The actual use of nintedanib/Vigat in PPF is different from the test environment

Real-world data on the use of the tyrosine kinase inhibitor nintedanib (Nintedanib) demonstrates significant inconsistency between how this therapy is used in clinical practice to treat nonidiopathic pulmonary fibrosis that progresses to progressive pulmonary fibrosis (nonIPF PPF) and how it is used in clinical trials. The report calls for further research to better understand how the therapy performs in the real world.

Nintedanib is approved for the treatment of IPF, chronic progressive interstitial lung disease (ILD) with a progressive phenotype, and systemic sclerosis-related ILD. It is the only antifibrotic drug approved for the treatment of progressive pulmonary fibrosis (PPF) without IPF. However, significant evidence gaps remain for its use in non-IPF PPF.

There are no actual data on the use ofnintedanibin nonIPF PPF. Furthermore, there is a lack of information on the combined use of antifibrotic and immunomodulatory drugs, particularly in PPF patients with CTD-ILD (connective tissue disease ILD). The researchers examined real-world data on the use of nintedanib to see how closely it matched usage patterns in clinical trials. They analyzed all patients treated with non-IPF PFF in 2022 and 2023. A total of 31 patients meeting the inclusion criteria were identified.

Among them,13 cases were diagnosed as CTD-ILD, and 10 cases were diagnosed as fibrotic idiopathic non-specific interstitial pneumonia (iNSIP). Patients in the real-world data set had forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) scores similar to patients in the nintedanib INBUILD clinical trial. In the study, the predominant radiographic pattern in more than half (58%) of the patients was fibrotic NSIP, and only 19% had the common interstitial pneumonia (UIP) pattern. This is significantly different from the INBUILD trial, in which the majority of patients (62.1%) had a UIP pattern.

In their real-world data, there were significant differences in dosage patterns. Of the 30 patients treated with nintedanib, six permanently stopped taking the drug due to side effects. Of the patients who were still on treatment at the end of follow-up and whose dose was known, only half (47%) were taking the full dose of 150 mg twice daily. An additional 10 patients with known doses were given a reduced dose of 100 mg twice daily.

The study had discontinuation rates similar tothe INBUILD trial. However, the proportion of patients taking reduced doses is high due to the relative lack of data on the efficacy of reduced doses. Although there is some real-world evidence supporting its efficacy at lower doses, the topic has not been extensively studied in randomized controlled trials.

However, the largest difference between their patient cohort and those in the INBUILD trial was related to the use of immunomodulatory therapy. In the INBUILD trial, patients treated with one of several immunomodulatory therapies were excluded. In the real-world data set, 87% of patients were taking immunomodulatory drugs.

The relatively high discontinuation rates they saw underscore the need for additional treatment options for patients with non-IPF PPF. They noted that the availability of pirfenidone in patients with IPF provides clinicians and patients with an alternative in the event of side effects or progression.

These findings are limited by the small sample size and the fact that all patients were treated within the same health care system and therefore may not be generalizable to the entire population. The significant differences they saw between real-world use and clinical trials suggest more research is necessary.

Reference: Updated December 1, 2025, https://www.ajmc.com/view/real-world-usage-of-nintedanib-for-ppf-differs-from-trial-settings