VIENNA, Austria-Data from the National Data Bank for Rheumatic Diseases in Wichita, Kansas, reveals that treatment of rheumatoid arthritis (RA) with methotrexate (MTX) and/or tumor necrosis factor-alpha (TNF-α) inhibitors reduces all-cause mortality and specifically reduces death due to cardiovascular (CV) and pulmonary disease, according to Kaleb Michaud, MD, and Frederick Wolfe, MD, who presented their findings here on Friday at the Annual European Congress of Rheumatology of the European League Against Rheumatism (EULAR). The study is important, indicated Dr. Michaud, because "there is no evidence of long-term benefit and concern about the long-term safety" of RA treatments.
"This is very interesting because if cardiovascular mortality is reduced, other risk factors should be reduced," Sir Ravinder Maini, FRCP, FRCP(E), FMedSci, emeritus professor of rheumatology and former director of The Kennedy Institute of Rheumatology at the Imperial College, University of London in the UK, tells CIAOMed.
The results were drawn from an analysis of 63,811 years of follow-up of 19,580 RA patients. During this time period, 1129 deaths occurred. In a multivariate analysis, the hazard ratio (HR) associated with age (per year) was 1.06; male gender, 1.90; education level (years), 0.95; baseline myocardial infarction, 1.77; and baseline pulmonary disease, 1.58.
While prednisone use was associated with increased mortality, (HR 1.60), MTX and anti-TNF-α monotherapy were associated with HRs for mortality of 0.84 and 0.72, respectively. Sulfasalazine, leflunomide, and hydroxychloroquine were not significantly associated with mortality risk in these analyses. The effects of combination regimens were also analyzed in the study, and the results are presented in Table 1 below.
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The inflammatory burden endured by RA patients is presumed to underlie the various comorbidities that accompany the disease. Although RA may flare and remit, the total effect over time is thought to contribute to mortality. "It's the area under the curve of the inflammatory burden," indicates Steven A. Paget, MD, professor of medicine at the Hospital for Special Surgery and the Weill Medical College of Cornell University in New York City. "The collateral damage we're trying to address includes cardiovascular and pulmonary disease."
Indeed, the idea that treatment of RA reduces the deleterious effects of accumulated inflammatory burden are indicated by the data presented here, suggesting that MTX, infliximab, and etanercept therapy are associated with a decrease in CV mortality (HR 0.55 to 0.69) and death from pulmonary disorders (HR 0.75 to 0.76).
Dr. Wolfe tells CIAOMed that data from the National Data Bank for Rheumatic Diseases is also being analyzed for outcomes other than mortality. He presented analyses of the incidence of lung cancer, breast cancer, and pain among RA patients, and the effects of TNF-α inhibitors on these rates. "We're currently looking at rates of infections and the effects of treatment and disease severity," he says, adding that more results will be presented at the 2005 ACR meeting.
"We're also looking at vasculitis and fracture," Dr. Michaud adds. "We're trying to capture as much information about everything as we can, so that if we miss anything important we can go back and look at it."
"We can answer a great deal of questions [with this data set]," Dr. Wolfe says. "We actually need help from community physicians. We're interested in recruiting more people who have rheumatic diseases." He indicated that interested physicians should contact the National Data Bank for Rheumatic Diseases at www.arthritis-research.org.
Reference:
Michaud K, Wolfe F. Reduced mortality among RA patients treated with anti-TNF therapy and methotrexate. Presented at: Annual European Congress of Rheumatology of EULAR; June 8-11, 2005; Vienna, Austria. Abstract OP0095.