What are the treatment options for Interstitial Lung Disease (ILD) associated with polymyositis?

Treatment Options for Interstitial Lung Disease Associated with Polymyositis

For patients with polymyositis-associated interstitial lung disease (PM-ILD), the recommended first-line treatment is high-dose corticosteroids combined with immunosuppressive agents such as mycophenolate mofetil, rituximab, or cyclophosphamide, with treatment selection based on disease severity and progression. 1, 2

First-Line Treatment Options

Non-Progressive PM-ILD

• Corticosteroids + Mycophenolate Mofetil (MMF)
  • First-line option for most patients with non-rapidly progressive disease
  • Better safety profile than cyclophosphamide
  • Typically initiated with high-dose corticosteroids (prednisone 1mg/kg/day)

Progressive or Severe PM-ILD

• Pulse IV Methylprednisolone

  • Recommended for rapidly progressive ILD (RP-ILD) due to rapid onset of action 1
  • Typically 500-1000mg daily for 3 days, followed by high-dose oral prednisone

• Cyclophosphamide

  • Indicated for severe, progressive disease
  • Has been shown to prevent further progression in patients with rapidly progressive ILD 3
  • Usually administered as monthly IV pulses

• Rituximab

  • Effective alternative to cyclophosphamide
  • Particularly useful in patients with anti-synthetase antibodies
  • Better toxicity profile than cyclophosphamide

Second-Line/Add-on Treatment Options

For patients with PM-ILD progression despite first-line therapy, the following options are recommended:

• Calcineurin Inhibitors (CNIs)

  • Cyclosporine or tacrolimus (FK506)
  • Particularly effective in refractory IIM-ILD 1, 4
  • Especially beneficial in anti-synthetase syndrome or MDA-5-ILD
  • May reduce recurrence risk in anti-ARS antibody positive patients 5

• JAK Inhibitors

  • Emerging evidence supports their use in IIM-ILD that progresses despite first-line treatment 1
  • Consider when other options have failed

• Intravenous Immunoglobulin (IVIG)

  • Add-on option for progressive IIM-ILD 1
  • Particularly useful when rapid onset of action is desired
  • Beneficial in cases with concurrent respiratory muscle weakness

Risk Factors for Progressive Disease and Recurrence

• Extensive ground-glass opacities on HRCT 3
• BAL neutrophilia 3
• Low pulmonary vital capacity at disease onset 5
• Presence of anti-ARS antibodies (associated with late recurrence) 5
• Active myositis 6

Monitoring and Follow-up

• Regular pulmonary function tests (PFTs) every 3-6 months
• HRCT when clinically indicated
• A 5% decline in FVC over 12 months is associated with doubled mortality 2
• Monitor for medication side effects, particularly with long-term corticosteroid use

Supportive Care

• Pneumocystis jirovecii pneumonia prophylaxis with trimethoprim-sulfamethoxazole for patients on high-dose corticosteroids 1
• Calcium and vitamin D supplementation; consider bisphosphonates if osteoporosis is present 1
• Vaccination (influenza, pneumococcus, COVID-19) 1
• Oxygen therapy as needed
• Pulmonary rehabilitation

Treatment Algorithm

1. Assess disease severity:

   • Non-progressive: Start with corticosteroids + MMF
   • Progressive/severe: Start with pulse IV methylprednisolone + cyclophosphamide or rituximab

2. Monitor response (PFTs, symptoms, HRCT if indicated)

3. If progression occurs:

   • Add or switch to calcineurin inhibitors (cyclosporine/tacrolimus)
   • Consider IVIG, especially with respiratory muscle weakness
   • Consider JAK inhibitors in refractory cases

4. For recurrent disease:

   • Patients with anti-ARS antibodies may benefit from calcineurin inhibitors
   • Consider more intensive immunosuppression

Caution

• Long-term corticosteroid use is associated with significant adverse effects including osteoporosis, weight gain, hypertension, diabetes, and cataracts 1
• Careful monitoring for drug toxicities is essential with all immunosuppressive agents
• Early intervention is critical, as delay in treatment may lead to irreversible fibrosis