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Frontiers in Pediatrics 2022To evaluate the efficacy and safety of omalizumab in the treatment of severe or uncontrolled allergic diseases in children.
OBJECTIVE
To evaluate the efficacy and safety of omalizumab in the treatment of severe or uncontrolled allergic diseases in children.
METHODS
We conducted a systematic search of the PubMed, Embase, CENTRAL, and clinicaltrials.gov databases up to 23rd July 2021, with no language limitations. Randomised controlled trials (RCTs) comparing omalizumab with other treatments or placebo in children with severe or inadequately controlled allergic diseases were considered. The primary outcomes of interest were asthma exacerbation rate, allergic symptom score, desensitisation achievement for food allergy (FA), and incidence of serious adverse events (SAEs). The study selection and data extraction were conducted independently by two researchers. Quality assessments were conducted using the Cochrane risk-of-bias tool, and data were pooled using a random-effects model if was 50% or greater in the Cochrane Review Manager.
RESULTS
Overall, 10 RCTs [six on severe asthma, one on atopic dermatitis (AD), one on seasonal allergic rhinitis [SAR], and one on FA] consisting of 2,376 participants met the inclusion criteria. For severe asthma, omalizumab may reduce exacerbations at 12 weeks [risk ratio (RR), 0.52; 95% confidence interval (CI), 0.31-0.89], 24 weeks (RR, 0.69; 95% CI, 0.55-0.85; GRADE: moderate-quality evidence), and 52 weeks (RR, 0.62; 95% CI, 0.40-0.94; GRADE: moderate-quality evidence) and reduce the dose of inhalation corticosteroid compared with placebo. For severe AD, the association between omalizumab and allergic symptom improvement [i.e., SCORing Atopic Dermatitis or Paediatric Allergic Disease Quality of Life Questionnaire (PADQLQ)] was not confirmed. For severe SAR, omalizumab showed greater improvement in symptom load scores and saved rescue medication days. For FA, omalizumab demonstrated superiority in desensitisation compared with placebo. To date, no clinically significant drug-related SAEs have been reported.
CONCLUSION
For severe or uncontrolled asthma, AD, SAR, and FA, omalizumab may be associated with improved allergic symptoms and safety in children. Future studies should focus on the benefits and pharmacoeconomic evaluation of omalizumab in multiple allergic diseases compared with other treatments.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/PROSPERO], identifier [CRD42021271863].
PubMed: 35372142
DOI: 10.3389/fped.2022.851177 -
Biomedicines Jan 2022Several biologic therapies that target inflammatory modulators are now used for treating patients with uncontrolled, severe asthma. Knowledge about how this type of... (Review)
Review
Several biologic therapies that target inflammatory modulators are now used for treating patients with uncontrolled, severe asthma. Knowledge about how this type of treatment modifies the molecular milieu is rapidly increasing. Thus, this systematic review aimed to compile the reported effects of therapeutic antibodies on the transcriptome or proteome of asthma patients. Studies of asthmatic patients under biological treatment describing transcriptomic or proteomic changes upon treatment were included. Preclinical or single gene/protein studies were not considered. PubMed and Scopus search was performed in August and September 2021. Following PRISMA guidelines and GRADE recommendations, we selected 12 studies on gene or protein expression changes in patients treated with the antibodies currently approved by EMA and the FDA. All studies were at low risk of bias as per the RoB2 tool. Different gene clusters have been identified to change upon omalizumab treatment, found a reduction in eosinophil-associated gene signatures after benralizumab treatment, and protein profiles were different in patients treated with mepolizumab and in those treated with benralizumab. The main potential biomarkers proposed by the selected studies are shown. These results may contribute to discovering biomarkers of response and selecting the best therapy for each patient.
PubMed: 35203504
DOI: 10.3390/biomedicines10020293 -
Biomedicines Sep 2021Airway hyperresponsiveness (AHR) represents a central pathophysiological hallmark of asthma, with airway smooth muscle (ASM) being the effector tissue implicated in the... (Review)
Review
Airway hyperresponsiveness (AHR) represents a central pathophysiological hallmark of asthma, with airway smooth muscle (ASM) being the effector tissue implicated in the onset of AHR. ASM also exerts pro-inflammatory and immunomodulatory actions, by secreting a wide range of cytokines and chemokines. In asthma pathogenesis, the overexpression of several type 2 inflammatory mediators including IgE, IL-4, IL-5, IL-13, and TSLP has been associated with ASM hyperreactivity, all of which can be targeted by humanized monoclonal antibodies (mAbs). Therefore, the aim of this review was to systematically assess evidence across the literature on mAbs for the treatment of asthma with respect to their impact on the ASM contractile tone. Omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab were found to be effective in modulating the contractility of the ASM and preventing the AHR, but no available studies concerning the impact of reslizumab on the ASM were identified from the literature search. Omalizumab, dupilumab, and tezepelumab can directly modulate the ASM in asthma, by specifically blocking the interaction between IgE, IL-4, and TSLP, and their receptors are located on the surface of ASM cells. Conversely, mepolizumab and benralizumab have prevalently indirect impacts against AHR by targeting eosinophils and other immunomodulatory effector cells promoting inflammatory processes. AHR has been suggested as the main treatable trait towards precision medicine in patients suffering from eosinophilic asthma, therefore, well-designed head-to-head trials are needed to compare the efficacy of those mAbs that directly target ASM contractility specifically against the AHR in severe asthma, namely omalizumab, dupilumab, and tezepelumab.
PubMed: 34572466
DOI: 10.3390/biomedicines9091281 -
PloS One 2021Asthma is one of the most common chronic diseases characterized by sex disparities. Gender bias is a well-documented issue detected in the design of published clinical...
Asthma is one of the most common chronic diseases characterized by sex disparities. Gender bias is a well-documented issue detected in the design of published clinical trials (CTs). International guidelines encourage researchers to analyze clinical data by sex, gender, or both where appropriate. The objective of this work was to evaluate gender bias in the published CTs of biological agents for the treatment of severe asthma. A systematic review of randomized controlled CTs of the biological agents (omalizumab, benralizumab, reslizumab, mepolizumab or dupilumab) for the treatment of severe asthma was conducted. The literature search was performed using PubMed and EMBASE without language restrictions. This study followed the corresponding international recommendations. We identified a total of 426 articles, of which 37 were finally included. Women represented 60.4% of patients included. The mean percentage of women in these trials was 59.9%, ranged from 40.8% to 76.7%. The separate analysis by sex of the main variable was only performed in 5 of the 37 publications included, and none of the trials analyzed secondary variables by sex. Only 1 of the articles discussed the results separately by sex. No study included the concept of gender in the text or analyzed the results separately by gender. The proportion of women included in CTs was higher compared to publications of other disciplines, where women were under-represented. The analysis of the main and secondary variables by sex or gender, even the discussion separately by sex, was insufficient. This gives rise to potential gender bias in these CTs.
Topics: Asthma; Biological Products; Female; Humans; Male; Patient Selection; Randomized Controlled Trials as Topic; Sexism
PubMed: 34555087
DOI: 10.1371/journal.pone.0257765 -
The Cochrane Database of Systematic... Sep 2021Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung... (Review)
Review
BACKGROUND
Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review.
OBJECTIVES
To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 09 September 2021. We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 16 August 2021.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager.
MAIN RESULTS
Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively.
AUTHORS' CONCLUSIONS
There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.
Topics: Antibodies, Anti-Idiotypic; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Cystic Fibrosis; Humans; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 34550603
DOI: 10.1002/14651858.CD010288.pub5 -
The Journal of Allergy and Clinical... Apr 2022Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear. (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: A systematic review and network meta-analysis.
BACKGROUND
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear.
OBJECTIVE
We compared the effects of mAbs and aspirin desensitization (ASA-D) for treatment of CRSwNP.
METHODS
We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, US Food and Drug Administration, and the European Medicines Agency databases from inception to August 4, 2021, for randomized controlled trials comparing the effects of mAbs and ASA-D for CRSwNP. We conducted network meta-analysis of sinusitis symptoms, heath-related quality of life, rescue oral corticosteroids and surgery, endoscopic and radiologic scores, and adverse events. We used the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach to assess certainty of evidence. PROSPERO CRD42020177334.
RESULTS
Twenty-nine randomized controlled trials evaluating 8 treatments (n = 3461) were included in the network meta-analysis. Compared to placebo, moderate to high certainty evidence showed that health-related quality of life (SNOT-22) improved with dupilumab (mean difference [MD] -19.91 [95% confidence interval (CI) -22.50, -17.32]), omalizumab (MD -16.09 [95% CI -19.88, -12.30]), mepolizumab (MD -12.89 [95% CI -16.58, -9.19], ASA-D (MD -10.61 [95% CI -14.51, -6.71]), and benralizumab (MD -7.68 [95% CI -12.09, -3.27]). The risk of rescue nasal polyp surgery likely decreased with dupilumab (risk difference [RD] -16.35% [95% CI -18.13, -13.48]), omalizumab (RD -7.40% [95% CI -11.04, -2.43]), mepolizumab (RD -12.33% [95% CI -15.56, -7.22]), and ASA-D (RD -16.00% [95% CI -19.79, 0.21]; all moderate certainty). Comparisons among agents show with moderate to high certainty that dupilumab ranks among the most beneficial for 7 of 7 outcomes, omalizumab for 2 of 7, mepolizumab for 1 of 7, and ASA-D for 1 of 7.
CONCLUSIONS
Multiple biologics and ASA-D credibly improve patient-important outcomes, with clinically important differences in effects among agents; dupilumab uniquely ranks among the most beneficial for all outcomes studied.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Aspirin; Chronic Disease; Humans; Nasal Polyps; Network Meta-Analysis; Omalizumab; Quality of Life; Sinusitis
PubMed: 34543652
DOI: 10.1016/j.jaci.2021.09.009 -
BMJ Open Sep 2021To assess the efficacy and safety of omalizumab for chronic rhinosinusitis with nasal polyps (CRSwNP) and to identify evidence gaps that will guide future research on... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the efficacy and safety of omalizumab for chronic rhinosinusitis with nasal polyps (CRSwNP) and to identify evidence gaps that will guide future research on omalizumab for CRSwNP.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
A comprehensive search was performed in PubMed, Embase, Web of Science and the Cochrane Library on 13 October 2020.
ELIGIBILITY CRITERIA
Randomised controlled trials (RCTs) comparing omalizumab with placebo, given for at least 16 weeks in adult patients with CRSwNP.
DATA EXTRACTION AND SYNTHESIS
Two independent authors screened search results, extracted data and assessed studies using the Cochrane risk of bias tool. Data were pooled using the inverse-variance method and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by the χ test and the I statistic.
RESULTS
A total of four RCTs involving 303 participants were identified. When comparing omalizumab to placebo, there was a significant difference in Nasal Polyps Score (MD=-1.20; 95% CI -1.48 to -0.92), Nasal Congestion Score (MD=-0.67; 95% CI -0.86 to -0.48), Sino-Nasal Outcome Test-22 (MD=-15.62; 95% CI -19.79 to -11.45), Total Nasal Symptom Score (MD=-1.84; 95% CI -2.43 to -1.25) and reduced need for surgery (risk ratio (RR)=5.61; 95% CI 1.99 to 15.81). Furthermore, there was no difference in the risk of serious adverse events ((RR=1.40; 95% CI 0.29 to 6.80), adverse events (RR=0.83; 95% CI 0.60 to 1.15) and rescue systemic corticosteroid (RR=0.52; 95% CI 0.17 to 1.61).
CONCLUSIONS
This was the first meta-analysis that identified omalizumab significantly improved endoscopic, clinical and patient-reported outcomes in adults with moderate to severe CRSwNP and it was safe and well tolerated.
PROSPERO REGISTRATION NUMBER
CRD42020207639.
Topics: Adult; Chronic Disease; Humans; Nasal Polyps; Omalizumab; Quality of Life; Randomized Controlled Trials as Topic; Sinusitis
PubMed: 34479933
DOI: 10.1136/bmjopen-2020-047344 -
Medicina (Kaunas, Lithuania) Aug 2021Linear IgA disease (LAD) is a rare autoimmune blistering disease with linear IgA deposits along the basement membrane zone. Direct immunofluorescence remains the gold... (Review)
Review
Linear IgA disease (LAD) is a rare autoimmune blistering disease with linear IgA deposits along the basement membrane zone. Direct immunofluorescence remains the gold standard for diagnosis, but other diagnostic measures reported in recent literature have proven useful in the setting of inconclusive preliminary results. Dapsone is a commonly used treatment, but many therapeutic agents have emerged in recent years. The objective of this study is to provide a comprehensive overview of updates on the diagnosis and management of LAD. A literature search was conducted from May to June of 2021 for articles published in the last 5 years that were related to the diagnosis and management of LAD. False-negative results in cases of drug-induced LAD and the presence of IgG and IgM antibodies on immunofluorescence studies were reported. Serration pattern analysis has been reported to be useful in distinguishing LAD from sublamina densa-type LAD. Rituximab, omalizumab, etanercept, IVIg, sulfonamides, topical corticosteroids, and others have been used successfully in adult and pediatric patients with varying disease severity. Topical corticosteroids were preferred for pediatric patients while rituximab and IVIg were used in adults with recalcitrant LAD. Sulfonamides were utilized in places without access to dapsone. In cases where preliminary biopsy results are negative and clinical suspicion is high, repeat biopsy and additional diagnostic studies should be used. Patient factors such as age, medical comorbidities, and disease severity play a role in therapeutic selection.
Topics: Adult; Autoimmune Diseases; Biopsy; Child; Dapsone; Humans; Immunoglobulin A
PubMed: 34441024
DOI: 10.3390/medicina57080818 -
JAMA Dermatology Nov 2021The comparative benefits and harms of all available treatments for H1 antihistamine-refractory chronic spontaneous urticaria (CSU) have not been established. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The comparative benefits and harms of all available treatments for H1 antihistamine-refractory chronic spontaneous urticaria (CSU) have not been established.
OBJECTIVE
To evaluate different treatment effects of pharmacologic treatments among patients with H1 antihistamine-refractory CSU.
DATA SOURCES
Searches were conducted of MEDLINE, Embase, PubMed, Cochrane Library, Web of Science, Scopus, and CINAHL from inception to April 19, 2021, with no language restrictions. Gray literature from Google Scholar, ongoing trial registers, and preprint reports was added to the searches of electronic databases.
STUDY SELECTION
Randomized clinical trials using validated measurement tools that investigated the benefits and harms of pharmacologic treatments among adolescent or adult patients with CSU who had an inadequate response to H1 antihistamines were screened for inclusion independently by 2 investigators.
DATA EXTRACTION AND SYNTHESIS
Two investigators independently extracted study data according to the predefined list of interests. A random-effects model was used to calculate the network estimates reported as standardized mean differences and odds ratios with corresponding 95% CIs.
MAIN OUTCOMES AND MEASURES
The primary outcomes that reflect the patient's perspective included changes in urticaria symptoms from baseline and unacceptability of treatment (all-cause dropouts).
RESULTS
Twenty-three randomized clinical trials with 2480 participants that compared 18 different interventions or dosages and placebo were included. The standardized mean differences for change in urticaria symptoms were -1.05 (95% CI, -1.37 to -0.73) for ligelizumab, 72 mg; -1.07 (95% CI, -1.39 to -0.75) for ligelizumab, 240 mg; -0.77 (95% CI, -0.91 to -0.63) for omalizumab, 300 mg; and -0.59 (95% CI, -1.10 to -0.08) for omalizumab, 600 mg. No significant differences in treatment unacceptability were observed. With respect to benefits and harms, the network estimates illustrated that the most efficacious treatments were achieved with ligelizumab, 72 or 240 mg (large beneficial effect) and omalizumab, 300 or 600 mg (moderate beneficial effect).
CONCLUSIONS AND RELEVANCE
The findings in this meta-analysis suggest that the biologic agents ligelizumab, 72 or 240 mg, and omalizumab, 300 or 600 mg, can be recommended as effective treatments for patients with CSU who have had an inadequate response to H1 antihistamines. Head-to-head trials with high methodologic quality and harmonized design and outcome definitions are needed to help inform subsequent international guidelines for the management of CSU.
Topics: Adolescent; Adult; Anti-Allergic Agents; Chronic Disease; Chronic Urticaria; Histamine H1 Antagonists; Humans; Network Meta-Analysis; Omalizumab; Treatment Outcome; Urticaria
PubMed: 34431983
DOI: 10.1001/jamadermatol.2021.3237 -
International Journal of Molecular... Jul 2021Airway inflammation represents an important characteristic in asthma, modulating airflow limitation and symptom control, and triggering the risk of asthma exacerbation....
Airway inflammation represents an important characteristic in asthma, modulating airflow limitation and symptom control, and triggering the risk of asthma exacerbation. Thus, although corticosteroids represent the cornerstone for the treatment of asthma, severe patients may be dependent on oral corticosteroids (OCSs). Fortunately, the current humanised monoclonal antibodies (mAbs) benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab have been proven to induce an OCS-sparing effect in randomized controlled trials (RCTs), thus overcoming the problem of OCS dependence in severe asthma. Nevertheless, a large discrepancy has been recognized between selected patients enrolled in RCTs and non-selected asthmatic populations in real-world settings. It is not possible to exclude that the OCS-sparing effect of mAbs resulting from the RCTs could be different than the real effect resulting in clinical practice. Therefore, we performed a systematic review and correlation analysis to assess whether mAbs are effective in eliciting an OCS-sparing effect and overcoming the OCS dependence in severe asthmatic patients in real-world settings. Overall, real-world studies support the evidence that OCS dependence is a real condition that, however, can be found only in a small number of really severe asthmatic patients. In most patients, the dependence on OCS can be related to modifying factors that, when adequately modulated, may lead to a significant reduction or suspension of OCS maintenance. Conversely, in severe asthmatics in whom OCS resistance is proved by a high daily dose intake, mAbs allow reversion of the OCS dependence, leading to the suspension of OCS therapy in most patients or >50% reduction in the daily OCS dose.
Topics: Administration, Oral; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Antibodies, Monoclonal; Asthma; Humans; Randomized Controlled Trials as Topic; Substance-Related Disorders
PubMed: 34281184
DOI: 10.3390/ijms22137132