Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis: Results of two 52-week, Phase III, randomized, placebo-controlled trials (INPULSIS™)
Bibliographic record
Abstract
Background: Nintedanib (formerly known as BIBF 1120) is an intracellular inhibitor that targets multiple tyrosine kinases. Methods: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 [NCT01335464] and INPULSIS-2 [NCT01335477]) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis (IPF). The primary end point was the annual rate of decline in forced vital capacity (FVC). Key secondary end points were the time to the first acute exacerbation and the change from baseline in the total score on the St. George's Respiratory Questionnaire, both assessed over a 52-week period. Results: A total of 1066 patients were randomly assigned in a 3:2 ratio to receive nintedanib or placebo. The adjusted annual rate of change in FVC was –114.7 ml with nintedanib versus –239.9 ml with placebo (difference, 125.3 ml; 95% confidence interval [CI], 77.7 to 172.8; p < 0.001) in INPULSIS-1 and –113.6 ml with nintedanib versus –207.3 ml with placebo (difference, 93.7 ml; 95% CI, 44.8 to 142.7; p < 0.001) in INPULSIS-2. In INPULSIS-2, there was a significant benefit with nintedanib in the time to the first acute exacerbation versus placebo (hazard ratio (HR), 0.38; 95% CI, 0.19 to 0.77; P= 0.005); in INPULSIS-1, no significant difference was found (HR, 1.15; 95% CI, 0.54 to 2.42; P= 0.67); The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% (nintedanib vs. placebo) in INPULSIS-1 as well as 63.2% and 18.3% in INPULSIS-2, respectively. Conclusions: In patients with IPF, nintedanib significantly reduced the decline in FVC by approximately 50%, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients. Presented at ATS 2014
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.004 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.004 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".