What is the initial management for a patient with Idiopathic Pulmonary Fibrosis (IPF)/Usual Interstitial Pneumonia (UIP)?

Management of Idiopathic Pulmonary Fibrosis (IPF)/Usual Interstitial Pneumonia (UIP)

Initiate antifibrotic therapy with either pirfenidone or nintedanib immediately upon diagnosis in patients with mild-to-moderate disease (FVC ≥50% predicted and DLCO ≥35% predicted), as these medications reduce FVC decline by approximately 44-57% annually and should be started before irreversible fibrosis develops. 1, 2

Pharmacological Treatment Algorithm

First-Line Antifibrotic Therapy

Choose between two evidence-based options:

• Pirfenidone 2,403 mg/day (divided into three doses with food): Reduces mean FVC decline and disease progression (defined as <10% decrease in FVC, <15% decrease in DLCO, or death) at 72 weeks 3, 4

• Nintedanib: Blocks pathways involved in fibrogenesis and slows disease progression with similar efficacy to pirfenidone 1, 2

Both medications have comparable efficacy in slowing FVC decline, so the choice depends primarily on side effect profile and patient tolerance 1, 5.

Initiation and Monitoring Requirements

For Pirfenidone:

• Must be initiated and supervised by a physician experienced in IPF diagnosis and management 3
• Perform liver function tests prior to initiation, then monthly for first 6 months, then every 3 months thereafter 3, 2
• Start with gradual dose titration to minimize gastrointestinal side effects 1
• Patient must discontinue smoking before and during treatment, as smoking increases pirfenidone metabolism 3
• Avoid concomitant use with fluvoxamine and omeprazole 3, 2
• Contraindicated in severe hepatic or renal impairment 3, 2

Common adverse effects of pirfenidone include nausea, rash, fatigue, diarrhea, dyspepsia, photosensitivity, and weight loss—manage with dose titration, taking medication with food, and strict sun protection 3, 1

Common adverse effects of nintedanib include diarrhea, nausea, abdominal pain, vomiting, and elevated liver enzymes—manage with dose reduction and temporary treatment interruption as needed 1

Disease Monitoring Schedule

• Pulmonary function tests (FVC and DLCO) every 3-6 months to assess treatment response and disease progression 1, 6
• High-resolution CT at baseline and repeat within 3-6 months to 1 year depending on disease behavior 6
• Continue treatment indefinitely if patient shows stabilization or improvement 3

Critical Treatments to AVOID

The following therapies are contraindicated or not recommended based on harm or lack of efficacy:

• Triple therapy (prednisone + azathioprine + N-acetylcysteine): Strongly contraindicated due to increased mortality 1, 2, 6
• Oral anticoagulants (warfarin): Associated with increased mortality (p=0.005) without survival benefit 3
• Ambrisentan: Contraindicated in IPF due to detrimental effects on disease progression and increased hospitalizations 3, 1
• Bosentan, macitentan, etanercept: No efficacy demonstrated in clinical trials 3
• Colchicine, cyclosporine A, interferon-γ-1b: No clinical benefit shown 3

Note on corticosteroids: The older 2000 ATS/ERS guidelines recommended combination corticosteroid therapy with azathioprine or cyclophosphamide 3, but this recommendation has been superseded by more recent evidence showing harm. Current guidelines reserve corticosteroids only for acute exacerbations or incapacitating cough, not as routine therapy 3, 1.

Supportive Care Measures

Vaccinations (Strongly Recommended)

• Annual influenza vaccination 3, 1, 2
• Pneumococcal vaccination (polysaccharide vaccine) 3, 1, 2

Oxygen Therapy

• Long-term oxygen therapy for patients with severe hypoxemia at rest (severe chronic respiratory failure) 3, 1, 2

Pulmonary Rehabilitation

• Initiate respiratory rehabilitation program in patients with exercise limitation causing significant impairment—improves walking distance, symptoms, and quality of life 3, 1, 2
• May not be feasible in advanced disease 3

Lung Transplantation Evaluation

• Consider for all patients aged <65 years with severe or worsening disease 3, 1, 2
• Refer when DLCO <39% predicted and FVC has decreased >10% over 6 months 3, 2
• Provide information about transplantation early in disease course and arrange early assessment at transplant center 3

Treatment Response Assessment

Evaluate response at 6-month intervals using:

• Change in FVC and DLCO from baseline 3
• Dyspnea assessment using established clinical scales 3
• Six-minute walk test distance 7
• High-resolution CT findings 1

If patient worsens at 6 or 12 months: Consider switching antifibrotic agents, evaluate for lung transplantation, or enroll in clinical trials 3

Common Pitfalls to Avoid

• Delaying treatment initiation: Response rates are higher when treatment starts early, before irreversible fibrosis develops 3, 8
• Discontinuing effective therapy: Some patients may show stabilization or even improvement on pirfenidone; restricted prescribing based solely on FVC thresholds may miss opportunities to influence disease trajectory 8
• Using immunosuppression in IPF: Unlike other ILDs, IPF does not respond to immunosuppressive therapy and may be harmed by it 1, 6
• Inadequate monitoring for adverse effects: Both antifibrotics require vigilant monitoring, particularly liver function tests 3, 2