What is the management of Connective Tissue Disease (CTD)-Associated Interstitial Lung Disease (ILD)?

Management of Connective Tissue Disease-Associated ILD

The management of Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD) requires a multidisciplinary approach involving pulmonologists and rheumatologists, with mycophenolate being the preferred first-line treatment alongside short-term glucocorticoids as recommended by the American College of Rheumatology. 1

Diagnostic Approach and Monitoring

Initial Evaluation

• HRCT is the gold standard for confirming ILD diagnosis 2
• Pulmonary Function Tests (PFTs) including FVC and DLCO are essential for baseline assessment
• Risk factors to assess:
  • For RA-ILD: male gender, smoking history, disease duration, disease severity, high RF or anti-CCP antibodies 2
  • For SSc: HRCT screening should be performed even without symptoms due to high ILD prevalence 2

Monitoring Protocol

• Initial evaluation requires:
  • Short-term PFTs within 3 months
  • HRCT within 6 months to determine progression rate 2
• Follow-up schedule:
  • Mild CTD-ILD (FVC ≥70%, <20% fibrosis on HRCT): PFTs every 6 months for first 1-2 years
  • Moderate-severe ILD: PFTs every 3-6 months
  • HRCT repeated within first 3 years to identify progressive disease 2, 1
  • Ambulatory desaturation testing every 3-12 months 1

Treatment Algorithm

First-Line Treatment Options

1. Mycophenolate mofetil:

   • Preferred first-line agent for most CTD-ILD subtypes 1
   • Demonstrated to stabilize lung function in SSc-ILD 3

2. Rituximab:

   • Particularly effective for patients with active inflammatory arthritis
   • First-line option for RA-ILD and IIM-ILD 1
   • Shows promise in RA-ILD based on observational data 3

3. Azathioprine:

   • Alternative first-line option 1
   • Commonly used in clinical practice for CTD-ILD 4

4. Cyclophosphamide:

   • First-line option for rapidly progressive disease 1
   • Randomized controlled trials show ILD stabilization in SSc-ILD 3

5. Adjunctive short-term glucocorticoids:

   • Use for ≤3 months 1
   • Pulse IV methylprednisolone for rapidly progressive disease
   • Caution: Avoid long-term use in SSc-ILD due to risk of scleroderma renal crisis 1

Treatments to Avoid as First-Line

• Methotrexate: uncertain benefit for ILD 1
• Leflunomide: may worsen ILD in rare cases 1
• TNF inhibitors: potentially harmful or ineffective for RA-ILD 1
• Abatacept: uncertain efficacy 1
• Inhaled corticosteroids: not recommended 1

Treatment Escalation for Progressive Disease

If progression occurs despite first-line therapy:

1. Add or switch to:

   • Rituximab
   • Cyclophosphamide
   • Nintedanib (particularly for SSc-ILD and RA-ILD)
   • Pirfenidone (for RA-ILD)
   • Tocilizumab (for SSc-ILD, MCTD-ILD, and RA-ILD) 1

2. For specific subtypes:

   • IIM-ILD progression: consider adding calcineurin inhibitors 1, 3
   • Consider JAK inhibitors over azathioprine for progressive SARD-ILD 1

3. Early referral for lung transplantation for patients with progressive disease despite optimal medical therapy 1

Disease-Specific Considerations

Rheumatoid Arthritis-ILD

• Most common pattern: Usual Interstitial Pneumonia (UIP) 4
• UIP pattern associated with poorer prognosis 2
• Dual combination therapy conditionally recommended over monotherapy 1
• Nintedanib shown to slow disease progression over time 2

Systemic Sclerosis-ILD

• Most common pattern: Non-Specific Interstitial Pneumonia (NSIP) 4
• HRCT screening recommended even without symptoms 2
• Avoid long-term glucocorticoids due to risk of scleroderma renal crisis 1
• Mycophenolate and cyclophosphamide have strongest evidence 3

Inflammatory Myopathy-ILD

• Requires aggressive immunosuppression 3
• Consider cyclophosphamide, mycophenolate, and calcineurin inhibitors 1, 3
• More frequent monitoring recommended (PFTs every 3-6 months) 1

Critical Considerations

• Early intervention is crucial: Delayed treatment can lead to irreversible fibrosis 1
• Regular monitoring: Inadequate monitoring can result in undetected disease progression 1
• Multidisciplinary approach: Collaboration between pulmonologists and rheumatologists improves diagnostic accuracy and likely improves patient outcomes 2
• Balance between anti-inflammatory and anti-fibrotic treatment: Evaluate the inflammatory vs. fibrotic ILD process to adapt treatment over time 2
• Comorbidity management: Address GERD and pulmonary hypertension which can exacerbate ILD 1

By implementing this structured approach to CTD-ILD management, clinicians can optimize outcomes while minimizing potential harms through appropriate treatment selection and monitoring.