What are the guidelines for starting antifibrotics (medications that slow fibrosis) during an acute Idiopathic Pulmonary Fibrosis (IPF) exacerbation with computed tomography (CT) chest evidence of progression of fibrosis and new Ground Glass Opacities (GGOs) suggesting exacerbation?

Management of Antifibrotic Therapy During Acute IPF Exacerbation

Antifibrotic therapy should not be initiated during an acute exacerbation of IPF, but should be continued if the patient is already on treatment. 1

Diagnosis of Acute Exacerbation

An acute exacerbation of IPF is characterized by:

• Recent worsening of dyspnoea (<30 days)
• New ground glass opacities on CT imaging in addition to pre-existing fibrotic changes
• Exclusion of other causes of respiratory deterioration (infection, pulmonary embolism, left heart failure) 2

Management Algorithm for Acute IPF Exacerbation

First-Line Treatment

• High-dose corticosteroids are the mainstay of therapy for acute exacerbations of IPF 2
  • Methylprednisolone 1-2 mg/kg/day IV initially for 3-5 days 1
  • Followed by oral prednisone (0.5-1 mg/kg/day) with taper over 4-6 weeks 1

Regarding Antifibrotic Therapy

1. For patients already on antifibrotics:

   • Continue current antifibrotic therapy during the acute exacerbation 3
   • Discontinuation should only be considered for safety issues (unbearable side effects) 3

2. For treatment-naïve patients:

   • Defer initiation of antifibrotic therapy until after resolution of the acute exacerbation
   • Start antifibrotic therapy once the patient is stabilized 4

Adjunctive Therapies

• Consider broad-spectrum antibiotics if infection cannot be definitively ruled out 2
• Intravenous cyclophosphamide may be considered in select cases 2
• Supportive care is essential (oxygen therapy, management of comorbidities) 2

Monitoring and Follow-up

• Assess clinical response after 72 hours of high-dose steroid therapy 1
• If no improvement or clinical deterioration occurs, consider:
  • Alternative diagnoses
  • Additional immunosuppressive therapy (cyclophosphamide, mycophenolate mofetil) 1
• Monitor for steroid-related adverse effects:
  • Hyperglycemia
  • Hypertension
  • Risk of opportunistic infections 1

Rationale and Evidence Quality

The recommendation to continue antifibrotics in patients already on treatment is based on evidence that:

• IPF is a progressive disease with linear decline in lung function 4
• Interruption of antifibrotic therapy may lead to accelerated disease progression 3
• Antifibrotic drugs slow decline in lung function and reduce the risk of acute respiratory deteriorations 4

The recommendation against initiating antifibrotics during an acute exacerbation is based on:

• The primary pathology during acute exacerbation is diffuse alveolar damage with inflammation 5
• High-dose corticosteroids are the established first-line treatment for the inflammatory component 2, 1
• The benefit of antifibrotics is in long-term disease modification rather than acute management 4

Important Caveats

• The mortality of acute exacerbation of IPF remains high (~50%) despite treatment 5
• There are no controlled trials demonstrating efficacy of corticosteroids in acute exacerbations, but they remain the standard of care based on clinical experience 2
• Mechanical ventilation should be avoided in most patients with IPF and acute respiratory failure due to high mortality, except in select cases (e.g., bridge to transplant) 2
• Pre-existing comorbidities do not appear to affect antifibrotic therapy discontinuation rates 6

After resolution of the acute exacerbation, prompt initiation of antifibrotic therapy is critical to preserving lung function and improving long-term outcomes 4.