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Revisión sistemática

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Tezepelumab compared with other biologics for the treatment of severe asthma: a systematic review and indirect treatment comparison.

Revista Journal of medical economics
Año 2022
Enlaces Pubmed DOI

Este artículo incluye 37 Estudios primarios 39 Estudios primarios (37 referencias)

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AIMS To compare the efficacy of tezepelumab with other approved biologics via indirect treatment comparisons (ITCs) in patients aged ≥12 years with severe uncontrolled asthma.MATERIALS AND METHODS Data from randomized controlled trials (RCTs) identified from a systematic literature review were synthesized using two different ITC approaches: network meta-analysis (NMA) and simulated treatment comparison (STC). Outcomes of interest were annualized asthma exacerbation rate (AAER) and AAER for exacerbations leading to hospitalization. To address potential heterogeneity between study populations, various subgroup analyses were performed for the NMA (based on blood eosinophil count [Eos], fractional exhaled nitric oxide level, and presence of allergic asthma), and for the STC, models were adjusted for potential treatment effect modifiers. Sensitivity analyses were performed to assess the impact of study design (exclusion of non placebo-controlled studies and non-phase 3 or 4 studies). Results were reported as rate ratios (RRs) with 95% credible/confidence intervals and ranking statistics were computed for the NMAs.RESULTS Sixteen RCTs were included in at least one of the ITCs. All biologics (tezepelumab, dupilumab, benralizumab, mepolizumab, reslizumab, and omalizumab) had similar efficacy, with no statistically significant RRs for either exacerbation outcome; however, tezepelumab was favorably associated with numerically lower AAERs and was ranked first in the network for both types of exacerbation outcome. This trend was consistent in the subgroup and sensitivity analyses. As with the primary NMA, the STC results did not demonstrate any significant differences between biologics, but point estimates were favorable towards tezepelumab.LIMITATIONS Heterogeneity between trials was observed among eligibility criteria and clinically important patient characteristics; however, impact on findings is expected to be low, based on consistency across analyses.CONCLUSIONS Findings from both ITCs (NMA and STC) support the use of tezepelumab in a broad patient population of severe uncontrolled asthma of any phenotype.

Revisión sistemática

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Comparative efficacy of mepolizumab, benralizumab, and dupilumab in eosinophilic asthma: A Bayesian network meta-analysis.

Revista The Journal of allergy and clinical immunology
Año 2022
Enlaces Pubmed DOI PubMed Central

Este artículo incluye 8 Estudios primarios 8 Estudios primarios (8 referencias)

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BACKGROUND: The comparative safety and efficacy of the biologics currently approved for asthma is unclear. OBJECTIVE: To compare the safety and efficacy of mepolizumab, benralizumab, and dupilumab in individuals with severe eosinophilic asthma. METHODS: Systematic review of peer-reviewed literature from 2000 through 2021, and Bayesian network meta-analyses of exacerbation rates, prebronchodilator FEV1, the Asthma Control Questionnaire (ACQ) and serious adverse events (SAE) in individuals with eosinophilic asthma. RESULTS: Eight randomized clinical trials (n=6,461) were identified. In individuals with ≥300 eosinophils per microliter (eosin/mcl), in reducing exacerbation rates in comparison to placebo: dupilumab (risk ratio [RR] 0.32; 95% credible interval [CI], 0.23-0.45), mepolizumab (RR, 0.37; 95%CI, 0.30-0.45), and benralizumab (RR, 0.49; 95%CI, 0.43-0.55). In improving FEV1: dupilumab (mean difference in milliliters [MD] 230; [CI], 160-300), benralizumab (MD 150; 95%CI, 100-200), and mepolizumab (MD 150; 95%CI, 66-220); and in reducing ACQ: mepolizumab (MD -0.63; [CI], -0.81 to -0.45), dupilumab (MD -0.48; 95%CI, -0.83 to -0.14), and benralizumab (MD -0.32; 95%CI, -0.43 to -0.21). In individuals with eosinophil counts of 150-299 eosin/mcl, benralizumab (RR, 0.62; 95%CI, 0.52-0.73) and dupilumab (RR, 0.60; 95%CI, 0.38-0.95) were associated with lower exacerbation rates; and only benralizumab (MD 81; 95% CI, 8-150) significantly improved FEV1. These differences were minimal in comparison to clinically important thresholds. For SAE in the overall population, mepolizumab (odds ratio, 0.67; 95% CI, 0.48-0.92) and benralizumab (0.74; 95% CI, 0.59-0.93) were associated with lower odds of a SAE, while dupilumab was not different from placebo (1.0; 95% CI, 0.74-1.4). CONCLUSIONS: There are minimal differences in the efficacy and safety of mepolizumab, benralizumab, and dupilumab in eosinophilic asthma. CLINICAL IMPLICATION: In individuals with eosinophilic asthma, mepolizumab, benralizumab, and dupilumab are similar in their effect on exacerbations, FEV1, or ACQ.

Revisión sistemática

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Comparative Efficacy and Safety of Tezepelumab and Other Biologics in Patients with Inadequately Controlled Asthma According to Thresholds of Type 2 Inflammatory Biomarkers: A Systematic Review and Network Meta-Analysis.

Autores Ando K , Fukuda Y , Tanaka A , Sagara H
Revista Cells
Año 2022
Enlaces Pubmed DOI PubMed Central

Este artículo incluye 8 Estudios primarios 8 Estudios primarios (8 referencias)

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The anti-thymic stromal lymphopoietin antibody (tezepelumab) has therapeutical potential for inadequately controlled asthma. However, evidence comparing tezepelumab with other biologics is scarce. To address this issue, we performed a network meta-analysis to compare and rank the efficacy of five treatments (tezepelumab, dupilumab, benralizumab, mepolizumab, and placebo) in overall participants and in subgroups stratified by the thresholds of type 2 inflammatory biomarkers, including peripheral blood eosinophil count (PBEC) and fractional exhaled nitric oxide (FeNO). The primary endpoints were annualized exacerbation rate (AER) and any adverse events (AAEs). In the ranking assessment using surface under the cumulative ranking curve (SUCRA) of AER, tezepelumab ranked the highest overall and across subgroups (based on PBEC and FeNO level thresholds). A significant difference was observed between tezepelumab and dupilumab in the patient subgroup with PBEC < 150, and between tezepelumab and benralizumab in overall participants and the patient subgroup with PBEC ≥ 300 and ≥150, respectively. There was no significant difference in the incidence of AAEs in the overall participants between each pair of five treatment arms. These results provide a basis for the development of treatment strategies for asthma and may guide basic, clinical, or translational research.

Revisión sistemática

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Pairwise indirect treatment comparison of dupilumab versus other biologics in patients with uncontrolled persistent asthma

Revista Respiratory medicine
Año 2022
Enlaces Pubmed DOI

Este artículo incluye 14 Estudios primarios 16 Estudios primarios (14 referencias)

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Background: Currently, five biologic treatment options are available for use in patients with uncontrolled persistent asthma: three interleukin (IL)-5 antagonists, which either bind to the anti-IL-5 ligand (mepolizumab, reslizumab) or to the IL-5 receptor (benralizumab); one anti-immunoglobulin E (anti-IgE) therapy (omalizumab); and one anti-IL-4/IL-13 therapy (dupilumab). To date, no comparative data from head-to-head clinical trials are available for these biologics. Objective: An indirect treatment comparison (ITC) of dupilumab versus each of the anti-IL-5 and anti-IgE therapies using the endpoints of annualized severe asthma exacerbation rates and change in pre-bronchodilator forced expiratory volume in 1 s (FEV1). Methods: Embase®, MEDLINE®, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for studies published between January 1, 1980 and March 25, 2019. Eligible articles included randomized controlled trials (RCTs) in patients aged ≥ 12 years with persistent/uncontrolled asthma using at least medium-to-high dose inhaled corticosteroid plus long-acting β2-agonist with add-on biologic therapy. Bucher ITCs were performed to compare subgroups of dupilumab patients with the anti-IL-5s and anti-IgE trial populations. Results: Fourteen RCTs were included in the analyses. The matched dupilumab subgroups were associated with greater reductions in annualized severe exacerbation rates compared with benralizumab, mepolizumab, reslizumab, and omalizumab (54%, 28%, 38%, and 26% greater reduction, respectively). A greater improvement in FEV1 was also observed for dupilumab at week 12 and/or week 24/52 than for the other biologics (0.06–0.14 L). Conclusion: In this ITC, dupilumab was associated with lower severe asthma exacerbation rates and greater improvements in lung function than anti-IL-5s and omalizumab. © 2020

Revisión sistemática

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The Clinical Efficacy of Type 2 Inflammation-Specific Agents Targeting Interleukins in Reducing Exacerbations in Severe Asthma: A Meta-Analysis

Autores Lee J , Song JU , Kim YH
Revista Yonsei medical journal
Año 2022
Enlaces Pubmed DOI

Este artículo incluye 17 Estudios primarios 19 Estudios primarios (17 referencias)

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PURPOSE: Monoclonal antibodies against type 2 inflammatory pathways are currently promising therapeutics for severe asthma. The aim of this study was to determine how well type 2 (T2) inflammation-specific agents targeting interleukins reduce the rate of asthma exacerbations (AE) in patients with severe asthma. MATERIALS AND METHODS: We performed a systematic review and meta-analysis in accordance with PRISMA guidelines. A systematic literature search was conducted in PubMed, Embase, and the Cochrane Central Register. The primary outcome was the reduction rate of annualized AEs. RESULTS: We analyzed 17 studies comprising 11800 subjects. A total of 6197 patients received T2-specific agents (benralizumab, dupilumab, lebrikizumab, mepolizumab, reslizumab, and tralokinumab). Overall, T2-specific agents were significantly associated with a lower risk of AE, compared with placebo [rate ratio (RR) 0.58, 95% confidence interval (CI) 0.51 to 0.66]. Among all studied agents, only tralokinumab did not demonstrate a reduction in AE. The efficacy of T2-specific agents in reducing AE was maintained regardless of the pathway used. A subgroup analysis indicated that T2-specific agents further reduced the risk of AE in patients with eosinophil counts of ≥300 cells/µL (RR 0.41, 95% CI 0.32 to 0.53). CONCLUSION: Our findings suggest that T2-specific agents are significantly associated with a reduced rate of AE, compared with placebo. Their efficacy appears to be enhanced in patients with eosinophil counts of ≥300 cells/µL.

Revisión sistemática

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Real-World Efficacy of Treatment with Benralizumab, Dupilumab, Mepolizumab and Reslizumab for Severe Asthma: A Systematic Review and Meta-analysis.

Revista Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
Año 2022
Enlaces Pubmed DOI PubMed Central

Este artículo incluye 22 Estudios primarios 25 Estudios primarios (22 referencias)

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BACKGROUND: Severe asthma is a major cause of morbidity. Some patients may benefit from biological therapies. Most evaluations of these treatments are derived from randomised controlled trials (RCTs), but few patients are eligible for these trials. Studies involving more diverse groups of participants exist but there is a lack of precise pooled estimates. OBJECTIVE: This systematic review aims to evaluate the real-world efficacy of recently and nearly licensed biological therapies for severe asthma to assess the generalisability of the RCT data. METHODS: Clinical outcomes including exacerbation rate, oral corticosteroid (OCS) usage, forced expiratory volume in 1 second (FEV1 ) and fractional exhaled nitric oxide (FeNO) were examined. Studies were assessed for risk of bias using the Critical Appraisal Skills Programme (CASP) checklist tool. The certainty of evidence was assessed using GRADE. RESULTS: A total of 21 studies examining biologicals in real-world settings were identified, they mostly focused on benralizumab and mepolizumab. The introduction of biologicals reduced the annualised exacerbation rate significantly by -3.79 (95% CI -4.53, -3.04), -3.17 (95% CI -3.74, -2.59) and -6.72 (95% CI -8.47, -4.97) with benralizumab, mepolizumab and reslizumab respectively. Likewise, improvements were observed in FEV1 (0.17 L 95% CI 0.11, 0.24) and FeNO (-14.23 ppb 95% CI -19.71, -8.75) following treatment with mepolizumab. After treatment with benralizumab there was an increase in FEV1 (0.21 L 95% CI 0.08, 0.34). CONCLUSIONS: These data demonstrate that anti-IL5 biologicals may improve the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs. The data were mainly retrospective and unadjusted, so estimated effect sizes may not be reliable. More data is needed to acquire accurate effect estimates in different subpopulations of patients.

Revisión sistemática

No clasificado

The Impact of Monoclonal Antibodies on Airway Smooth Muscle Contractility in Asthma: A Systematic Review.

Revista Biomedicines
Año 2021
Enlaces Pubmed DOI PubMed Central

Este artículo incluye 11 Estudios primarios 11 Estudios primarios (11 referencias)

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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.

Revisión sistemática

No clasificado

Gender bias in clinical trials of biological agents for severe asthma: A systematic review.

Revista PloS one
Año 2021
Enlaces Pubmed DOI PubMed Central

Este artículo incluye 37 Estudios primarios 39 Estudios primarios (37 referencias)

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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.

Revisión sistemática

No clasificado

Comparison of Monoclonal Antibodies for Treatment of Uncontrolled Eosinophilic Asthma.

Autores Koski RR , Grzegorczyk KM
Revista Journal of pharmacy practice
Año 2020
Enlaces Pubmed DOI

Este artículo incluye 21 Estudios primarios 23 Estudios primarios (21 referencias)

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OBJECTIVE: To summarize the current literature for Food and Drug Administration (FDA)-approved monoclonal antibodies used as add-on maintenance therapy in uncontrolled eosinophilic asthma. DATA SOURCES: PubMed was searched on December 17, 2018 using keywords: asthma, eosinophilic asthma, omalizumab, reslizumab, mepolizumab, benralizumab, and dupilumab. STUDY SELECTION: Studies evaluating safety and efficacy of monoclonal antibodies for treatment of severe or eosinophilic asthma were included. RESULTS: Twenty-one randomized, double-blind, placebo-controlled trials evaluating the current FDA-approved monoclonal antibodies (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) for the treatment of uncontrolled eosinophilic asthma were included. The studies demonstrated clinically significant reductions in asthma exacerbations, symptoms, emergency room visits, eosinophil counts, and improvements in pulmonary function and asthma-related quality of life. CONCLUSION: Five monoclonal antibodies are available for uncontrolled eosinophilic asthma. Choice depends on patient factors. Future studies should focus on cost-effectiveness of treatment, drug-drug comparisons, and long-term efficacy and safety.

Revisión sistemática

No clasificado

Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma.

Revista Allergy
Año 2020
Enlaces Pubmed DOI

Este artículo incluye 21 Estudios primarios 23 Estudios primarios (21 referencias)

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Five biologicals have been approved for severe eosinophilic asthma, a well-recognised phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic 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 for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (3 RCTs for benralizumab, 3 RCTs for dupilumab, 3 RCTs for mepolizumab, 4 RCTs for omalizumab, and 5 RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab rate ratio (RR) 0.53 (95% CI 0.39 to 0.72), dupilumab RR 0.43 (95% CI 0.32 to 0.59), mepolizumab RR 0.49 (95% CI 0.38 to 0.66), omalizumab RR 0.56 (95% CI 0.40 to 0.77), and reslizumab RR 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV1 , without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality adjusted life-years value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalisations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV1 and cost-effectiveness. More data on long term safety are needed together with more efficacy data in the paediatric population.