What is the drug of choice for Idiopathic Pulmonary Fibrosis (IPF)?

Drug of Choice for Idiopathic Pulmonary Fibrosis

Either pirfenidone or nintedanib should be used as first-line antifibrotic therapy for patients with IPF, as both drugs slow disease progression by reducing the rate of FVC decline and are conditionally recommended by the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association. 1, 2

First-Line Antifibrotic Options

Both approved antifibrotic agents have similar efficacy but different side effect profiles:

Pirfenidone

• FDA-approved for treatment of IPF 3
• Reduces rate of FVC decline by approximately 125 ml/year compared to placebo 1, 2
• Mechanism includes anti-inflammatory, antioxidant, and antiproliferative effects with antagonism of TGF-β1 1
• Conditionally recommended by ATS/ERS/JRS/ALAT guidelines (2015 update) based on moderate confidence in estimates of effect 1
• Dosing: 801 mg three times daily (2,403 mg/day total) after 14-day titration period 3

Nintedanib

• Equally effective alternative to pirfenidone for slowing FVC decline 2, 4
• Blocks multiple tyrosine kinase pathways involved in fibrogenesis 2
• Reduces proportion of patients experiencing ≥10% absolute FVC decline (RR 1.16,95% CI 1.06-1.27) 4
• Also conditionally recommended by ATS/ERS/JRS/ALAT for IPF and progressive pulmonary fibrosis 2, 5

Choosing Between the Two Drugs

Base your choice on the patient's tolerance for specific side effects:

Choose Pirfenidone if:

• Patient can avoid sun exposure and tolerate photosensitivity precautions 1, 3
• Gastrointestinal symptoms (especially diarrhea) would be particularly problematic 1
• Common adverse effects: photosensitivity, fatigue, stomach discomfort, anorexia, nausea, rash 1, 4

Choose Nintedanib if:

• Patient has significant sun exposure requirements or history of photosensitivity 2
• Patient has chronic kidney disease (hepatically metabolized, theoretically safer) 5
• Common adverse effects: diarrhea (2.8× increased risk), nausea (3.1×), vomiting (3.6×), abdominal pain (4.2×) 5, 4

Patient Selection Criteria

Treat patients with mild-to-moderate IPF (FVC >50% predicted and DLCO >35% predicted), as this was the population studied in pivotal trials 1, 2

• Evidence does not support withholding treatment in "stable" disease, as FVC decline is nearly linear regardless of baseline function 6
• For severe disease (FVC <50% or DLCO <35%), treatment may still be considered individually, though clinical trial data is limited 2

Critical Monitoring Requirements

Before Starting Treatment:

• Obtain baseline ALT, AST, and bilirubin 1, 3
• Confirm IPF diagnosis through clinical, radiographic, and if needed, histopathological evaluation 2

During Treatment:

• Monitor liver function tests monthly for first 6 months, then every 3 months 2, 5
• Assess FVC and DLCO every 3-6 months to monitor treatment response 2, 5
• For pirfenidone: educate on sun protection (sunscreen, protective clothing daily) 1, 3

Managing Adverse Effects

Do not discontinue therapy prematurely for manageable side effects:

• Dose reduction or temporary interruption is effective for managing adverse effects without compromising efficacy 1, 2, 6
• For pirfenidone: gradual dose titration and taking with food reduces GI symptoms 2, 3
• For nintedanib: dose reduction (7.9× more likely needed) or temporary interruption manages diarrhea 5

Treatments to AVOID

Never use these therapies, as they increase mortality or cause harm:

• Triple therapy (prednisone + azathioprine + N-acetylcysteine) is contraindicated - shown to increase mortality 1, 2, 5
• Corticosteroid monotherapy (except for incapacitating cough or acute exacerbations) 1, 2, 5
• Warfarin or oral anti-vitamin K anticoagulants for treating IPF 1, 2
• Ambrisentan (selective endothelin receptor antagonist) - causes respiratory decline 1, 2

Essential Supportive Care

All IPF patients should receive:

• Annual influenza and pneumococcal vaccinations (strongly recommended) 2, 5, 4
• Long-term oxygen therapy for severe hypoxemia at rest 2, 5
• Consider lung transplantation referral for patients <65 years with severe or worsening disease 2, 5

Common Pitfalls to Avoid

• Do not wait for disease progression before starting treatment - FVC decline is linear and irreversible 6
• Do not discontinue therapy for mild-moderate side effects - dose adjustment is usually sufficient 1, 6
• Do not combine pirfenidone and nintedanib outside clinical trials - safety data is limited 7
• Do not use these drugs for non-IPF ILD without documented progression despite standard immunosuppressive therapy 5