Walters Tyson M, Leong Marcus C H, Montesi Sydney B, Ryerson Christopher J, Khor Yet H
Department of Medicine, Austin Health, Heidelberg, Australia.
Faculty of Medicine, University of Melbourne, Melbourne, Australia.
Eur Respir Rev. 2025 Mar 19;34(175). doi: 10.1183/16000617.0238-2024. Print 2025 Jan.
Comorbidities can affect drug tolerability and health outcomes in patients with fibrotic interstitial lung disease. This systematic review and meta-analysis evaluated the types and prevalence of comorbidities amongst participants in pharmaceutical randomised controlled trials (RCTs) of idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF).
Ovid Medline, Embase and CENTRAL databases were searched to identify phase II and III pharmaceutical RCTs of IPF or PPF. Reporting of comorbidities was evaluated, with meta-analyses being performed for the prevalence of different conditions.
34 articles were included, with 23 unique trials for IPF and one for PPF. A mean of 14 (range 1-44) comorbidities per study was reported in the IPF RCTs, with 11 being reported in the PPF RCT. Common comorbidities in the IPF RCT cohorts were systemic hypertension (pooled prevalence 45%, 95% CI 39-50%), hyperlipidaemia (38%, 95% CI 27-49%), gastro-oesophageal reflux disease (45%, 95% CI 36-54%), ischaemic heart disease (18%, 95% CI 13-42%) and diabetes mellitus (16%, 95% CI 13-20%). The PPF trial cohort had similar types and prevalence of comorbidities to those reported in the IPF trial cohorts.
Reporting of comorbidities varied across previous IPF RCTs, with limited data available for PPF. Prevalence of comorbidities reported in the IPF and PPF trial cohorts appear to be lower than those reported in prospective patient registries. There is a need for careful consideration of trial eligibility criteria with detailed reporting of comorbidities in future pharmaceutical RCTs to better understand the applicability of trial findings to real-world patients.
合并症可影响纤维化间质性肺疾病患者的药物耐受性和健康结局。本系统评价和荟萃分析评估了特发性肺纤维化（IPF）和进行性肺纤维化（PPF）药物随机对照试验（RCT）参与者中合并症的类型和患病率。
检索Ovid Medline、Embase和CENTRAL数据库，以确定IPF或PPF的II期和III期药物RCT。评估合并症的报告情况，并对不同疾病的患病率进行荟萃分析。
纳入34篇文章，其中IPF有23项独立试验，PPF有1项试验。IPF RCT中每项研究报告的合并症平均为14种（范围1 - 44种），PPF RCT中报告了11种。IPF RCT队列中的常见合并症有系统性高血压（合并患病率45%，95%CI 39 - 50%）、高脂血症（38%，95%CI 27 - 49%）、胃食管反流病（45%，95%CI 36 - 54%）、缺血性心脏病（18%，95%CI 13 - 42%）和糖尿病（16%，95%CI 13 - 20%）。PPF试验队列的合并症类型和患病率与IPF试验队列报告的相似。
既往IPF RCT中合并症的报告存在差异，PPF的可用数据有限。IPF和PPF试验队列中报告的合并症患病率似乎低于前瞻性患者登记处报告的患病率。未来药物RCT需要仔细考虑试验纳入标准并详细报告合并症，以便更好地了解试验结果对真实世界患者的适用性。
