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Meta-Analysis
. 2025 Mar 19;34(175):240238.
doi: 10.1183/16000617.0238-2024. Print 2025 Jan.

Comorbidities in the idiopathic pulmonary fibrosis and progressive pulmonary fibrosis trial population: a systematic review and meta-analysis

Tyson M Walters  1 , Marcus C H Leong  2 , Sydney B Montesi  3 , Christopher J Ryerson  4   5 , Yet H Khor  6   7   8   9
Affiliations
Meta-Analysis

Comorbidities in the idiopathic pulmonary fibrosis and progressive pulmonary fibrosis trial population: a systematic review and meta-analysis

Tyson M Walters et al. Eur Respir Rev. .

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

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Conflict of interest statement

Conflict of interest: T.M. Walters and M.C.H. Leong have nothing to disclose. S.B. Montesi reports grants from NIH/NHLBI, Merck, Boehringer Ingelheim and Pliant Therapeutics; royalties or licenses from Wolters Kluwer; consulting fees from Roche, DevPro Biopharma, Mediar Therapeutics and Accendatech USA; payment or honoraria for lectures, presentations or educational events from Cowen; support for attending meetings from DevPro Biopharma; participation on a data safety monitoring board or advisory board with Pliant Therapeutics and APIE Therapeutics; and a leadership role with Massachusetts Thoracic Society. C.J. Ryerson reports grants from Boehringer Ingelheim, Hoffmann-La Roche and VIDA Diagnostics; payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim, Hoffmann-La Roche, Veracyte, Plaint Therapeutics, AstraZeneca, Cipla Ltd and Trevi Therapeutics; and a leadership role with the American Thoracic Society Documents Development and Implementation Committee. Y.H. Khor reports grants from NHMRC, MRFF, Air Liquide Healthcare (in-kind trial support), Austin Medical Research Foundation, Lung Foundation Australia/Thoracic Society of Australia and New Zealand and RACP; and leadership roles with the Thoracic Society of Australia and New Zealand (Board Director, Chair for Clinical Care and Resources Sub-Committee, OLIV Special Interest Group Convenor), American Thoracic Society (Clinical Problems Assembly Program Committee; guideline methodologist) and European Respiratory Society (Associate Editor for the European Respiratory Journal).

Figures

FIGURE 1
FIGURE 1
Study flow diagram. #: Primary articles refer to original publications of the randomised controlled trials. : Secondary articles refer to additional publications of post hoc analyses of previously published randomised controlled trials. CENTRAL: Cochrane Central Register of Controlled Trials; IPF: idiopathic pulmonary fibrosis; PPF: progressive pulmonary fibrosis; RCT: randomised controlled trial.
FIGURE 2
FIGURE 2
Reporting of comorbidities in randomised controlled trials of idiopathic pulmonary fibrosis (IPF). Studies are cited as first author, reference, year. a) Number of comorbidities reported for individual included randomised controlled trials of IPF. b) Percentages of included randomised controlled trials of IPF reporting comorbidity classified by organ system. ILD: interstitial lung disease.
See this image and copyright information in PMC

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