What is the treatment for interstitial fibrosis?

Treatment of Interstitial Fibrosis

For patients with interstitial fibrosis, pirfenidone and nintedanib are the primary antifibrotic medications that can slow disease progression, with treatment selection based on the specific type of interstitial fibrosis and disease progression pattern. 1

Treatment Options for Idiopathic Pulmonary Fibrosis (IPF)

First-line Treatments

• Pirfenidone is recommended for mild-to-moderate IPF, as it has shown significant effects on progression-free survival (PFS) and can reduce the risk of disease progression by 30% compared to placebo 1
• Nintedanib is an alternative first-line option that has demonstrated efficacy in slowing the decline in forced vital capacity (FVC) in patients with IPF 1
• Both medications work by targeting the fibrotic process rather than inflammation 1

Previously Used Treatments (No Longer Recommended)

• The previously widely accepted triple therapy of corticosteroids, azathioprine, and N-acetylcysteine (NAC) is no longer appropriate for IPF treatment 1
• The PANTHER-IPF study demonstrated increased risk of death and hospitalizations with triple therapy, leading to early termination of that study arm 1
• Strong recommendations against using combination therapy with prednisone, azathioprine and NAC for patients with definite IPF 1

Treatment for Progressive Pulmonary Fibrosis (PPF) in Non-IPF Conditions

Connective Tissue Disease-Related Interstitial Lung Disease (CTD-ILD)

• For systemic autoimmune rheumatic disease-related ILD (SARD-ILD) progression despite first-line treatment, nintedanib is conditionally recommended 1
• For rheumatoid arthritis-related ILD (RA-ILD) progression, both nintedanib and pirfenidone are conditionally recommended 1
• For systemic sclerosis-related ILD (SSc-ILD), nintedanib is conditionally recommended as a first-line treatment option 1
• Glucocorticoids are conditionally recommended for SARD-ILD other than SSc-ILD as first-line treatment, but strongly recommended against for SSc-ILD 1

Immunomodulatory Options

• For SARD-ILD, mycophenolate, azathioprine, rituximab, and cyclophosphamide are conditionally recommended as first-line ILD treatment options 1
• For inflammatory myopathy-related ILD (IIM-ILD), JAK inhibitors and calcineurin inhibitors are conditionally recommended as first-line options 1
• For SSc-ILD and mixed connective tissue disease-related ILD (MCTD-ILD), tocilizumab is conditionally recommended as a first-line option 1

Evidence for Antifibrotic Medications

Pirfenidone

• Pirfenidone has been evaluated in multiple phase 3 trials (CAPACITY studies and Japanese SP3 trial) showing efficacy in reducing FVC decline in IPF 1, 2
• In Study 1, pirfenidone reduced mean FVC decline by 193 mL compared to placebo over 52 weeks 2
• The RELIEF trial suggested that pirfenidone may attenuate disease progression in non-IPF progressive fibrotic ILDs, though the study was terminated early due to slow recruitment 3
• Common side effects include nausea, anorexia, and photosensitivity dermatitis 4

Nintedanib

• Nintedanib has demonstrated efficacy in slowing disease progression in both IPF and non-IPF interstitial lung diseases 5
• For progressive pulmonary fibrosis in non-IPF conditions, nintedanib has stronger evidence from well-designed trials compared to pirfenidone 5

Practical Approach to Management

Diagnosis and Monitoring

• High-resolution computed tomography (HRCT) is essential for diagnosis and monitoring of interstitial fibrosis 1
• Pulmonary function tests (PFTs) should be performed every 3-6 months to monitor disease progression 1
• For mild CTD-ILD (FVC ≥70% and <20% fibrosis extent on HRCT), PFTs should be scheduled every 6 months for the first 1-2 years 1
• Patients with moderate-to-severe ILD or progressive disease require more frequent PFTs (every 3-6 months) 1

Treatment Decision Algorithm

1. Identify the specific type of interstitial fibrosis (IPF vs. non-IPF)
2. Assess disease severity and progression pattern
3. For IPF: Start with pirfenidone or nintedanib 1
4. For non-IPF progressive fibrotic ILD:
   • For CTD-ILD: Consider immunomodulatory therapy first, then add antifibrotic therapy if progression occurs 1
   • For RA-ILD with progression: Consider adding pirfenidone or nintedanib 1
   • For SSc-ILD: Consider nintedanib as first-line or tocilizumab for early disease 1

Important Considerations

• Early identification of progressive pulmonary fibrosis is critical for timely initiation of antifibrotic therapy 1, 6
• The usual interstitial pneumonia (UIP) pattern in RA-ILD is associated with poor prognosis and requires careful evaluation 1
• Multidisciplinary collaboration between pulmonologists, rheumatologists, radiologists, and pathologists is essential for optimal management 1

Treatment Efficacy and Expectations

• Antifibrotic therapies slow disease progression rather than reverse existing fibrosis 6
• The decline in FVC appears to be almost linear in IPF patients, with similar rates of decline regardless of baseline FVC 6
• While individual trials were not powered to show mortality benefits, pooled analyses and observational studies suggest improved life expectancy with antifibrotic therapies 6