What is the treatment for Idiopathic Pulmonary Fibrosis (IPF)?

Treatment of Idiopathic Pulmonary Fibrosis

Treat IPF with either pirfenidone or nintedanib as first-line antifibrotic therapy, as these are the only two medications proven to slow disease progression and reduce mortality risk. 1, 2, 3

First-Line Antifibrotic Therapy

Pirfenidone and nintedanib are the cornerstone of IPF treatment, both demonstrating efficacy in slowing the decline in forced vital capacity (FVC) over time. 1, 2, 4

Pirfenidone Dosing and Administration

• Target dose: 801 mg three times daily (2,403 mg/day total) with food 3
• Titration schedule over 14 days: 3
  • Days 1-7: 267 mg three times daily (801 mg/day)
  • Days 8-14: 534 mg three times daily (1,602 mg/day)
  • Day 15 onward: 801 mg three times daily (2,403 mg/day)
• Mechanism: Anti-inflammatory, antioxidative, and antiproliferative effects that reduce progression-free survival risk by 30% compared to placebo 5, 2
• Best suited for: Patients with mild-to-moderate IPF (FVC >50% predicted and DLCO >35% predicted) 1, 2

Nintedanib

• Alternative first-line option that inhibits multiple tyrosine kinase pathways involved in fibrogenesis 1, 2
• Demonstrated efficacy in slowing FVC decline in IPF patients 1
• Consider as first choice when pirfenidone side effects are anticipated to be problematic 6, 7

Treatments to AVOID - Critical Safety Information

Strongly Contraindicated Therapies

Triple therapy (prednisone + azathioprine + N-acetylcysteine) is CONTRAINDICATED - the PANTHER-IPF trial demonstrated increased risk of death and hospitalizations, leading to early termination of this arm. 5, 2

Interferon gamma-1b received a Strong No recommendation based on lack of survival benefit in the INSPIRE trial (n=826) and unfavorable cost-risk profile. 5

Ambrisentan (selective endothelin receptor antagonist) is contraindicated due to documented decline in respiratory status and increased disease progression in clinical trials. 5, 2

Corticosteroid monotherapy is NOT recommended for routine IPF treatment, as no prospective randomized controlled trials have demonstrated efficacy, and only 10-30% of patients show partial, transient responses. 5 Corticosteroids should be reserved only for acute exacerbations or incapacitating cough. 2

Warfarin and oral anticoagulants should NOT be used for treating IPF in patients without other indications. 5, 2

Adjunctive and Supportive Therapies

Antacid Therapy

Recommend regular proton pump inhibitor (PPI) or H2-receptor antagonist use for all IPF patients, given that up to 90% have abnormal gastroesophageal reflux (often clinically silent). 5

• Evidence: Observational data showed survival benefit (HR 0.47; 95% CI 0.24-0.93) and smaller FVC decline (mean difference 0.07 L; P=0.05) 5
• Rationale: Reduces microaspiration-associated lung injury 5

Oxygen Therapy

Prescribe supplemental oxygen for patients with desaturation below 88% during 6-minute walk test or resting hypoxemia. 8

Pulmonary Rehabilitation

Recommend pulmonary rehabilitation programs to improve exercise capacity and quality of life (conditional recommendation). 8

Vaccinations

Administer annual influenza and pneumococcal vaccinations to all IPF patients. 2

Monitoring and Dose Adjustments

Regular Monitoring Schedule

• Pulmonary function tests (FVC, DLCO) every 3-6 months to assess treatment response 1, 2, 8
• Liver function tests monthly for first 6 months of pirfenidone, then every 3 months thereafter 2, 3
• Oxygen saturation at rest and with exercise at each visit 8

Pirfenidone Dose Modifications for Adverse Effects

For elevated liver enzymes (ALT/AST >3 but ≤5 × ULN without symptoms): Discontinue confounding medications, monitor closely, may maintain or reduce dose 3

For ALT/AST >3 but ≤5 × ULN WITH symptoms or hyperbilirubinemia: Permanently discontinue pirfenidone 3

For ALT/AST >5 × ULN: Permanently discontinue pirfenidone 3

For gastrointestinal symptoms, photosensitivity, or rash: Consider temporary dose reduction or interruption until symptoms resolve 3

If treatment interrupted <14 days: Resume previous dose 3

If treatment interrupted ≥14 days: Re-initiate with full 14-day titration schedule 3

Drug Interactions Requiring Dose Adjustment

With strong CYP1A2 inhibitors (fluvoxamine, enoxacin): Reduce pirfenidone to 267 mg three times daily (801 mg/day total) 3

Lung Transplantation

Refer patients aged <65 years with severe or worsening disease for lung transplant evaluation at diagnosis if they have high mortality risk factors. 2, 8 Lung transplantation is the only treatment proven to increase life expectancy in IPF. 9

Common Pitfalls to Avoid

• Do not use sildenafil routinely - the STEP-IPF trial showed no benefit on primary outcome (6-minute walk distance) in advanced IPF patients 5
• Do not use N-acetylcysteine monotherapy - evidence remains inconclusive despite initial promising data from IFIGENIA study 5
• Do not delay antifibrotic therapy - early treatment may prevent irreversible fibrosis, and rare cases show potential for disease reversal with pirfenidone 10
• Do not use mechanical ventilation for most patients with respiratory failure due to IPF progression (weak negative recommendation) 8