria (CSU) who are unresponsive to antihistamine therapy. There are few studies in the literature evaluating omalizumab treatment response in patients with symptomatic dermographism (SDerm). The aim of this study was to compare the response to omalizu­mab treatment in patients with CSU and SDerm. Methods: Patients treated with omalizumab for the diagnosis of CSU and SDerm were evaluated retrospectively. Treatment response to omalizumab was evaluated with the urticaria control test (UCT). Quality of life was evaluated with the dermatology quality of life questionnaire (DLQI). Baseline UCT and DLQI were compared with UCT and DLQI after omalizumab treatment. Results: Evaluation was made of a total of 116 patients (CSU: 92, SDerm: 24), comprising 36 (31%) males and 80 (69%) females with a mean age of 38.95 ± 13.64 years. The most common accompanying comorbid disease was allergic rhinitis (n = 40, 34.5%). There was no statistically significant difference between patients with CSU and SDerm in respect of response to omalizumab treatment (p = 0.890). After omalizumab treatment, the increase in UCT and decrease in DLQI was statistically significant in all patient groups (p < 0.001; p < 0.001, respectively), patients with CSU (p < 0.001; p < 0.001, respectively) and SDerm (p < 0.001; p < 0.001, respectively). There was no statistically significant difference between baseline (before omalizumab treatment) UCT (p = 0.804) and UCT after omalizumab treatment (p = 0.933) between patients with CSU and patients with SDerm. There was no statistically significant difference between baseline (before omalizumab treatment) DLQI (p = 0.356) and DLQI after omalizumab treatment (p = 0.145) between patients with CSU and patients with SDerm. Conclusion: Omalizumab treatment improved disease control and quality of life in patients with SDerm. The findings of this study should be supported by randomized placebo-controlled studies.

Omalizumab as a corticosteroid-sparing agent in the treatment of bullous pemphigoid.

Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease, characterized by the development of autoantibodies against hemidesmosomal components BP180 and BP230. The mainstay of therapy is topical and systemic corticosteroids (CS) and immunosuppressors. As this pathology mainly involves the elderly, subjects often have numerous comorbidities that influence the clinical management. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody which has recently emerged as a promising treatment for BP in patients for whom CS are contraindicated or conventional treatments have failed to control the disease. For this study, we selected five patients who presented with corticosteroid-dependent BP with a contraindication to the use of other immunosuppressive treatments. The objectives of our study were to evaluate the effectiveness of omalizumab in controlling BP and allowing to decrease the dosage of systemic CS, assessing the effects of omalizumab on the clinical manifestations and the titers of circulating anti-BP180 and BP230 antibodies, IgE and eosinophils. A reduction in the dose of systemic CS was possible in 100% of the patients and complete resolution of the clinical picture was seen in 100% for skin lesions and in 40% for pruritus. A reduction of circulating IgE was found in 40%, anti-BP180 and BP230 IgGs were decreased in 60% and eosinophils in 80%.

Successful combined treatment with omalizumab and tocilizumab in a case of chronic spontaneous urticaria and rheumatoid arthritis: A case report and literature review

Omalizumab is a recombinant humanized monoclonal anti-IgE antibody used to treat uncontrolled chronic spontaneous urticaria (CSU). Sometimes patients with CSU also have other autoimmune conditions. Recent studies have demonstrated the safety and efficacy of a combination treatment with omalizumab and other biologics. Here, we report the first successful treatment with omalizumab for CSU and tocilizumab for rheumatoid arthritis. Since omalizumab is unlikely to cause severe immunosuppression, it may be a treatment option for CSU, even in patients treated with other biologics.

Rapid Disease Control in First-Line Therapy-Resistant Mucous Membrane Pemphigoid and Bullous Pemphigoid with Omalizumab as Add-On Therapy: A Case Series Of 13 Patients.

The role of IgE autoantibodies has been demonstrated in the pathogenesis of bullous pemphigoid for many years. Recently, omalizumab (OMZ), a humanized monoclonal anti-IgE antibody that depletes total serum IgE, has been used off-label in a few case series of bullous pemphigoids demonstrating a rapid efficacy and allowing significant improvements or complete remission as add-on therapy in first-line treatment-resistant patients. Herein, we report the largest retrospective study to evaluate OMZ effectiveness in patients with subepidermal autoimmune blistering diseases. Our series included 13 patients from a single center with bullous pemphigoid or mucous membrane pemphigoid, of whom 7 had mucous membrane involvement. OMZ was added to the unchanged immunosuppressive therapies. Detailed clinical and immunological data during the first year were collected, notably for specific anti-BP180-NC16A IgE and IgG, and the median total follow-up was 30 months (range: 3–81). Our series demonstrated that OMZ induced a significant improvement in pruritus, urticarial score, and daily blister count on day 15, allowing disease control to be achieved in a 1-month median time and complete remission (CR) in a 3-month median time in 85% of these patients previously in therapeutic impasse. At the end of the follow-up, 31% of patients achieved CR on minimal therapy after OMZ weaning without relapses, and 54% achieved CR on OMZ continuation with a minimal dose of concomitant treatment. Two patients experienced therapeutic failure (15%). At baseline, clinical variables reflecting activity were significantly positively correlated with eosinophil blood count, total IgE serum level, specific anti-BP180 IgE and IgG. While baseline anti-BP180 IgG and specific anti-BP180 IgE were significantly positively correlated, only the two patients who experienced a therapeutic failure with OMZ did not fit with this correlation, demonstrating elevated levels of anti-BP180 IgG with no measurable BP180-specific IgE. Follow-up of immunological variables demonstrated a rapid decrease of eosinophilia towards normalization, whereas a slower decline towards negativation was observed over 1 year for anti-BP180 IgG and anti BP180 IgE in patients who responded to OMZ. This case series demonstrated that OMZ is a rapidly effective biologic therapy for refractory bullous pemphigoid and mucous membrane pemphigoid, permitting rapid disease control and reduction of concomitant therapeutics.

T Helper 2-Associated Immunity in the Pathogenesis of Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that mainly affects women in their reproductive years. A complex interaction of environmental and genetic factors leads to the disruption of immune tolerance towards self, causing overt immune activation and production of autoantibodies that attack multiple organs. Kidney damage, termed lupus nephritis, is the leading cause of SLE-related morbidity and mortality. Autoantibodies are central to propagating lupus nephritis through forming immune complexes and triggering complements. Immunoglobulin G (IgG) potently activates complement; therefore, autoantibodies were mainly considered to be of the IgG isotype. However, studies revealed that over 50% of patients produce autoantibodies of the IgE isotype. IgE autoantibodies actively participate in disease pathogenesis as omalizumab treatment, a humanized anti-IgE monoclonal antibody, improved disease severity in an SLE clinical trial. IgE is a hallmark of T helper 2-associated immunity. Thus, T helper 2-associated immunity seems to play a pathogenic role in a subset of SLE patients. This review summarizes human and animal studies that illustrate type 2 immune responses involved during the pathology of SLE.

Analysis of predictors of response to anti-IgE therapy in patients with severe atopic bronchial asthma in real clinical practice

Guidelines on Biological Therapy for Bronchial Asthma of the European Academy of Allergy and Clinical Immunology (EAACI) identified a number of controversial issues for additional outcome analysis using randomized clinical trials and data from routine clinical practice. In particular, there is unmet need to clarify algorithms for prescribing biologicals using predictors of response and its timing, taking into account risk factors and multimorbidity. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody of IgG1 class used for the treatment of severe refractory atopic bronchial asthma (BA) and a variety of IgE-mediated diseases. Among biological agents, this "pioneer molecule" has the greatest experience in the "allergology and immunology" profile. Detailed description of the "nonresponders" portraits will allow to perform the therapy response assessment on time and facilitate rational planning of individual therapy, which is a prerequisite for biologicals era. Using only routine methods, it is possible to perform initial and dynamic screening to phenotype a heterogeneous cohort of patients with severe asthma and chose the optimal strategy. To identify predictors of nonresponse to omalizumab anti-IgE therapy in patients with severe atopic BA and to establish optimal timing of efficacy assessment using retrospective analysis of data from the Biologic Therapy Registry of Allergology and Immunology in routine clinical practice. A retrospective single-center registry study was conducted at the Allergy and Immunology Reference Center from June 2017 to August 2021. 135 patients with severe BA, with confirmed perennial sensitization, who received omalizumab according to the recommendations of the current version of GINA, were selected from the clinical and dynamic observational system (registry). Dosing regimen and administration frequency of omalizumab were determined in accordance with the instructions for the drug. Assessment of therapy efficacy was performed at the time point 4, 6 and 12 months. Patients were subgrouped into "responders" and "non-responders" according to the following criteria: ACT score less than 19 and/or difference between initial ACT score in dynamics less than 3 points; forced expiratory volume in the first second less than 80%; combination of these two criteria. Nonparametric methods of descriptive statistics were used in data processing: median, interquartile range. Differences were considered significant at p0.05. MannWhitney U-test, KruskalWallis one-way analysis of variance, and Fisher's 2 test were used to compare quantitative characteristics. Heterogeneous subgroups of patients differing in reaching the criteria of "non-responders" to treatment were identified; the informativity of modifiable and unmodifiable factors differed at time-points of dynamic observation. In the differential analysis, two profiles of "nonresponders" were defined in combination with the most significant predictors of "nonrsponse" to omalizumab. According to the data obtained, one of the clinical phenotypes, namely the combination of severe asthma with the Samters triad, corresponded to the characteristics of the patient "nonresponders": age of onset is about 30 years, females, severe exacerbations of BA while taking non-steroidal anti-inflammatory drugs, accompanied with high levels of eosinophilia. The data obtained illustrates the hypothesis of pathogenetic heterogeneity of severe BA with the phenomenon of overlapping phenotypes and can serve as an additional orienteer for creating the individual plan of anti-IgE therapy in real clinical practice.

Ligelizumab for adolescent patients with CSU: first results from a dedicated Phase 2b study

The first results of the dose-finding Phase-2b study of ligelizumab, a next-generation high-affinity humanized monoclonal anti-IgE antibody, in adolescent chronic spontaneous urticaria (CSU) are reported here.

Omalizumab in food allergies – a therapeutic perspective

Food allergy is an important public health problem that affects up to 8% of the population in economically developed countries, especially children and adolescents. The management of allergic patients involves the avoidance of allergens and prompt treatment of immediate allergic reactions. Oral immunotherapy with the food incriminated in the allergic reaction (OIT) is a promising therapeutic alternative, but it is associated with frequent adverse reactions and increased costs. To reduce the adverse reactions of OIT, in a series of studies, omalizumab, a humanized anti-IgE monoclonal antibody, was used as add-on therapy for OIT. Studies with omalizumab as add-on therapy in OIT for peanuts, milk, eggs, or mixtures of several foods bring us promising results. In this article, we review the possibility of using omalizumab, as monotherapy or add-on therapy in OIT, as secondary prevention treatment in food allergies.

Clinical Experience with Anti-IgE Monoclonal Antibody (Omalizumab) in Pediatric Severe Allergic Asthma-A Romanian Perspective.

Background: Asthma is the most common chronic disease affecting children, with a negative impact on their quality of life. Asthma is often associated with comorbid allergic diseases, and its severity may be modulated by immunoglobulin E (IgE)-mediated allergen sensitization. Omalizumab is a humanized monoclonal anti-IgE antibody, the first biological therapy approved to treat patients aged ≥6 years with severe allergic asthma. The primary objective of our study was to investigate the efficacy and safety of Omalizumab in Romanian children with severe allergic asthma. Methods: In this observational real-life study, 12 children and adolescents aged 6 to 18 years (mean 12.4 years) with severe allergic asthma received Omalizumab as an add-on treatment. Asthma control, exacerbations, lung function, and adverse events were evaluated at baseline and after the first year of treatment. Results: We observed general improvement in total asthma symptom scores and reduction in the rate of exacerbation of severe asthma. Omalizumab treatment was associated with improvement in the measures of lung function, and no serious adverse reactions were reported. FEV1 improved significantly after one year of treatment with Omalizumab [ΔFEV1 (% pred.) = 18.3], and [similarly, ΔMEF50 (%) = 25.8]. The mean severe exacerbation rate of asthma decreased from 4.1 ± 2.8 to 1.15 ± 0.78 (p < 0.0001) during the year of treatment with Omalizumab. Conclusions: This study showed that Omalizumab can be an effective and safe therapeutic option for Romanian children and adolescents with severe allergic asthma, providing clinically relevant information on asthma control and exacerbation rate in children and adolescents. The results demonstrated the positive effect of Omalizumab in young patients with asthma, starting from the first year of treatment.

Severe asthma with fungal sensitization

Bronchial asthma is an inflammatory disease of the airways, which may be worsened due to many extrinsic factors. The most common trigger is the continuous exposure to allergens, of which fungal agents are important factors. A new phenotype of asthma called severe asthma with fungal sensitization (SAFS) has been described. It is diagnosed by the presence of severe asthma, fungal sensitization, and absence of allergic bronchopulmonary aspergillosis. SAFS is more of a diagnosis of exclusion. Treatment of SAFS initially should be similar to that of severe asthma including humanized anti-IgE monoclonal antibody and other biologics. These patients usually do not have their symptoms relieved with conventional treatment of severe asthma, i.e. high-dose inhaled corticosteroids and long-acting bronchodilators. Prolonged use of oral corticosteroids and pulse high-dose intravenous corticosteroid is effective. There are some evidence implicating the role of antifungal agents including itraconazole, but its use as a specific therapy requires further studies.

D101 EFFICACY OF LIGELIZUMAB IN PATIENTS WITH CHRONIC SPONTANEOUS URTICARIA INADEQUATELY CONTROLLED WITH OMALIZUMAB

In the Phase 2b core study, ligelizumab, a next generation high-affinity humanized monoclonal anti-IgE antibody, was effective in patients with chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines. This analysis evaluates the response to ligelizumab, during the Phase 2b extension study, in patients who did not achieve complete urticaria control with omalizumab in the core study.

Evaluating nonadherence to preventer inhaler therapy in severe asthmatic patients receiving omalizumab.

Asthma is one of the most common chronic diseases worldwide and can often be controlled by existing treatments, but in the 5%-10% of patients with severe asthma, control is frequently more challenging. The aim of this paper is to evaluate the adherence to preventer inhaler therapy in severe asthmatic patients receiving omalizumab, a recombinant humanized monoclonal anti-IgE antibody indicated for moderate-to-severe asthma. This study included 29 patients who were receiving omalizumab treatment as maintenance therapy. All patients completed the six question Turkish Modified Morisky Scale. In addition, patients were classified by adherence to their prescribed preventer therapy, based on pharmaceutical and medical device institution records from the preceding one year. Of the 29 enrolled patients, 24.1% had NSAID-exacerbated respiratory disease; 75.9% were female and median age was 47.2±12.99years. Severe asthma patients demonstrated high levels of motivation (98.8%, n=28) and knowledge (86.2%, n=22) about asthma treatment. Nevertheless, the rate of nonadherence to preventer inhaler therapy was only 34.5% (n=10). There were no significant differences among the characteristics of the patients that might affect the adherence to inhaler therapy. In patients with severe asthma, suboptimal adherence to preventer inhaler therapy is common before and after omalizumab treatment. Although patients have high levels of motivation and knowledge about asthma treatment, adherence to inhaler preventer therapy declined after omalizumab therapy. Given these findings, it is important to decide whether preventer inhaler therapy should be continued as monotherapy or be discontinued inpatients exhibiting impaired adherence to biological agents, such as omalizumab.

Fresh look on the urticaria problem.

Introduction. Nowadays urticaria is one of the most common diseases. According to the International Guidelines for the definition, classification, diagnosis and management of urticaria, 2nd-generation H1-antihistamines are recommended to be used as the first-line and second-line therapy. Omalizumab, a humanized monoclonal anti-IgE antibody, is assumed to be the third-line therapy in urticaria treatment.&#x0D; Summary. In this review we discuss the latest data on pathogenetic mechanisms of urticaria, focusing on the search of the new targets for the therapy. We represent the latest clinical trials of the new biological treatment for urticaria. Safety and efficiency of 4-folds higher therapeutical dose of the 2nd generation H1-antihistamines, and criteria for personalized selection of the antihistamines are discussed.

The place of Omalizumab in the treatment of allergic diseases

The article describes a modern approach to the use of anti-IgE therapy for allergic bronchial asthma and conditions associated with this disease. The humanized monoclonal anti-IgE antibody, Omalizumab (Xolar®), is a promising treatment for allergic diseases mediated by IgE. Much evidence has been obtained of the effectiveness of Omalizumab in allergic bronchial asthma and chronic spontaneous (idiopathic) urticaria, on the basis of which global meta-analyzes have been carried out confirming the effectiveness and safety of this therapeutic strategy. Recent scientific articles actively discuss the possibility of expanding indications for the medical use of Omalizumab. Clinical studies have been published on the efficacy and safety of Omalizumab for allergic rhinitis, allergic keratoconjunctivitis, chronic rhinosinusitis, nasal polyps, chronic idiopathic urticaria, food allergies, allergen-specific immunotherapy, atopic dermatitis, allergic bronchopulmonary aspergillosis – in cases of comorbidity with asthma. The clinical effect of Omalizumab in patients with allergic bronchial asthma is the most studied and proven. Currently, a number of clinical studies evaluate the long-term results of prolonged use of Omalizumab or the condition after its cancellation in patients with allergic bronchial asthma and various comorbidity.

Ligelizumab for Chronic Spontaneous Urticaria

BackgroundIn the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose–response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H1-antihistamines at approved or increased doses, alone or in combination with H2-antihistamines or leukotriene-receptor antagonists.MethodsIn a phase 2b dose-finding trial, we randomly assigned patients to receive ligelizumab at a dose of 24 mg, 72 mg, or 240 mg, omalizumab at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, or a single 120-mg dose of ligelizumab. Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose–response relationship for the complete control of hives (indicated by a weekly hives-severity score of 0, on a scale from 0 to 21, with higher scores indicating greater severity); the primary end point of this response was assessed at week 12. Complete symptom control was indicated by a weekly urticaria activity score of 0 (on a scale from 0 to 42, with higher scores indicating greater severity). Safety was analyzed throughout the trial.ResultsA total of 382 patients underwent randomization. At week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of hives, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. A dose–response relationship was established. At week 12, a total of 30%, 44%, and 40% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of symptoms, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. In this small and short trial, no safety concerns regarding ligelizumab or omalizumab emerged.ConclusionsA higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT02477332.)

Omalizumab for chronic spontaneous urticaria in "complex" patients: data from real-life clinical practice.

IntroductionOmalizumab is a recombinant humanized anti-IgE monoclonal antibody, approved for patients affected by chronic spontaneous urticaria resistant to antihistamines. Although the clinical benefit of omalizumab has been established in several clinical trials, there are very little data about long-term treatment with this drug and real-life reports regarding its use in patients affected by comorbidities other than urticaria are lacking.ObjectivesTo assess omalizumab efficacy and safety in a heterogeneous population of patients affected by chronic spontaneous urticaria and several comorbidities in a real-world setting.Materials and methodsPatients affected by chronic spontaneous urticaria with weekly urticaria activity score >16 resistant to antihistamines were treated with omalizumab 300 mg injection as add-on to H1-antihistamines administered every 4 weeks for 6 months. Clinical assessment of weekly urticaria activity score, dermatology life quality index and blood tests were performed at baseline, 12, 24 and 52 weeks of treatment. Response was assessed based on reduction weekly urticaria activity score.ResultsThirty-two patients (22F; 10M) with a mean age of 52.4 years (range 27–72) affected by chronic spontaneous urticaria were enrolled. Comorbidities affecting our study population were divided into 6 categories: cardio-metabolic (77%), oncologic (19%), infectious (16%), allergic (45%) immunologic (41%) and others (18%). Omalizumab determined a satisfactory reduction of symptoms of chronic spontaneous urticaria and an amelioration of quality of life within our population. No relevant alterations regarding patients’ underlying conditions were encountered. This is the first study regarding the use of omalizumab for chronic spontaneous urticaria in a population of adult patients affected by several comorbidities, eg, cardio-metabolic, oncologic, infectious, allergic, immunologic and psychiatric diseases. Real-life data represent a valuable source of information about a drug’s safety and efficacy profile, especially in patients affected by different comorbidities that are widely diffused in Western countries.