Effects of omalizumab combined with budesonide formoterol on clinical efficacy, pulmonary function, immune function, and adverse reactions in children with moderate and severe allergic asthma

Objective: To evaluate the clinical efficacy and safety of combining omalizumab with budesonide formoterol to treat children with moderate and severe allergic asthma, and investigate the effect of this combination therapy on pulmonary and immune functions. Methods: The data of 88 children with moderate and severe allergic asthma, who were admitted to our hospital between July 2021 and July 2022, were included in the study. The patients were randomly assigned either to control group (n = 44; received budesonide formoterol inhalation therapy) or experimental group (n = 44; received omalizumab subcutaneous injection + budesonide formoterol inhalation therapy) using computer-generated randomization. The clinical efficacy, asthma control (measured using childhood Asthma-Control Test [C-ACT] score), pulmonary function (forced expiratory volume in 1 s, forced vital capacity, and peak expiratory flow), immune function (cluster of differentiation 3 cells [CD3+ cells], cluster of differentiation 4 cells [CD4+ cells], immunoglobulin G, immunoglobulin A, and immunoglobulin E), and adverse reactions were observed and compared between both groups. Results: After treatment, the experimental group had improved levels of pulmonary function and immune function indexes, higher C-ACT scores, and a higher overall response rate than the control group (P < 0.05). In addition, the incidence of adverse reactions was not significantly different between both groups (P > 0.05). Conclusion: The combination of omalizumab with budesonide formoterol for treating moderate and severe allergic asthma in children demonstrated promising clinical efficacy and improved their pulmonary and immune functions, leading to more rational asthma control. The combined regimen demonstrated satisfactory clinical safety and deserved clinical promotion (AU)

Safety of Methotrexate in Chronic Urticaria Unresponsive to Omalizumab.

Omalizumab (humanized anti-immunoglobulin IgE) is currently the first choice of treatment for chronic urticaria refractory to high-dose second-generation antihistamines (sgAH). Despite its high safety profile, response to omalizumab is insufficient in one-third of patients. Some studies have suggested that methotrexate is effective in antihistamine-refractory chronic urticaria, but there are no studies on its efficacy and safety in patients unresponsive to omalizumab. This retrospective study aimed to investigate the clinical effectiveness and adverse effects of methotrexate in patients with chronic urticaria unresponsive to omalizumab + high-dose sgAH. The patients were evaluated in terms of age at disease onset, duration of the urticaria episode before methotrexate therapy, treatment before methotrexate therapy, final treatment, treatment responses, 7-day urticaria activity score (UAS7) before and after treatment, and total IgE levels. Methotrexate was administered subcutaneously at a dose of 15 mg once weekly as monotherapy or in combination with other drugs to 10 chronic urticaria patients with a history of nonresponse to omalizumab + high-dose sgAH. The mean age of the patients was 44.6±11.5 (31-65) years, and 9 (90%) of the patients were female. The mean duration of methotrexate therapy was 5.1±2.4 months (1.5-9 months). Complete response or well-controlled response was observed in 70% of the patients and partial response was observed in 1 patient (10%). Methotrexate was well tolerated by 80% of the patients. Methotrexate seems to be a useful treatment option both as monotherapy or combined therapy in patients resistant to omalizumab + sgAH.

A patient-oriented approach to long-term use of omalizumab in chronic spontaneous urticaria.

BACKGROUND: Omalizumab is an effective and safe treatment for antihistamine resistant chronic spontaneous urticaria (CSU), however, long-term efficacy and safety remains unclear. OBJECTIVE: To evaluate the efficacy and safety of omalizumab in CSU patients treated for long term and to identify long-term management strategies. METHODS: We retrospectively analyzed demographic characteristics, clinical features, laboratory parameters and treatment outcomes of 41 CSU patients who received omalizumab for at least 3 years. Treatment responses were evaluated with urticaria control test (UCT). Treatment safety was evaluated by comparing laboratory findings before and three years after omalizumab initiation as well as considering patients' adverse event reports. RESULTS: The patients (mean age 40.46 years; 63.4% women) received omalizumab for an average of 41.93 months (mean 31.68 injections/patient). The mean baseline UCT score was 5.56 and average number of injections to reach UCT score ≥12 was 3.3. Nine patients (22%) responded insufficiently to 300 mg/4 weeks omalizumab and required updosing. Thirty-eight patients (92.7%) could tolerate longer dose intervals (>4 weeks) and the dose interval was increased after a mean of 11.53 injections. There was no loss of efficacy of omalizumab. Sixteen patients (39%) had been retreated with omalizumab after a mean discontinuation time of 24 weeks. Five patients (12.2%) reported mild and transient adverse effects. Liver and renal function tests as well as full blood count before and after omalizumab were in normal ranges. CONCLUSION: For the long-term management of CSU, omalizumab is a safe and effective treatment which can be tailored according to patients' disease activity.

Effects of omalizumab in children with asthma: A protocol for systematic review and meta-analysis.

BACKGROUND: It is still controversial in the current literature whether omalizumab is beneficial for children with asthma. Given that there is no high-quality meta-analysis to incorporate existing evidence, the purpose of this protocol is to design a systematic review and meta-analysis of the level I evidence to ascertain whether omalizumab is beneficial and safe for children with asthma. METHODS: The systematic literature review is structured to adhere to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The following search terms will be used in PUBMED, Scopus, EMBASE, and Cochrane Library databases on June, 2021, as the search algorithm: (omalizumab) AND (asthma) AND (children). The primary outcome is the long-term safety and tolerability of omalizumab. The other outcomes include asthma control, quality of life, use of asthma controller medications, and spirometry measurements and emergency room visits due to asthma, and serum trough concentrations of omalizumab, free and total immunoglobulin E measured. Review Manager software (v 5.3; Cochrane Collaboration) will be used for the meta-analysis. RESULTS: The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings. REGISTRATION NUMBER: 10.17605/OSF.IO/G6N3P.

Case Report: Omalizumab for Chronic Spontaneous Urticaria in Pregnancy.

Most chronic spontaneous urticaria (CSU) patients are female, and pregnancy can aggravate the disease activity of patients, but little is known about the efficacy and safety of omalizumab in pregnant CSU patients. We report two pregnant CSU patients treated with omalizumab and review the published information on omalizumab treatment during 11 pregnancies. The outcomes reported on patients with known pregnancies showed they had normal pregnancies and healthy babies as well as complete control of their CSU. The two new cases we reported support the view that omalizumab could be an effective and safe treatment option for pregnant and breastfeeding CSU patients. Further high-quality studies need to be carried out in order to obtain more information on the long-term efficacy and safety of the use of omalizumab during pregnancy in patients with chronic urticaria, including CSU.

Response of peripheral blood basophils in subjects with chronic spontaneous urticaria during treatment with omalizumab.

BACKGROUND: Treatment of patients with asthma or food allergy with omalizumab results in several consistent changes in circulating basophils. The multiple basophil phenotypes observed in patients with chronic spontaneous urticaria (CSU) present some unique attributes that may not respond in a similar fashion to patients with asthma or food allergy. As part of a clinical study on the therapeutic outcomes of omalizumab treatment in CSU, the basophil compartment was examined for changes in characteristics predicted by prior studies. OBJECTIVE: This study sought to examine the changes in basophil function and its relationship to auto-antibodies in serum during treatment with omalizumab. METHODS: At multiple time points before and during omalizumab treatment of patients with CSU, basophil surface IgE and FcεRI expression, cellular spleen tyrosine kinase (SYK) expression, IgE-mediated histamine release (HR), and the presence of auto-antibodies in serum were determined. RESULTS: Three basophil phenotypes were enumerated in the clinical study and used to group results in this basophil study: subjects with (1) basopenia, (2) normal basophil numbers with normal IgE-mediated HR, and (3) normal basophil numbers with poor HR. Basopenia was highly associated with the presence of auto-antibodies to unoccupied FcεRI and basophil numbers did not change during treatment. Likewise, subjects who are basopenic showed no changes in SYK expression or HR during treatment. In basophils of subjects who are nonbasopenic, increases in SYK expression and HR showed the expected inverse relationship to starting SYK and HR levels. Treatment with omalizumab resulted in similar kinetics for decreases in surface FcεRI and IgE in all 3 groups. CONCLUSIONS: A unifying interpretation of the results revolves around the presence of auto-antibodies to FcεRI in CSU. If present, basopenia and an absence of changes in basophils during omalizumab treatment are observed. If auto-antibodies are absent, the changes in the basophil compartment are consistent with prior studies of asthma and food allergy. These group differences also are related to efficacy of the treatment for clinical outcomes, as found in the parent clinical study.

The efficacy of omalizumab treatment in chronic spontaneous urticaria is associated with basophil phenotypes.

BACKGROUND: The mechanisms underlying disease pathogenesis in chronic spontaneous urticaria (CSU) and improvement with omalizumab are incompletely understood. OBJECTIVES: This study sought to examine whether the rate of clinical remission is concordant with baseline basophil features or the rate of change of IgE-dependent functions of basophils and/or plasmacytoid dendritic cells during omalizumab therapy. METHODS: Adults (n = 18) with refractory CSU were treated with omalizumab 300 mg monthly for 90 days. Subjects recorded daily urticaria activity scores, and clinical assessments with blood sampling occurred at baseline and on days 1, 3, 6, 10, 20, 30, 60, and 90 following omalizumab. At baseline, subjects were categorized by basophil functional phenotypes, determined by in vitro histamine release (HR) responses to anti-IgE antibody, as CSU-responder (CSU-R) or CSU-non-responder (CSU-NR), as well as basopenic (B) or nonbasopenic (NB). RESULTS: CSU-R/NB subjects demonstrated the most rapid and complete symptom improvement. By day 6, CSU-R/NB and CSU-NR/NB had increased anti-IgE-mediated basophil HR relative to baseline, and these shifts did not correlate with symptom improvement. In contrast, CSU-NR/B basophil HR did not change during therapy. The kinetics of the decrease in surface IgE/FcεRI was similar in all 3 phenotypic groups and independent of the timing of the clinical response. Likewise, plasmacytoid dendritic cells' surface IgE/FcεRI decline and TLR9-induced IFN-α responses did not reflect clinical change. CONCLUSIONS: Changes in basophil IgE-based HR, surface IgE, or FcεRI bear no relationship to the kinetics in the change in clinical symptoms. Baseline basophil count and basophil functional phenotype, as determined by HR, may be predictive of responsiveness to omalizumab.

Real life study of the use of omalizumab for pediatric patients with multiple food allergies

Background Multiple food allergies (MFAs) affect 30% of the child population with food allergy. The current treatment is the exclusion diet, which frequently affects the quality of life for these patients. The objective of the study was to describe the effect of omalizumab treatment in children diagnosed with MFAs who experienced frequent anaphylactic reactions and the impact on their quality of life. Material and methods A descriptive observational study. Patients with severe food restrictions and high-risk due to multiple episodes of anaphylaxis were included. The allergy was confirmed by compatible clinical, skin tests, positive specific IgE and oral food challenges (OFCs). Omalizumab treatment was initiated and the impact on the life quality of patients and their families was assessed using the validated Food Allergy Quality of Life Questionnaire-Parent Form. Results Five patients with an average age at diagnosis of 3.58 years (range between 1.5–7.9 years), were diagnosed with MFAs. All patients presented with anaphylaxis. All patients were treated with omalizumab between 2013 and 2019. Omalizumab treatment was initiated at a mean age of 6.05 years (range between 4.5–8.25 years). All patients have undergone OFC to reintroduce food successfully. 2 patients had their dose of omalizumab reduced by half, and 1 patient has had the time interval extended between administrations due to the maintenance of food tolerance. No immediate local or systemic adverse reactions were documented. Two patients have commenced omalizumab administration at home without incident. Conclusions Children with MFAs who are treated with omalizumab do not show reactions in response to most of the foods to which they previously had anaphylaxis. Consequently, these patients were able to significantly expand the variety of their diet, improving the life quality and avoid anaphylaxis following the inadvertent intake of these foods (AU)

Real life study of the use of omalizumab for pediatric patients with multiple food allergies.

BACKGROUND: Multiple food allergies (MFAs) affect 30% of the child population with food allergy. The current treatment is the exclusion diet, which frequently affects the quality of life for these patients. The objective of the study was to describe the effect of omalizumab treatment in children diagnosed with MFAs who experienced frequent anaphylactic reactions and the impact on their quality of life. MATERIAL AND METHODS: A descriptive observational study. Patients with severe food restrictions and high-risk due to multiple episodes of anaphylaxis were included. The allergy was confirmed by compatible clinical, skin tests, positive specific IgE and oral food challenges (OFCs). Omalizumab treatment was initiated and the impact on the life quality of patients and their families was assessed using the validated Food Allergy Quality of Life Questionnaire-Parent Form. RESULTS: Five patients with an average age at diagnosis of 3.58 years (range between 1.5-7.9 years), were diagnosed with MFAs. All patients presented with anaphylaxis. All patients were treated with omalizumab between 2013 and 2019. Omalizumab treatment was initiated at a mean age of 6.05 years (range between 4.5-8.25 years). All patients have undergone OFC to reintroduce food successfully. 2 patients had their dose of omalizumab reduced by half, and 1 patient has had the time interval extended between administrations due to the maintenance of food tolerance. No immediate local or systemic adverse reactions were documented. Two patients have commenced omalizumab administration at home without incident. CONCLUSIONS: Children with MFAs who are treated with omalizumab do not show reactions in response to most of the foods to which they previously had anaphylaxis. Consequently, these patients were able to significantly expand the variety of their diet, improving the life quality and avoid anaphylaxis following the inadvertent intake of these foods.

Omalizumab in the Treatment of Chronic Urticaria: The Effect of Drug Co-Administration and Co-Morbidities.

BACKGROUND: Chronic Spontaneous Urticaria (CSU) is a disease presenting typical wheals characterized by itching, angioedema or both. Although CU is, by appearance, a relatively "simple" disease, yet it has a devastating effect on those suffering due to its immense social implications. AIMS: The aim of the present study was to investigate the effect of omalizumab in the treatment of CSU. In particular, gender, co-administration of drugs and comorbidities were taken into account. MATERIALS AND METHODS: 108 patients (25 Males/83 Females) admitted to our department were diagnosed with CSU and were treated for 30 months. CSU was estimated on a score basis, which was used in order to define disease severity. The mean total CSU score and the mean CSU score of the first trimester, as well as the first semester, were calculated. Patients were treated with omalizumab, and in several cases, with co-administration of dapsone, cyclosporine and anti-histamines. RESULTS: Females manifested significantly higher scores as compared to males. Further on, patients who relapsed manifested significantly higher scores during the whole time course, as well as at the end of the first semester. CONCLUSION: Females are more prone to CSU. Although CSU scores in patients with remission, relapse and poor response manifested no significant difference at diagnosis, relapsed patients manifested higher CSU scores in the first semester. Therefore, the first semester of treatment is probably critical for the final patient outcome. Further studies are necessary in order to understand the mechanisms of CSU for better treatment and prognosis.

Determinants of omalizumab dose-related efficacy in oral immunotherapy: Evidence from a cohort of 181 patients.

BACKGROUND: Omalizumab has been shown to improve the safety and feasibility of oral immunotherapy (OIT), but the optimal dosage strategy is unknown. OBJECTIVE: Our aim was to identify determinants of omalizumab dose-related efficacy in the context of OIT. METHODS: The study sample consisted of a clinical cohort of 181 patients treated with omalizumab-enabled oral immunotherapy at 3 centers. Patients received omalizumab for at least 2 months before an initial food escalation (IFE) with a mix of up to 6 allergens. Progression through IFE steps was assessed with survival analysis. Continued food dose tolerance with omalizumab weaning was also documented. RESULTS: Omalizumab dosage per weight alone was strongly associated with progression through the IFE (χ2 = 28.18; P < .0001), whereas the standard dosage per weight and total IgE level used for asthma was not (χ2 = 0.001; P = .97). When the values at time of IFE were estimated through pharmacokinetics and pharmacodynamics simulation, IFE outcome was best predicted by a model that includes levels of free allergen-specific IgE and their interaction with blocking omalizumab-IgE complexes and free omalizumab levels in serum (χ2 = 65.84; degrees of freedom [df] = 2; P < .0005). The occurrence of immediate-type reactions to food dosing subsequent to weaning of omalizumab was associated with a greater ratio of specific IgE level to total IgE level at baseline (geometric mean 0.39 vs 0.16 in those without symptom; P < .0001). CONCLUSION: In the context of OIT and IgE-mediated disease, omalizumab dosages should be adjusted for body weight alone, independently of total IgE level. The fraction of allergen-specific/total IgE may be useful to predict patients at greater risk of food dosing reactions subsequent to weaning.

Efficacy and safety of omalizumab in children with moderate-to-severe asthma: a meta-analysis.

OBJECTIVE: To assess the efficacy and safety of omalizumab in children with moderate-to-severe asthma. DATA SOURCES: We systematically searched MEDLINE, EMBASE, and Cochrane for randomized controlled trials (RCTs ) (inception to January 2020). STUDY SELECTIONS: All RCTs which were conducted in childhood and adolescence with asthma and compared the efficacy or safety of omalizumab were adopted. RESULTS: Three studies with four publications including 1380 pediatric patients met our criteria. For children with moderate-to-severe asthma, omalizumab decreased asthma exacerbations rate (OR 0.51, 95% CI: 0.44-0.58, p < 0.001) compared with placebo with no evidence of heterogeneity. Omalizumab reduced the rate of asthma exacerbations 0.58) with treatment period ≥30 weeks (p for heterogeneity = 0.03). Omalizumab treated patients had an excellent or good response rate of treatment effectiveness assessed by physicians (2.75, 2.45-3.09) and a bigger reduction in the dosage of inhaled corticosteroid (ICS) at the end of follow-up. For children with severe asthma, omalizumab also reduced the likelihood of asthma exacerbations and increased the odd of treatment effectiveness rated as excellent or good. Patients receiving omalizumab had a lower incidence of severe adverse events (0.36, 0.22-0.57). CONCLUSIONS: These findings suggested that omalizumab had beneficial effects on moderate-to-severe asthma in children. Patients may benefit more from long-term use of omalizumab. In addition, omalizumab reduces the rate of serious adverse events requiring hospitalizations.

Real-life, long-term data on efficacy, safety, response and discontinuation patterns of omalizumab in a Greek population with chronic spontaneous urticaria.

BACKGROUND: Omalizumab is approved for the treatment of chronic spontaneous urticaria (CSU) not responding to antihistamines. Data on omalizumab use in real-world settings and in different populations are lacking. OBJECTIVES: To record our five-year experience of omalizumab use in patients with refractory CSU in a real-world setting. MATERIALS & METHODS: A retrospective analysis of medical records of 80 patients with refractory CSU was performed. Demographic, and clinical characteristics, patterns of response, discontinuation strategies and rate of recurrence were analysed. RESULTS: Eighty individuals were included. UAS7 and DLQI significantly decreased from baseline. Complete response was achieved in 86.3%. Late response was observed at 27.5% of the patients. After discontinuation, 21.7% of patients reinitiated omalizumab due to relapse. The mean number of omalizumab administrations up to first discontinuation was 6.8 (based on an approach to shorten the treatment interval). Only 15.0% of patients experienced adverse events during treatment. CONCLUSION: Omalizumab, with long-term management, was highly effective and safe in achieving control of refractory CSU, with more favourable responses compared to Phase III clinical trials.

Multicentre experience of home omalizumab treatment for chronic spontaneous urticaria.

INTRODUCTION: Due to perceived risk of anaphylaxis, home treatment with omalizumab has been limited. Within the UK, most centres administer omalizumab in a hospital setting. However, the reported prevalence of anaphylaxis is low and in December 2018 home treatment became licensed. A home treatment pathway was previously reported by one UK centre, and this update describes three UK centres' experience of home omalizumab treatment. METHODS: The medical records of omalizumab patients were retrospectively reviewed. RESULTS: A total of 137 adult patients have received home omalizumab treatment; home treatment duration 0-44 months. There was no increase in adverse effects seen in patients treated at home. There were no reported adherence issues and no reduction in efficacy. Patients report they prefer home treatment due to increased flexibility and reduced impact on daily life/work. CONCLUSION: Home treatment with omalizumab is a safe and effective alternative to hospital administration.