From the Guidelines
Antifibrotic medications, such as nintedanib, should be considered as adjunctive therapy in patients with rheumatoid arthritis (RA) related fibrosis, particularly in those with progressive pulmonary involvement, as they have been shown to slow down disease progression 1. The use of antifibrotics in RA-related fibrosis is a topic of ongoing debate, with some studies suggesting a potential benefit in slowing down disease progression, particularly in patients with pulmonary involvement 1.
- Key considerations in the management of RA-related fibrosis include:
- Controlling underlying rheumatoid inflammation with conventional DMARDs or biologics to prevent fibrosis progression
- Using antifibrotics, such as nintedanib, as adjunctive therapy in patients with progressive fibrotic manifestations despite adequate control of inflammation
- Monitoring patients closely for signs of disease progression, including regular pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) scans
- Considering the potential benefits and risks of antifibrotic therapy, including the risk of adverse effects such as gastrointestinal disturbances and elevated liver enzymes
- The 2023 American College of Rheumatology (ACR) guidelines conditionally recommend adding antifibrotic treatment, such as nintedanib or pirfenidone, as therapeutic options for the management of progressive RA-ILD despite first-line treatment 1.
- Nintedanib has been shown to slow down disease progression in patients with RA-ILD, particularly in those with a UIP pattern of ILD 1.
- Pirfenidone has also been investigated as a potential treatment for RA-ILD, but the evidence is limited and the benefits and risks are still being studied 1.
- The decision to use antifibrotics in RA-related fibrosis should be made on a case-by-case basis, taking into account the individual patient's disease characteristics, medical history, and potential risks and benefits of treatment 1.
From the Research
Role of Antifibrotics in Rheumatoid Arthritis (RA) Related Fibrosis
The role of antifibrotics in RA related fibrosis can be understood through the following points:
- Antifibrotic agents, such as nintedanib and pirfenidone, have been shown to slow the progression of connective tissue disease-associated interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) 2, 3, 4.
- Studies have demonstrated that antifibrotic therapy can stabilize lung function, based on forced vital capacity (FVC) and total lung capacity (TLC), in patients with RA-ILD 2, 3, 4.
- A meta-analysis revealed that antifibrotic agents showed a significant reduction in FVC decline compared to placebo in patients with RA-ILD, with a mean difference of 88.30 (95% CI, 37.10-139.50) 4.
- Antifibrotic therapy has been associated with a modest improvement in the trajectory of %pFVC and stabilization in %pDLCO in patients with RA-ILD 2.
- Adverse events (AEs) are common with antifibrotic therapy, leading to discontinuation in some patients, with gastrointestinal events and hepatitis being the most frequent AEs 2, 3.
Efficacy of Antifibrotic Agents
The efficacy of antifibrotic agents in RA-ILD can be summarized as follows:
- Nintedanib and pirfenidone have been shown to have clinical utility in reducing disease progression in patients with RA-ILD 4.
- A systematic review and meta-analysis found that antifibrotic therapy offers protection against the rate of decline in FVC in progressive lung fibrosis, with similar efficacy shown between nintedanib and pirfenidone 5.
- The efficacy of antifibrotic therapy is similar in both IPF and non-IPF patients with progressive fibrosis, supporting the hypothesis of a common pathogenesis 5.
Real-World Data
Real-world data on the use of antifibrotics in RA-ILD patients has been reported in several studies:
- A longitudinal, retrospective, observational study found that antifibrotic initiation was associated with a modest improvement in the trajectory of %pFVC and stabilization in %pDLCO in patients with RA-ILD 2.
- A nationwide cohort study found that antifibrotic therapy was effective in stabilizing lung function, based on FVC and TLC, in patients with RA-ILD 3.
- A case report described a patient with RA-UIP who was successfully treated with nintedanib, with a reduction in FVC decline from -11.6%/year to -5.2%/year 6.