What is the recommended treatment for interstitial lung disease (ILD) in patients with systemic sclerosis?

Treatment of Interstitial Lung Disease in Systemic Sclerosis

Mycophenolate mofetil is the first-line treatment for interstitial lung disease (ILD) in systemic sclerosis (SSc), with tocilizumab, nintedanib, rituximab, and cyclophosphamide as additional options for progressive disease. 1

First-Line Treatment

Immunosuppressive Therapy

• Mycophenolate mofetil (MMF): 2-3g per day oral administration 1
  • Conditionally recommended as the preferred first-line therapy by the 2023 ACR/CHEST guidelines 1
  • Similar efficacy to cyclophosphamide but with a more favorable adverse effect profile 1
  • Stabilizes or improves lung function in most patients

Important Caution Regarding Glucocorticoids

• Strong recommendation AGAINST glucocorticoids as first-line treatment for SSc-ILD 1
• Glucocorticoids are associated with scleroderma renal crisis (SRC), particularly at doses >15mg/day of prednisone equivalent 1
• If considered in rare circumstances, use the lowest effective dose (<15mg/day) 1

Treatment for Progressive Disease

When ILD progresses despite first-line therapy, the following options should be considered:

Additional Therapeutic Options (in order of preference) 1

1. Tocilizumab: 162mg subcutaneously once weekly or 4-8mg/kg IV monthly

   • FDA-approved in 2021 to slow the rate of declining lung function in SSc-ILD 1
   • Based on the phase III focuSSced trial showing less decline in lung function 1

2. Nintedanib: 150mg twice daily (reduce to 100mg twice daily if not tolerated)

   • Approved in many countries for SSc-ILD 1
   • SENSCIS trial showed slowing of FVC decline 1
   • May be used alone or in combination with MMF for enhanced effect 1

3. Rituximab: Two IV infusions 2 weeks apart, then one infusion every 6 months

   • Growing evidence supporting its use as an alternative to cyclophosphamide 1
   • Better tolerated than cyclophosphamide with fewer adverse events 1

4. Cyclophosphamide: 600mg/m² IV monthly or 100-150mg oral daily

   • Demonstrated efficacy in two high-quality RCTs 1
   • Higher toxicity profile compared to other options 1, 2
   • Not typically used in combination with other therapies 1

Management of Rapidly Progressive ILD

For severe or rapidly progressive SSc-ILD: 1

• Consider combination of two therapies from the above options
• For severe cases, consider:
  • Autologous hematopoietic stem cell transplantation (AHSCT) for suitable candidates 1
  • Early referral for lung transplantation evaluation 1

Supportive Interventions

Aggressive Management of Gastroesophageal Reflux Disease (GERD) 1

• Proton pump inhibitors (often exceeding maximum approved dose)
• H2 antagonists, prokinetic drugs, sucralfate, antacids as needed
• Lifestyle modifications:
  • Raise head of bed
  • No food after supper
  • Chew food well and eat slowly
  • Avoid trigger foods
• Consider fundoplication surgery for severe reflux with aspiration

Additional Supportive Measures 1

• Smoking cessation
• Vaccinations (influenza, COVID-19, pneumococcal)
• Oxygen therapy if hypoxia or desaturation with exercise
• Pulmonary rehabilitation
• Early intervention for infections
• Antibiotic prophylaxis for recurrent pulmonary infections
• Pneumocystis jirovecii pneumonia prophylaxis if on significant immunosuppression

Monitoring

• Regular pulmonary function tests every 3-6 months
• HRCT when clinically indicated
• A 5% decline in FVC over 12 months is associated with doubled mortality 3
• Close monitoring is especially important in the first few years after SSc diagnosis, when risk of ILD progression is highest 4

Emerging Therapies

• Pirfenidone: May be considered in some cases, though with fewer supporting data than nintedanib 1
• JAK inhibitors: Emerging evidence for use in refractory cases 3
• Combination therapies: MMF plus nintedanib or MMF plus pirfenidone are being studied 1, 5

The treatment approach should be guided by disease severity, progression rate, and patient-specific factors, with early detection and intervention offering the best opportunity to improve outcomes in patients with SSc-ILD 6.