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International Forum of Allergy &... Jan 2024The heterogeneity of existing studies, along with the fact that there are no published head-to-head trials, are the main reasons for the lack of guidelines regarding the... (Review)
Review
Chronic rhinosinusitis with nasal polyps (CRSwNP) treated with omalizumab, dupilumab, or mepolizumab: A systematic review of the current knowledge towards an attempt to compare agents' efficacy.
BACKGROUND
The heterogeneity of existing studies, along with the fact that there are no published head-to-head trials, are the main reasons for the lack of guidelines regarding the selection of the proper biologic in treatment of chronic rhinosinusitis (CRS) with nasal polyps. The aim of this study is to summarize the current knowledge regarding the efficacy of omalizumab, dupilumab, and mepolizumab in CRS treatment. We also attempt to proceed to an indirect comparison of the agents and try to answer the tricky question: which agent to select and why?
METHODS
An extensive search in English literature was conducted in PubMed/Medline, Embase, Google Scholar, and Cochrane Database/Library. Eligibility criteria included papers with full text published in English, adult population studies, clearly described intervention protocol, and documented primary and secondary outcomes.
RESULTS
The studies included numbered 37. All agents provided significant improvement in polyp size, sinuses opacification, severity of symptoms, need for surgery and systemic corticosteroids use. Analysis of available systematic reviews, meta-analyses and indirect treatment comparison studies showed that dupilumab appeared to be the most beneficial agent, in terms of primary and secondary outcomes. However, these results are of relatively low level of evidence due to several methodological limitations.
CONCLUSIONS
Although the present analysis showed a moderate supremacy of dupilumab, there is still no evidence-based answer to the question "which biologic agent is the most effective in CRS treatment?" Improved statistical methodology, head-to-head trials, and real-life studies could lead to more robust conclusions, establishing the real role of the specific biologic agents.
Topics: Adult; Humans; Nasal Polyps; Omalizumab; Rhinosinusitis; Sinusitis; Chronic Disease; Biological Products; Rhinitis; Quality of Life; Antibodies, Monoclonal, Humanized
PubMed: 37394893
DOI: 10.1002/alr.23234 -
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... Aug 2023Omalizumab is the only biological agent approved for patients with chronic spontaneous urticaria (CSU), but no biomarker is well established for predicting clinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Omalizumab is the only biological agent approved for patients with chronic spontaneous urticaria (CSU), but no biomarker is well established for predicting clinical response to omalizumab.
OBJECTIVE
We aimed to determine the association between baseline total serum IgE levels and the effects of omalizumab in patients with CSU.
METHODS
PubMed, Web of Science, Scopus, and Cochrane Library were systematically searched for relevant studies from inception to August 23, 2022. The research protocol was registered on PROSPERO (CRD42022355592). No language restrictions were applied. A random-effects model was used for meta-analysis.
RESULTS
Ten interventional studies, including 1 randomized controlled trial, were included in the final meta-analysis, and a total of 866 patients with CSU were included. A pooled analysis showed significantly higher serum total IgE levels in complete responders (CRs) than in nonresponders (NRs) (mean difference [MD]: 56.509 IU/mL; 95% confidence interval [CI]: 24.230-88.789) and in partial responders (PRs) than in NRs (MD: 62.688 IU/mL; 95% CI: 32.949-92.427), but no significant difference was detected between CRs and PRs. The mean total IgE levels for CRs, PRs, and NRs were 163.154, 179.926, and 51.535 IU/mL, respectively. Further, the serum total IgE levels in early CRs were significantly higher compared with late CRs (MD: 55.194 IU/mL; 95% CI: 13.402-96.986). The sensitivity analyses with the leave-one-out method validated the robustness of all findings.
CONCLUSIONS
This systematic review and meta-analysis provide convincing evidence that pretreatment total serum IgE levels in patients with CSU are associated with clinical responses to omalizumab.
Topics: Humans; Omalizumab; Anti-Allergic Agents; Urticaria; Immunoglobulin E; Treatment Outcome; Chronic Urticaria; Chronic Disease; Randomized Controlled Trials as Topic
PubMed: 37263348
DOI: 10.1016/j.jaip.2023.05.033 -
Journal of Investigational Allergology... Dec 2023Impairment of smell is more commonly related to chronic rhinosinusitis with nasal polyps (CRSwNP) than without, especially when asthma and/or NSAID-exacerbated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Impairment of smell is more commonly related to chronic rhinosinusitis with nasal polyps (CRSwNP) than without, especially when asthma and/or NSAID-exacerbated respiratory disease and type 2 inflammation are also present. Therapeutic options include intranasal and systemic corticosteroids, surgery, and, more recently, biological therapy. We summarize current knowledge on the effect of biologics on olfaction in patients with CRSwNP.
METHODS
We performed a systematic search of the PubMed and Cochrane databases from January 2001 to June 2022. The inclusion criteria were as follows: adult patients with CRS treated with dupilumab, omalizumab, mepolizumab, benralizumab, or reslizumab; and studies published in English reporting outcomes for sense of smell based on psychophysical and/or subjective tools. We excluded reports that did not assess CRSwNP, loss of smell evaluated with a method other than those accepted in the inclusion criteria, review articles, and expert opinions. No funding was received.
RESULTS
Dupilumab has demonstrated rapid and sustained long-term improvement in smell in clinical trials and in real life. Omalizumab improves smell at 24 weeks. This improvement is maintained in the long-term, although it is not clinically relevant. Mepolizumab and benralizumab improved smell in the long term based on a subjective scale. No studies examining the improvement in smell in patients with CRSwNP treated with reslizumab were found. Indirect comparisons by meta-analysis consistently conclude that dupilumab is the most effective biologic for improving impaired sense of smell.
CONCLUSION
Dupilumab seems to be more efficacious for improving the sense of smell than omalizumab, mepolizumab, and benralizumab.
Topics: Adult; Humans; Antibodies, Monoclonal; Nasal Polyps; Omalizumab; Smell; Rhinosinusitis; Chronic Disease; Sinusitis; Rhinitis; Quality of Life
PubMed: 37669083
DOI: 10.18176/jiaci.0939 -
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 -
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 -
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 -
Current Medical Research and Opinion Nov 2020We conducted a systematic literature review (SLR) to determine the epidemiology and clinical burden of chronic rhinosinusitis with nasal polyps (CRSwNP) and to describe...
OBJECTIVES
We conducted a systematic literature review (SLR) to determine the epidemiology and clinical burden of chronic rhinosinusitis with nasal polyps (CRSwNP) and to describe how the addition of biologics has affected outcomes for patients with CRSwNP.
METHODS
The SLR adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Embase, MEDLINE, and Evidence-Based Medicine Reviews databases were searched using OVID. Relevant studies published between 1 January 2008 and 8 February 2019, for epidemiology, and 1 January 2008 and 16 February 2019, for clinical burden, and relevant conference abstracts from 1 January 2017 to 7 March 2019, for epidemiology and 1 January 2017-16 February 2019 for clinical burden were included.
RESULTS
For the epidemiology and clinical burden SLR, 147 and 119 records, respectively, met the inclusion criteria. We found the prevalence of CRSwNP was 1-2.6% and was greater in men. Asthma, allergy, and allergic rhinitis were the most common comorbidities identified. Reported risk factors included asthma, gene polymorphisms, age, and eosinophilia. Studies indicated that dupilumab, mepolizumab, and omalizumab each improved different clinical outcomes. Non-biologics (drugs such as corticosteroids or antibiotics, surgery, or aspirin desensitization) improved clinical outcomes as well.
CONCLUSIONS
CRSwNP is fairly prevalent in the general population. Despite the significant efficacy of existing treatments, several unmet needs remain. The high burden of uncontrolled symptoms, frequent recurrence of nasal polyps after surgery, and long-term adverse effects of oral corticosteroids indicate that new therapies addressing these unmet needs should be developed. Although data on biologics from randomized controlled trials look promising, the efficacy of biologics in the real world has yet to be established. The SLR of the epidemiology and clinical burden of CRSwNP revealed key gaps in the literature. There was a paucity of prevalence data across many geographic areas, and no prevalence projections could be determined. Studies showed varying efficacy of non-biologics and no studies directly compared biologics for efficacy. Data regarding clinical efficacy of agents for eosinophilic CRSwNP or severe CRSwNP were lacking, and these patient populations would be served by more trials.
Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal, Humanized; Asthma; Biological Products; Chronic Disease; Humans; Nasal Polyps; Omalizumab; Prevalence; Rhinitis; Risk Factors; Sinusitis; Treatment Outcome
PubMed: 32847417
DOI: 10.1080/03007995.2020.1815682