Long-term Mortality Decline in RA Skips Those Who Also Have Interstitial Lung Disease

The rise of disease-modifying agents has led to an overall decline in mortality for patients with rheumatoid arthritis (RA), but not everyone has benefited equally. Mortality rates have not budged for those with RA and interstitial lung disease (ILD), according to a study and editorial appearing in this month’s Annals of the American Thoracic Society.

First, authors led by Niranjan Jeganathan, MD, of Loma Linda University, analyzed data from the CDC Multiple Case Database, segmenting out both overall RA mortality rates and trends from 2005 to 2018 as well as those for patients with RA-ILD, using International Classification of Disease, Tenth Revision codes. They found the following:

• RA- and RA-ILD related morality rates were higher in women and older patients.
• Despite the first finding, prevalence of ILD was higher in men who died with RA compared with women who with the disease, (13.3% vs 8.7%).
• RA-related mortality rates were highest among Native American individuals followed by White individuals. Compared with White patients, Hispanic patients had lower RA-related mortality rates but higher RA-ILD related morality rates.
• Overall RA-related morality rates per 1 million population decreased from 30.6 in 2005 to 22.2 in 2018 and declined across all demographic groups. But RA-ILD mortality rates remained stable in both sexes, all races, and all age groups except for those aged 65 to 84 years of age, in which rates declined.

In their accompanying editorial, Pankti Reid, MD, MPH, of the University of Chicago, and Sabina A. Guler, MD, MHSc, of the University of Bern in Switzerland, note that age- and sex-matched data from Denmark that show a 5-year mortality of 36% for RA patients with ILD, compared with 18% for RA patients without this comorbidity. ILD is caused by inflammation that leads to scarring of the lungs; it causes shortness of breath, dry cough, and fatigue; data show it doubles mortality risk in RA.

The RA-ILD combination is not rare. Some level of ILD is present in 60% of RA cases; it’s clinically significant in at least 10% and is a leading cause of death in these patients, according to the European Respiratory Review.

Why is ILD such a problem? According to Reid and Guler, the mortality discrepancy “can only partially be explained by more frequent comorbidities (e.g., heart disease and diabetes) affecting patients with RA-ILD.”

They explain that most treatment recommendations for RA-ILD rely on extrapolation from other connective tissue diseases and observational studies or small uncontrolled studies; there are no large, randomized controlled trials specifically in RA-ILD to inform therapeutic decisions.

“Antifibrotic medications show promise for patients with connective tissue disease–associated ILD; however, their efficacy in RA-ILD is still largely unknown,” Reid and Guler write.

Falling RA mortality rates “is not a novel finding,” the editorial notes; this trend was first tracked by the World Health Organization. However, Jeganathan et al, do find discrepancies in some populations within the data set, and say the findings for RA-ILD should be “of particular concern for pulmonologists and rheumatologists because RA or ILD was the underlying cause of death in 77% of the RA-ILD population and mortality from other causes (cancer, heart, or cerebrovascular disease) was less frequent than that in the overall RA population.”

They state, “the interaction between smoking and race in the context of RA mortality remains to be determined.”

The editorial calls for better strategies for RA-ILD management, and states that “We should focus our attention to particularly vulnerable RA subpopulations by ensuring adequate representation in future clinical trials and equal access to health care for all.”

References

1. Jeganathan N, Nguyen E, Sathananthan M. Rheumatoid arthritis and associated interstitial lung disease: mortality rates and trends. 2021;18(12):1970-1977. doi: 10.1513/AnnalsATS.202102-115OC.
2. Reid P, Guler SA. Mortality trends in rheumatoid arthritis: zooming in on interstitial lung disease. 2021;18(12): https://doi.org/10.1513/AnnalsATS.202108-899ED