What is the recommended treatment approach for patients with fibrosing nonspecific interstitial pneumonia (NSIP) and rheumatoid arthritis (RA)?

Treatment of Fibrosing NSIP in Rheumatoid Arthritis

For patients with fibrosing nonspecific interstitial pneumonia (NSIP) associated with rheumatoid arthritis, mycophenolate is the preferred first-line immunosuppressive therapy, with azathioprine and rituximab as additional first-line options. 1

Initial Treatment Approach

Preferred First-Line Therapy

• Mycophenolate is the conditionally recommended preferred first-line treatment for RA-ILD, including fibrosing NSIP patterns 1
• The 2023 ACR/CHEST guideline establishes a clear hierarchy with mycophenolate ranked above other immunosuppressive options 1

Additional First-Line Options

• Azathioprine can be used as an alternative first-line agent, though it ranks below mycophenolate in the treatment hierarchy 1
• Rituximab is conditionally recommended as another first-line option for RA-ILD 1, 2
• Cyclophosphamide may be considered as an additional option, particularly in more severe or rapidly progressive cases 1

Glucocorticoid Use

• Short-term glucocorticoids (≤3 months) are conditionally recommended as an additional option for initial treatment 1
• Long-term glucocorticoids are strongly recommended against due to significant adverse effects including osteoporosis, cardiovascular disease, and infections 1

Treatment Monitoring and Assessment

Frequency of Monitoring

• Pulmonary function tests (PFTs) should be performed every 3-6 months during the first 1-2 years for patients with mild ILD (FVC ≥70%) 1
• More frequent PFTs (every 3 months) are indicated for patients with moderate-to-severe ILD at baseline or those showing progression 1
• HRCT should be repeated within 3-6 months to 1 year to assess treatment response and identify early progression 1

Defining Treatment Response

• Initial assessment should occur at 3 months, though maximal therapeutic effect may not be evident until 6 months 1, 3
• Stabilization or improvement in FVC and DLCO indicates adequate response 4
• Progressive decline in pulmonary function despite therapy warrants treatment escalation 1

Management of Progressive Disease

When First-Line Therapy Fails

If RA-ILD progresses despite initial immunosuppressive therapy:

• Mycophenolate (if not already used) remains a preferred option 1
• Rituximab is conditionally recommended for progressive disease 1, 2
• Tocilizumab can be considered as a second-line option 1
• Cyclophosphamide may be used for refractory cases 1

Role of Antifibrotic Therapy

Nintedanib is conditionally recommended for progressive RA-ILD, particularly in patients with a usual interstitial pneumonia (UIP) pattern or fibrotic features, though the ACR/CHEST guideline panel could not reach consensus on its use as first-line therapy 1, 2

• Antifibrotics should be considered when ILD progresses despite immunosuppression 1, 5
• Real-world data show nintedanib can stabilize or modestly improve FVC trajectory in progressive RA-ILD 4
• Pirfenidone is conditionally recommended against as first-line therapy due to limited evidence, though it may be considered for progressive disease 1, 2
• Adding antifibrotics to stable mycophenolate therapy (without progression) is conditionally recommended against due to cost, adverse effects, and limited efficacy data 1

Antifibrotic Tolerability Considerations

• Gastrointestinal adverse events (particularly diarrhea with nintedanib) occur in approximately 81% of patients 4
• Dose reduction is required in 40% of nintedanib-treated patients 4
• Discontinuation rates in real-world practice (37%) exceed those in clinical trials 4

Critical Management Considerations

Pattern-Specific Approach

• Fibrosing NSIP may progress to a UIP-like pattern with honeycombing, requiring serial HRCT monitoring 1
• Patients with UIP pattern have worse prognosis and may benefit more from antifibrotic therapy 1, 2, 5
• Immunosuppression should be considered regardless of imaging pattern, as recent data suggest benefit even in UIP patterns 5

Rheumatoid Arthritis Disease Activity

• RA disease activity must be assessed concurrently using composite measures (DAS28, CDAI, SDAI) every 1-3 months 1
• The target for RA control is remission or low disease activity 1
• Treatment decisions must balance control of both articular and pulmonary manifestations 2, 5

Medication-Specific Cautions

• Methotrexate may be continued in patients with stable ILD receiving it for articular disease, but should be stopped if ILD develops or worsens while on methotrexate, or if methotrexate pneumonitis is suspected 1
• TNF inhibitors have uncertain benefit for RA-ILD, with observational data suggesting potential harm or no effect; they can be used for articular disease but some experts would discontinue if ILD develops during therapy 1
• Abatacept does not worsen ILD and may be emerging as a potential treatment option, though efficacy data are limited 1, 5

Multidisciplinary Management

• Rheumatology and pulmonology co-management is essential for integrated assessment of both articular and pulmonary disease 1
• Treatment decisions should account for ILD severity, RA activity, comorbidities, and infection risk 2, 5
• Early referral for lung transplantation evaluation should be considered for patients with progressive disease despite optimal medical therapy 1

Common Pitfalls to Avoid

• Do not use long-term glucocorticoids beyond 3 months due to significant toxicity without proven long-term benefit 1
• Do not delay treatment escalation in patients showing clear progression at 3-6 months 1
• Do not assume all RA-ILD will respond to immunosuppression alone—fibrotic patterns may require antifibrotic therapy 2, 5, 4
• Do not overlook infection risk—immunosuppression increases susceptibility to opportunistic infections and should be balanced against disease severity 2, 5