New research showing a dose-related relationship between prednisone use and pneumonia risk in rheumatoid arthritis (RA) calls into question the commonly held belief that low-dose prednisone is safe, according to a new study that appears in the February issue of Arthritis & Rheumatism.¹

Pneumonia is a well-known cause of mortality in RA patients, but until now much of the research has focused on secondary lung disease and adverse pulmonary effects of specific treatments such as injectable gold, methotrexate (MTX), and leflunomide. However, this new study found that average daily dosages of <e;5 mg of prednisone were associated with an increased risk of pneumonia. In  contrast, no increased risk was seen for anti-tumor necrosis factor alpha (TNF-a) therapy, MTX, or sulfasalazine, the study showed. Leflunomide, however, did slightly increase the risk of pneumonia.

For this study, 16,788 RA patients were assessed semiannually for 3.5 years. Pneumonia was confirmed by medical records or detailed patient interview. Covariates included RA severity measures, diabetes, pulmonary disease, and myocardial infarction. Cox proportional hazards regression was used to determine the multivariable risk associated with RA treatments.

After adjustment for covariates, prednisone use conferred a 70% increased risk of pneumonia hospitalization, including a dose-related increase in risk, with patients treated with the highest dose showing the greatest increase in risk. Leflunomide use was associated with a 20% increased risk of developing pneumonia. In addition, the data showed that diabetes, prior myocardial infarction, and prior pulmonary disease also increased the risk of pneumonia.

Important public health problem

"Given the broad spectrum of cellular mechanisms provoked by glucocorticoids (in relative contrast to the relatively specific actions of other DMARDs), it is perhaps not surprising that prednisone exhibited the strongest association with subsequent pneumonia," conclude the researchers, led by chief researcher Frederick Wolfe, MD, of the National Data Bank for Rheumatic Disease in Wichita, Kansas. "If the results of this study are correct, they may undermine the current belief that low-dose prednisone is safe. Given the prevalence of prednisone use, the findings of this investigation suggest a potentially important public health problem."

Aryeh Fischer, MD, assistant professor of medicine in the division of rheumatology at the National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, both in Denver, Colorado, tells CIAOMed that "the things that were surprising in this study [were] that we did not see an increased risk of pneumonia with anti-TNF agents or MTX and that even low-dose prednisone seems to be a risk factor for pneumonia in patients with RA, and this is one more piece of information that needs to be factored in to the risk-benefit profile when treating RA."

More research still required

The new set of findings, however, does not address the net benefit of prednisone use. "It is possible that discontinuing prednisone or not using prednisone in the first place might prove to have equally undesirable adverse effects," conclude the authors, who suggest that since this research has broad public health implications, a randomized controlled trial should be undertaken to confirm their conclusions.

Reference

1. Wolfe F, Caplan L, Michaud K. Treatment for rheumatoid arthritis and the risk of hospitalization of pneumonia. Associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy. Arthritis Rheum. 2006;54:628-634.