Comment on: “Comprehensive analysis of patients with rheumatoid arthritis-associated interstitial lung disease” by Kim et al.
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To the Editor,
We read with great interest the article by Kim et al. [1] entitled “Comprehensive analysis of patients with rheumatoid arthritis-associated interstitial lung disease,” recently published in the Korean Journal of Internal Medicine. The authors are to be commended for presenting a large retrospective cohort spanning more than two decades, which provides valuable insights into the prognostic role of interstitial lung disease (ILD) progression, disease duration, and radiological patterns, particularly the usual interstitial pneumonia (UIP) subtype, in patients with rheumatoid arthritis (RA).
The study demonstrated that ILD progression was the strongest determinant of mortality (hazard ratio, 27.22), while male sex and the UIP pattern independently predicted progression. These findings are clinically relevant, underscoring that RA-ILD remains a major contributor to morbidity and mortality. The observation that methotrexate use did not worsen outcomes is timely, challenging long-standing concerns of methotrexate-related pulmonary toxicity and supporting recent data indicating its safety in RA-ILD [2,3].
Several limitations warrant attention. The retrospective, single-center design limits generalizability, and the long inclusion period (1999–2022) spans an era of evolving imaging modalities and therapeutic approaches. Early cases may not have benefited from high resolution computed tomography or antifibrotic therapy, which may have contributed to an apparent increase in progression rates. Moreover, the relatively low utilization of biologic and targeted disease modifying anti rheumatic drugs (DMARDs) and antifibrotic agents, reflecting restricted access in Korea, may have led to an underestimation of their potential benefits. Registry and multicenter studies suggest that abatacept, rituximab, and Janus kinase inhibitors may stabilize or even improve lung function in RA-ILD [4–7]. Treatment heterogeneity, including variability in DMARD exposure and corticosteroid use, further complicates interpretation.
An intriguing observation was the apparent trend toward lower mortality among leflunomide-treated patients, which contrasts with prior concerns regarding pulmonary toxicity. Although confounding factors and preserved baseline function may account for this finding, the signal deserves further investigation and could influence future perceptions of leflunomide use in early RA-ILD.
Importantly, the authors highlighted that ILD progression, rather than comorbidities, was the principal driver of mortality, whereas earlier studies had implicated age, corticosteroid exposure, or chronic obstructive pulmonary disease [8,9]. This finding underscores the urgent need for strategies aimed at preventing disease progression through early recognition, personalized management, and timely access to antifibrotic or biologic therapies. Despite major therapeutic advances, pulmonary involvement remains the most life-threatening manifestation of RA and a leading cause of death in this population.
In conclusion, Kim et al. [1] have made an important contribution by demonstrating that the UIP pattern and longer disease duration predict ILD progression and that progression itself drives mortality. Prospective, multicenter studies integrating antifibrotic agents with contemporary DMARD strategies are urgently needed to validate these findings and optimize outcomes in this high-risk population.
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Acknowledgments
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