Increased risk of severe COVID-19 outcomes in patients with rheumatoid arthritis and interstitial lung disease

Patients with chronic autoimmune disorders are naturally at higher risk of infection, and immunosuppressive therapy increases this risk. The COVID-19 pandemic in many ways provided a perfect storm for patients with rheumatoid arthritis, especially for those with systemic complications such as interstitial lung disease. In the absence of evidence, their responsible clinicians had no way of knowing whether continuing immunosuppressive therapy increased or reduced survival during the pandemic. The Article by Gabriel Figueroa-Parra and colleagues¹ in The Lancet Rheumatology shows that patients with rheumatoid arthritis are at increased risk of severe COVID-19 (ie, hospitalisation or death after COVID-19) compared with matched comparators without rheumatoid arthritis (hazard ratio [HR] 1·75 [95% CI 1·45–2·10]). When examining phenotypic features of rheumatoid arthritis, patients with rheumatoid arthritis-related interstitial lung disease had an even greater risk (HR 2·50 [1·66–3·77]) for severe outcomes than those without rheumatoid arthritis following infection with SARS-CoV-2.¹ These data add to previous evidence that patients with interstitial lung disease are at increased risk of adverse outcomes from COVID-19.2, 3 However, at present, it remains impossible to estimate the degree to which rheumatoid arthritis, the associated interstitial lung disease, and the medication that these patients require for their disease individually contribute towards this increased risk. The number of patients on each specific drug was too small for reliable statistical analysis in this study. Understanding which drugs are safe to use during the pandemic is a complex but key issue for clinicians managing patients with rheumatoid arthritis-related interstitial lung disease, as some drugs used, or proposed, for the treatment of rheumatoid arthritis-related interstitial lung disease have also been trialled in the treatment of COVID-19 pneumonia, which shares overlapping clinical features with acute-onset interstitial lung disease in patients with rheumatoid arthritis.⁴

Glucocorticoids, interleukin (IL)-6 inhibitors, and Janus kinase (JAK) inhibitors have been shown to have potential benefit in the treatment of patients with acute pneumonia from COVID-19.⁵ Although oral prednisone is no longer considered standard treatment for rheumatoid arthritis-related interstitial lung disease, there is some evidence for the efficacy of IL-6 and JAK inhibitors in this condition.⁶ By contrast, there is concern that rituximab might increase the risk of mortality in patients with acute COVID-19,⁷ despite being associated with improved outcomes in the management of rheumatoid arthritis-related interstitial lung disease.⁸ The data available from the admittedly small numbers of participants from Figueroa-Parra and colleagues supports the evidence that rituximab increases the risk of mortality in patients with COVID-19 in suggesting that worse outcomes might have been associated with rituximab therapy, whereas reduced risk of mortality might have been accorded to those on JAK inhibitors.¹

There is good evidence that the subset of interstitial lung disease is a major determinant of prognosis of rheumatoid arthritis-related interstitial lung disease. Patients with rheumatoid arthritis-related interstitial lung disease with a usual interstitial pneumonia pattern on imaging have a four-fold increased risk of death compared with those with non-specific interstitial pneumonia.⁹ Furthermore, the extent of lung involvement, as assessed by imaging, is an additional determinant of prognosis.¹⁰ Neither of these variables were assessed in the study by Figueroa-Parra and colleagues, making it difficult to predict whether the adverse outcomes of COVID-19 in people with rheumatoid arthritis-related interstitial lung disease are confined to those with extensive usual interstitial pneumonia or whether they apply to all patients with interstitial lung disease.

Women with rheumatoid arthritis appeared to be at considerably higher risk of severe COVID-19 (HR 2·03 [1·62–2·55] compared with women without rheumatoid arthritis) than were men with rheumatoid arthritis (1·23 [0·88–1·74] compared with men without rheumatoid arthritis).¹ This increased risk might appear counterintuitive given that interstitial lung disease develops more frequently in men. However, the respiratory reserve is usually greater in men, and obesity, which increases the risk of adverse outcomes, might be more common in women. Other known risk factors for interstitial lung disease in people with rheumatoid arthritis analysed in this study included age, smoking, and seropositivity. Increased articular disease activity is also associated with interstitial lung disease; however, this study was unable to assess the potential influence of disease activity on outcomes due to its retrospective design. Clinicians treating patients with rheumatoid arthritis-related interstitial lung disease need to balance their enthusiasm to reduce the activity of disease in the joints and lungs against the potential increased risk of severe COVID-19 from immunosuppression.

It is important to note that this study was done in the first 15 months of the COVID-19 epidemic. As a result, only 21 (4%) of the patients included had the opportunity to receive vaccination before enrolment. The risk of developing severe COVID-19 in patients with rheumatoid arthritis-related interstitial lung disease is likely to be reduced by vaccination (as this study recognises), and repeating this study in a vaccinated rheumatoid arthritis population could provide valuable guidance for clinicians and public health physicians.

The key message from this Article is that people with rheumatoid arthritis are at higher risk of developing severe COVID-19, and that, for those with interstitial lung disease, the risk appears especially high. However, several factors remain unknown, including the degree of vaccination that attenuates the risks of severe COVID-19 and how much of the risk is due to the disease rather than drugs used to treat it. Detailed answers to these questions are essential for clinicians if they are to offer patients accurate evidence-based advice. Additional data on the potential contributions of high disease activity and interstitial lung disease subtype could also be provided in a large prospective study designed to address these issues in a vaccinated rheumatoid arthritis population with detailed therapeutic documentation.

© 2022 K H Fung/Science Photo Library

I declare no competing interests.