ABSTRACT
BACKGROUND: Trials have not directly compared biologics for the treatment of asthma. OBJECTIVE: To compare the relative efficacy of biologics in asthma. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to May 31, 2022 for randomized trials addressing biologic therapies for asthma. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist network meta-analysis and assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations approach. We present dichotomous outcomes as absolute risk differences per 1000 patients and relative risk with 95% confidence intervals (95% CI) and continuous outcomes as mean difference (MD) and 95% CI. RESULTS: We identified 64 trials, including 26,630 patients. For patients with eosinophilic asthma, tezepelumab (329 fewer exacerbations per 1000 [95% CI, 272.6-366.6 fewer]) and dupilumab (319.6 fewer exacerbations per 1000 [95% CI, 272.6-357.2 fewer]) reduce exacerbations compared with placebo (high certainty). Tezepelumab (MD, 0.24 L [95% CI, 0.16-0.32]) and dupilumab (0.25 L [95% CI, 0.21-0.29]) improve lung function compared with placebo (high certainty). Both tezepelumab (110.97 fewer hospital admissions per 1000 [95% CI, 94.53-120.56 fewer]) and dupilumab (97.27 fewer hospitalizations [4.11-124.67 fewer]) probably reduce hospital admissions compared with placebo (moderate certainty). For patients with low eosinophils, biologics probably do not improve asthma outcomes. For these patients, tezepelumab (MD, 0.1 L [95% CI, 0-0.19]) and dupilumab (MD, 0.1 L [95% CI, 0-0.20]) may improve lung function (low certainty). CONCLUSION: Tezepelumab and dupilumab are effective at reducing exacerbations. For patients with low eosinophils, however, clinicians should probably be more judicious in using biologics, including tezepelumab, because they probably do not confer substantial benefit.
Subject(s)
Asthma , Biological Products , Humans , Network Meta-Analysis , Asthma/drug therapy , Biological Products/therapeutic use , Biological TherapyABSTRACT
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder with a poor prognosis. Our objective is to assess the comparative effectiveness of 22 approved or studied IPF drug treatments. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov from inception to 2 April 2021. We included randomised controlled trials (RCTs) for adult patients with IPF receiving one or more of 22 drug treatments. Pairs of reviewers independently identified randomised trials that compared one or more of the target medical treatments in patients with IPF. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for network meta-analysis. We calculated pooled relative risk (RR) ratios and presented direct or network estimates with 95% credibility intervals (95% CI), within the GRADE framework. RESULTS: We identified 48 (10 326 patients) eligible studies for analysis. Nintedanib [RR 0.69 (0.44 to 1.1), pirfenidone [RR 0.63 (0.37 to 1.09); direct estimate), and sildenafil [RR (0.44 (0.16 to 1.09)] probably reduce mortality (all moderate certainty). Nintedanib (2.92% (1.51 to 4.14)), nintedanib+sildenafil (157 mL (-88.35 to 411.12)), pirfenidone (2.47% (-0.1 to 5)), pamrevlumab (4.3% (0.5 to 8.1)) and pentraxin (2.74% (1 to 4.83)) probably reduce decline of overall forced vital capacity (all moderate certainty). Only sildenafil probably reduces acute exacerbation and hospitalisations (moderate certainty). Corticosteroids+azathioprine+N-acetylcysteine increased risk of serious adverse events versus placebo (high certainty). CONCLUSION AND RELEVANCE: Future guidelines should consider sildenafil for IPF and further research needs to be done on promising IPF treatments such as pamrevlumab and pentraxin as phase 3 trials are completed.
