• Luca Richeldi, Arata Azuma, Vincent Cottin, Christian Hesslinger, Susanne Stowasser, Claudia Valenzuela, Marlies S Wijsenbeek, Donald F Zoz, Florian Voss, Toby M Maher, and 1305-0013 Trial Investigators.
• From Unità Operativa Complessa di Pneumologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome (L.R.); Nippon Medical School, Tokyo (A.A.); Hôpital Louis Pradel, Centre National de Référence des Maladies Pulmonaires Rares, Hospices Civils de Lyon, Unité Mixte de Recherche 754 Institut National de la Recherche Agronomique and Université Claude Bernard Lyon 1, ERN-LUNG (European Reference Network on Rare Respiratory Diseases), RespiFil, OrphaLung, Lyon, France (V.C.); Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim International, Biberach (C.H.), and TA Inflammation Medicine (S.S.), Boehringer Ingelheim Pharma (F.V.), Ingelheim am Rhein - both in Germany; the Interstitial Lung Disease Unit, Department of Pulmonology, Hospital Universitario de la Princesa, University Autonoma de Madrid, Madrid (C.V.); the Department of Respiratory Medicine, Erasmus Medical Center, Rotterdam, the Netherlands (M.S.W.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (D.F.Z.); Keck School of Medicine, University of Southern California, Los Angeles (T.M.M.); and the National Heart and Lung Institute, Imperial College London, London (T.M.M.).
• N. Engl. J. Med. 2022 Jun 9; 386 (23): 2178-2187.

BackgroundPhosphodiesterase 4 (PDE4) inhibition is associated with antiinflammatory and antifibrotic effects that may be beneficial in patients with idiopathic pulmonary fibrosis.MethodsIn this phase 2, double-blind, placebo-controlled trial, we investigated the efficacy and safety of BI 1015550, an oral preferential inhibitor of the PDE4B subtype, in patients with idiopathic pulmonary fibrosis. Patients were randomly assigned in a 2:1 ratio to receive BI 1015550 at a dose of 18 mg twice daily or placebo. The primary end point was the change from baseline in the forced vital capacity (FVC) at 12 weeks, which we analyzed with a Bayesian approach separately according to background nonuse or use of an antifibrotic agent.ResultsA total of 147 patients were randomly assigned to receive BI 1015550 or placebo. Among patients without background antifibrotic use, the median change in the FVC was 5.7 ml (95% credible interval, -39.1 to 50.5) in the BI 1015550 group and -81.7 ml (95% credible interval, -133.5 to -44.8) in the placebo group (median difference, 88.4 ml; 95% credible interval, 29.5 to 154.2; probability that BI 1015550 was superior to placebo, 0.998). Among patients with background antifibrotic use, the median change in the FVC was 2.7 ml (95% credible interval, -32.8 to 38.2) in the BI 1015550 group and -59.2 ml (95% credible interval, -111.8 to -17.9) in the placebo group (median difference, 62.4 ml; 95% credible interval, 6.3 to 125.5; probability that BI 1015550 was superior to placebo, 0.986). A mixed model with repeated measures analysis provided results that were consistent with those of the Bayesian analysis. The most frequent adverse event was diarrhea. A total of 13 patients discontinued BI 1015550 treatment owing to adverse events. The percentages of patients with serious adverse events or severe adverse events were similar in the two trial groups.ConclusionsIn this placebo-controlled trial, treatment with BI 1015550, either alone or with background use of an antifibrotic agent, prevented a decrease in lung function in patients with idiopathic pulmonary fibrosis. (Funded by Boehringer Ingelheim; 1305-0013 ClinicalTrials.gov number, NCT04419506.).Copyright © 2022 Massachusetts Medical Society.

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