Omalizumab Treatment Research Articles

Omalizumab Drug Survival in Chronic Urticaria: A Retrospective Multicentric French Study

Omalizumab (OMA) dramatically improves disease control and quality of life in patients with chronic urticaria (CU). We aimed to evaluate the discontinuation patterns of OMA and their determinants in a cohort of French patients with CU. We conducted a retrospective multicenter study in 9 French tertiary referral hospitals. All patients diagnosed with either spontaneous (CSU) and/or inducible (CIndU) CU who received at least 1 injection of OMA between 2009 and 2021 were included. We analyzed OMA drug survival and investigated possible determinants using Kaplan-Meier curves and log-rank tests. A total of 878 patients were included in this study; 48.8% had CSU, 10.1% CIndU, and 41.1% a combination of both. OMA was discontinued in 408 patients, but the drug was later reintroduced in 50% of them. The main reason for discontinuing treatment was the achievement of a well-controlled disease in 50% of patients. Half of the patients were still being treated with OMA 2.4 years after the initiation of treatment. Drug survival was shorter in patients with CIndU and in those with an autoimmune background. In atopic patients, OMA was discontinued earlier in patients achieving a well-controlled disease. A longer OMA drug survival was observed in patients with a longer disease duration at initiation. In French patients with CU, the drug survival of OMA appears to be longer than that observed in previous studies conducted elsewhere, highlighting discrepancies in prescription and reimbursement possibilities. Further studies are warranted to develop customized OMA treatment schemes based on individual patterns.

Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study

Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. Across 2769 COVID-19-vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination-induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination-induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine-related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated.

Exacerbation of Chronic Spontaneous Urticaria Following Coronavirus Disease 2019 (COVID-19) Vaccination in Omalizumab-Treated Patients.

The rapid development and rollout of vaccines against coronavirus disease 2019 (COVID-19) has led to more than half of the world's population being vaccinated to date. Real-world data have reported various adverse cutaneous reactions, including delayed-onset urticaria, which was highly ranked as a common manifestation across studies. However, the impact of these novel mRNA or viral vector COVID-19 vaccines on preexisting chronic spontaneous urticaria (CSU) remains largely unknown. To investigate the impact of COVID-19 vaccination on the clinical status of patients with relatively stable CSU who are undergoing omalizumab treatment and to identify risk factors for exacerbation. We conducted a questionnaire-based cross-sectional study in a tertiary hospital. Adult patients with relatively stable CSU under regular omalizumab treatments who had received at least one COVID-19 vaccination were included. There were 105 study subjects who received 230 COVID-19 vaccinations between March and December 2021. Fifteen patients (14.3%) experienced aggravation of urticaria at least once after COVID-19 vaccination. The demographics and clinical characteristics of the patients were comparable regardless of the exacerbation of CSU. However, case-level analysis revealed that the presence of urticaria (vs none) before vaccination (odds ratio [OR]= 4.99; 95% CI, 1.57-15.82) and the development of systemic reactogenicity (OR= 4.57; 95% CI, 1.62-12.90) were associated with a higher risk for exacerbation. The novel COVID-19 vaccination induced exacerbation in more than one-tenth of patients with well-controlled CSU. The establishment of a proper management strategy during COVID-19 vaccination is necessary for patients with CSU.

The ratio of total IgE level at week 16 to baseline significantly correlated with the clinical response to omalizumab in moderate to severe allergic rhinitis patients

ObjectiveTo analyze whether the ratio of total IgE level at week 16 to baseline could be used as an indicator to evaluate clinical efficacy of patients treated with omalizumab. MethodsWe retrospectively analyzed the clinical characteristics of 62 patients with moderate-to-severe allergic rhinitis treated with omalizumab, and compared the pre-and post-treatment nasal visual analog scale (n-VAS) scores, the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Rhinitis Control Assessment Test (RCAT), improvement in nasal congestion, number of acute episodes of rhinitis, and total IgE levels in serum. The relationship between the efficacy of treatment with omalizumab and the change in total IgE levels before and after treatment was further analyzed. ResultsThis study included 62 patients with moderate-to-severe allergic rhinitis, of which 48 demonstrated significant improvement after 16 weeks of omalizumab therapy; the results of 16 weeks’ omalizumab treatment in 14 patients did not show significant improvements in allergic rhinitis symptoms based on RACT scores. After 16 weeks of omalizumab treatment, the RQLQ score decreased from (36.6 ± 13.7) at baseline level to (9.1 ± 12.6) after 16 weeks treatment.The ratio of total IgE at week 16 to total IgE levels at baseline was (2.9 ± 1.4) KU/L in 62 patients. And the ratio of total IgE levels at week 16 to total IgE levels at baseline was (3.3 ± 1.4) KU/L for responders and (1.6 ± 0.5) KU/L for non-responders. ConclusionThe ratio of total IgE level at week 16 to baseline significantly correlated with the clinical response to omalizumab in moderate to severe allergic rhinitis patients, when the ratio of total IgE level at week 16 to baseline was ≥2.0. Omalizumab effectively treated patients with moderate-to-severe allergic rhinitis, and improved their quality of life.

Omalizumab in the treatment of various forms of chronic urticaria

BACKGROUND: Chronic urticaria is a skin disease characterized by the appearance of itchy weals and/or angioedema for 6 or more weeks. Chronic urticaria is subdivided into chronic spontaneous urticaria, which occurs due to an unknown cause, and chronic inducible urticaria, which occurs as a result of exposure to various physical factors (water, cold, heat, pressure, mechanical irritation), can occur simultaneously or independently of each other. Omalizumab, anti-IgE monoclonal antibody, is approved for the treatment of patients with chronic spontaneous urticaria and is the second choice in cases of resistance to antihistamine treatment. In patients with a combination of chronic spontaneous urticaria and chronic inducible urticaria, the effectiveness of treatment with omalizumab has been little studied.&#x0D; AIM: compare the effectiveness of omalizumab treatment in patients with chronic spontaneous urticaria and patients with a combination of chronic spontaneous and chronic induced urticaria.&#x0D; MATERIALS AND METHODS: Under supervision there were 30 patients with chronic spontaneous urticaria and combined chronic spontaneous and inducible urticaria (15 patients in each group). Evaluation of the effectiveness of treatment was carried out according to the results of the questionnaires DLQI (dermatological index of quality of life), CU-Q2oL (questionnaire for quality of life in chronic urticaria), UCT (urticaria control test), UAS (urticaria activity scale), HADS (Hospital Anxiety and Depression Scale) and provocation tests in dynamics before and during treatment.&#x0D; RESULTS: All patients received omalizumab 300 mg subcutaneously once a month for 6 to 12 months. After the first injection of omalizumab, we noted a decrease in the severity of urticaria, an increase in the level of disease control and quality of life when comparing parameters before and during treatment in more than 90% of patients. Improved performance remained at this level throughout all subsequent months of treatment.&#x0D; CONCLUSION: Omalizumab is equally effective in patients with an isolated form of chronic spontaneous urticaria and in patients with a combined form of chronic spontaneous and inducible urticaria. The use of omalizumab allows you to control the symptoms of chronic spontaneous and inducible urticaria, even with prolonged use.

Effective omalizumab treatment influenced eosinophil function in severe allergic asthmatics.

Omalizumab is an effective anti-immunoglobulin E (IgE) treatment for allergic asthma. Eosinophil plays a critical role in the pathogenesis of allergic airway inflammation. This study aimed to explore the influence of effective omalizumab treatment on circulating eosinophils. Allergic asthmatics enrolled in the study were treated with omalizumab for at least 16 weeks and exhibited a good or excellent response according to the global evaluation of treatment effectiveness (GETE) assessed by each patient and specialist physician. For eosinophil functional evaluation, peripheral blood eosinophils were separated; and examined the expression of human leukocyte antigen (HLA)-DR and co-stimulatory molecules cluster of differentiation (CD) 80, CD86 and CD40 by Flow Cytometry and serum were to measure the concentration of eotaxin-1 before and after 16 weeks of omalizumab treatment. Totally 32 allergic asthma patients who responded positively to omalizumab treatment were included. Omalizumab responders showed a significant decline in the expression of co-stimulatory molecules CD40, CD80, and CD86 on peripheral eosinophils and in serum eotaxin-1 concentration after treatment. Negative correlations (r=-0.61, P=0.048) were observed between the change in CD80+ eosinophils and the change in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC)% predicted and maximal expiratory flow (MEF) 25% after omalizumab treatment. Omalizumab improved FEV1/FVC% predicted (3.88, P=0.033), fractional exhaled nitric oxide (FeNO, -22.24, P=0.028), asthma control test (ACT, 4.22, P<0.001), mini asthma quality of life questionnaire (mini-AQLQ, -14.44, P=0.019), Leicester cough questionnaire (LCQ, 3.03, P=0.009) and visual analogue scale (VAS) for allergic symptoms (-13.00, P=0.001) in patients with severe allergic asthma statistically; reduced mini rhino-conjunctivitis quality of life questionnaire (mini-RQLQ, -8.50, P=0.047), and self-rating anxiety scale (SAS, -5.08, P=0.040) in allergic asthmatics with concomitant allergic rhinitis (AR) or anxiety, respectively. Our findings show a unique role of omalizumab in reducing co-stimulatory molecules expression on eosinophil and serum eotaxin-1 levels in severe allergic asthmatics accompanied by improvement of multiple clinical parameters of allergic diseases.

Real-World Safety and Effectiveness of Omalizumab in Moderate to Severe Allergic Asthma Patients in China: A Post-Authorization Study.

Omalizumab was first approved in China in 2017 for the treatment of moderate to severe allergic asthma for adult and adolescent patients aged ≥12 years. In accordance with the Chinese Health Authority requirement, the post-authorization safety study (PASS) was conducted to evaluate the safety and effectiveness of omalizumab in a real-world setting in patients with moderate to severe allergic asthma in China over a 24-week observation period. This is a single-arm, non-interventional, multicenter, PASS conducted in adult, adolescent, and pediatric patients (≥6 years old) with moderate to severe allergic asthma receiving omalizumab in a real-world clinical setting from 2020 to 2021 in 59 sites of mainland China. In total, 1546 patients were screened and 1528 were enrolled. They were stratified according to age (6 to <12 years [n = 191]; ≥12 years [n = 1336]; unknown [n = 1]). Among the overall population, 23.6% and 4.5% of patients reported adverse events (AEs) and serious adverse events (SAEs), respectively. Among pediatric patients (6 to <12 years), 14.1% and 1.6% patients reported AEs and SAEs, respectively. AEs that led to treatment discontinuation in both age groups were <2%. No new safety signals were reported. Effectiveness results showed improvement in lung function, asthma control, and quality of life (QoL). The findings of the current study demonstrated that the safety profile of omalizumab was consistent with its known profile in allergic asthma, and no new safety signals were reported. Omalizumab treatment was effective in improving the lung function and QoL in patients with allergic asthma.

Expression of CCR8 and CCX-CKR on Basophils in Chronic Urticaria Is Amplified by IgE-Mediated Activation.

Recruitment to the local tissue and alerted phenotype are the hallmarks of basophils in chronic urticaria (CU). Chemokine receptors such as chemokine (C-C motif) receptor 4 (CCR4) or CCR8 have been studied in skin diseases, e.g., atopic dermatitis, but not in CU. In this study, we aimed to define CU's basophil homing potential and receptor profile and the effect of Omalizumab treatment on these. Unstimulated and activated (anti-IgE, fMLP, C5a, and Substance P) whole blood basophils from 11 Omalizumab-treated CU patients and 10 healthy subjects were investigated with flow cytometry. Unstimulated basophils in CU showed higher expression of the skin-associated (CCR8) and scavenger (CCX-CKR) receptors and lower expression of the lung-associated (CCR3) receptor in contrast to healthy ones. IgE-mediated activation increased the percentage of CCR8 and CCX-CKR in CU compared to healthy group and elevated the expression of the lung-associated chemokine receptor, XCR1, in all groups. A trend of augmented expression of the coagulation cascade (CD87) and fMLP (FPR1) receptors was seen on basophils in CU, while a tendency of reduced expression was seen for itch (IL-31RA) and immunotolerance (CD109) receptors. fMLP and C5a increased the expression of CCR4, CCR8, CCX-CKR, and CD87 and decreased CCR2 and CCR3, though no changes between the groups were found. In conclusion, CU basophils exhibit skin-homing potential amplified by IgE-mediated stimulation.

Abstract #1398759: Rituximab Therapy for Refractory Insulin Allergy in Type-1 Diabetes Mellitus

Hypersensitivity reactions to insulin have decreased significantly since the introduction of human insulin preparations, but up to 3% of diabetic patients can still be affected with both immediate and delayed reactions described. There were previous reports of rituximab use in severe, refractory insulin allergies in Type-1 Diabetes Mellitus (T1DM) prior to omalizumab treatment. Here, we describe another case of T1DM with severe insulin allergy that was successfully treated with rituximab monotherapy. A 40-year-old female presents to an Endocrinology clinic for care of her T1DM. She was diagnosed with T1DM at age 37, initially treated with multiple daily injections of insulin glargine and aspart, which were switched to pod pump therapy 6 months later. Within 2 years, she experienced painful and itchy rashes with erythema and wheals at the pod insertion sites that developed within 1 to 4 hours of pod placement. Barrier adhesives, topical and oral antihistamines, and topical glucocorticoids were ineffective. Over the next 12 months, she was trialed on insulin aspart, lispro, regular, and glulisine with similar results despite using syringe and pen injectors. Skin reactions lasted several days, with nodules and surrounding lipodystrophy. Inhaled human insulin was implemented but discontinued due to cough. She was referred to our drug allergy clinic, where testing that included a positive immediate intradermal insulin lispro test and negative m-cresol skin test was performed. Serum insulin-specific IgG antibody testing was positive, but IgE antibody was negative, suggesting the reaction was related to tissue-bound IgE. Skin biopsy revealed sub-lobular panniculitis. She was empirically started on metformin, dapagliflozin, and liraglutide to reduce insulin needs, with only mild improvement achieved. However, 4 doses of rituximab 100mg weekly as intravenous infusion significantly reduced her skin reactions with a durable response out to 18 months, when the injection site reactions recurred. Rituximab treatment was repeated weekly for 4 weeks. Her skin reactions improved again after this second round of immunotherapy, and the patient continues to do well 30 months afterward. Suspected patients with insulin allergy should have a thorough evaluation including immediate and delayed skin testing, serum IgE assessment, skin biopsy, and exclusion of other skin disorders. Treatment approaches include changing insulin preparations, changing injection technique and rotating sites, antihistamines, or even desensitizing with an insulin pump. Our case reinforces that systemic immunotherapy can be a viable option in refractory cases.

Thyroid Autoimmunity in CSU: A Potential Marker of Omalizumab Response?

The response of severe chronic spontaneous urticaria (CSU) to omalizumab largely depends on the autoimmune or autoallergic endotype of the disease. Whether thyroid autoimmunity may predict omalizumab response along with total IgE in CSU is still unclear. Three hundred and eighty-five patients (M/F 123/262; mean age 49.5 years; range 12-87 years) with severe CSU were studied. Total IgE levels and thyroid autoimmunity (levels of anti-thyroid peroxidase [TPO] IgG) were measured before omalizumab treatment. Based on the clinical response, patients were divided into early (ER), late (LR), partial (PR) and non (NR) responders to omalizumab. Thyroid autoimmunity was detected in 92/385 (24%) patients. Altogether, 52%, 22%, 16% and 10% of patients were ER, LR, PR and NR to omalizumab, respectively. Response to omalizumab was not associated with thyroid autoimmunity (p = 0.77). Conversely, we found a strongly positive association between IgE levels and omalizumab response (p < 0.0001); this association was largely driven by early response (OR = 5.46; 95% CI: 2.23-13.3). Moreover, the predicted probabilities of early response strongly increased with increasing IgE levels. Thyroid autoimmunity alone cannot be used as a clinical predictor of omalizumab response. Total IgE levels remain the only and most reliable prognostic marker for omalizumab response in patients with severe CSU.

Analysis of the Efficacy and Recurrence of Omalizumab Use in the Treatment of Chronic Spontaneous Urticaria and Chronic Inducible Urticaria

Introduction: Chronic urticaria (CU) is a common skin condition that can be divided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Omalizumab is one treatment option for CU, but currently there are limited clinical studies of omalizumab’s efficacy for treating CU in Chinese patients. This study sought to investigate the efficacy and safety of omalizumab treatment for CU patients in a Chinese patient population. Specifically, we aimed to compare the differential efficacy of omalizumab for CSU and CIndU patients and predict risk factors for recurrence. Methods: We completed a retrospective clinical data review of 130 CU patients who received omalizumab treatment from August 2020 to May 2022, with a maximum follow-up period of 18 months. Results: A total of 108 CSU patients and 22 CIndU patients were included in the study. After treatment with omalizumab, the response rate in the CSU group was higher than that in the CIndU group (93.5% vs. 68.2%), and CSU patients accounted for a higher proportion of responders and early responders (responders: 87.1% vs. 12.9%, p < 0.001; early responders: 95.7% vs. 4.3%, p = 0.001). Nonresponders had lower total immunoglobulin E (IgE) levels (75.0 vs. 167.5 IU/mL, p = 0.046) and a relatively shorter duration of treatment (1.0 vs. 3.0 months, p = 0.009) compared to responders. Early responders had shorter disease duration (1.0 vs. 3.0 years, p = 0.028), higher baseline UCT (4.0 vs. 2.0, p = 0.034), lower baseline DLQI (18.0 vs. 18.5, p = 0.026), and shorter total treatment time (2.0 vs. 4.0 months, p < 0.001) compared to late responders. All adverse events reported during treatment were mild. Seventy-four patients with CU discontinued the drug after achieving complete disease control, of which 26 (35.1%) relapsed for 2.0 months (interquartile range: 1.0–3.0 months). Compared with nonrelapsed patients, relapsed patients often had other allergic diseases (42.3% vs. 18.8%, p = 0.029), higher basal levels of total IgE (263.0 vs. 140.0 IU/mL, p = 0.033), and longer disease duration (4.2 vs. 1.0 years, p = 0.002). Relapsed patients could still achieve good disease control after restarting omalizumab therapy. Conclusion: Omalizumab was effective and safe for CSU and CIndU patients. Patients with CSU responded more quickly to omalizumab and showed a relatively better treatment effect. However, there was a possibility of relapse after discontinuation of omalizumab after complete control of CU, and in these cases, restarting omalizumab treatment after relapse was effective.

Evaluation of the clinical features and laboratory data of patients with severe asthma classified as super-responder or non super-responder to omalizumab treatment: a single-center real-life study

Introduction Omalizumab is used for the treatment of severe allergic asthma. Objective The aim of this study was to evaluate the clinical features and laboratory data of patients with severe allergic asthma classified as super-responder or non super-responder to omalizumab. Methods Comparisons were made of the laboratory data and clinical features of patients with severe allergic asthma. Patients who had no asthma exacerbation, no oral corticosteroid (OCS) use, asthma control test (ACT) score >20 and forced expiratory volume in 1 s (FEV1) >80% were considered super-responder after omalizumab. Results A total of 90 patients were included in the study, comprising 19 (21.1%) males. The age at onset of asthma, allergic rhinitis rate, number of endoscopic sinus surgeries (ESS), intranasal corticosteroid (INS) use, baseline FEV 1 (%) and ACT score were significantly higher in the omalizumab super-responder group (p = 0.013, p = 0.015, p = 0.002, p = 0.001, p = 0.001 and p < 0.001, respectively). The duration of asthma, rate of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), regular use of OCS, baseline eosinophil count and eosinophil-to-lymphocyte ratio were significantly higher in the omalizumab non super-responder group (p = 0.015, p < 0.001, p = 0.004, p < 0.001 and p < 0.001, respectively). Blood eosinophil count (AUC: 0.187, p < 0.001), eosinophil-to-lymphocyte ratio (AUC: 0.150, p < 0.001) and FEV1 (%) (AUC:0.779, p = 0.001) were determined to have diagnostic value in predicting the treatment response to omalizumab of patients with severe allergic asthma. Conclusion High-blood eosinophil levels, CRSwNP and low pretreatment lung capacity may affect omalizumab treatment response in patients with severe allergic asthma. These results should be supported by further multicenter real-life studies.

Omalizumab ameliorates extrarespiratory symptoms in patients with aspirin-exacerbated respiratory disease

Omalizumab, an anti-immunoglobulin E antibody, has clinical efficacy against respiratory symptoms of aspirin-exacerbated respiratory disease (AERD). However, some patients with AERD also present with extra-respiratory (chest, gastrointestinal, and/or cutaneous) symptoms, which are resistant to conventional treatment but can be alleviated by systemic corticosteroids. To evaluate the efficacy of omalizumab on extra-respiratory symptoms related to AERD. In Study 1, 27 consecutive patients with AERD initially prescribed omalizumab at Sagamihara National Hospital between July 2009 and March 2019 were studied retrospectively. The frequency of exacerbations of AERD-related extra-respiratory symptoms was compared before and after the initiation of omalizumab treatment. In Study 2, we reported three AERD cases with aspirin challenge-induced extra-respiratory symptoms among patients studied in our previous randomized trial (registration number: UMIN000018777), which evaluated the effects of omalizumab on hypersensitivity reactions during aspirin challenge to AERD patients. The extra-respiratory symptoms induced during the aspirin challenge were compared between the placebo and omalizumab phases. In Study 1, omalizumab treatment was associated with a decrease in the frequency of exacerbation of chest pain (n [%] of patients with exacerbation frequency ≥1 time per year, 6 [22.2%] vs. 0 [0%]; P<0.001), gastrointestinal symptoms (9 [33.3%] vs. 2 [7.4%]; P=0.016), and cutaneous symptoms (16 [59.3%] vs. 2 [7.4%]; P<0.001), even under conditions of a treatment-related reduction in systemic corticosteroid dose. Omalizumab also attenuated all the extra-respiratory symptoms during the aspirin challenge in Study 2. Omalizumab ameliorated the extra-respiratory symptoms at baseline (without aspirin exposure) and during aspirin challenge.

PK/PD modeling to characterize placebo and treatment effect of omalizumab for chronic spontaneous urticaria.

The pharmacokinetic (PK) characteristics of omalizumab and its pharmacodynamic (PD) effect in patients has yet to be fully characterized in chronic spontaneous urticaria, which could elucidate its pathogenesis and treatment response. This study has two objectives; (1) characterize the population PK of omalizumab and its PD effect on IgE, and (2) develop a drug effect model of omalizumab in urticaria (via change in weekly itch severity score). The target-mediated population of PK/PD model incorporating omalizumab-IgE binding and turnover adequately described PK and PD of omalizumab. The effect compartment model and linear drug effect and additive placebo response adequately described placebo and treatment effects of omalizumab. Several baseline covariates were identified for PK/PD and drug effect models. The developed model has the potential to aid in understanding variability in PK/PD as well as response to omalizumab treatment.

Clinical efficacy observation of omalizumab on patients with moderate to severe allergic asthma for one year

To observe the symptom control, pulmonary function changes and safety of use of omalizumab in patients with moderate to severe allergic asthma for 1 year. A small sample self-controlled study before and after treatment was conducted to retrospective analysis involved 17 patients with moderate to severe asthma who received omalizumab therapy for 12 months in Peking University People's Hospital and Beijing Jishuitan Hospital from January 2020 to December 2021. The clinical symptoms and pulmonary function changes were compared before treatment, after 6 months and 12 months of treatment, and the clinical data such as the use of other drugs and adverse reactions were observed. Statistical data are collected using the median method, and non-parametric paired Wilcoxon analysis was used for pairwise comparison. Before treatment with omalizumab, the patients' FeNO value was 79(58, 121) ppb, and the total serum IgE was 228(150.5, 345.5) IU/ml. After 6 months of omalizumab therapy, the percent predicted value of the forced expiratory volume in 1 second (FEV1%) before inhaled bronchodilator increased from 86.70(82.65, 91.35)% to 90.90(87.70, 95.85)% (Z=-3.626, P<0.001). The FEV1%pred after inhaled bronchodilator increased from 92.60(85.75, 96.90)% to 94.30(89.95, 98.15)% (Z=-2.178, P=0.029). The absolute value of improvement in FEV1 decreased from 150(95, 210)ml to 50(20, 125) ml (Z=-2.796, P=0.005), and the improvement rate decreased from 6.60(3.80, 7.85)% to 1.90(0.75, 4.85)% (Z=-2.922, P=0.003). After 12 months of treatment, the FEV1%pred before inhaled bronchodilator further increased to 92.90 (91.60, 98.15)% (Z=-3.575, -2.818, and P<0.001, 0.005 compared with before treatment and 6 months after treatment, respectively). The FEV1%pred after inhaled bronchodilator increased to 96.80 (91.90, 101.25)% (Z=-3.622, -1.638, and P<0.001, 0.008 compared with before treatment and after 6 months of treatment, respectively). The absolute value of improvement in FEV1 was 70 (35, 120) ml (P=0.004, 0.842 before treatment and 6 months after treatment, respectively), and the improvement rate was 3.0(1.0, 5.0)% (Z=-2.960, -0.166, and P=0.003, 0.868, compared with before treatment and after 6 months of treatment, respectively). After 12 months of treatment, ACT increased from 13 (10.5, 18) before treatment to 24 (23, 25) (Z=-3.626,P<0.001). Only 1 patient experienced an injection site skin reaction during treatment. Therefore, after 6 months and 12 months of treatment with omalizumab, the patient's lung function improved and symptoms were relieved, which could effectively prevent the acute exacerbation of asthma. Omalizumab treatment is safe and well tolerated, and no effect on blood pressure and blood glucose was observed.

Clinical efficacy of omalizumab for treatment of moderate or severe allergic asthma in children with serum immunoglobulin E levels >1 500 IU/mL: a prospective study

To evaluate the clinical efficacy of omalizumab in the treatment of moderate or severe allergic asthma in children with serum total immunoglobulin E (IgE) levels >1 500 IU/mL. A total of 95 children with moderate or severe allergic asthma, who were treated at the Department of Respiratory Medicine in Anhui Provincial Children's Hospital from December 2020 to May 2022, were enrolled. Based on their serum total IgE levels and whether they received omalizumab treatment, they were divided into a control group (IgE >1 500 IU/mL, no omalizumab treatment), a normal treatment group (IgE levels between 30 and 1 500 IU/mL, omalizumab treatment), and an ultra-high IgE treatment group (IgE >1 500 IU/mL, omalizumab treatment). The differences in clinical characteristics, Childhood Asthma Control Test (C-ACT) scores before and after treatment, the proportion of acute attacks, IgE levels, pulmonary function indicators, and fractional exhaled nitric oxide (FeNO) concentrations were analyzed among the three groups. At the 8th week of treatment, the normal treatment group and the ultra-high IgE treatment group had higher C-ACT scores, forced expiratory volume in first second (FEV1) as a percentage of predicted value (FEV1%pred), FEV1/forced vital capacity (FVC) ratio (FEV1/FVC), and peak expiratory flow (PEF) as a percentage of predicted value (PEF%pred), as well as a lower proportion of acute attacks and FeNO concentration compared to the control group (P<0.05). There were no statistically significant differences in the comparison of various indicators between the ultra-high IgE treatment group and the normal treatment group (P>0.05). At the 16th week of treatment, the normal treatment group and the ultra-high IgE treatment group had higher C-ACT scores and pulmonary function indicators including FEV1%pred, FEV1/FVC, PEF%pred, and forced expiratory flow at 25% vital capacity (FEF25) as a percentage of predicted value (FEF25%pred) compared to the control group (P<0.05). The proportion of acute attacks and FeNO concentration in the ultra-high IgE treatment group were lower than those in the control group (P<0.05). There were no statistically significant differences in the comparison of various indicators between the ultra-high IgE treatment group and the normal treatment group (P>0.05). Omalizumab therapy has a certain clinical efficacy in children with moderate or severe allergic asthma and serum total IgE levels >1 500 IU/mL, with no significant difference in efficacy compared to children with serum total IgE levels between 30 and 1 500 IU/mL.

Changes of Gut Microbiome in Adolescent Patients with Chronic Spontaneous Urticaria After Omalizumab Treatment.

Omalizumab is a humanized anti-immunoglobulin (Ig) E monoclonal antibody that is effective in treating some patients with chronic spontaneous urticaria (CSU) who do not respond to antihistamines. Gut microbiome plays a role in the pathogenesis of allergies and autoimmune diseases. Here, we investigated differences in the gut microbiome of adolescent CSU patients before and after omalizumab treatment, which has not been previously reported. Ten adolescent CSU patients were given 300 mg omalizumab subcutaneously in three treatments at 4-week intervals. Urticaria Activity Score (UAS7) was applied to evaluate the efficacy of each omalizumab treatment during follow-up. Fecal samples were collected before and 12 weeks after the first treatment. Total DNA of the gut microbiota in all fecal samples were extracted. The 16S rRNA gene-targeted sequencing technology was used for the analysis of the diversity and distribution of gut microbiome, followed by bioinformatics analysis. UAS7 scores decreased significantly after each treatment compared with the baseline (all P < 0.0001). There were five well-controlled responders and five non-responders after three treatment sessions of omalizumab. The dominant bacteria phyla in all fecal samples were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Alpha diversity analysis showed no significant difference before and after treatment (P >0.05), whereas beta diversity analysis revealed a significant difference in the bacterial abundance before and after treatment (P < 0.01). The relative abundance of Alphaproteobacteria and Betaproteobacteria at the class level and Burkholderia, Rhodococcus, and Sphingomonas at the genus level decreased significantly after treatment (linear discriminant analysis >4, P <0.05). The functional prediction results showed that the dioxin and xylene degradation pathways were more abundant before treatment. Omalizumab is effective in treating CSU and the abundance of Alphaproteobacteria and Betaproteobacteria was reduced after treatment, which may help improve the treatment outcomes in adolescent CSU patients.

Real-World Benefits of Mepolizumab in Patients With Overlapping Allergic and Eosinophilic Endophenotypes: Post Hoc Analysis of REALITI-A by Omalizumab Eligibility

Up to 73% of patients with severe asthma have overlapping allergic and eosinophilic endophenotypes and are eligible for treatment with anti-eosinophilic (e.g., mepolizumab) or anti-IgE (omalizumab) biologics. We assessed mepolizumab real-world effectiveness in patients with severe asthma and overlapping endophenotypes based on omalizumab treatment eligibility.

Efficacy and safety of omalizumab in adult patients with wheat-dependent exercise-induced anaphylaxis: Reduction of in vitro basophil activation and allergic reaction to wheat

BackgroundIn patients with wheat-dependent exercise-induced anaphylaxis (WDEIA), anaphylactic shock occurs frequently, therefore avoidance of wheat products is recommended. We aimed to evaluate efficacy and safety of long-term omalizumab treatment for adult patients with WDEIA. MethodsIn this phase 2, multicentre single-arm trial, 20 adult patients with WDEIA were enrolled (UMIN 000019250). All patients were administered 150–600 mg of omalizumab subcutaneously and evaluations (basophil activation and blood examination) were performed at regular intervals during administration period (0–48 weeks) and observation period (48–68 weeks). Primary endpoint was proportion of the patients who achieved a basophil activation rate below 10% with fractionated wheat preparations, and secondary endpoint was proportion of the patients with no allergic reactions after wheat products ingestion. ResultsDuring the omalizumab treatment, more than 80% of the patients achieved the basophil activation rate less than 10% against all fractionated wheat preparations, and 68.8% of the patients who achieved the primary endpoint experienced no allergic reaction. During the observation period, the proportion of the patients who achieved a basophil activation rate below 10% decreased gradually, and the proportion of patients with positive allergic reactions increased gradually thereafter and reached maximum of 46.7%. Severe adverse events were not observed during the study. ConclusionsLong-term omalizumab treatment is safe and effective for adult patients with WDEIA when assessed by basophil activation rate with wheat allergens as well as allergic reactions after lifting of restrictions on wheat intake. However, this is not enough to achieve desensitization.

The effect of COVID-19 on patients recieving omalizumab treatment

Background and aimAlthough exposure during drug administration and susceptibility to coronavirus disease-19 (COVID-19) infection secondary to immunomodulatory effects constitute potential risks for patients with chronic spontaneous urticaria (CSU) or asthma on omalizumab (OMZ), there is a risk of loss of response following discontinuation of OMZ. There are few studies describing the clinical course of COVID-19 in patients receiving OMZ. Materials and methodsA total of 103 patients on OMZ were included in the study between February 2021 and January 2022. ResultsFourteen (13.6%) of the patients participating in the study had SARS-CoV-2 infection, of whom 3 (21.4%) required hospitalization and 11 (78.6%) were treated in an outpatient clinic. During the pandemic, 17 (16.5%) of the patients interrupted their OMZ treatment. Patients on OMZ for six months or less had a lower rate of interruption (2.5%) than those on OMZ for more than 6 months (25.4%). Patients interrupted treatment for the following reasons: 3 (17.6%) had COVID-19, 10 (58.9%) did not attend the hospital visit due to concern about contamination with SARS-CoV-2, and 4 (23.5%) thought that OMZ treatment would facilitate contamination with SARS-CoV-2. After interrupting OMZ, 3 (25%) female patients and 5 (100%) male patients presented no worsening of their symptoms. Three (13%) of the patients on OMZ for asthma and 11 (13.8%) of those on the drug for urticaria had COVID-19 infection. Patients presenting CSU and severe asthma are completely different, with different potential consequences of OMZ interruption. Nine (52.9%) patients had aggravated symptoms following interruption of OMZ treatment. Three of them described worsening of asthma symptoms and a need to increment their maintenance therapy due to asthma exacerbation after nearly three weeks of interruption, and 6 of them had hives and pruritus as urticaria exacerbation nearly four weeks after interruption of OMZ. The asthma patients did not stop their other treatments, including inhaled corticosteroids. ConclusionUse of OMZ does not increase the risk of SARS-CoV-2 infection, COVID-19-related pneumonia, or COVID-19-related hospitalization. We advise patients not to interrupt OMZ treatment during the COVID-19 pandemic unless advised to do so by their doctors, and we recommend that they receive instruction concerning self-administration of OMZ to avoid visiting hospitals in the event of a pandemic.