Trial of a Preferential Phosphodiesterase 4B Inhibitor for Idiopathic Pulmonary Fibrosis
Open accessAbstract
BACKGROUND: Phosphodiesterase 4 (PDE4) inhibition is associated with antiinflammatory and antifibrotic effects that may be beneficial in patients with idiopathic pulmonary fibrosis. METHODS: In 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. RESULTS: A 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. CONCLUSIONS: In 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.).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A 12-week study is a relatively short time frame to capture long-term disease events or trajectory.
“however, a 12-week study is a relatively short time frame to capture such long-term disease events or trajectory44.”
From A generative AI-discovered TNIK inhibitor for idiopathic pulmonary fibrosis: a randomized phase 2a trial (2025) · cites this paper as [44]
A phase II clinical trial in 147 patients with IPF indicated that nerandomilast stabilises lung function compared with placebo within 12 weeks while showing acceptable tolerability and safety.
“A phase II clinical trial in 147 patients with IPF indicated that nerandomilast stabilises lung function compared with placebo within 12 weeks of treatment while showing acceptable tolerability and safety (Richeldi et al., 2022).”
From PDE4B inhibition by nerandomilast: Effects on lung fibrosis and transcriptome in fibrotic rats and on biomarkers in human lung epithelial cells (2024) · cites this paper as Richeldi et al., 2022
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 25 · Cited by 236
Research works printed but not linked: 20
- Wong AW, Ryerson CJ, Guler SA. Pro- gression of fibrosing interstitial lung dis- ease. Respir Res 2020; 21: 32.
- Richeldi L, Costabel U, Selman M, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med 2011; 365: 1079-87.
- Noble PW, Albera C, Bradford WZ, et al. Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials. Eur Respir J 2016; 47: 243-53.
- Sisson TH, Christensen PJ, Muraki Y, et al. Phosphodiesterase 4 inhibition re- duces lung fibrosis following targeted type II alveolar epithelial cell injury. Physiol Rep 2018; 6(12): e13753.
- Phillips JE. Inhaled phosphodiester- ase 4 (PDE4) inhibitors for inflammatory respiratory diseases. Front Pharmacol 2020; 11: 259.
- Matsuhira T, Nishiyama O, Tabata Y, et al. A novel phosphodiesterase 4 inhibi- tor, AA6216, reduces macrophage activity and fibrosis in the lung. Eur J Pharmacol 2020; 885: 173508.
- Ti H, Zhou Y, Liang X, Li R, Ding K, Zhao X. Targeted treatments for chronic obstructive pulmonary disease (COPD) us- ing low-molecular-weight drugs (LMWDs). J Med Chem 2019; 62: 5944-78.
- Schmidli H, Gsteiger S, Roychoud- hury S, O'Hagan A, Spiegelhalter D, Neuenschwander B. Robust meta-analyt- ic-predictive priors in clinical trials with historical control information. Biomet- rics 2014; 70: 1023-32.
- Neuenschwander B, Capkun-Niggli G, Branson M, Spiegelhalter DJ. Summa- rizing historical information on controls in clinical trials. Clin Trials 2010; 7: 5-18.
- Maher TM, Stowasser S, Nishioka Y, et al. Biomarkers of extracellular matrix turn- over in patients with idiopathic pulmonary fibrosis given nintedanib (INMARK study): a randomised, placebo-controlled study. Lancet Respir Med 2019; 7: 771-9.
- Kolb M, Raghu G, Wells AU, et al. Nintedanib plus sildenafil in patients with idiopathic pulmonary fibrosis. N Engl J Med 2018; 379: 1722-31.
- Lancaster L, Goldin J, Trampisch M, et al. Effects of nintedanib on quantitative lung fibrosis score in idiopathic pulmo- nary fibrosis. Open Respir Med J 2020; 14: 22-31.
- Vancheri C, Kreuter M, Richeldi L, et al. Nintedanib with add-on pirfenidone in idiopathic pulmonary fibrosis: results of the INJOURNEY trial. Am J Respir Crit Care Med 2018; 197: 356-63.
- Herrmann FE, Hesslinger C, Wollin S-L, Nickolaus P. BI 1015550 is a PDE4B inhibitor and a clinical drug candidate for the oral treatment of idiopathic pulmo- nary fibrosis. Front Pharmacol 2022; 13: 838449 (https://www . frontiersin . org/ articles/ 10 . 3389/ fphar . 2022 . 838449/ full). · DOI
- Raghu G, Remy-Jardin M, Myers J, Richeldi L, Wilson KC. The 2018 diag- nosis of idiopathic pulmonary fibrosis guidelines: surgical lung biopsy for ra- diological pattern of probable usual in- terstitial pneumonia is not mandatory. Am J Respir Crit Care Med 2019; 200: 1089-92.
- Macintyre N, Crapo RO, Viegi G, et al. Standardisation of the single-breath de- termination of carbon monoxide uptake in the lung. Eur Respir J 2005; 26: 720- 35.
- Swigris J, Cutts K, Male N, Baldwin M, Rohr KB, Bushnell DM. The Living with Pulmonary Fibrosis questionnaire in progressive fibrosing interstitial lung dis- ease. ERJ Open Res 2021; 7: 00145-2020.
- Cazzola M, Calzetta L, Rogliani P, Matera MG. The discovery of roflumilast for the treatment of chronic obstructive pulmonary disease. Expert Opin Drug Discov 2016; 11: 733-44.
- Khan FA, Stewart I, Moss S, et al. Three-month FVC change: a trial end- point for IPF based on individual partici- pant data meta-analysis. Am J Respir Crit Care Med 2022; 205: 936-48.
- Dietsch GN, Dipalma CR, Eyre RJ, et al. Characterization of the inflamma- tory response to a highly selective PDE4 inhibitor in the rat and the identification of biomarkers that correlate with toxicity. Toxicol Pathol 2006; 34: 39-51.
- Authors
- Richeldi, L., Azuma, A., Cottin, V., Hesslinger, C., Stowasser, S., Valenzuela, C., Wijsenbeek, M. S., Zoz, D. F., Voss, F., & Maher, T. M.
- Affiliations
- Lyon 1 Université (FR)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2022-06-09
- Volume
- 386
- Issue
- 23
- Pages
- 2178-2187
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W4280599153
- Cited by
- 236
- References
- 25
- Citations by year
- 2026: 36 · 2025: 64 · 2024: 65 · 2023: 58 · 2022: 13
- FWCI
- 32.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- HAL (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by-nd)
- Use Siena air (University of Siena) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Boehringer Ingelheim (N/A)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Keywords
- idiopathic pulmonary fibrosis, forced vital capacity, antifibrotic agents, drug safety, diarrhea, Bayesian analysis, antifibrotic therapy, drug repurposing, anti-inflammatory therapy
- MeSH terms
- Bayes Theorem, Double-Blind Method, Humans, Phosphodiesterase Inhibitors, Vital Capacity, Treatment Outcome, Cyclic Nucleotide Phosphodiesterases, Type 4, Idiopathic Pulmonary Fibrosis, Phosphodiesterase 4 Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
