Real-World Usage of Nintedanib for PPF Differs From Trial Settings

Real-world data on usage of the tyrosine kinase inhibitor nintedanib (Ofev; Boehringer Ingelheim) suggest there is significant dissonance between how the therapy is being used to treat non–idiopathic pulmonary fibrosis that has progressed to progressive pulmonary fibrosis (non-IPF PPF) in clinical practice and how it was used in clinical trials.¹

The report, published in BMJ Open, suggests additional research is needed to better understand how the therapy performs in real-world practice.

Nintedanib is approved to treat IPF, chronic progressive interstitial lung diseases (ILDs) with a progressive phenotype, and systemic sclerosis-associated ILD. The study authors noted that it is the only antifibrotic approved for the treatment of non-IPF progressive pulmonary fibrosis (PPF). Yet, they explained that significant evidentiary gaps remain related to its usage in non-IPF PPF.

“To our knowledge, there is no real-life data on the use of nintedanib in non-IPF PPF,” they explained. “Additionally, there is a lack of information regarding the combined use of antifibrotic and immunomodulatory drugs, particularly in patients with PPF in CTD-ILD (connective tissue disease-ILD).”

The investigators examined real-world data for nintedanib usage to see how closely it aligned with usage patterns in clinical trials. They analyzed all patients who were treated for non-IPF PFF at the Hospital District of Helsinki and Uusimaa in Finland in 2022 and 2023. A total of 31 patients were identified who met inclusion criteria.

Of those, 13 patients were diagnosed with CTD-ILD, and 10 patients were diagnosed with fibrotic idiopathic non-specific interstitial pneumonia (iNSIP). Patients in the real-world data set had forced vital capacities (FVCs) and diffusion capacities for carbon monoxide (DLCO) scores that were similar to the patients in the INBUILD clinical trial of nintedanib.

“However, in our study, the predominant radiological pattern was fibrotic NSIP in more than half (58%) of the patients, and only 19% had a usual interstitial pneumonia (UIP) pattern,” the investigators said. “This differs markedly from the INBUILD trial, in which most patients (62.1%) had a UIP pattern.”²

The authors also found significant differences in dosage patterns in their real-world data.¹ Of the 30 patients who received nintedanib, 6 permanently stopped taking the drug due to side effects. And only half (47%) of the patients who were still taking the therapy at the end of follow-up and for whom dosage was known were taking the full dose of 150 mg twice daily. The other 10 patients for whom dosage was known were taking a reduced dose of 100 mg twice daily.

The discontinuation rate in the study was similar to the INBUILD trial. However, the high rate of patients taking a reduced dose is notable because of the relative lack of data on the efficacy of reduced doses. The topic has not been extensively studied in randomized controlled trials, the authors noted, though there is some real-world evidence supporting its efficacy at lower doses.³

The authors said, however, that the biggest difference between their patient cohort and the patients in the INBUILD trial has to do with the use of immunomodulatory treatments.¹ In the INBUILD trial, patients who were treated with one of several immunomodulatory therapies were excluded. In the real-world data set, 87% of patients were taking immunomodulatory drugs.

The investigators added that the relatively high rate of discontinuation they saw underscores the need for additional treatment options for patients with non-IPF PPF. They noted that in patients with IPF, the availability of pirfenidone gives clinicians and patients an alternative in cases where side effects or progression occur.

The findings were limited by the small sample size and the fact that all of the patients were treated in the same health care system, the authors noted, and therefore they may not be generalizable to all populations. They said the significant differences they saw between real-world usage and clinical trials show that more studies are warranted.

References

1. Renner A, Vertanen E, Sutinen E, Ainola M, Myllärniemi M, Hollmén M. Characterisation of patients with antifibrotic-treated non-idiopathic pulmonary fibrosis progressive pulmonary fibrosis: a retrospective real-life study. BMJ Open. 2025;15(11):e097246. doi:10.1136/bmjopen-2024-097246
2. Flaherty KR, Cottin V, Devaraj A, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381(18):1718-1727. doi:10.1056/NEJMoa1908681.
3. Porse S, Hoyer N, Shaker SB. Impact of reduction in antifibrotic treatment on mortality in idiopathic pulmonary fibrosis. Respir Med. 2022;204:107015. doi:10.1016/j.rmed.2022.107015