What is the recommended treatment for rheumatoid arthritis (RA) associated interstitial lung disease (ILD)?

Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease

For rheumatoid arthritis-associated interstitial lung disease (RA-ILD), mycophenolate is conditionally recommended as the preferred first-line treatment, with short-term glucocorticoids as adjunctive therapy. 1

First-Line Treatment Options

Preferred Treatment

• Mycophenolate mofetil: Conditionally recommended as the preferred first-line agent for RA-ILD 1
  • Demonstrated improvement in FVC and DLCO after 12 months of treatment compared to pretreatment trajectory 2
  • Effective regardless of radiologic pattern (UIP vs non-UIP) 2

Additional First-Line Options

• Azathioprine: Conditionally recommended as an alternative first-line agent 1
• Rituximab: Conditionally recommended as an alternative first-line agent 1
• Cyclophosphamide: Conditionally recommended as an alternative first-line agent 1

Adjunctive Therapy

• Short-term glucocorticoids: Conditionally recommended for RA-ILD 1
  • Should be limited to ≤3 months duration
  • Dose should not exceed 10 mg/day of prednisone 3
  • Consider divided dosing (e.g., 5 mg twice daily) for better control of inflammation 3
  • Always initiate calcium (800-1000 mg/day) and vitamin D (400-800 units/day) supplementation 3

Treatments to Avoid as First-Line

• Leflunomide: Conditionally recommended against 1
• Methotrexate: Conditionally recommended against 1
• TNF inhibitors: Conditionally recommended against 1
• Abatacept: Conditionally recommended against as first-line 1
• Pirfenidone: Conditionally recommended against as first-line 1

Management of Progressive RA-ILD Despite First-Line Treatment

For patients with RA-ILD who show progression despite first-line treatment, the following options are recommended:

1. Mycophenolate: If not used as first-line 1
2. Rituximab: If not used as first-line 1
3. Cyclophosphamide: If not used as first-line 1
4. Nintedanib: Conditionally recommended for progressive RA-ILD 1, 4
5. Pirfenidone: Conditionally recommended specifically for RA-ILD progression 1, 4
6. Tocilizumab: Conditionally recommended for RA-ILD progression 1

Long-term Glucocorticoids

• Conditionally recommended against for progressive RA-ILD 1
• Associated with increased risk of adverse effects without clear long-term benefit

Monitoring and Assessment

1. Regular pulmonary function tests (PFTs):

   • A 5% decline in FVC over 12 months is associated with approximately 2-fold increase in mortality 5
   • Monitor every 3-6 months initially, then every 6-12 months if stable

2. High-resolution CT scans:

   • Baseline and as needed to assess progression
   • Pattern of ILD (UIP vs non-UIP) does not necessarily dictate treatment choice 2

3. Symptom assessment:

   • Dyspnea
   • Cough
   • Exercise tolerance

Special Considerations

Rapidly Progressive ILD

For patients with rapidly progressive RA-ILD:

• Pulse intravenous methylprednisolone is conditionally recommended 1
• Combination therapy is conditionally recommended over monotherapy 1
• Early referral for lung transplantation is conditionally recommended 1
• Consider rituximab, cyclophosphamide, IVIG, or mycophenolate 1

Common Pitfalls to Avoid

1. Delaying treatment: Progressive fibrosis can become irreversible; early intervention is crucial 5

2. Overreliance on imaging pattern: Recent data suggest immunosuppression may be beneficial even in patients with UIP pattern 6

3. Inadequate monitoring: Regular assessment of pulmonary function is essential to detect early progression 5

4. Neglecting comorbidities: Address GERD, pulmonary hypertension, and other conditions that may exacerbate ILD 5

5. Avoiding all immunosuppressants due to concern for infection: The benefit of treatment typically outweighs the risk in progressive disease 6

Treatment Algorithm

1. Initial assessment:

   • Confirm RA-ILD diagnosis
   • Assess disease severity and progression rate
   • Evaluate for contraindications to specific therapies

2. First-line treatment:

   • Start mycophenolate mofetil
   • Consider short-term glucocorticoids for acute symptoms
   • If contraindicated, consider azathioprine or rituximab

3. Monitor response (every 3-6 months):

   • PFTs (FVC, DLCO)
   • Symptoms
   • Imaging as needed

4. If progression occurs:

   • Add or switch to alternative agent (rituximab, cyclophosphamide)
   • Consider adding antifibrotic (nintedanib or pirfenidone)
   • Consider tocilizumab

5. If rapidly progressive:

   • Implement combination therapy
   • Consider early referral for lung transplantation evaluation