Add-on therapy for pulmonary fibrosis, a forthcoming era with implications for practice: the BI 101550 and RELIEF trials

The therapeutic landscape for idiopathic pulmonary fibrosis (IPF) and progressive fibrosing interstitial lung disease (PFILD) is increasingly complex, with add-on antifibrotic options now in clinical trials, or available for patients progressing on first-line therapy in both conditions. Here, we review two recent trials of potential add-on therapeutic options, the BI 101550 and RELIEF trials. BI 101550 was a phase 2 randomised control trial (RCT) of a novel phosphodiesterase-4 inhibitor in patients with IPF, with a primary end-point of change in forced vital capacity (ΔFVC) (in mL) at 12 weeks. The RELIEF trial was a phase 2 RCT in patients with PFILD, with a primary end-point of ΔFVC (absolute % predicted) over 48 weeks. Whilst the BI 101550 and RELIEF trials showed positive results in their primary end-points, the strengths and weaknesses of both trials are discussed with importance for their interpretation and clinical impact. We review current clinical practice in IPF and PFILD and place the BI101550 and RELIEF trial results in context, highlighting advances and problems with antifibrotic therapies. COMMENTARY ON: Richeldi L, et al. Trial of a preferential phosphodiesterase 4B inhibitor for idiopathic pulmonary fibrosis. N Engl J Med 2022; 386: 2178–2187. Behr J, et al. Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF): a double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Respir Med 2021; 9: 476–486.