From Research to Practice: The Latest Data on Evolving Treatments for Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) should be on every dermatology practitioner's radar. CSU is a skin disorder marked by wheals, angioedema, or both for more than 6 weeks. Patients with CSU experience unexplained, itchy wheals that appear and disappear, traveling around the body and lasting less than 24 hours per area. Angioedema accompanies wheals for up to 48 hours in around half of cases. CSU is a diagnosis of exclusion, relying heavily on patient history to differentiate CSU symptoms from other causes of urticaria or angioedema. But reassuringly, CSU has a simple diagnostic algorithm and a clear initial treatment path. First-line strategies include non-pharmacologic approaches, and second-generation antihistamines (2gAH) administered up to 4 times their standard dose. Omalizumab and cyclosporine (off-label) are second- and third-line options, respectively. However, many patients will continue to have CSU symptoms despite consistent maximum-dose treatment. Novel therapies, including biologic agents and small molecule drugs targeting mast cell activation and inflammatory mediators, show promise in treating CSU refractory to standard therapy. However, further research is needed to establish their efficacy and safety in clinical practice. J Drugs Dermatol. 2024;23:9(Suppl 2):s5-14.Access the CME Activity.

Favorable clinical course after discontinuation of omalizumab treatment in patients with allergic severe asthma: A real-world clinical practice.

The success rate of omalizumab discontinuation is 50-75.5%. However, such data are scarce in Japan. We retrospectively investigated the clinical progression following the cessation of long-term omalizumab treatment (>5 years) in severe allergic asthma patients who have achieved super-responder status, defined as being off any oral maintenance corticosteroids without experiencing exacerbations requiring systemic corticosteroids for >1 year. Six (28.6%) among 21 patients recommenced after a median period of 5.5 (4.3-12.5) months later due to exacerbated asthma control, resulting in improved asthma management for all patients. The rates of patients who successfully remained off omalizumab treatment for 1 and 2 years were 72.4% and 65.8%, respectively. Specific IgE levels after discontinuing omalizumab treatment significantly decreased compared to those at initiating this treatment in 10 patients who successfully remained off this treatment. Therefore, discontinuing omalizumab treatment may be considered for patients continuing treatment beyond 5 years and achieving super-responder status.

Characterization of omalizumab updosing patterns and predictive factors in chronic spontaneous urticaria: A prospective multicentric observational study.

BACKGROUND: Limited information is available on the use of omalizumab (OMA) updosing since its introduction as a second-line therapy in chronic spontaneous urticaria (CSU) in 2014. Practical guidelines from health authorities are lacking, and the specific characteristics of patients requiring higher doses remain unknown. Our objectives were to characterize the patterns of OMA updosing (defined as changes in dose and/or injection intervals), to identify the predictive factors associated with updosing, and to improve CSU management. METHODS: We conducted a prospective, multicentric, real-life observational study, including patients diagnosed with CSU and starting OMA. The data were collected at 0, 3, 6, and 9 months. The primary endpoint was the frequency of OMA updosing at 3 months. The secondary endpoints included an analysis of updosed patients' profile, and an assessment of OMA efficacy and safety. RESULTS: We included 153 patients. Twenty percent of patients were updosed at 3 months, and 27% in total during the 9-month follow-up. Practitioners mainly chose to increase the frequency of injections (66%). At baseline, the updosed patients were more likely to have more severe CSU (UCT < 4, p < 0.030), a lower lymphocyte count (<2000/mm3, p = 0.037), and low IgE levels (<70 UI/mL, p = 0.024). The side effects of OMA were not more frequent after updosing. CONCLUSION: One in five patient underwent updosing within just 3 months. OMA updosing is frequent in particular in cases of severe disease and low IgE blood levels.

Time-course and dose-effect of omalizumab in treating chronic idiopathic urticaria/chronic spontaneous urticaria.

PURPOSE: Several studies have shown that subcutaneous injections of omalizumab can treat chronic idiopathic/spontaneous urticaria (CIU/CSU) patients by only assessing the efficacy on specific endpoints. This study aimed to quantitatively analyze different doses of omalizumab in CIU/CSU and compare it with ligelizumab. METHODS: Literature searches were performed in PubMed, Embase, and Web of Science databases. A model-based meta-analysis (MBMA) was utilized to develop a model incorporating time since the initiation of treatment and dose for omalizumab, with the change from baseline in Urticaria Activity Score (CFB-UAS7) as the primary efficacy endpoint. The time-course and dose-effect relationship throughout the omalizumab treatment period was analyzed, and the findings were compared with those of the investigational ligelizumab. RESULTS: The model equation for the CFB-UAS7 was established as E = -Emax × time/(ET50 + time) × (b0 + b1 × dose). The estimated values of the model parameters E max , ET 50 , b 0 , and b 1 were -1.16, 1.26 weeks, -9.90, and -0.0361 mg-1, respectively. At week 12 after the first dose, the model-predicted CFB-UAS7 for 150 mg and 300 mg of omalizumab were -16.0 (95% CI, -17.2 to -14.8) and -21.7 (95% CI, -22.9 to -20.5), respectively. In the PEARL-1 trial, the CFB-UAS7 for 72 mg and 120 mg of ligelizumab were -19.4 (95% CI, -20.7 to -18.1) and -19.3 (95% CI, -20.6 to -18.0), respectively. In the PEARL-2 trial, these values were -19.2 (95% CI, -20.5 to -17.9) and -20.3 (95% CI, -21.6 to -19.0), respectively. CONCLUSION: Omalizumab showed a significant dose-dependent effect in the treatment of CSU. Both 72 mg and 120 mg ligelizumab might have the potential to outperform 150 mg (but not 300 mg) omalizumab.

Multinational Drug Survival Study of Omalizumab in Patients With Chronic Urticaria and Potential Predictors for Discontinuation.

Importance: Treating patients with chronic urticaria using omalizumab has been shown to be safe and effective in randomized clinical trials. Multinational studies on long-term omalizumab performance in chronic urticaria in clinical practice settings are lacking, especially on drug survival. Drug survival, which refers to the length of time that patients are treated with a specific drug, is a comprehensive outcome covering effectiveness, safety, and patient and physician preferences. Furthermore, little is known about the reasons and potential predictors for omalizumab discontinuation. Objective: To investigate omalizumab drug survival as well as reasons and potential predictors for discontinuation in a large, diverse population. Design, Setting, and Participants: This international multicenter cohort study was conducted at 14 Urticaria Centers of Reference and Excellence in 10 countries, including all patients with chronic urticaria from these centers who were ever treated with omalizumab. Main Outcomes and Measures: Drug survival analysis was performed to assess time to discontinuation. Patient characteristics and treatment protocols were investigated by Cox regression analysis to identify potential predictors for omalizumab discontinuation. Results: In 2325 patients with chronic urticaria who started omalizumab between June 2009 and July 2022, the mean (SD) age of the cohort was 42 (6) years, and 1650 participants (71%) were female. Overall omalizumab survival rates decreased from 76% to 39% after 1 to 7 years, respectively (median survival time, 3.3 [95 % CI, 2.9-4.0] years), primarily due to discontinuation from well-controlled disease in 576 patients (65%). Ineffectiveness and adverse effects were reasons for discontinuation in a far smaller proportion of patients, totaling 164 patients (18%) and 31 patients (4%), respectively. Fast treatment response was associated with higher rates of omalizumab discontinuation due to well-controlled disease (hazard ratio, 1.45 [95% CI, 1.20-1.75]), and disease duration of more than 2 years was associated with lower rates of discontinuation due to well-controlled disease (HR, 0.81 [95% CI, 0.67-0.98]). Immunosuppressive cotreatment at the start of omalizumab and autoimmune disease was associated with a higher risk for discontinuation due to ineffectiveness (HR, 1.65 [95% CI, 1.12-2.42]). The presence of spontaneous wheals (HR, 0.62 [95% CI, 0.41-0.93]) and access to higher dosages (HR, 0.40 [95% CI, 0.27-0.58) were both associated with a lower risk for discontinuation of omalizumab due to ineffectiveness. Conclusion and Relevance: This multinational omalizumab drug survival cohort study demonstrated that treatment of chronic urticaria with omalizumab in a clinical setting is effective and safe, and well-controlled disease is the main reason for treatment discontinuation. These findings on omalizumab drug survival rates and reasons and potential predictors for discontinuation may guide patients and physicians in clinical decision-making and expectation management. These results may call for the identification of biomarkers for chronic urticaria remission in complete responders to omalizumab treatment.

Treatment of patients with evidence of mast cell-mediated itch in the absence of hives with omalizumab.

PURPOSE: The presence of wheals or hives has been viewed as a hallmark symptom of urticaria, a highly debilitating disease. This study explores our experience with omalizumab in patients with apparent mast-cell mediated pruritus in the absence of hives. MATERIALS AND METHODS: This is a retrospective case series examining all patients with mast cell-mediated pruritus in the absence of hives from April 2022 to May 2024 at a tertiary referral clinic at Icahn School of Medicine at Mount Sinai in New York. Peak pruritus-numerical rating scale (PP-NRS) itch score changes over time were recorded and analyzed. RESULTS: Six patients (67% women; mean [SD] age, 47.67 [13.52] years) were included in the analysis. The median [IQR] pruritus PP-NRS itch score before omalizumab injection was 9 [6 - 10] and the final median [IQR] PP-NRS itch score was 2.5 [0 - 5]. The mean [SD] reduction in the PP-NRS itch score was 6 [3.16]. CONCLUSIONS: This study suggests that patients with evidence of mast cell-mediated pruritus can be identified based on clinical features and may benefit from omalizumab therapy.

Omalizumab in the treatment of bullous pemphigoid: A single-center series of 15 cases.

Bullous pemphigoid (BP) is a chronic autoimmune disease affecting the elderly population and characterized by the formation of subepidermal tense bullae. Treatment options include topical steroids, systemic steroids, immunosuppressants, and antimicrobials, and there is emerging evidence of the efficacy of omalizumab. In this study, we aimed to demonstrate omalizumab's efficacy for treating BP, and we also reported treatment-related adverse events. The retrospective cohort study included patients with BP who were followed up in our clinic's bullous diseases department between 2016 and 2023. Patients who received omalizumab were included in the study. Treatment responses of all patients were assessed by BP Disease Area Index activity and damage scores, treatment scale scoring, steroid dose reduction, and the presence/absence of pruritus. Also, total IgE levels of patients before the treatment onset and at the last visit were compared. There were 15 (male/female = 8/7) BP patients receiving omalizumab treatment. Omalizumab therapy allowed steroid dose reduction at a median of 1 month. Omalizumab (25.5 mg, 95% confidence interval 17.2-33.9, P < .001) provided a significant steroid dose reduction at the last visit compared to the beginning of treatment. Omalizumab resulted in a decrease in BP Disease Area Index activity score of 80.8 (95% confidence interval 71.8-89.8, P < .001). Also, omalizumab caused significant decline in IgE levels compared to baseline (1102.5 ±â€…834.5 vs 834.6 ±â€…613.6, P = .002). In this study, omalizumab treatment was an effective and safe option in BP patients with high baseline IgE levels who are refractory to or cannot tolerate other immunosuppressive therapies.

[The effectiveness of targeted therapy of various genetically engineered biological drugs in the treatment of bronchial asthma].

This article presents the experience of successfully switching therapy from omalizumab 150 mg to benralizumab 30 mg/1 ml in a patient with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs. The effectiveness of biological therapy was evaluated when switching from omalizumab 150 mg subcutaneously at a dose of 600 mg for 36 weeks. Therapy for the drug benralizumab 30 mg/1 ml subcutaneously the first three injections monthly, the rest a month later for 52 weeks with bronchial asthma (BA), a severe uncontrolled course with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs in a patient Ch., born in 2004. Switching therapy from omalizumab 150 mg to benralizumab 30 mg/1 ml allowed to achieve complete control of asthma symptoms (AST = 23 points), to achieve the absence of asthma exacerbations during 52 weeks, restore respiratory function to normal values, as well as improve the quality of life. The study reflects the good tolerability, high efficacy and safety of biological therapy when switching from one genetically engineered biological drug (GIBP) omalizumab 150 mg to another GIBP benralizumab 30 mg/1 ml in severe uncontrolled asthma with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs. Therapy with benralizumab 30 mg/1 ml in severe BA has demonstrated a more effective clinically significant improvement in the course of the disease, control of symptoms of the disease. Reduction of exacerbations, normalization of respiratory function indicators, complete control of the disease has been achieved. Consequently, the use of different biological molecules for the therapy of BA with a combined allergic and eosinophilic phenotype contributes to achieving disease control, improving the patient's quality of life and reducing the dose of oral glucocorticosteroids. The targeted biological drug benralizumab 30 mg/1 ml has a targeted effect on the key links in the pathogenesis of severe uncontrolled asthma with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs and reduces the burden of severe disease.

Inflammatory cytokine levels and changes during omalizumab treatment in chronic spontaneous urticaria.

While several studies have examined the role of T cells and related cytokines in the development of chronic spontaneous urticaria (CSU), there is a limited amount of research focusing on the changes in cytokine levels during omalizumab treatment. The primary objective of this study was to investigate the inflammatory cytokine profile (including IL-4, IL-5, IL-10, IL-13, IL-17, IL-31, IL-33, and TNFα) among CSU patients undergoing to omalizumab treatment. Plasma levels of cytokines were measured using ELISA. Measurements were taken before CSU treatment, at the 3rd and 6th months of omalizumab treatment, and once in the control group. The severity of the patients' disease was assessed using the weekly Urticaria Activity Score(UAS7), and disease control was evaluated using the Urticaria Control Test(UCT). Thirty-one CSU patients and 56 age- and gender-matched healthy controls were included. Plasma levels of IL-4 and IL-33 were significantly lower in patients with CSU compared to healthy controls (p = 0.001; p = 0.038, respectively). During omalizumab treatment, IL-4 levels showed a significant increase in the 3rd month compared to baseline (p = 0.01), and IL-5 levels significantly decreased in the 6th month compared to both the 3rd month and baseline (6th month vs. baseline; p = 0.006, 6th month vs. 3rd month; p = 0.001). One potential mechanism of action for omalizumab may involve its regulatory effects on type 2 inflammatory cytokines in CSU patients. This finding partially explains the efficacy of anti-IL-4/13 treatments in chronic spontaneous urticaria. Further investigations on drugs targeting type 2 inflammatory cytokines in CSU are warranted.

Comparative efficacy and safety of the treatment by Omalizumab for chronic idiopathic urticaria in the general population: A systematic review and network meta-analysis.

BACKGROUND: Omalizumab is the only licensed drug that serves as a third-line treatment for chronic idiopathic urticaria (CIU). The optimum doses of omalizumab remain controversial. Therefore, this study aims to estimate the efficacy and safety of different doses of omalizumab in the treatment of CIU patients. MATERIALS AND METHODS: Four databases were searched from the database's creation to April 8, 2023. Several keywords such as omalizumab and urticarias were used to retrieve related studies. The meta-analytical outcomes were analyzed in R 4.2.1 software and Stata 15.1 software. Cochrane risk-of-bias tool Ver. 2 was used to evaluate the risk of bias in randomized controlled trials (RCTs). RESULTS: In total, 2331 patients were included. Five indexes were employed to assess, including weekly Itch Severity Score (ISS7), weekly Hive Severity Score (HSS7), weekly Urticaria Activity Score (UAS7), Dermatology Life Quality Index (DLQI), and adverse events (AE). A 300 mg dose of omalizumab was the optimum dose to treat CIU, followed by the 150 mg dose. Furthermore, 600 mg of omalizumab only showed a significant difference from the placebo in HSS7. No significant statistical difference was observed in AE. Meta-regression analysis revealed that time, as a covariate, was statistically significant in the comparison of omalizumab 150 mg with placebo. CONCLUSION: 300 mg of omalizumab was the optimum dosage to treat CIU patients, with a 150 mg dose also exhibiting good efficacy. Further studies are required to explore the efficacy and safety of different doses of omalizumab in the treatment of CIU patients.

Clinical Impacts of Omalizumab on the Psychiatric Comorbidities of Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis.

Individuals with chronic spontaneous urticaria (CSU) experience significant sleep disturbances and are at risk of anxiety and depression.

A practical guide for implementing omalizumab therapy for food allergy.

The recent approval of omalizumab for the treatment of IgE-mediated food allergy is an important step forward for the millions of food allergy patients in the United States. Through the depletion of circulating IgE and the subsequent reduction of FcεR1 on key effector cells, patients increase their tolerance to food allergens. However, omalizumab does not permit patients to eat foods that they are allergic to with impunity. Rather, it protects them from most accidental exposures. In addition, omalizumab does not cure food allergy and has not demonstrated true immunomodulation. Thus, omalizumab might be a lifelong therapy for some patients. Furthermore, there are many important questions and issues surrounding the appropriate administration of omalizumab to treat food allergy, which we discuss. Managing treatment of patients with disease that falls outside the dosing range, assessing treatment response or nonresponse, addressing its appropriateness for patients older than 55, and determining whether immunotherapy plus omalizumab provides any advantage over omalizumab alone all need to be examined. Identifying appropriate patients for this therapy is critical given the cost of biologics. Indeed, not all food allergy patients are good candidates for this therapy. Also, when and how to stop omalizumab therapy in patients who may have outgrown their food allergy needs to be elucidated. Thus, although this therapy provides a good option for patients with food allergies, much information is needed to determine how best to use this therapy. Despite many unanswered questions and issues, we provide clinicians with some practical guidance on implementing this therapy in their patients.

Bioequivalence Between a New Omalizumab Prefilled Syringe With an Autoinjector or with a Needle Safety Device Compared with the Current Prefilled Syringe: A Randomized Controlled Trial in Healthy Volunteers.

Omalizumab is an anti-IgE monoclonal antibody currently approved for the treatment of asthma, nasal polyps/chronic rhinosinusitis with nasal polyps, and chronic spontaneous urticaria. Omalizumab is available as an injection in a prefilled syringe (PFS) with a needle safety device (NSD). New product configurations were developed to reduce the number of injections per dose administration, improve patient convenience and treatment compliance. The objective of this randomized open-label 12-week study was to demonstrate pharmacokinetic bioequivalence between (1) new PFS with autoinjector (PFS-AI), (2) new PFS-NSD configuration, and (3) current PFS-NSD configuration. Each new configuration was considered bioequivalent to the current configuration if the confidence intervals (CIs) for the geometric mean ratios (GMR) were contained in the 0.80-1.25 range for maximum concentration (Cmax), area under the concentration-time curve until the last quantifiable measurement (AUClast), and AUC extrapolated to infinity (AUCinf). Safety was assessed throughout the study. In total, 193 healthy volunteers were randomized at 1:1:1 ratio to omalizumab 1×300 mg/2 mL via new PFS-AI (n = 66), omalizumab 1×300 mg/2 mL via new PFS-NSD (n = 64), or omalizumab 2×150 mg/1 mL via current PFS-NSD (n = 63). Comparing new PFS-AI versus current PFS-NSD, the GMRs were: Cmax, 1.085; AUClast, 1.093; AUCinf, 1.100. Comparing new PFS-NSD versus current PFS-NSD, the GMRs were: Cmax, 1.006; AUClast, 1.016; AUCinf, 1.027. The 95% CIs for all GMR parameters were contained within the 0.80-1.25 range. Safety findings were consistent with the known safety profile of omalizumab. Single-dose omalizumab administered as the new PFS-AI or new PFS-NSD was bioequivalent to the current PFS-NSD.

Biomarkers predicting the controller dose of omalizumab in patients with chronic spontaneous urticaria.

BACKGROUND: Clinical trials showed the efficacy of 300 mg/4 weeks of omalizumab (OMA) during 6 months in patients with severe chronic spontaneous urticaria (CSU). Nevertheless, in real life, many patients require higher doses and/or longer treatment. This study assesses the real-life performance of OMA in severe CSU and identifies factors associated with the response. METHODS: CSU patients eligible for OMA were recruited prospectively. Clinical data and a blood test were collected before OMA initiation. Urticaria Activity Score 7 (UAS7) was calculated at baseline and every 3 months during OMA treatment. CSU control was defined as UAS7 <7 points. This work was partially sponsored by OMA manufacturer. RESULTS: Eighty-nine adults (19.1% males) with severe CSU were recruited. Median duration of CSU prior to OMA initiation was 2 years, and median severity by UAS7 at baseline was 24 points (range 10-42 points). OMA controlled 94.4% of patients, but 17.9% of responders required doses >300 mg/4 weeks. A blood basophil count >20 cells/µL (OR 13.33; 95% CI 3.32-52.63; p < .001) and the absence of hypothyroidism (OR 3.65; 95% CI 0.78-16.95; p = .099) were identified as predictive factors to achieve control with 300 mg/4 weeks. Twelve patients were able to stop OMA during the study (responders in remission, RR). RR had received OMA for a median of 29 months (12-53 months). Conversely, 32 patients had been on OMA for >29 months at the end of the study (active responders, AR). AR had received OMA for a median of 45 months (30-100 months). There were no significant differences in clinical or analytical factors between RR and AR patients. CONCLUSIONS: Low blood basophil count and the presence of hypothyroidism might serve as biomarkers for the controller dose of OMA in severe CSU patients.

Mepolizumab in children and adolescents with severe eosinophilic asthma not eligible for omalizumab: a single Center experience.

BACKGROUND: Mepolizumab is an anti-interleukin-5 monoclonal antibody shown to reduce asthma exacerbations in adults and adolescents with severe eosinophilic asthma. AIM: To assess the impact of mepolizumab on children and adolescents over 12 months by examining steroid usage, asthma-related hospitalizations, Asthma Control Test (ACT) scores, fractional exhaled nitric oxide concentration (FeNO), forced expiratory volume in 1 s (FEV1), mid expiratory flow (FEF25-75%), and blood eosinophil count. METHODS: Retrospective analysis performed between October 2015 and December 2022. Data was reviewed 12 months before and after commencing mepolizumab. Mepolizumab was offered if the patient had severe eosinophilic asthma and were unresponsive to or ineligible for omalizumab. RESULTS: Sixteen participants (age 7-17, 8 males, 8 females) received subcutaneous mepolizumab monthly with no serious adverse reactions. Incidence of hospital admissions fell significantly (IRR 0.33, p = 0.007). Among the 11 patients receiving daily oral corticosteroids, 3 were weaned off daily oral steroids and 3 patients' daily dose was significantly reduced (mean Δ-0.095 ± 0.071 mg/kg, p = 0.0012). Eosinophil count was decreased (mean Δ-0.85 x 109/L, p < 0.001). There was no significant change in mean overall steroid burden per patient (mean Δ-1445.63 ± 1603.18 mg, p = 0.10), ACT scores (mean Δ2.88 ± 6.71, p = 0.17), FEV1 z-scores (mean Δ-0.99 ± 1.88, p = 0.053), FEF25-75% z-scores (mean Δ-0.65 ± 1.61, p = 0.13), FeNO (mean Δ-20.09 ± 80.86, p = 0.34), or number of courses of oral steroids given for asthma attacks (IRR 0.71, p = 0.09). CONCLUSION: Among children and adolescents with severe eosinophilic asthma ineligible for or not responsive to omalizumab, mepolizumab therapy exhibited significant reduction in rate of asthma-related hospitalizations and significant decrease in daily steroid dosage.

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.