How to manage rheumatoid arthritis (RA) with interstitial lung disease (ILD)?

Management of Rheumatoid Arthritis with Interstitial Lung Disease

For RA-ILD, initiate mycophenolate 1000-1500 mg twice daily as first-line therapy, combined with short-term glucocorticoids (≤3 months), and monitor disease progression with pulmonary function tests every 3-6 months. 1, 2

Initial Treatment Strategy

Preferred First-Line Therapy

• Mycophenolate is the conditionally recommended preferred agent over all other options for RA-ILD, dosed at 1000-1500 mg twice daily 1, 2
• Add short-term glucocorticoids (≤3 months) as part of initial combination therapy, using oral prednisone for gradual-onset disease 1, 2
• Monitor complete blood count every 2-4 months while on mycophenolate 2

Alternative First-Line Options (if mycophenolate contraindicated or not tolerated)

• Azathioprine is conditionally recommended as an alternative first-line agent 1, 2
• Cyclophosphamide represents another first-line option, particularly for more severe disease 1, 2

Disease Monitoring Protocol

Pulmonary Function Assessment

• Perform pulmonary function tests (FVC and DLCO) every 3-6 months to detect disease progression 2
• Obtain high-resolution CT scanning at baseline and annually, or when significant PFT changes occur 2

Key Monitoring Parameters

• Assess for declining FVC as the primary marker of ILD progression 2
• Monitor DLCO trends as an additional indicator of disease activity 2

Management of Progressive RA-ILD Despite First-Line Therapy

If RA-ILD progresses on initial therapy, add pirfenidone or nintedanib as second-line agents, or switch to rituximab, cyclophosphamide, or tocilizumab. 1, 2

Conditionally Recommended Second-Line Options

• Pirfenidone is specifically recommended for progressive RA-ILD (unique among SARD-ILD subtypes) 1, 2
• Nintedanib is conditionally recommended as a treatment option for progressive RA-ILD 1, 2
• Tocilizumab is conditionally recommended for progressive RA-ILD despite first-line treatment 1, 2
• Mycophenolate, rituximab, or cyclophosphamide if not already used as first-line agents 1, 2

Agents to Avoid in Progressive Disease

• Long-term glucocorticoids are conditionally recommended against due to substantial adverse effects without proven long-term efficacy 1, 2
• Calcineurin inhibitors are conditionally recommended against for RA-ILD progression (reserved for IIM-ILD) 1
• JAK inhibitors are conditionally recommended against for RA-ILD (reserved for IIM-ILD) 1

Management of Rapidly Progressive RA-ILD

For rapidly progressive RA-ILD, initiate pulse intravenous methylprednisolone combined with upfront double or triple therapy using rituximab, cyclophosphamide, IVIG, mycophenolate, calcineurin inhibitors, or JAK inhibitors. 1, 2

First-Line Treatment for Rapidly Progressive Disease

• Pulse intravenous methylprednisolone is conditionally recommended as first-line treatment 1, 2
• Upfront combination therapy (double or triple therapy) is conditionally recommended over monotherapy 1, 2
• Rituximab, cyclophosphamide, IVIG, mycophenolate, calcineurin inhibitors, or JAK inhibitors are all conditionally recommended first-line options that can be combined 1, 2

Agents Conditionally Recommended Against for Rapidly Progressive RA-ILD

• Methotrexate, leflunomide, azathioprine are conditionally recommended against 1
• TNF inhibitors, abatacept, tocilizumab are conditionally recommended against 1
• Nintedanib and pirfenidone are conditionally recommended against for rapidly progressive disease 1
• Plasma exchange is conditionally recommended against 1

Transplantation Considerations

• Early referral for lung transplantation is conditionally recommended over later referral after progression on optimal medical management 1
• Stem cell transplantation is conditionally recommended against as first-line treatment for rapidly progressive RA-ILD 1

Critical Pitfalls to Avoid

Glucocorticoid Management

• Avoid long-term glucocorticoid monotherapy as it lacks proven long-term efficacy and carries substantial adverse effects 1, 2
• Limit glucocorticoid use to ≤3 months for gradual-onset RA-ILD 1, 2

DMARD Selection for Joint Disease

• Recognize that TNF inhibitors may not improve or could worsen ILD despite controlling joint disease 3, 4
• Drugs targeting adaptive immune responses (abatacept, rituximab) appear more promising for stabilizing RA-ILD while controlling arthritis 3, 4
• Methotrexate and leflunomide should be avoided in rapidly progressive RA-ILD 1

Disease Activity Assessment

• Achieving remission or low disease activity of arthritis is essential to prevent new emergence, progression, or acute exacerbation of RA-ILD 3
• Do not rely solely on joint disease activity to guide ILD management decisions 2

Multidisciplinary Collaboration

• Management decisions require collaboration between rheumatologists and pulmonologists to balance control of articular disease with ILD progression 2
• Coordinate monitoring strategies to assess both joint and lung disease activity simultaneously 2