Drug therapies for treatment of idiopathic pulmonary fibrosis: a systematic review, Bayesian network meta-analysis, and cost-effectiveness analysis

Chunyang Zhao; Yan Yin; Chengrui Zhu; Min Zhu; Tianlong Ji; Zhonghao Li; Jiayi Cai

doi:10.1016/j.eclinm.2023.102071

Drug therapies for treatment of idiopathic pulmonary fibrosis: a systematic review, Bayesian network meta-analysis, and cost-effectiveness analysis

EClinicalMedicine. 2023 Jun 29:61:102071. doi: 10.1016/j.eclinm.2023.102071. eCollection 2023 Jul.

Authors

Chunyang Zhao^{1

2}, Yan Yin³, Chengrui Zhu⁴, Min Zhu⁵, Tianlong Ji⁶, Zhonghao Li⁷, Jiayi Cai¹

Affiliations

¹ School of Pharmacy, China Medical University, Shenyang, China.
² Department of Pharmacy, The First Hospital of China Medical University, Shenyang, China.
³ Department of Pulmonary and Critical Care Medicine, The First Hospital of China Medical University, Shenyang, China.
⁴ Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, China.
⁵ School of Health Management, China Medical University, Shenyang, China.
⁶ Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China.
⁷ China Medical University-The Queen's University of Belfast Joint College, China Medical University, Shenyang, China.

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis and a high economic burden for individuals and healthcare resources. Studies of the costs associated with the efficiency of IPF medications are scarce. We aimed to conduct a network meta-analysis (NMA) and cost-effectiveness analysis to identify the optimum pharmacological strategy among all currently available IPF regimens.

Methods: We first performed a systematic review and network meta-analysis. We searched eight databases for eligible randomised controlled trials (RCTs) published, in any language, between January 1, 1992 and July 31, 2022, that investigated the efficacy or tolerability (or both) of drug therapies for the treatment of IPF. The search was updated on February 1, 2023. Eligible RCTs were enrolled, with no restriction on dose, duration, or length of follow-up, if they included at least one of: all-cause mortality, acute exacerbation rate, disease progression rate, serious adverse events, and any adverse events under investigation. A subsequent Bayesian NMA within random-effects models was performed, followed by a cost-effectiveness analysis using the data obtained from our NMA, by developing a Markov model from the US payer's perspective. Assumptions were checked by deterministic and probabilistic sensitivity approaches to identify sensitive factors. We prospectively registered the protocol (CRD42022340590) in PROSPERO.

Findings: 51 publications comprising 12,551 participants with IPF were analysed for the NMA, and the findings indicated that pirfenidone and N-acetylcysteine (NAC) + pirfenidone were the most efficacious and tolerable. The pharmacoeconomic analysis showed that NAC + pirfenidone was associated with the highest potentiality of being cost-effective at willingness-to-pay (WTP) thresholds of US$150,000 and $200,000, on the basis of quality-adjusted life years (QALYs), disability-adjusted life years (DALYs) and mortality, with the probability ranging from 53% to 92%. NAC was the minimum cost agent. Compared with placebo, NAC + pirfenidone improved effectiveness by increasing QALYs by 7.02, and reducing DALYs by 7.10 and deaths by 8.40, whilst raising overall costs by $516,894.

Interpretation: This NMA and cost-effectiveness analysis suggests that NAC + pirfenidone is the most cost-effective option for treatment of IPF at WTP thresholds of $150,000 and $200,000. However, given that clinical practice guidelines have not addressed the application of this therapy, large well-designed and multicentre trials are warranted to provide a better picture of IPF management.

Funding: None.

Keywords: Acute exacerbation; All-cause mortality; Bayesian network meta-analysis; Cost-effectiveness analysis; Drug strategy; Idiopathic pulmonary fibrosis.