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Archives of Dermatological Research May 2024While 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...
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.
Topics: Humans; Omalizumab; Female; Male; Adult; Chronic Urticaria; Middle Aged; Cytokines; Anti-Allergic Agents; Severity of Illness Index; Treatment Outcome; Case-Control Studies; Young Adult
PubMed: 38795119
DOI: 10.1007/s00403-024-02966-6 -
Medicina (Kaunas, Lithuania) Apr 2024The guidelines for chronic urticaria in children contain recommendations that are often based on adult studies. The diagnostic pathway has not been standardized and the... (Observational Study)
Observational Study
The guidelines for chronic urticaria in children contain recommendations that are often based on adult studies. The diagnostic pathway has not been standardized and the effectiveness of anti-H1, omalizumab, montelukast, and systemic glucocorticoids is rarely reported in the pediatric population. There is a wide variation in the rate of remission of chronic urticaria between studies. The aim of this study is to enhance our understanding of pediatric chronic urticaria. This study enrolled 37 children with chronic urticaria aged from 0 to 18 years. Demographic parameters, medical history, clinical features, laboratory data and treatment information were collected. Children were treated with the recommended dosage of second-generation H1-antihistamines, which was increased by up to twofold. Omalizumab was added for refractory anti-H1 patients. A three-day course with systemic glucocorticoids was administered for severe exacerbations. Montelukast was administered to some children. : Wheals without angioedema were common. Chronic urticaria was spontaneous in 32 children (86.48%), inducible in 2 (5.41%), induced by a parasite in 1 and vasculitic in 2. Treatment of the potential causes of chronic urticaria was of no benefit, except for eradication of Dientamoeba fragilis. Chronic urticaria was resolved within three years in 45.9% of cases. Allergic diseases were present in nine children (24.32%) and autoimmune diseases were present in three (8.11%). All children were treated with anti-H1 at the licensed dose or at a higher dose. A partial or complete response to anti-H1 was observed in 29 (78.38%) patients. Montelukast showed no benefit. All children treated with omalizumab responded. Systemic glucocorticoids were successfully used to treat exacerbations. Our findings indicate that laboratory tests should not be routinely performed in children with chronic urticaria without clinical suspicion. However, comorbidities such as thyroid autoimmune disease and coeliac disease are suggested to be monitored over the chronic urticaria course. These clinical conditions could be diagnosed from the diagnostic framework of chronic urticaria. Increasing the dosage of anti-H1 and omalizumab was effective in children resistant to standard treatment but we still need further studies to generate a standard patient-centered treatment.
Topics: Humans; Child; Female; Male; Child, Preschool; Adolescent; Chronic Urticaria; Infant; Sulfides; Cyclopropanes; Quinolines; Acetates; Omalizumab; Histamine H1 Antagonists; Glucocorticoids; Anti-Allergic Agents; Infant, Newborn; Chronic Disease; Urticaria
PubMed: 38792886
DOI: 10.3390/medicina60050704 -
Biomedicines May 2024Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and...
BACKGROUND
Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and NSAID hypersensitivity. An overproduction of leukotrienes characterizes the pathomechanism of the disease. N-ERD patients often report breathing difficulties after consuming alcohol. These symptoms have been observed in patients receiving either aspirin therapy after desensitization (ATAD), therapy with the biologics dupilumab (anti-IL-4Ra antibody) and omalizumab (anti-IgE antibody), or intranasal corticosteroid treatment (INCS).
METHODS
This retrospective, real-world study assessed the severity of alcohol-related and non-alcohol-related respiratory symptoms in CRSwNP/N-ERD patients 3-6 months after ATAD, biologic (dupilumab or omalizumab), or INCS therapy. A total of 171 patients (98 women and 73 men) were enrolled in the study. All groups received standard INCS therapy. Sixty-three patients were treated with ATAD; 48 received biologics (dupilumab = 31; omalizumab = 17); and 60 received INCS only and served as a control group. Alcohol-dependent symptoms and typical CRS symptoms (alcohol-independent) were quantified using visual analog scales (VAS).
RESULTS
ATAD and biological therapy significantly reduced VAS scores for alcohol dependence and CRS symptoms. In the control group receiving INCS, only non-alcohol dependent CRS symptoms improved significantly ( < 0.05). The most significant differences in pre/post scores were observed in patients receiving dupilumab, with the most significant improvement in alcohol-dependent and CRS symptoms (dupilumab > omalizumab > ATAD).
CONCLUSIONS
This real-world study shows that alcohol-related respiratory symptoms are a relevant parameter in CRSwNP/N-ERD patients. Patients benefit more from biologic therapy than from ATAD in terms of their alcohol-related symptoms and other CRS symptoms. Future studies should include placebo-controlled oral alcohol challenge.
PubMed: 38790987
DOI: 10.3390/biomedicines12051025 -
Terapevticheskii Arkhiv Jan 2024This 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...
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.
Topics: Humans; Asthma; Antibodies, Monoclonal, Humanized; Omalizumab; Anti-Asthmatic Agents; Treatment Outcome; Female; Drug Substitution; Quality of Life
PubMed: 38785050
DOI: 10.26442/00403660.2023.12.202491 -
Skin Research and Technology : Official... May 2024Omalizumab is the only licensed drug that serves as a third-line treatment for chronic idiopathic urticaria (CIU). The optimum doses of omalizumab remain controversial.... (Meta-Analysis)
Meta-Analysis Comparative Study
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.
Topics: Omalizumab; Humans; Chronic Urticaria; Anti-Allergic Agents; Treatment Outcome; Network Meta-Analysis; Randomized Controlled Trials as Topic; Quality of Life; Dose-Response Relationship, Drug
PubMed: 38776128
DOI: 10.1111/srt.13749 -
Case Reports in Otolaryngology 2024In her late 50 s, a woman with a medical history of endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps (CRSwNP) experienced a relapse of nasal...
Ciliary Functional Analysis in Chronic Rhinosinusitis with Polyps after Multimodal Intervention: Oral Corticosteroid, Functional Endoscopic Sinus Surgery, and Omalizumab Injection.
In her late 50 s, a woman with a medical history of endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps (CRSwNP) experienced a relapse of nasal polyps, significantly impacting her breathing and sense of smell. She underwent a multifaceted treatment approach, including oral corticosteroids, functional endoscopic sinus surgery, and omalizumab injections. Digital high-speed videomicroscopy (DHSV) revealed only partial improvement in ciliary beat pattern and ciliary beat frequency with oral corticosteroid treatment, while significant improvement in these ciliary parameters was observed with omalizumab injections. Furthermore, administration of omalizumab resulted in a decrease in her SNOT-22 (Sinonasal Outcome Test 22) score. Notably, this case report represents the first study investigating ciliary function using DHSV in a patient treated with omalizumab.
PubMed: 38774124
DOI: 10.1155/2024/5559001 -
The Journal of Allergy and Clinical... May 2024Chronic inducible urticaria (CIndU) management often follows chronic spontaneous urticaria (CSU) guidelines, but a step-by-step evaluation of their effectiveness in...
BACKGROUND
Chronic inducible urticaria (CIndU) management often follows chronic spontaneous urticaria (CSU) guidelines, but a step-by-step evaluation of their effectiveness in CIndU is lacking.
OBJECTIVE
To assess the clinical impact of adapting CSU international guidelines for CIndU management.
METHODS
We conducted a prospective cohort study involving patients diagnosed with CIndU based on challenge tests and a Urticaria Control Test (UCT) score of ≤11 points. Following the guidelines, a stepwise approach was used: avoidance measures, antihistamines, omalizumab, and cyclosporine. Treatment steps were added based on individual response, with control defined as UCT ≥12 points. Pharmacological steps were evaluated for at least 1 month, with the next step initiated in case of a UCT score ≤11 points.
RESULTS
We enrolled 194 patients with CIndU. Of them, 134 patients had CIndU with concomitant CSU and 60 had CIndU only. Following the step-by-step approach outlined in the guidelines, a total of 159 (81.9%) patients reach a UCT ≥12 points, with avoidance measures 23 (11.8%) patients, antihistamines 84 (43.2%), omalizumab 35 (18%), and cyclosporine 17 (8.7%).
CONCLUSIONS
This study supports the use of a stepwise approach based on CSU guidelines for CIndU management. However, a significant proportion of patients, particularly those with CIndU only, did not achieve adequate control. This highlights the heterogeneity within CIndU and the need for further research to develop new therapies for patients with CIndU who remain uncontrolled.
PubMed: 38761861
DOI: 10.1016/j.jaip.2024.05.011 -
The Journal of Allergy and Clinical... May 2024
PubMed: 38754637
DOI: 10.1016/j.jaci.2024.05.004 -
BMJ Open May 2024Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent condition affecting approximately 2% of the population. Medical treatment consists long-term use of...
INTRODUCTION
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent condition affecting approximately 2% of the population. Medical treatment consists long-term use of intranasal corticosteroids and short-term use of oral corticosteroids, in adjunct with saline solution rinses. Surgical management is proposed in patients who failed after medical treatment. In France, two biologics are reimbursed in case of severe uncontrolled CRSwNP despite medical treatment and endoscopic sinus surgery. Waiting for head-to-head biologics comparison, studies should report the efficacy and safety of biologics in large real-life cohorts. This study protocol describes the aims and methods of a prospective, observational, national, multicentric cohort of patients with CRSwNP treated with biologics.
METHODS AND ANALYSIS
The BIOlogics in severe nasal POlyposis SurvEy is a French multicentre prospective observational cohort study. The main aim is to assess the efficacy and tolerance of biologics in patients with CRSwNP, with or without association with other type 2 diseases, and to determine the strategies in case of uncontrolled disease under biologics. Patients over 18 years old requiring biologics for CRSwNP in accordance with its marketing approval in France (ie, severe nasal polyposis, with lack of control under nasal corticosteroid, systemic corticosteroids and surgery) are invited to participate. Collected data include topical history of surgical procedures and biologics, medication and use of systemic corticosteroids, visual analogical scales for specific symptoms, Sino-Nasal Outcome Test-22 questionnaire, nasal polyp score, asthma control test, Lund-Mackay score on CT scan and IgE concentration and eosinophilic count on blood sample.
TRIAL REGISTRATION
NCT05228041/DRI_2021/0030.
Topics: Humans; Nasal Polyps; Sinusitis; Chronic Disease; Rhinitis; Prospective Studies; Biological Products; France; Observational Studies as Topic; Omalizumab; Multicenter Studies as Topic; Rhinosinusitis
PubMed: 38749694
DOI: 10.1136/bmjopen-2023-083112 -
Allergy May 2024Food allergy (FA) is a potentially life-threatening chronic condition that is becoming an increasing public health problem worldwide. This systematic review (SR) was... (Review)
Review
UNLABELLED
Food allergy (FA) is a potentially life-threatening chronic condition that is becoming an increasing public health problem worldwide. This systematic review (SR) was carried out to inform the development of clinical recommendations on the treatment of IgE-mediated FA with biologics and/or IT for the update of the EAACI guidelines. A SR of randomized-controlled trials or quasi-controlled trials was carried out. Studies were identified via comprehensive search strategies in Medline, Embase, and Cochrane Library, up to April 2022.
POPULATION
Human adults, children, and adolescents with IgE-mediated FA.
INTERVENTION
IT and/or biologics.
COMPARATOR
Placebo or standard-of-care (allergen avoidance).
OUTCOME
Efficacy (desensitization, sustained unresponsiveness (SU), remission), quality of life, and safety (systemic and local adverse reactions (AR)). The Cochrane RoB tool was used to assess the risk of bias. It was reported according to PRISMA and registered in PROSPERO CRD4202229828. After screening, 121 studies were included (111 for IT and 10 for biologics). Most studies had a high risk of bias and showed high heterogeneity in design and results. Metanalysis showed a positive effect of biologics and IT in terms of relative risk (RR) for achieving tolerance to the culprit food compared to avoidance or placebo. Omalizumab for any FA showed a RR of 2.17 [95% confidence interval: 1.22, 3.85]. For peanut allergy, oral IT (OIT) had a RR of 11.94 [1.76, 80.84] versus avoidance or placebo, sublingual IT (SLIT) had a RR of 3.00 [1.04, 8.66], and epicutaneous IT (EPIT) of 2.16 [1.56, 3.00]. OIT had a RR of 5.88 [2.27, 15.18] for cow's milk allergy, and of 3.43 [2.24, 5.27] for egg allergy. There was insufficient data on SLIT or EPIT for the treatment of egg and milk allergies. Most ARs reported were mild. For OIT the most common AR involved the gastrointestinal system and for EPIT, AR's most commonly affected the skin. There was limited data on severe or life-threatening ARs. There was limited evidence for long term efficacy and quality of life. In conclusion, biologics and IT, alone or in combination, are effective in achieving desensitization while on active treatment but more evidence is needed on long-term tolerance as current evidence is not of high quality. Adverse events while on therapy are generally mild to moderate but a long-term comprehensive safety profile is missing. There is a critical need to optimize and standardize desensitization protocols and outcome measures to facilitate our understanding of the efficacy and safety as well as to allow for comparison between interventions.
PubMed: 38747333
DOI: 10.1111/all.16129