In a patient with rheumatoid arthritis‑associated interstitial lung disease, restrictive pulmonary function pattern, rheumatoid factor 90 IU/mL and C‑reactive protein 5.6 mg/L, can hydroxychloroquine be used as sole therapy?

Hydroxychloroquine Monotherapy is Inadequate for RA-ILD

Hydroxychloroquine alone should not be used as sole therapy for rheumatoid arthritis-associated interstitial lung disease with restrictive pulmonary function and elevated inflammatory markers. This patient requires immunosuppressive therapy with mycophenolate, azathioprine, rituximab, or cyclophosphamide as first-line treatment. 1, 2

Why HCQ Monotherapy is Insufficient

The 2023 American College of Rheumatology/American College of Chest Physicians guidelines explicitly recommend mycophenolate, azathioprine, and rituximab as first-line treatment options for RA-ILD, with mycophenolate being the preferred agent. 1, 2 Hydroxychloroquine is not mentioned as an appropriate treatment for RA-ILD in any major guideline. 1, 2, 3

While the 2021 ACR guidelines for RA recommend hydroxychloroquine for patients with low disease activity affecting only the joints, this patient has significant extra-articular manifestations (ILD with restrictive pattern) and elevated inflammatory markers (RF 90 IU/mL, CRP 5.6 mg/L), indicating moderate-to-high disease activity. 1

Recommended First-Line Treatment Approach

Start mycophenolate as the preferred first-line immunosuppressive agent for this patient with RA-ILD, regardless of the radiologic pattern on high-resolution CT. 1, 2, 3, 4 Mycophenolate has demonstrated favorable efficacy and tolerability compared with alternative agents across all SARD-ILD subtypes. 4

Alternative First-Line Options if Mycophenolate is Contraindicated:

• Rituximab: Particularly beneficial if the patient has active inflammatory arthritis alongside ILD, as it addresses both manifestations simultaneously. 1, 2
• Azathioprine: Another conditionally recommended first-line option for RA-ILD. 1, 2
• Cyclophosphamide: Reserved for severe cases, typically used as monotherapy without combining with other immunosuppressants. 1, 2, 4

Role of Short-Term Glucocorticoids

Short-term glucocorticoids (≤3 months) are conditionally recommended as part of initial therapy for RA-ILD to bridge to immunosuppressive therapy or manage acute inflammatory flares. 1, 2 However, long-term glucocorticoid use should be avoided in progressive disease due to infection risk and other toxicities. 1

When to Add Antifibrotic Therapy

Do not start with antifibrotic agents (nintedanib or pirfenidone) as first-line therapy. 1, 2 Add nintedanib (preferred) or pirfenidone only if the patient develops progressive pulmonary fibrosis despite immunosuppression, defined as: 1, 2, 3

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

Critical Monitoring Parameters

Establish baseline with pulmonary function tests (including spirometry and DLCO) and high-resolution CT scan. 3 Perform short-term follow-up PFTs within 3 months and repeat HRCT within 6 months to determine rate of progression. 2

Common Pitfalls to Avoid

Do not use methotrexate, leflunomide, TNF inhibitors, or abatacept for treating RA-ILD, as these agents are advised against for ILD treatment despite their efficacy for articular disease. 1, 4 Some experts would discontinue these medications if ILD develops while using them. 1

Multidisciplinary co-management with pulmonology is essential for initiation of ILD treatment, particularly to determine treatment necessity and monitor for progression. 1, 2, 3