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Comparative efficacy of biologics for patients with inadequately controlled asthma: A network meta-analysis.

ABSTRACT: Few studies have evaluated the comparative efficacy of biologics for asthma. This network meta-analysis aimed to compare the efficacy of biologics. This study included randomized controlled trials (RCTs) evaluating the efficacy of a biologic compared to a placebo or another biologic in patients with inadequately controlled asthma despite high-intensity treatment, published by January 6, 2022. Two researchers independently searched the PubMed, Embase, Web of Science, and Scopus and assessed the risk of bias using the Cochrane tool. The outcomes of interest were the annual asthma exacerbation rate (AER), forced expiratory volume per second before bronchodilator use (preBD FEV1), the asthma control questionnaire (ACQ), and asthma quality of life questionnaire (AQLQ) results. A frequentist network meta-analysis was conducted, and a random effects model was used to draw pooled incidence rate ratio or standardized mean differences. Twenty-three RCTs with 8376 participants were retrieved. All biologics included in this study were associated with significantly better effects than placebo in AER, preBD FEV1, and ACQ outcomes. Although there were no significant differences between the biologics in the overall study population, patients with eosinophil levels ≥300 cells/μL or eosinophilic asthma showed that dupilumab and tezepelumab were significantly better than anti-IL-5 biologics in improving preBD FEV1. Additionally, in patients with eosinophil levels ≥300 cells/μL, benralizumab, unlike reslizumab, performed significantly better than placebo in improving ACQ and AQLQ outcomes. The comparative effects of biologics can be considered with phenotypes and biomarkers to help clinicians select an appropriate treatment for inadequately controlled asthma.

SUBMITTER: Kim H

PROVIDER: S-EPMC11293571 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Comparative efficacy of biologics for patients with inadequately controlled asthma: A network meta-analysis.

Kim Hayeon H Kim Myeong Gyu MG Kim Sung-Ryeol SR Lee Jae-Hyun JH Byun Youngjoo Y Park Jiwon J Kim Kyungim K

The World Allergy Organization journal 20240718 7

<h4>Background</h4>Few studies have evaluated the comparative efficacy of biologics for asthma. This network meta-analysis aimed to compare the efficacy of biologics.<h4>Methods</h4>This study included randomized controlled trials (RCTs) evaluating the efficacy of a biologic compared to a placebo or another biologic in patients with inadequately controlled asthma despite high-intensity treatment, published by January 6, 2022. Two researchers independently searched the PubMed, Embase, Web of Scie ...[more]

PMID: 39091592

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Project description:ObjectiveTo determine the comparative efficacy of once-weekly semaglutide relative to sodium-glucose cotransporter 2 inhibitors (SGLT-2is) licensed in Europe and North America among patients with type 2 diabetes (T2D) inadequately controlled with 1-2 oral antidiabetics (OADs), using a network meta-analysis (NMA). Design systematic review and network meta-analysis. Data Sources EMBASE, MEDLINE and CENTRAL were searched from January 1994 to August 2017.MethodsRandomised controlled trials with ≥20 weeks of treatment evaluating once-weekly semaglutide or SGLT-2is. Primary outcomes included change from baseline in: HbA1c, weight, systolic blood pressure, postprandial blood glucose and fasting plasma glucose. Fixed-effect and random-effect Bayesian NMA were used to indirectly compare treatment effects at 26 (±4) weeks. Metaregression and sensitivity analyses were conducted. Model selection was performed using the deviance information criterion and consistency was assessed by comparing indirect (edge-splitting) to direct evidence.ResultsForty-eight publications representing 21 trials were included. The mean differences (MD) in change from baseline in HbA1c of once-weekly semaglutide 1.0 mg versus SGLT-2is ranged from -0.56% for canagliflozin 300 mg (95% credible interval (CrI): -0.76 to -0.33%), to -0.95% for dapagliflozin 5 mg (95% CrI: -1.20 to -0.69%). The MD in change from baseline in weight of once-weekly semaglutide 1.0 mg versus SGLT-2is ranged from -1.35 kg for canagliflozin 300 mg to -2.48 kg for dapagliflozin 5 mg, while change from baseline in fasting plasma glucose ranged from -0.41 mmol/L for canagliflozin 300 mg to -1.37 mmol/L for dapagliflozin 5 mg. Once-weekly semaglutide was not statistically differentiable than all SGLT-2is in reducing systolic blood pressure. NMA was not feasible for postprandial blood glucose and safety outcomes.ConclusionOnce-weekly semaglutide demonstrated statistically significant and clinically meaningful reductions in HbA1c and body weight in T2D patients inadequately controlled with 1-2 OADs compared to all SGLT-2is licensed in Europe and North America.

Project description:BackgroundThe comparative safety and efficacy of the biologics currently approved for asthma are unclear.ObjectiveWe compared the safety and efficacy of mepolizumab, benralizumab, and dupilumab in individuals with severe eosinophilic asthma.MethodsWe performed a systematic review of peer-reviewed literature published 2000 to 2021. We studied Bayesian network meta-analyses of exacerbation rates, prebronchodilator FEV1, the Asthma Control Questionnaire, and serious adverse events in individuals with eosinophilic asthma.ResultsEight randomized clinical trials (n = 6461) were identified. We found in individuals with eosinophils ≥300 cells/μL the following: in reducing exacerbation rates compared to placebo: dupilumab (risk ratio [RR], 0.32; 95% credible interval [CI], 0.23 to 0.45), mepolizumab (RR, 0.37; 95% CI, 0.30 to 0.45), and benralizumab (RR, 0.49; 95% CI, 0.43 to 0.55); in improving FEV1: dupilumab (mean difference in milliliters [MD] 230; 95% CI, 160 to 300), benralizumab (MD, 150; 95% CI, 100 to 200), and mepolizumab (MD, 150; 95% CI, 66 to 220); and in reducing Asthma Control Questionnaire scores: mepolizumab (MD, -0.63; 95% 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 eosinophils 150-299 cells/μL, benralizumab (RR, 0.62; 95% CI, 0.52 to 0.73) and dupilumab (RR, 0.60; 95% CI, 0.38 to 0.95) were associated with lower exacerbation rates; and only benralizumab (MD, 81; 95% CI, 8 to 150) significantly improved FEV1. These differences were minimal compared to clinically important thresholds. For serious adverse events in the overall population, mepolizumab (odds ratio, 0.67; 95% CI, 0.48 to 0.92) and benralizumab (odds ratio, 0.74; 95% CI, 0.59 to 0.93) were associated with lower odds of a serious adverse event, while dupilumab was not different from placebo (odds ratio, 1.0; 95% CI, 0.74 to 1.4).ConclusionThere are minimal differences in the efficacy and safety of mepolizumab, benralizumab, and dupilumab in eosinophilic asthma.

Project description:BackgroundChronic sinonasal disease is common in asthmatic patients and associated with poor asthma control; however, there are no long-term trials addressing whether chronic treatment of sinonasal disease improves asthma control.ObjectiveWe sought to determine whether treatment of chronic sinonasal disease with nasal corticosteroids improves asthma control, as measured by the Childhood Asthma Control Test and Asthma Control Test in children and adults, respectively.MethodsA 24-week multicenter, randomized, placebo-controlled, double-blind trial of placebo versus nasal mometasone in adults and children with inadequately controlled asthma was performed. Treatments were randomly assigned, with concealment of allocation.ResultsTwo hundred thirty-seven adults and 151 children were randomized to nasal mometasone versus placebo, and 319 participants completed the study. There was no difference in the Childhood Asthma Control Test score (difference in change with mometasone - change with placebo [ΔM - ΔP], -0.38; 95% CI, -2.19 to 1.44; P = .68; age 6-11 years) or the Asthma Control Test score (ΔM - ΔP, 0.51; 95% CI, -0.46 to 1.48; P = .30; age ≥12 years) in those assigned to mometasone versus placebo. In children and adolescents (age 6-17 years) there was no difference in asthma or sinus symptoms but a decrease in episodes of poorly controlled asthma defined by a decrease in peak flow. In adults there was a small difference in asthma symptoms measured by using the Asthma Symptom Utility Index (ΔM - ΔP, 0.06; 95% CI, 0.01 to 0.11; P < .01) and in nasal symptoms (sinus symptom score ΔM - ΔP, -3.82; 95% CI, -7.19 to -0.45; P = .03) but no difference in asthma quality of life, lung function, or episodes of poorly controlled asthma in adults assigned to mometasone versus placebo.ConclusionsTreatment of chronic sinonasal disease with nasal corticosteroids for 24 weeks does not improve asthma control. Treatment of sinonasal disease in asthmatic patients should be determined by the need to treat sinonasal disease rather than to improve asthma control.

Project description:Background: Crohn disease (CD) is a chronic inflammatory disease that affects quality of life. There are several drugs available for the treatment of CD, but their relative efficacy is unknown due to a lack of high-quality head-to-head randomized controlled trials. Aim: To perform a mixed comparison of the efficacy and safety of biosimilars, biologics and JAK1 inhibitors for CD. Methods: We searched PubMed, Web of Science, embase and the Cochrane Library for randomized controlled trials (RCTs) up to Dec. 28, 2020. Only RCTs that compared the efficacy or safety of biosimilars, biologics and JAK1 inhibitors with placebo or another active agent for CD were included in the comparative analysis. Efficacy outcomes were the induction of remission, maintenance of remission and steroid-free remission, and safety outcomes were serious adverse events (AEs) and infections. The Bayesian method was utilized to compare the treatments. The registration number is CRD42020187807. Results: Twenty-eight studies and 29 RCTs were identified in our systematic review. The network meta-analysis demonstrated that infliximab and adalimumab were superior to certolizumab pegol (OR 2.44, 95% CI 1.35-4.97; OR 2.96, 95% CI 1.57-5.40, respectively) and tofacitinib (OR 2.55, 95% CI 1.27-5.97; OR 3.10, 95% CI 1.47-6.52, respectively) and revealed the superiority of CT-P13 compared with placebo (OR 2.90, 95% CI 1.31-7.59) for the induction of remission. Infliximab (OR 7.49, 95% CI 1.85-34.77), adalimumab (OR 10.76, 95% CI 2.61-52.35), certolizumab pegol (OR 4.41, 95% CI 1.10-21.08), vedolizumab (OR 4.99, 95% CI 1.19-25.54) and CT-P13 (OR 10.93, 95% CI 2.10-64.37) were superior to filgotinib for the maintenance of remission. Moreover, infliximab (OR 3.80, 95% CI 1.49-10.23), adalimumab (OR 4.86, 95% CI 1.43-16.95), vedolizumab (OR 2.48, 95% CI 1.21-6.52) and CT-P13 (OR 5.15, 95% CI 1.05-27.58) were superior to placebo for steroid-free remission. Among all treatments, adalimumab ranked highest for the induction of remission, and CT-P13 ranked highest for the maintenance of remission and steroid-free remission. Conclusion: CT-P13 was more efficacious than numerous biological agents and JAK1 inhibitors and should be recommended for the treatment of CD. Further head-to-head RCTs are warranted to compare these drugs.

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Comparative efficacy of biologics for patients with inadequately controlled asthma: A network meta-analysis.

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Comparative efficacy of biologics for patients with inadequately controlled asthma: A network meta-analysis.

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