Treatment of idiopathic pulmonary fibrosis

The management of cryptogenic fibrosing alveolitis may include:

• pulmonary rehabilitation
  
• corticosteroid therapy - there has been no placebo - controlled trial to show corticosteroids improve survival; however there is evidence that symptoms improve in half of treated patients, and there is improvement in lung function in one quarter (2). The dose regimens have varied widely between studies. No trials using corticosteroids have been undertaken
• other immunosuppressive therapy - drugs such as cyclophosphamide and azathioprine have been used as a steroid sparing agents; combination therapy witih prednisolone and azathioprine can be initiated (3). If monitoring tests are improved or stable then the corticosteroids should be slowly reduced and a maintenance dose continued for at least one year
  • NICE guidance suggests that corticosteroids and other listed therapies should not be used as disease-modifying interventions (5)
  • however others (6) state that in an acute exacerbation of idiopathic pulmonary fibrosis, then this usually treated with corticosteroids with the possible addition of other immunosuppressive agents despite a lack of clear data to suggest any therapy is beneficial
• lung transplantation – see menu item
• antifibrotic agents:
  • pirfenidone is an immunosuppressant that is thought to have anti-inflammatory and antifibrotic effects
    • mechanism of action is not fully understood but it is likely that pirfenidone exerts its effects by suppressing fibroblast proliferation, reducing the production of fibrosis-associated proteins and cytokines and reducing the response to growth factors such as transforming growth factor-beta and platelet-derived growth factor
    • NICE suggest (4) that "...pirfenidone is recommended as an option for treating idiopathic pulmonary fibrosis only if the person has a forced vital capacity (FVC) between 50% and 80% predicted.."
      • serious liver injury has been reported during treatment with pirfenidone in the first year after initiation, including 2 cases with a fatal outcome. Measure alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin levels before starting pirfenidone treatment, monthly for the first 6 months of treatment, and then every 3 months thereafter (5)
      • monitor closely for signs of toxicity if pirfenidone is being used concomitantly with inhibitors of one or more other CYP isoenzymes involved in the metabolism of pirfenidone (5)
        
  • nintedanib targets 3 growth factor receptors involved in pulmonary fibrosis. Nintedanib is thought to block the signalling pathways involved in fibrotic processes, and may reduce disease progression by slowing the decline of lung function. It is administered orally.
    • NICE suggest: that
      • "..Nintedanib is recommended as an option for treating idiopathic pulmonary fibrosis, if the person has a forced vital capacity (FV C) between 50% and 80% of predicted.." (5)
      • "..Nintedanib is recommended as an option for treating idiopathic pulmonary fibrosis in adults, if they have a forced vital capacity of above 80% predicted .." (9)
    • NICE suggest (7) that "Nintedanib is recommended, within its marketing authorisation, as an option for treating chronic progressive fibrosing interstitial lung diseases (PF-ILD) in adults."
      • "...the clinical trial evidence suggests that nintedanib slows the decline of lung function compared with placebo."
• oxygen - to palliate symptoms of breathlessness

Treatment should be monitored using serial chest radiology, lung function tests and high resolution CT scans.

Notes:

• NICE suggests (4):
  • disease-modifying pharmacological interventions
    • no conclusive evidence to support the use of any drugs to increase the survival of people with idiopathic pulmonary fibrosis
    • should not use any of the drugs below, either alone or in combination, to modify disease progression in idiopathic pulmonary fibrosis:
      • ambrisentan
      • azathioprine
      • bosentan
      • co-trimoxazole
      • mycophenolate mofetil
      • prednisolone
      • sildenafil
      • warfarin
    • N-acetylcysteine is used for managing idiopathic pulmonary fibrosis, but its benefits are uncertain
  • cough
    • thalidomide is sometimes considered for management of an intractable cough

Reference:

1. British Thoracic Society Recommendations (1999). The diagnosis, assessment and treatment of diffuse parenchymal lung disease in adults. Thorax, 54, Suppl 1.
2. NICE (April 2013). Pirfenidone for treating idiopathic pulmonary fibrosis
3. NICE (May 2017). Idiopathic pulmonary fibrosis: the diagnosis and management of suspected idiopathic pulmonary fibrosis
4. Bhatti H et al. Approach to acute exacerbation of idiopathic pulmonary fibrosis.Ann Thorac Med. 2013 Apr;8(2):71-7.
5. Drug Safety Update volume 14, issue 4: November 2020: 2.
6. NICE (November 2021). Nintedanib for treating progressive fibrosing interstitial lung diseases
7. NICE (February 2023). Nintedanib for treating idiopathic pulmonary fibrosis when forced vital capacity is above 80% predicted