"Nintedanib for Idiopathic Pulmonary Fibrosis". The New England Journal of Medicine. 2014. 370(22):2071-2082. PubMed • Full text • PDF

Contents

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcomes
8.2 Secondary Outcome
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

Does nintedanib, a multiple tyrosine kinase inhibitor, slow the progression of idiopathic pulmonary fibrosis?

Bottom Line

Nintedanib reduced the annual rate of decline in forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis.

Major Points

Idiopathic pulmonary fibrosis is a chronic, progressive lung disease with limited treatment options, characterized by a decline in lung function and quality of life. The INPULSIS trials were two replicate phase 3 studies that demonstrated that nintedanib significantly reduced the rate of decline in FVC over a 52-week treatment period in patients with idiopathic pulmonary fibrosis, suggesting a slowing of disease progression.

Guidelines

As of the latest updates, these trials have contributed to nintedanib being included in clinical guidelines as a treatment option for idiopathic pulmonary fibrosis.

Design

- Two replicate 52-week, randomized, double-blind, placebo-controlled phase 3 trials (INPULSIS-1 and INPULSIS-2).
- N=1066 patients were randomly assigned in a 3:2 ratio to receive nintedanib or placebo.
- Intervention: 150 mg of nintedanib twice daily.

Population

- Participants were 40 years or older with a diagnosis of idiopathic pulmonary fibrosis within the last 5 years.
- Patients required an FVC of ≥50% and a diffusion capacity of the lungs for carbon monoxide (DLCO) of 30-79%.
- High-resolution computed tomography (HRCT) was performed within 12 months prior to trial.

Inclusion Criteria
- Age ≥40 years
- Diagnosis of idiopathic pulmonary fibrosis within previous 5 years
- FVC ≥50% of predicted value
- DLCO 30-79% of the predicted value

Exclusion Criteria
- Prednisone >15 mg/day (or equivalent)
- Investigational treatments for idiopathic pulmonary fibrosis
- Recent surgical lung biopsy incompatible with idiopathic pulmonary fibrosis

Baseline Characteristics
- Similar across intervention and placebo groups in each trial.

Interventions

- Nintedanib 150 mg twice daily or placebo for 52 weeks.

Outcomes

Primary Outcomes
- Adjusted annual rate of decline in FVC
INPULSIS-1: −114.7 ml (nintedanib) vs. −239.9 ml (placebo); difference: 125.3 ml, P<0.001
INPULSIS-2: −113.6 ml (nintedanib) vs. −207.3 ml (placebo); difference: 93.7 ml, P<0.001

Secondary Outcome
- Time to first acute exacerbation
INPULSIS-1: No significant difference (HR 1.15; P=0.67)
INPULSIS-2: Significant benefit (HR 0.38; P=0.005)
- Change from baseline in SGRQ score
INPULSIS-1 and INPULSIS-2: Inconsistent significant differences
- Diarrhea was the most common adverse event associated with nintedanib.

Criticisms

- Not applicable for the summary format.

Funding

- Funded by Boehringer Ingelheim.
- Some authors reported receiving various fees from pharmaceutical companies.

Further Reading

- The article link provided in the reference leads to the full text article and supplementary materials.