Rheumatoid arthritis (RA) is the most common inflammatory form of arthritis and affects approximately 2 million Americans. RA is a chronic, systemic autoimmune disease that preferentially attacks the joints but also attacks other organ systems such as the lungs, eyes, skin, and cardiovascular system.



The notion that "it's just arthritis" does not apply to RA. Many recent epidemiologic studies have demonstrated that mortality rate in RA patients is higher than in people without rheumatoid arthritis.

What is more disturbing is that this increase in mortality seems to be getting worse according to a study reported in the November 2007 issue of Arthritis and Rheumatism.

"We found no evidence indicating that RA subjects experienced improvements in survival over the last 4 - 5 decades," senior author Dr. Sherine E. Gabriel from the Mayo Clinic in Rochester, Minnesota, said in a news release. "In fact, RA subjects did not even experience the same improvements in survival as their peers without arthritis, resulting in a worsening of the relative mortality in more recent years, and a widening of the mortality gap between RA subjects and the general population throughout time."

During the past few decades of increased survival in the population at large, patients with RA have also benefited from earlier diagnosis, newer drug protocols, and more aggressive treatment programs. However, whether these improvements in management are associated with improved survival has not been well defined.

Using the medical record database of all residents of Olmsted County, Minnesota (where the Mayo Clinic is located), the investigators identified 822 subjects with RA by American College of Rheumatology criteria, aged 18 years or older. This included all residents of Rochester, Minnesota, first diagnosed with RA between January 1, 1955, and January 1, 1995, as well as all residents of Olmsted County diagnosed with RA between January 1, 1995, and January 1, 2000.

The mean age at RA onset was 57.6 years; 71.5% of the patients were women. Follow-up continued until death or January 1, 2007. During follow-up of a median duration 11.7 years, 445 patients with RA died.

Using statistical models adjusting for age and gender, the investigators compared the survival rates of patients diagnosed with RA from 1955 to 1964, 1965 to 1974, 1975 to 1984, 1985 to 1994, and 1995 to 2000. During these 5 time periods, survival rates for RA patients did not change significantly, indicating no significant improvement in lifespan.

Although the expected mortality rate in the general population dropped dramatically for both men and women between 1965 and 2005, the mortality rate for female and male RA patients was constant at 2.4 and 2.5 per 100 person-years, respectively, during the same time period. For women in the Minnesota general population, mortality decreased from 1.0 per 100 person-years in 1965 to 0.2 per 100 person-years in 2000, whereas for men, mortality decreased from 1.2 per 100 person-years in 1965 to 0.3 per 100 person-years in 2000.

"Although the reasons for the widening mortality gap are unclear, cardiovascular deaths constitute at least half of the deaths in subjects with RA, and it is possible that the cardiovascular interventions that improved life expectancy in the general population may not have had the same beneficial effects in persons with RA," Dr. Gabriel said.

The authors do point out some potential flaws in their analysis. One study limitation was the fact that the study was conducted in 1 geographic area and the majority of subjects were Caucasian. Another shortcoming is that the study could not count individuals with RA who did not present for medical care. Finally, it is not possible to extrapolate the findings to patients diagnosed with RA after 2000, who may have been treated more aggressively with biologic therapy.

The authors urgently recommend research that will clarify the reasons behind this mortality discrepancy and that will lead to solutions improving survival in patients with RA. (Arthritis Rheum. 2007;56:3583-3587).

Author's note: Currently, there is an enormous amount of research being done to develop more effective, more selective, and safer RA therapies. Whether these therapies will have a significant impact on mortality is still unsure. There is intriguing evidence that TNF inhibitors might possibly reduce the rate of atherosclerotic disease in RA. And there is also some evidence that these drugs may reduce the incidence of lymphoma in patients with RA. This is counterbalanced by the increase in respiratory infections that occur in patients treated with TNF inhibitors. Only time and more research will give us the answers.