What is the appropriate management for a 72‑year‑old woman with rheumatoid arthritis‑associated interstitial lung disease (rheumatoid factor 90 U), elevated C‑reactive protein (5.2 mg/dL), and worsening dyspnea?

Management of RA-Associated Interstitial Lung Disease with Active Inflammation

This 72-year-old woman with RA-ILD, elevated inflammatory markers (RF 90, CRP 5.2), and worsening dyspnea requires immediate initiation of immunosuppressive therapy, with mycophenolate mofetil as the preferred first-line agent, or rituximab if she has active inflammatory arthritis requiring concurrent treatment. 1, 2

Immediate Assessment Required

Before initiating therapy, determine:

• ILD severity and pattern: Obtain high-resolution CT (HRCT) to identify usual interstitial pneumonia (UIP) versus non-specific interstitial pneumonia (NSIP) pattern 1, 2
• Baseline pulmonary function: Perform spirometry with DLCO to establish forced vital capacity (FVC) and diffusion capacity 1, 2
• Articular disease activity: Assess whether she has active inflammatory arthritis requiring treatment beyond ILD management 3
• Infection risk: Given her elevated CRP and planned immunosuppression, maintain low threshold for bronchoscopy to exclude pulmonary infection 2

First-Line Treatment Selection

Preferred Option: Mycophenolate Mofetil

Mycophenolate is the preferred first-line immunosuppressive agent for RA-ILD across all radiological patterns (UIP and NSIP). 1, 2 This recommendation comes from the 2023 ACR/Chest guidelines and is supported by retrospective data showing efficacy even in UIP-pattern disease. 4

Alternative: Rituximab

If this patient has active inflammatory arthritis alongside her ILD, rituximab should be chosen instead, as it provides dual benefit for both joint disease and ILD, with potential mortality reduction. 3, 1

Other First-Line Options

• Azathioprine is another acceptable first-line choice 1, 4
• Cyclophosphamide can be considered in severe cases 1

Corticosteroid Use

Short-term glucocorticoids (≤3 months) can be added as bridging therapy while immunosuppression takes effect. 3, 1 For acute inflammatory flares, pulse methylprednisolone 500-1000 mg IV daily for 3 days followed by oral prednisone taper may be used. 2

Critical caveat: Long-term glucocorticoid use must be avoided in progressive disease and should only serve as a bridge to definitive immunosuppression. 3

Monitoring for Progression

Establish baseline and monitor closely for progression, defined as:

• ≥10% predicted FVC decline within 24 months 1
• 5-10% FVC decline plus worsening symptoms or increased fibrosis on HRCT 1
• Worsening respiratory symptoms with increased fibrosis on HRCT 1

Schedule short-term follow-up: PFTs within 3 months and repeat HRCT within 6 months to determine rate of progression. 1

If Disease Progresses Despite Immunosuppression

Add nintedanib (preferred) or pirfenidone if she meets progression criteria while on adequate immunosuppression. 1, 4 Nintedanib is the preferred antifibrotic based on randomized controlled trial data showing slowed FVC decline in RA-ILD. 4

Do not add antifibrotics upfront: The guidelines conditionally recommend against combining antifibrotics with immunosuppression before documented progression. 1

Medications to Avoid

Methotrexate, leflunomide, TNF inhibitors, and abatacept should be avoided for RA-ILD treatment, though they may be appropriate for isolated articular disease. 3 Some experts would stop these medications if ILD develops while using them. 3

Multidisciplinary Co-Management

Co-management with pulmonology is essential for treatment initiation, monitoring, and determining need for escalation. 3 This collaboration is particularly important given her worsening dyspnea and elevated inflammatory markers.

Risk Factors Present

This patient has multiple high-risk features:

• Elevated rheumatoid factor (90 U) - high-titer RF is a known risk factor for RA-ILD development and progression 1, 2
• Female gender at age 72 - older age is associated with worse outcomes 5
• Active inflammation (CRP 5.2) - suggests need for aggressive immunosuppression 2

Early Transplant Referral Consideration

If she develops need for high-flow oxygen or shows rapid progression despite optimal medical management, early referral for lung transplantation evaluation should be initiated, as the pre-transplantation evaluation process is lengthy. 3, 1