Safety and survival data in patients with idiopathic pulmonary fibrosis treated with nintedanib: pooled data from six clinical trials
Open accessAbstract
Introduction: Nintedanib slows disease progression in patients with idiopathic pulmonary fibrosis (IPF) by reducing the rate of decline in forced vital capacity, with an adverse event profile that is manageable for most patients. We used data from six clinical trials to characterise the safety and tolerability profile of nintedanib and to investigate its effects on survival. Methods: Data from patients treated with ≥1 dose of nintedanib 150 mg two times per day or placebo in the 52-week TOMORROW trial and/or its open-label extension; the two 52-week INPULSIS trials and/or their open-label extension, INPULSIS-ON; and a Phase IIIb trial with a placebo-controlled period of ≥6 months followed by open-label nintedanib were pooled. All adverse events, irrespective of causality, were included in descriptive analyses. Parametric survival distributions were fit to pooled Kaplan-Meier survival data from the trials and extrapolated to estimate long-term survival. Results: There were 1126 patients in the pooled nintedanib group and 565 patients in the pooled placebo group. The mean duration of nintedanib treatment was 28 months. No new safety signals were observed. Incidence rates of bleeding, liver enzyme elevations and cardiovascular events were consistent with those observed in the INPULSIS trials. Diarrhoea was reported at a lower event rate in the pooled nintedanib group than in nintedanib-treated patients in the INPULSIS trials (76.5 vs 112.6 events per 100 patient exposure-years) and infrequently led to permanent treatment discontinuation (3.6 events per 100 patient exposure-years). Based on the Weibull distribution, mean (95% CI) survival was estimated as 11.6 (9.6, 14.1) years in nintedanib-treated patients and 3.7 (2.5, 5.4) years in placebo-treated patients. Conclusions: Based on pooled data from six clinical trials, the adverse event profile of nintedanib was manageable for most patients. Exploratory analyses based on extrapolation of survival data suggest that nintedanib extends life expectancy in patients with IPF.
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Pirfenidone and nintedanib have been shown to slow disease progression and improve transplant-free survival, but neither halts disease worsening.
“While both drugs have been shown to slow disease progression and improve transplant-free survival, neither halts disease worsening.1-5”
From Deupirfenidone Compared with Pirfenidone and Placebo in Idiopathic Pulmonary Fibrosis (ELEVATE-IPF): a Phase 2b Randomized Placebo-Controlled Trial (2026) · cites this paper as [5]
The Introduction says nintedanib slows disease progression by reducing the rate of FVC decline, rather than halting it. The Results and Discussion suggest longer survival with nintedanib based on extrapolated estimates, but do not establish improved transplant-free survival. The paper does not provide corresponding evidence for pirfenidone. (LLM, conf=0.88)
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Self-citation
- Authors
- Lancaster, L., Crestani, B., Hernandez, P., Inoue, Y., Wachtlin, D., Loaiza, L., Quaresma, M., Stowasser, S., & Richeldi, L.
- Affiliations
- Vanderbilt University Medical Center (US)
- Assistance Publique – Hôpitaux de Paris (FR)
- Queen Elizabeth II Health Sciences Centre (CA)
- NHO Kinki Chuo Chest Medical Center (JP)
- Boehringer Ingelheim (Germany) (DE)
- Università Cattolica del Sacro Cuore (IT)
- Corresponding author
- Lancaster, Lisa
- ORCID
- Venue
- BMJ Open Respiratory Research
- Publisher
- BMJ
- Published
- 2019-03
- Volume
- 6
- Issue
- 1
- Pages
- e000397
- ISSN
- 2052-4439 (ISSN-L)
- PMC
- PMC6530503
- OpenAlex
- W2923176155
- Cited by
- 209
- References
- 27
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 21 · 2023: 28 · 2022: 31 · 2021: 44 · 2020: 42 · 2019: 9
- FWCI
- 23.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- BMJ Open Respiratory Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, other-oa)
- Funders
- Boehringer Ingelheim
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Keywords
- idiopathic pulmonary fibrosis, nintedanib, drug safety, tolerability, survival, adverse events, hemorrhage, elevated liver enzymes, cardiovascular events, diarrhea, disease progression, forced vital capacity
- MeSH terms
- Aged, Clinical Trials as Topic, Female, Humans, Indoles, Male, Middle Aged, Survival Rate, Protein Kinase Inhibitors, Idiopathic Pulmonary Fibrosis
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