Pharmacoeconomic evaluation of omalizumab in the treatment of severe allergic asthma / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of omalizumab in the treatment of severe allergic asthma from the perspective of healthcare providers in China. METHODS Based on the data from an international multicenter study of omalizumab in the treatment of severe allergic asthma， the Markov model was constructed according to the progression of severe allergic asthma， with a cycle of 4 weeks. Long-term health outcomes and costs of omalizumab combined with standard of care（SoC） regimen versus SoC regimen in the treatment of severe allergic asthma were simulated by using quality-adjusted life years （QALYs） and incremental cost-effectiveness ratio（ICER） as output indexes. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis were performed to test the robustness of the results. RESULTS Compared with the SoC regimen， ICER for the omalizumab combined with SoC regimen was 107 723.05 yuan/QALY， which was less than the willingness-to-pay（WTP） threshold （268 074 yuan/QALY） calculated by three times per capita gross domestic product（GDP） in China in 2023. The one-way sensitivity analysis showed that the baseline serum level of immunoglobulin E had the greatest impact on the robustness of the model. The probabilistic sensitivity analysis showed that the omalizumab+SoC regimen had a 93.00% probability of being cost- effective. The scenario analysis showed that in the real world， the billing method of omalizumab based on specifications rather than actual usage may increase ICER. CONCLUSIONS Compared with the SoC regimen， the combination of omalizumab and SoC regimen for treating severe allergic asthma is cost-effective， with a WTP threshold of three times China’s per capita GDP

Perfil de pacientes com urticária crônica espontânea submetidos ao tratamento com omalizumabe em Chapecó, SC / Profile of patients with chronic spontaneous urticaria treated with omalizumab in Chapecó, south of Brazil

Introdução: A urticária crônica espontânea é caracterizada por lesões máculo-papulares eritematosas, associadas a prurido e angioedema, que não possui estímulo externo reconhecido e de difícil controle. A primeira e a segunda linha terapêutica, disponibilizadas pelo Sistema Único de Saúde, não apresentam resultados significativos, os quais se tornam refratários. O omalizumabe, considerado terceira linha terapêutica e que não é amplamente disponibilizado pelo Sistema Único de Saúde, pode apresentar resultado significativo na interrupção dos sintomas da doença. Objetivo: O presente estudo tem como objetivo avaliar pacientes com urticária crônica espontânea que usaram ou estão em uso de omalizumabe. Métodos: Trata-se de um estudo observacional transversal do tipo série de casos, cuja análise foi feita através dos prontuários, com população de 34 pacientes com urticária crônica espontânea submetidos ao tratamento com omalizumabe no Instituto de Olhos de Santa Catarina (IOSC). Resultados: Constatou-se no estudo que a maioria dos pacientes com urticária crônica espontânea em uso de omalizumabe é constituída do sexo feminino (76,5%) e idade média de 41 anos. A doença mais associada à urticária crônica espontânea foi depressão (38,2%). O sucesso do tratamento com omalizumabe é medido pelo questionário UAS7 (Urticaria Activity Score), o qual, segundo os dados dos prontuários, todos os pacientes apresentavam resultado maior que 35 pontos antes do uso da medicação, e 32 conseguiram alcançar um índice de 0 após o uso do omalizumabe, variando apenas no tempo de tratamento. Conclusão: A urticária crônica espontânea é uma doença que não tem cura e possui alta refratariedade, mas pode ter seus sintomas reduzidos, principalmente com o uso do omalizumabe, que se mostrou eficiente nos casos analisados.

Introduction: Chronic spontaneous urticaria is a disease characterized by erythematous maculopapular eruption, associated with itching and angioedema, that has no recognized external stimulus and is difficult to control. First- and second-line treatments, available through the Brazilian Unified Health System, do not yield meaningful results, and patients become refractory. Omalizumab, considered a third-line treatment and not widely available through the Brazilian Unified Health System, may yield meaningful results in halting disease symptoms. Objective: To evaluate patients with chronic spontaneous urticaria who have used or are using omalizumab. Methods: We conducted a cross-sectional case series observational study with a review of the medical records of 34 patients with chronic spontaneous urticaria treated with omalizumab at the Eye Institute of Santa Catarina, south of Brazil. Results: Most patients with chronic spontaneous urticaria receiving omalizumab were female (76.5%) with a mean age of 41 years. The disease most commonly associated with chronic spontaneous urticaria was depression (38.2%). Omalizumab treatment success was measured with the Urticaria Activity Score (UAS7). Based on data extracted from the medical records, all 34 patients had a score greater than 35 before treatment. After receiving omalizumab, 32 patients managed to reach a score of 0, differing only in the duration of treatment. Conclusion: Chronic spontaneous urticaria is an incurable, highly refractory disease, but its symptoms can be reduced mainly with the use of omalizumab, which proved to be effective in the cases analyzed here.

Coexistência de doenças autoimunes: oportunidade para a associação de imunobiológicos? / Coexisting autoimmune diseases: an opportunity to associate immunobiologicals?

O tratamento das doenças autoimunes com imunobiológicos é uma opção segura na prática clínica. A simultaneidade na ocorrência de doenças imunomediadas em um mesmo indivíduo pode determinar a necessidade da associação dos imunobiológicos para controle dos sintomas e melhora da qualidade de vida dos doentes. Relatamos o caso de uma paciente com artrite reumatoide em uso de etanercepte, que necessitou da associação de omalizumabe para o tratamento de urticária crônica espontânea.

Autoimmune diseases can be safely treated in clinical practice with immunobiologicals. The simultaneous occurrence of multiple immune-mediated diseases in the same individual could require a combination of immunobiologicals to control symptoms and improve quality of life. We report the case of a patient with rheumatoid arthritis who was receiving etanercept and required additional omalizumab for chronic spontaneous urticaria.

O omalizumabe no tratamento da urticária no contexto da pandemia de COVID-19 / Omalizumab as urticaria treatment in the context of the COVID-19 pandemic

O início da pandemia de COVID-19 foi marcado por incertezas diante do desconhecimento sobre a doença. Uma série de dúvidas relacionadas ao uso de imunobiológicos no contexto da pandemia foi levantada, inclusive em relação ao tratamento com omalizumabe em pacientes com urticária crônica (UC). Este estudo teve como objetivo analisar os dados relacionados à gravidade da COVID-19 e a evolução da urticária em pacientes em terapia com omalizumabe acompanhados por especialistas no Brasil. Foi realizada análise retrospectiva de dados de pacientes com UC tratados com omalizumabe entre julho/2020 e junho/2021 que apresentaram COVID-19. Foram avaliados dados relacionados às características clínicas dos pacientes e evolução da urticária durante a infecção pelo SARS-CoV2. Foram incluídos 28 pacientes em tratamento com omalizumabe, sendo 27 com urticária crônica espontânea (UCE), dos quais 25% tinham alguma urticária induzida associada. A maior parte dos pacientes (71%) estavam utilizando doses quadruplicadas de anti-histamínicos modernos de 2ª geração associados ao omalizumabe. Todos os pacientes estavam com os sintomas controlados. Entre os sintomas apresentados durante a COVID-19, os mais frequentes foram: febre (43%), cefaleia (36%), mal-estar (32%), hipo/anosmia (29%) e tosse (21%). Quatro pacientes foram hospitalizados, um deles em unidade de terapia intensiva. Um paciente relatou piora dos sintomas da UC durante a COVID-19. Cinco (18%) pacientes apresentaram piora dos sintomas da UC após a resolução da COVID-19. Todos os pacientes se recuperaram da COVID-19 sem sequelas graves. O OMA não pareceu aumentar o risco de COVID-19 grave e poderia ser usado com segurança em pacientes com UC.

The beginning of the COVID-19 pandemic was marked by uncertainty due to lack of knowledge about the disease. Questions were raised about the use of immunobiologicals in the pandemic context, including omalizumab for patients with chronic urticaria (UC). This study assessed COVID-19 severity and the clinical course of urticaria in Brazilian patients on omalizumab therapy who were monitored by specialists. We retrospectively analyzed data from chronic urticaria patients treated with omalizumab between July, 2020 and June, 2021 who presented with COVID- 19. Clinical characteristics and the course of urticaria during SARS-CoV2 infection were analyzed. The sample consisted of 28 patients treated with omalizumab, 27 of whom had chronic spontaneous urticaria (UCE) and 25% of whom had associated chronic inducible urticaria. Most of the patients (71%) were using quadruple doses of second-generation antihistamines associated with omalizumab. The symptoms of all patients were controlled. The most frequent symptoms during COVID-19 were: fever (43%), headache (36%), malaise (32%), hypo/anosmia (29%) and cough (21%). Four patients were hospitalized, including 1 in intensive care. One patient reported worsening chronic urticaria symptoms while infected with COVID-19. Five (18%) patients experienced worsening chronic urticaria symptoms after recovery from COVID-19. All patients recovered from COVID-19 without serious sequelae. Omalizumab did not appear to increase the risk of severe COVID-19 and can be safely used in patients with chronic urticaria.

Impact of COVID-19 pandemic on the course of refractory chronic spontaneous urticaria under omalizumab treatment

Abstract Background: The course of chronic spontaneous urticaria (CSU) can be influenced by infections, depression, and stress. Objectives: Our aim was to investigate the impact of the COVID-19 pandemic on the course of refractory CSU together with patient adherence to omalizumab and treatment adjustments. Methods: Urticaria Activity Score (UAS7) was used to assess disease activity. Fear of COVID-19 Scale (FC-19s), and Depression Anxiety Stress Scale (DASS-21s) were performed to assess mental health status. All scales were performed during the Quarantine Period (QP) and Return to the Normal Period (RTNP). UAS7 Before Pandemic (BP) was recorded from the patients medical records. Results: The authors evaluated 104 omalizumab-receiving CSU patients. UAS7 scores during QP were significantly higher than those in RTNP and BP (p < 0.01). DASS-21 and FC-19 scores were significantly higher during QP compared to RTNP (p < 0.01). Nineteen (18.2%) patients ceased omalizumab, 9 patients prolonged the intervals between subsequent doses during the pandemic. UAS7 scores in QP were significantly higher in patients who ceased omalizumab than in those who continued (p < 0.001). Among patients who continued omalizumab, 22.4% had an increase in urticaria activity and higher FC-19 scores in comparison with those with stable disease activity (p = 0.008). Study limitations: The small sample size of patients with prolonged intervals of omalizumab and the lack of mental health evaluation with the same tools prior to the study. Conclusions: Fear induced by COVID-19 can determine an increase in disease activity. Therefore, patients on omalizumab should continue their treatment and prolonged interval without omalizumab can be considered in patients with good urticaria control.

Consenso para el manejo práctico de la urticaria en atención primaria

Introduction: urticaria has a high impact on the quality of life of patients with this condition. While there are multiple evidence-based guidelines, these tend to be aimed at providing management recommendations for specialists rather than primary care physicians, who are usually the first to care for patients with urticaria. Objective: to develop a consensus document aimed at presenting evidence-based recommendations to help general practitioners, family doctors, pediatricians, internists and emergency physicians provide timely care for patients with urticaria, facilitating its diagnosis and timely care, and thus avoiding delays for the patients. Methods: international urticaria guidelines with recommendations based on the GRADE system were used as the source of information. Delegates of the interested scientific societies were convened, and, through structured meetings, treatment barriers and possible solutions for the application of the recommendations in primary care were identified. Results: the main barriers for primary care physicians in applying the guidelines were identified: confusion in the diagnosis, proper timing of treatment, first-line medications, and management of special situations. Possible consensus solutions were proposed for each identified barrier. Conclusion: this consensus document contains recommendations for the management and treatment of acute and chronic urticaria which help primary care physicians provide timely and effective treatment for patients with this disease. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2722).

Application of Omalizumab combined with allergen immunotherapy in the treatment of allergic asthma in children / 中华实用儿科临床杂志

Objective:To analyze the efficacy and safety of Omalizumab (OMA) combined with allergen immunotherapy (AIT) on children with allergic asthma.Methods:Clinical data of 43 children with allergic asthma from the Second Hospital of Tianjin Medical University between August 2018 and October 2022, who were managed by OMA combined with double mite subcutaneous immunotherapy (SCIT) were retrospectively analyzed, including 30 males and 13 females with the age of 5-15 years.Twenty children with allergic asthma who were managed by the monotherapy for SCIT during the same period, including 16 males and 4 females with the age of 4-13 years were included in the control group(group1: conventional immunotherapy; group2: cluster immunotherapy). Among the 43 cases managed by OMA combined with SCIT, 20 were treated with OMA, followed by AIT (OMA-AIT group), and 23 were treated with AIT, followed by OMA (AIT-OMA group). Notably, 6 cases in AIT-OMA group who were additionally given OMA due to the difficulty in increasing doses were subgrouped in AO1 group, and 17 who were additionally given OMA due to poor control of asthma or comorbidities during the course of AIT and frequent adverse events were subgrouped in AO2 group.The number of asthma exacerbations within 1 year and during the combination therapy, the Childhood Asthma Control Test/Asthma Control Test (C-ACT/ACT) findings, the Visual Analogue Scale (VAS) for grading rhinitis, inhaled corticosteroid (ICS) dosage converted to budesonide equivalent, the Total Medication Score (TMS), comorbidities, lung function [percent-predicted forced expiratory volume in 1 second(FEV 1% pred), percent-predicted peak expiratory flow(PEF%pred), percent-predicted maximal mild-expiratory flow(MMEF%pred)], exhaled nitric oxide (FeNO), completion of the initial SCIT and adverse effects [local adverse reactions (LRs) and systemic adverse reactions (SRs)] were analyzed for assessing the efficacy and safety of OMA combined with AIT on children with allergic asthma.The t-test of two independent samples was used for comparison of measurement data that followed normal distribution.Wilcoxon′s test was used for non-normally distributed between-group comparisons.The χ2 test was used for the between-group comparison of counting data. Results:(1)Baseline comparison showed that the male ratio (17/20 cases vs.13/23 cases) and the proportion of moderate-to-severe persistent asthma (18/20 cases vs.18/23 cases) in the OMA-AIT group were significantly higher than those of the AIT-OMA group (all P<0.05). (2)Efficacy: ①In OMA-AIT group, all children reached the AIT maintenance treatment stage successfully after combination therapy.At the maintenance treatment stage, the C-ACT/ACT, VAS and TMS scores(26.0±1.25 vs.24.55±2.28, 1.50±1.24 vs.2.55±1.70, 3.60±1.47 vs.5.45±1.19)were significantly improved from baseline(all P<0.05). There were no significant differences in lung function indexes FEV 1%pred, PEF%pred, and MMEF%pred ( P>0.05), and FeNO level did not change significantly than baseline.After the combination treatment, ICS dosage significantly decreased from 240.00 (160.00, 380.00) μg/d at baseline to 140.00 (80.00, 300.00) μg/d ( P<0.05). Comorbidities, including allergic rhinitis, food allergy, atopic dermatitis and angioedema were improved.Five cases (25.00%) had once asthma exacerbation during the treatment.The duration of maintenance dose of conventional (22.70±7.10 vs.15.20±1.32) and cluster immunotherapy (13.00±4.97 vs.7.30±1.06) were longer than those of the corresponding control group(all P<0.05). ②AIT-OMA group: In AO1 group, the C-ACT/ACT score were improved from baseline( P<0.05), and VAS score, TMS score decreased from 3.00(1.75, 3.00), (4.67±1.97) points at baseline to 1.00(0, 1.00), (2.83±1.60) points by the maintenance dose in AO1 group (all P<0.05). There were no significant differences in the FEV 1%pred, PEF%pred, MMEF%pred and FeNO compared with baseline in AO1 group.ICS dosage in AO1 group significantly decreased from (180.00±78.99) μg/d at baseline to (88.88±26.23) μg/d ( P<0.05). In AO2 group, the C-ACT/ACT, VAS and TMS scores at the completion of OMA treatment[26.53±0.94 vs.25.06±2.05, 1.00 (0, 2.00) vs.2.00(2.00, 3.50), 3.41±0.94 vs.5.53±1.23]were significantly improved from baseline (all P<0.05). PEF%pred[(106.47±22.37)% vs.(94.47±26.39)%] significantly increased than baseline ( P<0.05), and the remaining lung function indexes and FeNO were not significantly improved.ICS dosage significantly decreased from 240.00(160.00, 400.00) μg/d at baseline to 80.00 (20.00, 160.00) μg/d ( P<0.05). During the combination treatment, 1 case (5.88%) had once asthma exacerbation, and all 8 cases with food allergy or atopic dermatitis or conjunctivitis had improved comorbidities.(3)Safety: adverse events during OMA injection were not reported.①In OMA-AIT group, a total of 165 OMA injections were performed in the initial treatment stage of the conventional immunotherapy group, with 13 (7.88%) reported LRs and 2 (1.21%) grade-1 SRs.A total of 143 OMA injections were performed in the initial treatment stage of the cluster immunotherapy group, with 19(13.29%) reported LRs and none of SRs.②In AIT-OMA group, there were 6 cases of adverse events in the initial treatment stage of AIT who were successfully reached the maintenance treatment stage after the addition of OMA in AO1 group.In AO2 group, children who were additionally given OMA due to adverse events in the maintenance treatment phase did not report adverse events during the combination therapy. Conclusions:OMA combined with AIT not only expands the scope of AIT, improves allergic and asthma symptoms in children, reduces the use of drugs, but also enhance the safety of AIT and compliance, reduces adverse events during AIT treatment, and even shortens the time of initial treatment.

Efficacy and safety of Omalizumab for the treatment of pediatric allergic asthma: a retrospective multicenter real-world study in China / 中华实用儿科临床杂志

Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.

Application of biologic agents in the treatment of bullous pemphigoid / 中华皮肤科杂志

In recent years, new therapeutic targets for bullous pemphigoid (BP) have continued to emerge, and new biologic agents targeting pathogenic antibodies, complements, T helper type 2 (Th2) and Th17 cytokines in BP have also successively entered clinical trials, e.g., the CD20-targeting antibody rituximab and the IgE-targeting antibody omalizumab have been applied in clinical practice and have benefited some patients with refractory BP. This review summarizes the literature and clinical trials related to biologic agents as the treatment strategy for BP, analyzes and discusses clinical application of new biological agents in BP, in order to provide new ideas for the treatment of refractory BP.

Progress on omalizumab treatment for refractory asthma in children / 国际儿科学杂志

The incidence of refractory asthma in children is increasing year by year, bringing a heavy disease burden to families and society.As the immunological, pathophysiological and neurological mechanisms of asthma be elucidated, typeⅠallergic reactions mediated by the immunoglobulin E play an important role in the development of asthma.Omalizumab, targeting IgE, is using in clinical.This paper reviews the mechanism of action and clinical efficacy of omalizumab based on a review of the pathogenesis of refractory asthma, with the aim of guiding the individualized treatment of children with refractory asthma, improving the overall control rate.

Clinical research of Omalizumab in treatment of children with allergic diseases / 国际儿科学杂志

Objective:To investigate the therapeutic effect of Omalizumab in children suffering from multiple allergic diseases.Methods:The clinical data of children treated with Omalizumab in the Affiliated BenQ Hospital of Nanjing Medical University from September 2020 to September 2022 were retrospectively analyzed.Their gender, age, type of allergic disease, serum total IgE(TIgE), skin prick test and/or serum allergen specific IgE(sIgE)levels, Omalizumab dosage, therapeutic effect and adverse drug reactions were analyzed.Results:Forty-three children(male/female, 24/19)were treated with Omalizumab.The age is(9.3±2.5)years.Types of allergic diseases: 43 cases of asthma(100%), 43 cases of allergic rhinitis(100%), 5 cases of allergic conjunctivitis(11.6%), 18 cases of atopic dermatitis(41.9%), 1 case of milk protein allergy(2.3%). All the 43 patients had elevated TIgE[(613.27±616.21)Ku/L]. Allergen testing for all the children were positive, with dust mite allergy accounting for the highest proportion(93%). After treatment, the frequency of wheezing attacks was reduced and the nasal symptoms were alleviate in 43 children with asthma combined with allergic rhinitis; 5 children with allergic conjunctivitis had significantly improved symptoms of redness and itching; the skin itching in 17 children with atopic dermatitis was alleviated, and 1case had poor improvement; 1 child with milk allergy could tolerate dairy products.Conclusion:There are significant therapeutic benefits of Omalizumab in children with multiple allergic diseases.

Predictive factors for the efficacy of omalizumab in the treatment of refractory chronic spontaneous urticaria / 中华皮肤科杂志

Objective:To explore predictive factors for the efficacy of omalizumab in the treatment of refractory chronic spontaneous urticaria (CSU) .Methods:Totally, 40 patients with refractory CSU treated with omalizumab were enrolled from Department of Dermatology, the Second Affiliated Hospital of Soochow University from 2019 to 2021. Before treatment, clinical data including the urticaria activity score over 7 days (UAS7) and dermatology life quality index (DLQI) were collected; venous blood samples were collected for the detection of total immunoglobulin E (IgE) antibodies, eosinophil counts and basophil counts, anti-thyroid peroxidase (TPO) IgG antibody levels, mean platelet volume, as well as C-reactive protein (CRP) , D-dimer, complements C3 and C4, interleukin (IL) -2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor (TNF) -α and interferon (IFN) -γ levels, and percentages of CD4 + T cells and CD8 + T cells; meanwhile, the autologous serum skin test (ASST) was performed. After 12-week treatment with omalizumab, 40 CSU patients were divided into well-responding group and poorly-responding group according to the UAS7 score, and the above laboratory indicators were compared between the two groups. For continuous variable indicators with significant differences, the accuracy of prediction and optimal cut-off values were determined by using the receiver operating characteristic (ROC) curve; for categorical variable indicators with significant differences, the sensitivity and specificity for the prediction of poor clinical response to omalizumab were calculated; correlations among the above indicators were analyzed by Pearson correlation analysis. Results:After 12-week treatment with omalizumab, 28 CSU patients responded well to omalizumab, and 12 responded poorly. Before treatment, the poorly-responding group showed significantly increased proportions of patients with eosinopenia (6/12) , basopenia (7/12) , decreased C3 (6/12) , decreased C4 (6/12) , positive anti-TPO IgG antibodies (5/12) and low total IgE levels (8/12) , increased proportion of CD4 + T cells (71.13% ± 3.26%) , and increased IL-17A levels (27.16 ± 9.75 pg/ml) compared with the well-responding group (14.3%, 10.7%, 14.3%, 7.1%, 10.7%, 14.3%, 60.33% ± 5.12%, 19.24 ± 10.84 pg/ml, respectively; all P < 0.05) , but decreased IL-6 levels compared with the well-responding group ( t = 5.75, P < 0.05) . According to the ROC analysis and calculation of sensitivity, specificity and accuracy, the above indicators showed high accuracy in predicting therapeutic effect of omalizumab, and the optimal cut-off values of IL-6, IL-17A, and CD4 + T cell proportion were 8.672 pg/ml, 23.415 pg/ml, and 67.95%, respectively. In addition, the IL-6 level was significantly positively correlated with the total IgE level in CSU patients at baseline ( r = 0.43, P = 0.006) . Conclusion:Before the selection of omalizumab for the treatment of refractory CSU, there is a need to detect the eosinophil and basophil counts, levels of complements C3, C4, anti-TPO IgG antibodies, total IgE, IL-17A and IL-6, and CD4 + T cell proportions to predict therapeutic effect of omalizumab, so as to determine whether omalizumab is suitable for the patients.

Autologous serum skin test: immunological mechanisms and its associations with clinical features and prognosis of chronic spontaneous urticaria / 中华皮肤科杂志

Autologous serum skin test (ASST) is commonly used as a screening test to assess immune subtypes of chronic spontaneous urticaria (CSU) in clinical practice, but its immunological mechanisms and associations with clinical features and prognosis of CSU are not yet clear. Studies have shown that positive ASST is associated with increased immunoglobulin G autoantibodies, decreased eosinophil and basophil counts, increased CD63 expression on basophils, and changes in circulating inflammatory cytokine levels in CSU patients, but not associated with age, disease duration, and personal or family history of CSU patients, and may be a predictor of severity of chronic urticaria. ASST-positive patients may respond poorly to second-generation H1 antihistamines, slowly to omalizumab, but respond well to cyclosporine and autologous whole blood/serum injections. This review summarizes the immunological and clinical characteristics of ASST-positive patients, and discusses the predictive value of positive ASST for the efficacy of different treatment regimens.

Efficacy of omalizumab in the treatment of chronic urticaria patients with poor response to antihistamines: a single-center retrospective study / 中华皮肤科杂志

Objective:To investigate the efficacy and safety of omalizumab in the treatment of chronic urticaria (CU) patients with poor response to H1 antihistamines.Methods:CU patients, who showed poor response to H1 antihistamines and received omalizumab treatment, were collected from the Department of Dermatology, Xiangya Hospital, Central South University from June 2020 to June 2021. The efficacy of omalizumab was evaluated by using the 7-day urticaria activity score (UAS7) and urticaria control test (UCT) score at weeks 4, 12 and 24 after the start of treatment. The t-test, chi-square test, and Pearson correlation analysis were used to analyze the relationship between the clinical characteristics and efficacy. Results:A total of 121 CU patients who met the inclusion criteria and had relatively complete medical records were included in this study, including 54 males (44.63%) and 67 females (55.37%) , and their ages ranged from 13 to 70 years (39.88 ± 14.36 years) ; 88 patients were diagnosed with chronic spontaneous urticaria (72.73%) , 10 with chronic inducible urticaria (8.26%) , and 23 with chronic spontaneous urticaria accompanied by chronic inducible urticaria (19.01%) . At week 4 after the start of omalizumab treatment, the response rate was 50.86% (59/116) , and the complete response rate was 25.86% (30/116) ; at week 12, the response rate was 78.26% (54/69) , and the complete response rate was 34.78% (24/69) ; at week 24, the response rate was 64.71% (22/34) , and the complete response rate was 23.53% (8/34) . At week 4, CU patients with baseline serum total IgE levels of < 40 IU/ml had a lower response rate (26 cases, 30.77%) than those with baseline serum total IgE levels of ≥ 40 IU/ml (61 cases, 65.57%; χ2 = 8.93, P = 0.004) . Correlation analysis showed that the age at treatment, age at onset, allergic diseases, concomitant symptoms, baseline erythrocyte sedimentation rates, and baseline C-reactive protein levels were significantly correlated with the UCT scores (all P < 0.05) , while the course of disease, clinical types, serum total IgE levels, peripheral blood counts, dermatology life quality index scores, and UAS7 scores were not significantly correlated with the UCT scores. Among the 121 CU patients, 8 (6.61%) reported mild to moderate adverse reactions. Conclusion:Omalizumab could effectively improve clinical symptoms and signs of CU patients with poor response to H1 antihistamines, and was well tolerated;omalizumab treatment may be more beneficial to patients without allergic comorbidities such as allergic rhinitis, without concomitant symptoms such as angioedema, and with lower erythrocyte sedimentation rates and C-reactive protein levels.

Omalizumab for the treatment of 74 patients with chronic spontaneous urticaria accompanied by other allergic diseases: a clinical analysis / 中华皮肤科杂志

Objective:To evaluate the clinical efficacy of omalizumab in the treatment of patients with chronic spontaneous urticaria accompanied by other allergic diseases.Methods:Clinical data were retrospectively collected from 74 patients, who were clinically diagnosed with chronic spontaneous urticaria and other allergic diseases, and received subcutaneous injections of omalizumab in the Department of Allergy, Tianjin Medical University General Hospital from June 2020 to September 2022. Types of allergic diseases, serum total IgE (tIgE) and allergen-specific IgE (sIgE) levels before treatment, treatment outcomes and adverse drug reactions were analyzed. Differences before and after treatment were assessed using paired t-test and Wilcoxon signed-rank sum test. Results:A total of 74 patients with chronic spontaneous urticaria were involved, including 29 with complicated allergic asthma (39.2%) , 61 with complicated allergic rhinitis (82.4%) , 6 with complicated atopic dermatitis (8.1%) , and 4 with food allergy (5.4%) . Before treatment, elevated serum tIgE or sIgE levels were observed in 44 (59.5%) patients. After the first omalizumab treatment, the urticaria control test (UCT) score significantly increased compared with that before treatment (16.00 [13.0.0, 16.00] vs. 6.00 [5.75, 9.00], Z = 7.39, P < 0.001) ; after 4 sessions of the omalizumab treatment, 82.5% (33/40) of the patients achieved complete control of urticaria symptoms or showed complete response. After omalizumab treatment, asthmatic attacks were decreased in 29 patients with allergic asthma, and asthma control test (ACT) scores significantly increased compared with those before treatment (21.07 ± 2.88 points [after the first treatment] vs. 18.48 ± 3.20 points [before treatment], t = 8.87, P < 0.001) ; among 61 patients with allergic rhinitis, global rhinitis symptom-based visual analog scale (VAS) scores (before treatment: 5.89 ± 1.29 points; after the first treatment: 3.28 ±1.46 points) and rhinoconjunctivitis quality of life questionnaire (RQLQ) scores (before treatment: 60.10 ± 20.53 points; after the first treatment: 37.26 ± 18.83 points) both significantly decreased after the first treatment ( t = 15.04, 10.01, respectively, both P < 0.001) , and rhinitis symptoms were relieved at the same time; skin itching was relieved in 4 patients with atopic dermatitis, and allergic symptoms after contact with food allergens were also relieved in the 2 patients with food allergy after omalizumab treatment. During the treatment, only 1 patient experienced erythematous swelling, induration, and pain at the injection site. Conclusions:In the treatment of chronic spontaneous urticaria accompanied by allergic diseases, the use of omalizumab not only effectively improved urticaria symptoms, but also well controlled allergic diseases, with a good safety profile. Multiple benefits may be achieved by the use of omalizumabin in patients with chronic spontaneous urticaria accompanied by other allergic diseases.

Efficacy and safety of omalizumab in the treatment of chronic urticaria: a retrospective analysis / 中华皮肤科杂志

Objective:To retrospectively analyze clinical efficacy and safety of omalizumab in the treatment of chronic urticaria (CU) in southern Zhejiang, China.Methods:A retrospective observational study was conducted on CU patients who received omalizumab treatment at the First Affiliated Hospital of Wenzhou Medical University from January 1st, 2018 to August 1st, 2021. Through the outpatient follow-up visits, the disease activity, condition control, and quality of life were evaluated using the 7-day urticaria activity score (UAS7) , urticaria control test (UCT) , and dermatology life quality index (DLQI) . In addition, changes in disease condition, recurrence after withdrawal, and adverse events were assessed. Independent-sample t test was used for intergroup comparisons of normally distributed measurement data, Wilcoxon signed-rank sum test or Kruskal-Wallis H test was used for comparisons of non-normally distributed measurement data, and chi-square test or Fisher′s exact test was used for comparisons of enumeration data. Results:A total of 252 CU patients with poor response to antihistamines were included, with a baseline UCT score of 5.0 ± 2.4 points, a UAS7 score of 25.6 ± 6.2 points, and a DLQI score of 17.5 ± 4.7 points; among them, 204 (81.0%) were treated with omalizumab at an initial dose of 300 mg, and 48 (19.0%) with omalizumab at an initial dose of 150 mg. At the end points (12.0 ± 1.4 months after the start of treatment) , an overall control rate of 90.3% (224/248) was achieved after the omalizumab treatment; concretely, 137 (55.2%) patients achieved complete control (UCT = 16 points) , 87 (35.1%) achieved partial control (12 points ≤ UCT < 16 points) , and 24 (9.7%) showed no response (UCT < 12 points) , while 10 with partial response shifted to complete control after dose increase. During the treatment period, recurrence occurred in 50 patients (36.5%) , of whom 32 patients opted for retreatment with omalizumab, and then 30 (93.8%) achieved partial or complete control. Adverse events were reported in 8 patients (3.2%) , and all were mild or moderate.Conclusion:Omalizumab was effective in the real-world treatment of CU, and could improve patients′ quality of life, with a favorable safety profile.

Clinical features of chronic spontaneous urticaria in China: results from a hospital-based multicenter epidemiological survey / 中华皮肤科杂志

Objective:To investigate clinical features of patients with chronic spontaneous urticaria (CSU) in China.Methods:A questionnaire survey was carried out in CSU patients at the first visit and 4 follow-up visits in Departments of Dermatology of 12 third-grade hospitals in northern and southern China from January to December 2019. The survey content included demographic characteristics, pruritus intensity, the number of wheals, concomitant symptoms (such as pain in skin lesions, arthralgia, fever) during the last week prior to the admission, classification and subtypes of urticaria, and previous and current treatment regimens, etc., and the 7-day urticaria activity score (UAS7) was used to evaluate the therapeutic effect. Patients from 9 hospitals in Sichuan, Hubei and Fujian provinces were enrolled into the southern China group, and patients from 3 hospitals in Beijing municipality and Liaoning province were enrolled into the northern China group. Differences between groups were analyzed by two-independent-sample t-test, Mann-Whitney U test or chi-square test. Results:Overall, 1 396 CSU outpatients were enrolled, including 592 males and 804 females; their age was 38.32 ± 16.13 years, 1 109 (79.5%) were aged between 20 and 60 years, and 660 (47.3%) were aged between 20 and 40 years. Their age at onset was 35.85 ± 16.03 years, and the disease duration was 0.50 (0.25, 2.00) years. Allergic diseases were the most common concomitant diseases, 269 (19.3%) patients were diagnosed with accompanied allergic rhinitis or conjunctivitis, 169 (14%) with accompanied eczema/dermatitis, 39 (2.8%) with accompanied asthma; only 19 (1.4%) CSU patients had a history of thyroid diseases, but 133 (9.5%) were positive for anti-thyroid peroxidase (TPO) or anti-thyroglobulin (Tg) antibodies at the visit; elevated serum total IgE levels were observed in 437 (31.3%) patients, and 104 (7.4%) were positive for autoantibodies. There were 1 078 (77.2%) patients in the southern China group and 318 (22.8%) in the northern China group, and the southern China group showed significantly longer disease duration (2.16 ± 4.76 years vs. 1.53 ± 2.80 years, P < 0.001) , and significantly higher proportions of patients with family history (10.7% vs. 3.5%) , with painful lesions (5.8% vs. 0.9%) , and those with arthralgia (10.7% vs. 0) compared with the northern China group (all P < 0.05) . The three most prevalent urticaria subtypes were CSU (835 cases, 49.9%) , symptomatic dermographism (437 cases, 31.3%) , and angioedema (138 cases, 9.9%) , and the proportion of patients with the single diagnosis of CSU was significantly higher in the southern China group (53%) than in the northern China group (38.9%, P < 0.001) . In terms of treatment, 1 365 (97.8%) patients received conventional-dose second-generation H1 antihistamines alone or in combination, and only 31 (2.2%) were treated with antihistamines at high doses; other medicines were mostly administered in combination, and compound glycyrrhizin was most frequently prescribed (36.6%) , while omalizumab was only administered in 7 patients (0.5%) . Conclusions:Significant differences in the clinical features of CSU were observed between northern and southern China. Nowadays traditional modalities are inadequate for the treatment of CSU, and new therapeutic drugs are somewhat promising.

The progress of combined therapy of omalizumab and allergen immunotherapy in children with moderate to severe allergic asthma / 国际儿科学杂志

Allergen immunotherapy(AIT)is considered the treatment capable of modifying the natural history of allergic respiratory disorders.The adverse reactions associated with AIT limit its clinical use in moderate to severe allergic asthma.Omalizumab is currently approved for the treatment of allergic asthma, chronic spontaneous urticaria, allergic rhinitis and other allergic diseases.A few trials have demonstrated the clinical efficacy of AIT and omalizumab combination therapy in children with moderate to severe allergic asthma.This review summarizes the research progress, mechanisma and application of omalizumab combined with AIT in children with moderate to severe allergic asthma.

Safety of omalizumab in the treatment of children with allergic diseases / 中国药房

OBJECTIVE To analyze the safety of omalizumab in the treatment of allergic diseases in children. METHODS Clinical data of children with allergic diseases who were prescribed omalizumab therapy were collected from our hospital during February 2019 to July 2023， including the children’s basic conditions， allergen test results， serum levels of total immunoglobulin E （IgE）， omalizumab application and the occurrence of adverse events. The information on telephone follow-up was collected among the children who had completed treatment 12th month after drug withdrawal. At the same time， the causal relationship between adverse events and omalizumab was also evaluated by using the Naranjo assessment scale. RESULTS A total of 30 children were enrolled and received subcutaneous injections of omalizumab 245 times， accumulating 473 times. Four children suffered from four times of immediate-type hypersensitivity reactions （degree Ⅰ and Ⅱ every two times）， with an incidence of 13.3%； among them， two cases occurred after the first injection， one after the third injection， and one after the fifth injection； the results of the causality evaluation showed that two cases were “very likely” and two cases were “likely”. The telephone follow-up of 21 children showed that the children were in good health and there were no adverse events， such as malignant tumors， worm infections， serum disease- like reactions and arterial thromboembolism. CONCLUSIONS Omalizumab in children with allergic diseases is of good safety with a low incidence of adverse reactions， which are mainly mild immediate-type hypersensitivity reactions with a high long-term safety profile.

Omalizumab Treats Aspirin-Induced Asthma Complicated With Nasosinusitis and Otitis Media:Report of One Case / 中国医学科学院学报

Omalizumab,as a biological agent targeting IgE,is a recombinant humanized monoclonal antibody and the first targeted drug approved for treating moderate-to-severe bronchial asthma.By reviewing one case of aspirin-induced asthma complicated with nasosinusitis and otitis media,we discussed the value of omalizumab in the treatment of asthma and its complications,aiming to provide a reference for clinical practice.