From the Guidelines
The management of interstitial pulmonary fibrosis (IPF) in rheumatoid arthritis (RA) patients should involve a multidisciplinary approach with rheumatologists and pulmonologists, and may include the use of antifibrotic medications such as nintedanib or pirfenidone, as conditionally recommended by the 2023 ACR guidelines 1.
Key Considerations
- IPF is a recognized extra-articular manifestation of RA, occurring in approximately 10-20% of RA patients.
- The 2023 ACR guidelines propose a preferred ILD therapy for each underlying condition, but disease evaluation is complex and needs to be carefully addressed through a multidisciplinary team for an individualized approach 1.
- The early identification of progressive pulmonary fibrosis is crucial for determining which patients may benefit from antifibrotic therapies 1.
- Treatment typically begins with optimizing the underlying RA therapy, often using disease-modifying antirheumatic drugs (DMARDs) like methotrexate, although this medication should be used cautiously as it can rarely cause lung toxicity itself.
- Corticosteroids are frequently used, starting with prednisone 0.5-1 mg/kg/day with gradual tapering based on clinical response.
- Immunosuppressants like mycophenolate mofetil or cyclophosphamide are often added as steroid-sparing agents.
- Rituximab has shown promise in refractory cases.
Monitoring and Follow-up
- Short-term PFTs (within 3 months) and HRCT (within 6 months) should be considered to determine the rate of progression.
- In mild CTD-ILD, PFTs should be scheduled every 6 months for the first 1 to 2 years.
- Patients with moderate-to-severe ILD at baseline or progressive disease must have more frequent PFTs (every 3–6 months).
- HRCT and PFT should be repeated within 3–6 months to 1 year, depending on the underlying disease, the ILD pattern and the extent, in order to determine the response to treatment and to allow for early identification of progression of inflammation or PPF 1.
From the Research
IPF in Rheumatoid Arthritis
- Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with rheumatoid arthritis (RA) 2.
- The use of biological disease-modifying antirheumatic drugs (DMARDs) has been associated with the development or exacerbation of ILD in RA patients, but a causative relationship is difficult to establish 2.
- Antifibrotic agents, such as nintedanib and pirfenidone, have been shown to be effective in slowing the decline of lung function in patients with RA-ILD 3, 4, 5.
- A systematic review and meta-analysis found that antifibrotic agents demonstrated stabilization of %pFVC, with less robust evidence for %pDLCO in RA-ILD 5.
- Experimental studies have shown that pirfenidone and nintedanib can alleviate joint inflammation and pulmonary fibrosis in a mouse model of RA-ILD, with mechanisms of action related to the inhibition of the TGF-β signaling pathway, Jak2/Stat3 signaling pathway, and polarization of macrophages to the M2 phenotype 6.
Treatment Options
- Nintedanib and pirfenidone are antifibrotic agents that have been shown to be effective in treating RA-ILD 3, 4, 5.
- The choice of treatment depends on various factors, including the severity of the disease, the presence of comorbidities, and the patient's overall health status.
- A standardized staging system for pulmonary conditions of RA-ILD patients is needed to guide therapeutic decisions at baseline and monitoring during biological DMARD therapy 2.
Safety and Tolerability
- Antifibrotic agents have been associated with adverse events, such as gastrointestinal symptoms and hepatotoxicity, which can lead to treatment discontinuation 3, 4, 5.
- The safety and tolerability of antifibrotic agents in patients with RA-ILD are similar to those seen in other patient populations 4.
- Close monitoring of patients receiving antifibrotic agents is necessary to minimize the risk of adverse events and optimize treatment outcomes.