Rheumatoid Arthritis Mortality Has Not Changed in 20 Years

Janis C. Kelly

February 18, 2014

Rheumatoid arthritis (RA) has continued to have higher mortality rates compared with the general population, and these have not improved since 1990, researchers report in an article published online February 4 in Arthritis Care & Research.

Mortality was particularly elevated in autoantibody-positive patients, write J. H. Humphreys, MBChB, MRCP, from the Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, United Kingdom, and colleagues.

"Mortality rates in early RA have improved, but so have the rates in the general population," senior author Suzanne M. M. Verstappen, PhD, also from the Arthritis Research UK Centre for Epidemiology, told Medscape Medical News.

"We hoped that mortality rates might be starting to approach that of the general population in more recent times, as studies have demonstrated marked improvements in other early RA outcomes. The question that remains is whether we will see this improvement in the future. Mortality is a latent outcome, and it may take many years before changes in disease management impact overall mortality rates. If early RA mortality rates continue to be elevated compared to the general population, despite achieving low disease activity/remission in patients, we need to investigate further what the underlying causes of early death are and how we might target those," Dr. Verstappen said.

Rheumatoid Arthritis Death Rates Still Higher Than Normal

The researchers analyzed data from 2519 patients in the Norfolk Arthritis Register. Since 1990, the register has been recruiting adults registered with a primary care physician and presenting for the first time with early inflammatory arthritis (EIA), defined as 2 or more swollen joints for 4 or more weeks. Of these, 1419 participants fulfilled the 2010 ACR/EULAR classification criteria for RA.

The investigators divided patients into 3 cohorts depending on year of enrolment: cohort 1 (1990 - 1994; n = 629), cohort 2 (1995 - 1999; n = 629), and cohort 3 (2000 - 2004; n = 629). The researchers followed-up patients for 7 years, with a total of 16,485 person-years of follow-up included in the analysis.

Crude 7-year mortality rates were 21.25, 21.43, and 19.96 per 1000 person years for all-cause mortality in the 3 cohorts, respectively. Cardiovascular-specific mortality was 8.78, 7.87, and 7.07 per 1000 person years.

The all-cause mortality SMR for the Norfolk Arthritis Register patients with early inflammatory arthritis was 1.16 (95% confidence interval [CI], 1.04 - 1.29), and for the patients with RA, all-cause SMR was 1.22 (95% CI, 1.07-1.40). Both measures are significantly higher than that of the general population.

Moreover, when the researchers analyzed the populations individually, they found that the SMRs remained relatively constant for patients meeting the RA criteria at 1.18 for cohort 1, 1.30 for cohort 2, and 1.19 for cohort 3.

Cardiovascular SMRs for patients with RA were 1.11 for cohort 1, 1.13 for cohort 2, and 1.19 for cohort 3, for an average SMR of 1.13.

Patients who did not meet the 2010 RA diagnostic criteria at baseline had an all-cause SMR of 0.90 (95% CI, 0.73 - 1.11), which is not significantly different from the general population. The all-cause SMR for patients with RA with rheumatoid factor or anticitrullinated protein antibodies was 1.39 (95% CI, 1.18 - 1.65), the highest observed for any subgroup.

The authors write, "We have shown that all cause mortality in the first 7 years of [early inflammatory arthritis] and RA, defined according to the 2010 [American College of Rheumatology/European League Against Rheumatism (ACR/EULAR)] criteria, is higher than that in the general population, but the SMR has remained stable over the past 20 years. We have demonstrated, for the first time, increased SMRs in patients classified as RA according to the 2010 ACR/EULAR classification criteria."

Effects of Tighter Control, Use of Biologicals in RA Still Unclear

Dr. Verstappen said that some patients in cohort 2 (1995 - 1999) and cohort 3 (2000 - 2004) would have received biological therapy. "However, the percentage of patients receiving biologics would not have been higher than 7% to 10%, reflecting the [UK] national figures," she said.

The mortality data are thought to be broadly generalizable to the United States. "As the healthcare system in the US is different from the UK, the treatment early RA patients receive may differ, affecting the results. However, the approach to disease management of early aggressive therapy has been adopted in both UK and US, so this may not be that significant. There may, however, be other differences in US patients that could affect mortality rates there," Dr. Verstappen said.

"The Manchester group [does] very high quality research," Fred Wolfe, MD, clinical professor of medicine at the University of Kansas School of Medicine and director of the National Data Bank for Rheumatic Diseases, Wichita, told Medscape Medical News. "Theirs is a very important study and looks sound. If current biologic therapy has a beneficial effect on mortality (and it is by no means clear that it does), that effect may be seen in future years. Also, if biologic therapy is effective in reducing mortality, it is possible that mortality results could differ in the US and UK because of the wider use of biologics in the US."

"But that remains to be seen, for it is possible that there will be no difference in mortality or even that mortality will be greater in the US," added Dr. Wolfe, who was not involved in the study.

According to Dr. Wolfe, RA mortality is best predicted by functional status, and more research into functional status is needed in assessing the health and longevity of patients with RA.

NOAR and Dr. Humphreys are funded by Arthritis Research UK. The other authors and Dr. Wolfe have disclosed no relevant financial relationships.

Arthritis Care Res. Published online February 4, 2014. Abstract


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