Impact of Pharmacological Interventions on Clinical and Humanistic Outcomes in Idiopathic Pulmonary Fibrosis (IPF): A Systematic Literature Review (SLR)

OBJECTIVES: IPF is a chronic, fibrosing interstitial pneumonia with poor prognosis. This SLR aimed to identify evidence for the impact of treatments on clinical and humanistic outcomes in patients with IPF.

METHODS: SLR following Cochrane and PRISMA guidelines conducted from January 2011-September 2023 in Embase, MEDLINE, Cochrane Library supplemented with conference searches.

RESULTS: 31 RCTs were included. In 19 studies, patients were treated with antifibrotic (AF) alone or combination with other agents (sildenafil or N-acetylcysteine). Forced vital capacity (FVC) (N=30), DLCO (N=21), acute exacerbations (AEs) (N=9), hospitalization due to respiratory cause (N=8) and time to death (N=3) were assessed. Mean change from baseline (CFB) in absolute FVC with nintedanib (150mg twice-daily) was –20mL (vs placebo [–109mL]) at 24 weeks (w). At 52w, mean CFB in absolute FVC with AF monotherapies ranged from –51mL (vs placebo [-188mL]) to –227.9mL (vs placebo [-421.9mL]). Mean CFB in absolute FVC was less with nintedanib+pirfenidone (–13.3mL) versus nintedanib alone (–40.9mL) at 12w. Mean CFB in absolute FVC varied across other combination therapies ranging from –80mL (vs pirfenidone [-55mL]) to –142mL (vs N-acetylcysteine [-220mL]) for pirfenidone+N-acetylcysteine at 24w; and was –145mL with pirfenidone+sildenafil (vs pirfenidone [–93mL]) at 52w. Proportion of patients treated with nintedanib reporting AEs was 3.6% (vs placebo [9.6%]) and 6.1% (vs placebo [5.4%]) at 52w. Proportion of patients experiencing adverse events at 52w were similar between AF monotherapies (90.7%-96.6%) and placebo (88.7%- 90.6%). Respiratory related death rate (52w) ranged from 1%-17% with AF monotherapies and 2.5%-9.4% with placebo. 23 studies assessed HRQoL using SGRQ, SoBQ, EQ-5D, L-PF, MRC, HADS, CAT, and CASA-Q. No meaningful improvement in HRQoL was observed following treatment.

CONCLUSIONS: Results suggest a high unmet need remains for a well-tolerated treatment option for IPF patients. Whilst current AF slow down the decline in lung function, limited impact is observed on HRQoL.