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Allergy May 2020Allergic asthma is a frequent asthma phenotype. Both IgE and type 2 cytokines are increased, with some degree of overlap with other phenotypes. Systematic reviews...
Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma.
Allergic asthma is a frequent asthma phenotype. Both IgE and type 2 cytokines are increased, with some degree of overlap with other phenotypes. Systematic reviews assessed the efficacy and safety of benralizumab, dupilumab and omalizumab (alphabetical order) vs standard of care for patients with uncontrolled severe allergic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. All three biologicals reduced with high certainty the annualized asthma exacerbation rate: benralizumab incidence rate ratios (IRR) 0.63 (95% CI 0.50 - 0.81); dupilumab IRR 0.58 (95%CI 0.47 - 0.73); and omalizumab IRR 0.56 (95%CI 0.42 - 0.73). Benralizumab and dupilumab improved asthma control with high certainty and omalizumab with moderate certainty; however, none reached the minimal important difference (MID). Both benralizumab and omalizumab improved QoL with high certainty, but only omalizumab reached the MID. Omalizumab enabled ICS dose reduction with high certainty. Benralizumab and omalizumab showed an increase in drug-related adverse events (AEs) with low to moderate certainty. All three biologicals had moderate certainty for an ICER/QALY value above the willingness to pay threshold. There was high certainty that in children 6-12 years old omalizumab decreased the annualized exacerbation rate [IRR 0.57 (95%CI 0.45-0.72)], improved QoL [relative risk 1.43 (95%CI 1.12 -1.83)], reduced ICS [mean difference (MD) -0.45 (95% CI -0.58 to -0.32)] and rescue medication use [ MD -0.41 (95%CI -0.66 to -0.15)].
Topics: Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Biological Products; Child; Humans; Omalizumab; Quality of Life
PubMed: 32064642
DOI: 10.1111/all.14235 -
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 -
Rheumatology (Oxford, England) Nov 2015To systematically review and establish the prevalence of antibody positivity in assays not currently included in the APS classification criteria to detect antibodies... (Review)
Review
OBJECTIVE
To systematically review and establish the prevalence of antibody positivity in assays not currently included in the APS classification criteria to detect antibodies directed against other phospholipids (PLs), PL binding proteins, coagulation factors and a mechanistic test for resistance of Annexin A5 (AnxA5) anticoagulant activity in APS and control populations.
METHODS
We searched PubMed and EMBASE using the key words APS, antiphospholipid antibodies, non-criteria, new assays, IgA anticardiolipin antibodies, lupus anticoagulant, anti-Domain I, IgA anti-β2-glycoprotein I antibodies, antiphosphatidylserine, anti-phosphatidylethanolamine, anti-phosphatidic acid, antiprothrombin, antiphosphatidylserine-prothtombin, anti-vimentin/cardiolipin complex and Annexin A5 resistance. Studies that met inclusion criteria to describe prevalence of non-criteria aPLs in APS patients (n > 10), disease and healthy control subjects were systematically examined.
RESULTS
We selected 16 retrospective studies of 1404 APS patients, 1839 disease control and 797 healthy controls. The highest prevalence of non-criteria aPLs in the largest number of patients with APS was found in IgA anti-β2GPI studies (129/229, 56.3%), AnxA5R (87/163, 53.4%) and IgG anti-Domain I (241/548, 44.0%).
CONCLUSION
Our finding of a significantly high prevalence of all non-criteria aPLs studied in patients with APS compared with controls was tempered by wide variation in sample size, retrospective collection, assay methodology and different determination of positivity. Therefore, prospective studies of sufficient size and appropriate methodology are required to evaluate the significance of these assays and their utility in the management of patients with APS.
Topics: Annexin A5; Antibodies, Anti-Idiotypic; Antiphospholipid Syndrome; Case-Control Studies; Humans; Immunoglobulin A; Immunoglobulin G; Phospholipids; Prevalence; Retrospective Studies; beta 2-Glycoprotein I
PubMed: 26152548
DOI: 10.1093/rheumatology/kev226 -
The Journal of Allergy and Clinical... Feb 2022Cold urticaria is a subtype of chronic inducible urticaria (CIndU) associated with significant morbidity and a risk for anaphylaxis. Few studies have assessed the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cold urticaria is a subtype of chronic inducible urticaria (CIndU) associated with significant morbidity and a risk for anaphylaxis. Few studies have assessed the prevalence, management, and prevalence of associated anaphylaxis of cold urticaria.
OBJECTIVES
To evaluate the prevalence of cold urticaria among CIndU and chronic urticaria (CU) cases, to assess the management of cold urticaria, and to determine the prevalence of associated anaphylaxis.
METHODS
We searched PubMed and EMBASE for studies pertaining to cold urticaria and/or CIndU published in the past 10 years. We conducted meta-analyses to evaluate the prevalence of cold urticaria among CIndU and CU cases, the management of cold urticaria with H1-antihistamines and omalizumab, and the prevalence of associated anaphylaxis.
RESULTS
Twenty-two studies were included in the systematic review and 14 in the meta-analysis. The pooled prevalence of cold urticaria among patients with CU and CIndU was 7.62% (95% confidence interval [CI], 3.45% to 15.99%; I = 98%) and 26.10% (95% CI, 14.17% to 43.05%; I = 97%), respectively. Cold urticaria was managed by H1-antihistamines in 95.67% (95% CI, 92.47% to 97.54%; I = 38%) of patients and omalizumab in 5.95% (95% CI , 2.55% to 13.27%; I = 83%) of patients. The pooled prevalence of anaphylaxis among patients with cold urticaria was 21.49% (95% CI, 15.79% to 28.54%; I = 69%).
CONCLUSIONS
Cold urticaria constitutes an appreciable proportion of CIndU and CU cases and is predominantly managed with H1-antihistamines; few patients receive omalizumab. Anaphylaxis is common, and an epinephrine autoinjector prescription may be considered.
Topics: Anaphylaxis; Chronic Disease; Chronic Urticaria; Humans; Omalizumab; Prevalence; Urticaria
PubMed: 34673287
DOI: 10.1016/j.jaip.2021.10.012 -
The Journal of Allergy and Clinical... Apr 2019Several treatment options for cold urticaria (ColdU) have been studied and reported, but systematic reviews and meta-analyses are limited. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several treatment options for cold urticaria (ColdU) have been studied and reported, but systematic reviews and meta-analyses are limited.
OBJECTIVES
We sought to meta-analyze and review the efficacy and safety of ColdU treatments.
METHODS
We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Suitable reports were identified by searching PubMed, Scopus, and Web of Science. Our systematic review included 16 studies, 9 of which met the eligibility criteria for the meta-analysis. We analyzed the effects of treatments on critical temperature thresholds (CTTs) and critical stimulation time thresholds (CSTTs), as well as on rates of complete response and adverse events.
RESULTS
Our pooled meta-analyses showed that nonsedating second-generation H-antihistamines (nsAHs) are effective in the treatment of ColdU and that updosing of nsAHs significantly reduced CTTs relative to their own standard doses and placebos. In 4 studies involving CSTTs, updosing of nsAHs also resulted in significantly better CSTTs than their own standard doses or placebos. Omalizumab resulted in a marked reduction of CTTs in H-antihistamine-resistant patients. Of 118 adverse events in 8 studies, standard-dose nsAHs, updosed nsAHs, and omalizumab produced lower numbers of adverse events than first-generation antihistamines.
CONCLUSIONS
Our study showed that greater dosages of nsAHs were more effective than standard dosages in controlling ColdU symptoms. Increasing the dosages was not significantly associated with higher adverse event rates. Omalizumab at 150 and 300 mg every 4 weeks was shown to be effective for patients with ColdU refractory to antihistamines.
Topics: Anti-Allergic Agents; Cold Temperature; Histamine Antagonists; Humans; Omalizumab; Urticaria
PubMed: 30776418
DOI: 10.1016/j.jaci.2019.02.005 -
Otolaryngology--head and Neck Surgery :... Jul 2024Provide clinicians with current evidence for biologic therapy in children with chronic rhinosinusitis with nasal polyposis (CRSwNP). (Review)
Review
OBJECTIVE
Provide clinicians with current evidence for biologic therapy in children with chronic rhinosinusitis with nasal polyposis (CRSwNP).
DATA SOURCES
PubMed, MEDLINE, Cochrane, and clinical trial registries.
REVIEW METHODS
Key search terms related to biologic therapy in pediatric CRSwNP were identified via a structured query of current medical literature and clinical trial databases.
CONCLUSIONS
There is a dearth of active clinical trials and research studies for biologics targeting pediatric CRSwNP. There is an ongoing compassionate-use clinical trial involving Dupilumab for children with nasal polyps as well as only 1 published work specifically focused on Dupilumab for pediatric CRSwNP in the setting of aspirin-exacerbated respiratory disease.
IMPLICATIONS FOR PRACTICE
For children with atopic dermatitis, asthma, and chronic idiopathic urticaria, biologic therapies such as Omalizumab, Dupilumab, and Mepolizumab have gained Food and Drug Administration approval. The role of biologic therapy in pediatric CRSwNP demonstrates significant promise in the comprehensive management of the unified airway. Additional Phase III trials are necessary to broaden clinical indications for children with comorbid conditions and complex sinonasal disease.
Topics: Humans; Sinusitis; Chronic Disease; Rhinitis; Child; Biological Therapy; Nasal Polyps; Omalizumab; Rhinosinusitis; Antibodies, Monoclonal, Humanized
PubMed: 38488239
DOI: 10.1002/ohn.717 -
Discovery Medicine Jun 2023Omalizumab is a recombinant humanized monoclonal antibody against immunoglobulin E., which can specifically bind to in blood and inhibit the release of inflammatory... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Omalizumab is a recombinant humanized monoclonal antibody against immunoglobulin E., which can specifically bind to in blood and inhibit the release of inflammatory mediators to improve the symptoms of -mediated asthma effectively. This meta-analysis was used to retrieve the studies in recent years to provide a clinical reference for the omalizumab in treating allergic asthma (AA).
METHODS
The databases Ovid, Embase, Pubmed, the Cochrane Library of clinical trials, CNKI (China National Knowledge Infrastructure) (China), and Wangfang Data (China) were searched for all studies on omalizumab involvement in treating allergic childhood asthma up to January 2022. Effectiveness, rate of exacerbation within 24 weeks (and 52 weeks), and the incidence of adverse reactions and serious adverse reactions were used as the primary data analysis indicators.
RESULTS
Seven eligible pieces of literature were included. Meta-analysis indicated that omalizumab could significantly improve the treatment efficacy in children with asthma [ (Risk Ratio) = 1.24, 95% CI (Confidential Interval) (1.09, 1.41), = 3.30, = 0.001], reduced the incidence of significant clinical exacerbation in children with asthma within 24 weeks [ = 0.55, 95% CI (0.35, 0.85), = -2.67, = 0.001], reduced the incidence of significant clinical exacerbation in children with asthma within 52 weeks [ = 0.52, 95% CI (0.39, 0.71), = -4.2, < 0.0001], and the incidence of total serious adverse reactions was not statistically different from placebo [ = 1.00, 95% CI (0.98, 1.03), = 0.71, = 0.479], the incidence of serious adverse reactions was significantly decreased [ = 0.53, 95% CI (0.36, 0.77), = -3.35, = 0.001].
CONCLUSIONS
In treating (immunoglobulin E)-mediated asthma in children, adding oral (or subcutaneous) omalizumab to a glucocorticoid regimen can enhance the effectiveness of treatment, reduce the probability of significant exacerbation during treatment, and reduce the incidence of serious adverse reactions.
Topics: Child; Humans; Omalizumab; Anti-Asthmatic Agents; Antibodies, Monoclonal; Asthma; Immunoglobulin E
PubMed: 37272090
DOI: 10.24976/Discov.Med.202335176.24 -
International Journal of Dermatology Jan 2017Omalizumab is a recombinant humanized monoclonal antibody targeting the high-affinity Fc receptor of IgE, registered for the treatment of chronic spontaneous urticaria... (Review)
Review
Omalizumab is a recombinant humanized monoclonal antibody targeting the high-affinity Fc receptor of IgE, registered for the treatment of chronic spontaneous urticaria and severe allergic asthma. We present a case series of nine patients with atopic dermatitis (AD) treated off-label with omalizumab and a systematic review of the existing literature. Patients were selected consecutively from a tertiary dermatological referral center during a 5-year period. All patients were treated with omalizumab at a starting dose of 300 mg subcutaneously every 4 weeks. Systematic literature searches were performed in PubMed, Web of Science, EMBASE, and ClinicalTrials.gov to identify any study (case reports, case series, and controlled trials) evaluating the effect of treatment with omalizumab in AD. Based on physicians' assessment, 50% of our patients had a good or excellent response to treatment with omalizumab; a further 12.5% had a moderate response, while 37.5% experienced no response or deterioration of symptoms during treatment. Treatment was generally well tolerated. Twenty-six studies with a median of four patients each (range 1-21), comprising 174 patients, were included in the systematic review. Summed over all studies, a total of 129 patients (74.1%) experienced a beneficial effect of treatment ranging from little to complete response. Omalizumab appears to be a safe and well tolerated, however expensive, treatment with some clinical benefit in patients with severe recalcitrant AD. Recommendation for use in clinical practice awaits evidence from larger randomized controlled trials.
Topics: Adult; Aged; Anti-Allergic Agents; Dermatitis, Atopic; Female; Humans; Male; Middle Aged; Off-Label Use; Omalizumab; Treatment Outcome; Young Adult
PubMed: 27337170
DOI: 10.1111/ijd.13353 -
Respiratory Medicine Feb 2017Severe asthma is a heterogeneous disease. Patients with both eosinophilic and allergic asthma phenotypes may be eligible for treatment with mepolizumab and omalizumab.... (Comparative Study)
Comparative Study Review
BACKGROUND
Severe asthma is a heterogeneous disease. Patients with both eosinophilic and allergic asthma phenotypes may be eligible for treatment with mepolizumab and omalizumab. Evidence on the relative effectiveness of these treatments in this 'overlap' population would be informative for clinical and payer decision making.
METHODS
A systematic literature review and indirect treatment comparison (Bayesian framework) were performed to assess the comparative effectiveness and tolerability of mepolizumab and omalizumab, as add-ons to standard of care. Studies included in the primary analysis were double-blind, randomized controlled trials, ≥12 weeks' duration enrolling patients with severe asthma with a documented exacerbation history and receiving high-dose inhaled corticosteroids plus ≥1 additional controller. Two populations were examined: patients potentially eligible for 1) both treatments (Overlap population) and 2) either treatment (Trial population).
RESULTS
In the Overlap population, no differences between treatments in clinically significant exacerbations and exacerbations requiring hospitalization were found, although trends favored mepolizumab (rate ratio [RR]:0.66 [95% credible intervals (Crl):0.37,1.19]; 0.19[0.02,2.32], respectively). In the Trial population, mepolizumab treatment produced greater reductions in clinically significant exacerbations (RR:0.63 [95% CrI:0.45,0.89]) but not exacerbations requiring hospitalization compared with omalizumab (RR:0.58 [95% Crl: 0.16,2.13]), although the trend favored mepolizumab. Both treatments had broadly comparable effects on lung function, and similar tolerability profiles.
CONCLUSIONS
Whilst this analysis has limitations due to a restricted evidence base and residual heterogeneity, it showed that in patients with severe asthma, mepolizumab seems to be at least as effective as omalizumab and that the tolerability profiles of the two treatments did not meaningfully differentiate.
Topics: Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Comparative Effectiveness Research; Forced Expiratory Volume; Humans; Omalizumab
PubMed: 28137490
DOI: 10.1016/j.rmed.2016.12.009 -
Allergy and Asthma Proceedings Jul 2017There are limited pediatric data about the use of omalizumab, especially the effectiveness and safety of omalizumab in the real-world management of allergic asthma. (Review)
Review
BACKGROUND
There are limited pediatric data about the use of omalizumab, especially the effectiveness and safety of omalizumab in the real-world management of allergic asthma.
OBJECTIVE
The objective of this study was to summarize the safety and efficacy of omalizumab in both randomized clinical trials (RCT) used for U.S. Food and Drug Administration registration and real-world studies (RWS) based on clinical care of children with moderate-to-severe asthma.
METHODS
Studies that evaluated omalizumab use in patients <18 years old and with asthma, published between January 2003 and October 2016, were retrieved from medical literature data bases. Assessed outcomes included the following: exacerbation rates, spirometric indices, changes in asthma medication use, asthma control, patient-reported outcomes, and health care resource utilization.
RESULTS
A total of five RWS were identified; outcomes reported were compared with three omalizumab RCTs. Overall, the mean rate of annual exacerbations was significantly lower after 6 months to 2 years of treatment with omalizumab in both RCTs and RWS. In two RCTs and three RWS, inhaled corticosteroid use was significantly reduced in patients who used omalizumab. Similar reductions in the use of rescue medication were also observed in the RCTs and RWS on omalizumab. Real-world evidence demonstrated improvement in forced expiratory volume in the first second of expiration (% predicted) in patients treated with omalizumab as well as significant improvement in the level of asthma control observed over 1 year. There also was evidence that omalizumab treatment reduced health care resource utilization, including fewer hospitalizations, emergency department visits, and unscheduled medical visits. Safety outcomes in all five RWS showed no new safety signals and demonstrated that omalizumab was well tolerated.
CONCLUSION
Overall, RCT evidence strongly supported omalizumab efficacy and safety as add-on treatment in children 6 to 11 years old with moderate-to-severe persistent allergic asthma. RWS data confirmed these findings in an extended patient population of children and adolescents that is more generalizable to the actual day-to-day management of these patients.
Topics: Adolescent; Age Factors; Anti-Asthmatic Agents; Asthma; Child; Humans; Lung; Omalizumab; Randomized Controlled Trials as Topic; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome
PubMed: 28631599
DOI: 10.2500/aap.2017.38.4067