According to guidelines, what is the recommended treatment approach for systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD‑ILD)?

Treatment of SARD-ILD According to Guidelines

Mycophenolate is the preferred first-line immunosuppressive agent for all SARD-ILD subtypes, with disease-specific modifications for glucocorticoids, additional agents, and progression management based on the underlying autoimmune condition. 1

First-Line Treatment by SARD Subtype

Systemic Sclerosis-ILD (SSc-ILD)

• Mycophenolate (1000-1500 mg twice daily) is the preferred first-line agent 1, 2
• Tocilizumab is conditionally recommended as first-line therapy 1
• Cyclophosphamide serves as an additional first-line option 1
• Nintedanib is conditionally recommended as first-line therapy 1
• Strongly recommend AGAINST glucocorticoids as first-line treatment due to increased risk of scleroderma renal crisis 1

Myositis-ILD (IIM-ILD)

• Mycophenolate is the preferred agent 1
• Azathioprine is an alternative first-line option 1
• JAK inhibitors are conditionally recommended specifically for IIM-ILD 1
• Calcineurin inhibitors (CNIs) are conditionally recommended for IIM-ILD 1
• Short-term glucocorticoids (≤3 months) are conditionally recommended 1

Mixed Connective Tissue Disease-ILD (MCTD-ILD)

• Mycophenolate is the preferred agent 1
• Azathioprine is an alternative first-line option 1
• Tocilizumab is conditionally recommended 1
• Short-term glucocorticoids (≤3 months) with caution in patients with SSc phenotype due to renal crisis risk 1

Rheumatoid Arthritis-ILD (RA-ILD)

• Mycophenolate is the preferred agent 1, 2
• Azathioprine is an alternative first-line option 1, 2
• Cyclophosphamide serves as an additional option 1, 2
• Short-term glucocorticoids (≤3 months) are conditionally recommended 1, 2
• No consensus on nintedanib as first-line therapy 1

Sjögren's Disease-ILD (SjD-ILD)

• Mycophenolate is the preferred agent 1
• Azathioprine is an alternative first-line option 1
• Cyclophosphamide serves as an additional option 1
• Short-term glucocorticoids (≤3 months) are conditionally recommended 1

Agents to AVOID as First-Line Therapy

• Leflunomide, methotrexate, TNF inhibitors, and abatacept are conditionally recommended AGAINST for all SARD-ILD 1
• Pirfenidone is conditionally recommended AGAINST as first-line therapy for all SARD-ILD 1
• IVIG and plasma exchange are conditionally recommended AGAINST as first-line options 1
• Upfront combination of nintedanib or pirfenidone with mycophenolate is recommended AGAINST; use mycophenolate alone first 1

Management of Progressive SARD-ILD Despite First-Line Treatment

General Progression Management

• Strongly recommend AGAINST long-term glucocorticoids for SSc-ILD progression 1
• Conditionally recommend AGAINST long-term glucocorticoids for other SARD-ILD progression 1
• Mycophenolate, rituximab, cyclophosphamide, and nintedanib are conditionally recommended for progressive SARD-ILD 1

Disease-Specific Progression Management

RA-ILD Progression:

• Pirfenidone is conditionally recommended as add-on therapy specifically for progressive RA-ILD 1, 2
• Tocilizumab is conditionally recommended 1
• Nintedanib is conditionally recommended 2

SSc-ILD Progression:

• Tocilizumab is conditionally recommended 1
• Referral for stem cell transplantation and/or lung transplantation is conditionally recommended 1

MCTD-ILD Progression:

• Tocilizumab is conditionally recommended 1
• IVIG is conditionally recommended for adding to therapy 1

IIM-ILD Progression:

• CNIs are conditionally recommended 1
• JAK inhibitors are conditionally recommended 1
• IVIG is conditionally recommended for adding to therapy 1
• Conditionally recommend AGAINST tocilizumab 1

SjD-ILD Progression:

• Conditionally recommend AGAINST tocilizumab 1

Management of Rapidly Progressive SARD-ILD (RP-ILD)

First-Line RP-ILD Treatment

• Pulse intravenous methylprednisolone is conditionally recommended 1, 2
• Rituximab, cyclophosphamide, IVIG, mycophenolate, CNIs, and JAK inhibitors are all conditionally recommended first-line options 1, 2
• Upfront combination therapy is preferred over monotherapy: triple therapy for confirmed or suspected MDA-5 positive patients; double or triple therapy for MDA-5 negative patients 1, 2

Agents to AVOID in RP-ILD

• Conditionally recommend AGAINST: methotrexate, leflunomide, azathioprine, TNF inhibitors, abatacept, tocilizumab, nintedanib, pirfenidone, and plasma exchange 1
• Conditionally recommend AGAINST stem cell transplantation as first-line therapy 1
• Early referral for lung transplantation is conditionally recommended over delayed referral after progression 1

Monitoring Strategy

• Pulmonary function tests (PFTs) including FVC and DLCO every 3-6 months to assess progression 2, 3
• High-resolution CT scanning at baseline and annually, or with significant PFT changes 2, 3
• Significant progression is defined as ≥10% absolute or relative decline in FVC over 6 months, or ≥15% decline in DLCO over 6 months 3
• Monitor complete blood count with differential every 2-4 months for patients on mycophenolate 2

Critical Pitfalls to Avoid

• Never use long-term glucocorticoid monotherapy for fibrotic NSIP or SSc-ILD due to substantial adverse effects without proven long-term efficacy 2, 3
• Do not delay treatment escalation when functional decline occurs (FVC drop ≥10% or DLCO drop ≥15%) 3
• Avoid the triple therapy regimen of prednisone, azathioprine, and N-acetylcysteine, which is contraindicated due to increased mortality 3
• Do not combine antifibrotics with mycophenolate upfront without evidence of progression on mycophenolate alone 1
• Exercise caution with glucocorticoids in MCTD patients with SSc phenotype due to increased renal crisis risk 1