What are the clinical aspects of Idiopathic Pulmonary Fibrosis (IPF)?

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Dainyal Siddiqui, MD

Internal Medicine

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Manuel Jimenez, MD

Cardiology

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Franz Pierre-Louis, MD

Infectious Disease

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Last updated: May 12, 2025 • View editorial policy

From the Guidelines

Idiopathic pulmonary fibrosis (IPF) should be managed with a combination of pharmacological and nonpharmacological therapies, including nintedanib and pirfenidone, oxygen supplementation, and pulmonary rehabilitation, as outlined in the 2022 ATS/ERS/JRS/ALAT clinical practice guideline 1. The clinical management of IPF involves a multifaceted approach, considering both treatment of the disease itself and management of associated comorbidities.

  • Key aspects of IPF management include: + Pharmacological therapies: nintedanib and pirfenidone are recommended as antifibrotic medications to slow disease progression 1. + Nonpharmacological therapies: oxygen supplementation and pulmonary rehabilitation are essential for improving symptoms and quality of life 1. + Comorbidity management: patients should be evaluated and treated for existing comorbidities, such as pulmonary hypertension, gastroesophageal reflux, obstructive sleep apnea, and lung cancer 1. + Palliative care: involvement of palliative care can help with symptom management, including cough, dyspnea, and anxiety 1. + Regular monitoring: patients should be evaluated every 3-6 months or more often for disease progression, and acute exacerbations may be treated with corticosteroids 1. + Lung transplantation: patients at increased risk of mortality should be referred for lung transplantation at diagnosis 1. The goal of IPF management is to improve quality of life, slow disease progression, and reduce morbidity and mortality, as outlined in the 2022 ATS/ERS/JRS/ALAT clinical practice guideline 1.

From the FDA Drug Label

The efficacy of pirfenidone was evaluated in patients with IPF in three phase 3, randomized, double-blind, placebo-controlled, multicenter trials (Studies 1, 2, and 3). Study 1 was a 52-week trial comparing pirfenidone 2,403 mg/day (n=278) versus placebo (n=277) in patients with IPF Study 2 and Study 3 were nearly identical to each other in design, with few exceptions, including an intermediate dose treatment arm in Study 2. Study 2 compared treatment with either pirfenidone 2,403 mg/day (n=174) or pirfenidone 1,197 mg/day (n=87) to placebo (n=174), while Study 3 compared pirfenidone 2,403 mg/day (n=171) to placebo (n=173) The primary endpoint was the change in percent predicted forced vital capacity (%FVC) from baseline to study end, measured at 52 weeks in Study 1, and at 72 weeks in Studies 2 and 3 In all three trials, over 80% of patients completed study treatment A total of 1,247 patients with IPF were randomized to receive pirfenidone 2,403 mg/day (n=623) or placebo (n=624) in these three trials. Baseline characteristics were generally balanced across treatment groups. The study population ranged from 40 to 80 years of age (mean age 67 years). Most patients were male (74%), white (95%), and current or former smokers (65%) Approximately 93% of patients met criteria for definite IPF on high resolution computed tomography (HRCT). Baseline mean %FVC and %DLCO were 72% and 46%, respectively. Approximately 15% subjects discontinued from each treatment group Change from Baseline in Percent Predicted Forced Vital Capacity In Study 1, the primary efficacy analysis for the change in %FVC from baseline to Week 52 demonstrated a statistically significant treatment effect of pirfenidone 2,403 mg/day (n=278) compared with placebo (n=277) using a rank ANCOVA with the lowest rank imputation for missing data due to death In Study 2, there was a statistically significant difference at Week 72 for the change in %FVC from baseline. In Study 3, there was no statistically significant difference at Week 72 for the change in %FVC from baseline.

The clinical aspects of IPF addressed in the studies include:

  • Patient demographics: The study population ranged from 40 to 80 years of age (mean age 67 years), with most patients being male (74%), white (95%), and current or former smokers (65%).
  • Disease severity: Approximately 93% of patients met criteria for definite IPF on high resolution computed tomography (HRCT), with baseline mean %FVC and %DLCO being 72% and 46%, respectively.
  • Treatment efficacy: Pirfenidone 2,403 mg/day demonstrated a statistically significant treatment effect in reducing the decline in %FVC from baseline to study end in Study 1 and Study 2, but not in Study 3.
  • Survival: All-cause mortality did not show a statistically significant difference between pirfenidone and placebo in Studies 1, 2, and 3 2. Key clinical findings include:
  • A reduction in the mean decline in FVC (in mL) was observed in patients receiving pirfenidone 2,403 mg/day compared to placebo in Study 1 and Study 2.
  • The proportion of patients declining in lung function was lower on pirfenidone than on placebo in Study 1 and Study 2.

From the Research

Clinical Aspects of Idiopathic Pulmonary Fibrosis (IPF)

  • IPF is a chronic, progressive, fibrosing interstitial lung disease characterized by progressive scarring of the lung and associated with a high burden of disease and early death 3.
  • The pathogenesis of IPF is believed to involve repeated lung injury and abnormal wound repair, although the exact mechanisms are not fully understood 4.

Diagnosis and Treatment

  • Antifibrotic therapy with nintedanib or pirfenidone slows disease progression and reduces mortality in patients with IPF 5, 6.
  • Patients with advanced IPF, defined by forced vital capacity (FVC) < 50% and/or diffusion capacity for carbon monoxide (DLCO) < 30% of predicted, have poorer transplant-free survival and progression- and transplant-free survival compared to those with mild-moderate IPF 5.
  • Real-world studies have shown that pirfenidone and nintedanib are effective in slowing down the decline of lung function in IPF patients, with a lower incidence of adverse events compared to clinical trial data 7.

Prognosis and Mortality

  • The average life expectancy of untreated patients with IPF is only 3 to 4 years 6.
  • Antifibrotic therapies have been shown to improve life expectancy, although individual clinical trials have not been powered to show reductions in mortality 6.
  • Mortality rates and acute exacerbation of IPF incidence rates in real-world settings are higher than those in previous clinical trials, with pirfenidone patients showing a higher mortality rate 7.

Future Directions

  • Several clinical phase I-III trials are focusing on novel therapeutic targets, and new approaches in nonpharmacological treatments aim to improve symptom control and quality of life 3, 4.
  • Further large-sample studies are needed to investigate the risks and benefits of antifibrotic therapies in IPF patients, including stratified analyses based on factors such as patients' baseline lung function, comorbidities, and age 7.

References

3
Research

The therapy of idiopathic pulmonary fibrosis: what is next?

European respiratory review : an official journal of the European Respiratory Society, 2019

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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