What is the initial treatment approach for patients diagnosed with interstitial lung diseases?

Initial Treatment Approach for Interstitial Lung Disease

Mycophenolate is the preferred first-line therapy across all subtypes of systemic autoimmune rheumatic disease-associated ILD (SARD-ILD), with typical dosing of 1000-1500 mg twice daily. 1, 2

Disease-Specific First-Line Treatment Algorithm

For Systemic Sclerosis-Associated ILD (SSc-ILD)

• Strongly avoid glucocorticoids due to the risk of scleroderma renal crisis, particularly at doses >15 mg/day prednisone equivalent 1, 2
• Preferred options (in hierarchical order): Mycophenolate, rituximab, nintedanib, tocilizumab, cyclophosphamide 1, 2
• Tocilizumab is particularly effective when elevated acute phase reactants, diffuse skin involvement, or early progressive disease is present 1, 2
• Nintedanib slows annual FVC decline by approximately 44-57% and is especially useful when fibrotic features predominate 3

For Inflammatory Myopathy-Associated ILD (IIM-ILD)

• Preferred options: Mycophenolate, rituximab, calcineurin inhibitors (CNIs), nintedanib, cyclophosphamide 1, 2
• CNIs (tacrolimus preferred over cyclosporine) are conditionally recommended specifically for IIM-ILD due to rapid onset of action and effectiveness in anti-synthetase syndrome and MDA-5 positive disease 1
• Tacrolimus dosing: 3 mg/kg/day adjusted for target trough levels between 100-150 ng/mL 1
• JAK inhibitors are conditionally recommended as an additional option, particularly in anti-MDA-5 positive patients 1, 2

For Rheumatoid Arthritis-Associated ILD (RA-ILD)

• Preferred options: Mycophenolate, rituximab, nintedanib, tocilizumab, cyclophosphamide 1, 2
• Rituximab may be particularly advantageous when active inflammatory arthritis coexists, as it addresses both articular and pulmonary manifestations 1
• Pirfenidone slows annual FVC decline by approximately 44-57% in IPF and may be considered 4, 3

For Mixed Connective Tissue Disease-Associated ILD (MCTD-ILD)

• Preferred options: Mycophenolate, rituximab, nintedanib, tocilizumab, cyclophosphamide 1, 2
• When elevated CRP is present, tocilizumab demonstrates particular efficacy 2

For Sjögren's Disease and Systemic Lupus Erythematosus-Associated ILD

• Preferred options: Mycophenolate, rituximab, nintedanib, cyclophosphamide 1, 2

Additional First-Line Options Across All SARD-ILD Subtypes

• Rituximab is conditionally recommended across all SARD-ILD subtypes and was shown in the RECITAL trial to have similar mortality rates and FVC outcomes as cyclophosphamide in severe and progressive ILD 1, 2
• Cyclophosphamide (500-750 mg/m² IV every 4 weeks for 6 months OR oral 2 mg/kg/day for 6 months) is conditionally recommended but typically not used in combination with other therapies 1
• Azathioprine (2-3 mg/kg/day) is conditionally recommended for all SARD-ILD subtypes except SSc-ILD 1, 2

Critical Glucocorticoid Guidance

• Short-term glucocorticoids may be considered as bridging therapy when switching treatments or during disease flares in non-SSc SARD-ILD 1
• Long-term glucocorticoid use should be avoided in all SARD-ILD subtypes except as part of combination therapy for rapidly progressive disease 1
• In SSc-ILD specifically, glucocorticoids are strongly contraindicated due to association with scleroderma renal crisis at any dose, but particularly >15 mg/day 1, 2

Medications to Avoid in SARD-ILD

The following agents are recommended against for ILD treatment, though they may be appropriate for extrapulmonary manifestations 1:

• Methotrexate
• Leflunomide
• TNF inhibitors
• Abatacept

Consider discontinuing these medications if ILD develops while using them 1

Monitoring Requirements

• Mycophenolate: CBC with differential and LFTs at baseline, 2-3 weeks after starting, 2-3 weeks after dose increases, then every 3 months 1, 5
• Cyclophosphamide: CBC with differential 10-14 days after IV administration and before next dose; urinalysis every 4-8 weeks; annual urine cytology after any cyclophosphamide exposure 1
• Tacrolimus: BP, serum creatinine, BUN, CBC, serum magnesium, potassium, uric acid, lipid profile every 2 weeks for first 3 months, then monthly 1
• Pulmonary function tests (FVC and DLCO) every 3-6 months to assess disease progression 5, 3

Common Pitfalls to Avoid

• Do not delay immunosuppression while awaiting complete diagnostic workup—early treatment prevents irreversible fibrosis 2
• Do not use long-term high-dose glucocorticoids as monotherapy—this increases mortality risk without addressing underlying pathophysiology 2
• Do not overlook the need for co-management between rheumatology and pulmonology 1
• A 5% decline in FVC over 12 months is associated with approximately 2-fold increase in mortality and warrants treatment escalation 3

When to Consider Lung Transplantation Referral

• Early referral for lung transplantation evaluation should occur in patients presenting with advanced disease or those requiring high-flow oxygen 1
• Median survival after lung transplant is 5.2-6.7 years compared to less than 2 years in advanced ILD without transplant 3
• Pre-transplantation evaluation takes considerable time, so referral should not be delayed until severe deterioration occurs 1