Despite the absence of a new therapy for systemic lupus erythematosus (SLE) in the past 30 years, mortality from SLE and disease activity at presentation are declining—findings that may be attributed in part to the greater use of immunosuppressive agents and lower steroid doses, according to a review of 35 years of data presented here Wednesday at the 69th Annual Meeting of the American College of Rheumatology.1
What accounts for this long-term trend of lower SLE mortality and less disease activity is not fully understood, but lead researcher Murray B. Urowitz, MD, a rheumatologist at Toronto Western Hospital in Ontario, Canada, speculates that more aggressive treatment with less toxic agents may play a role. "It may just be becoming milder over time like RA. It's not nearly as severe at presentation today," Dr. Urowitz tells CIAOMed. "The disease is quieter and there are no new drugs to give credit to, although less use of steroids may be a factor."
Dr. Urowitz notes that "today, 20-year survival is 75%. That's a very big difference from a few years ago, when only 50% of SLE patients were alive at 5 years."
The 35-year longitudinal observational cohort study comprised 1184 SLE patients drawn from four registered groups encompassing roughly four decades (1970–1979, 1979–1987, 1988–1996, and 1997–2005). The SLE patients were seen every 2 to 6 months at the University of Toronto Lupus Clinic.
CIAOMed recently reported that patients with early RA presenting in recent years have less severe disease activity at presentation, as well as a more favorable disease course.2 The reasons are not fully understood, but the study by Welsing and colleagues observed that a shorter duration of symptoms at the time of diagnosis and more aggressive use of drug therapy may account for the decline in RA.
Standardized mortality rate declines in SLE
In the 1970s, SLE patients died 14.4 times more frequently than age- and sex-matched controls from the normal population. In the 1980s, the increased risk fell to 6.9 times that of the general population. In the 1990s, it fell again to 4.5 times that of lupus-free controls. By 2005, SLE patients died 3.2 times more frequently than normal controls. "The increased rate at which SLE patients die fell from 14.4 to 3.2 over four decades," Dr. Urowitz says. "The bad news is that they still die three times more frequently than people in the general population."
Disease activity also on the decline
SLE disease activity index (SLEDAI)-2K at presentation was much higher in the earlier decades, the study showed, but the scores have decreased substantially over the past 35 years.
Today, when lupus patients first present to their doctor, they are less sick than they were decades ago, Dr. Urowitz says, and rheumatologists are also using less cortisone and more immunosuppressive agents to treat SLE patients. "There has been a shift away from steroids and toward other immunosuppressants and an increase in the use of hydroxychloroquine [Plaquenil®]," he notes. "We know cortisone is a major factor in causing morbidity and mortality, he says, adding, "No matter how you look at it, lupus is less aggressive than in earlier decades."
Future appears even brighter
"The prognosis for SLE patients will increase even more if some of the new drugs turn out to be beneficial and we are able to decrease steroid use further with the use of these new drugs," Dr. Urowitz tells CIAOMed. "We are hopeful that the new drugs get at the basic mechanism of lupus. This is a good era, and something to look forward to."
While potential new lupus drugs "are in a very early phase, in theory, they target the right pathogenic mechanism, whether BlyS or B cells," Dr. Urowitz says. Pharmacogenetics will also help further improve patient outcome in SLE, he predicts. "All of the drug trials are now collecting DNA, so they can link genes to response."
References
- Urowitz MB, Ibanez DM, Gladman DD. Changing outcomes in SLE
over 35 years. Presented at: 69th American College of Rheumatology
annual meeting; November 12–17, 2005; San Diego, Calif. Abstract 1957. - Welsing PMJ, Fransen J, van Riel PLCM. Is the disease course of rheumatoid arthritis becoming milder? Time trends since 1985 in an inception cohort of early rheumatoid arthritis. Arthritis Rheum. 2005;52:2616-2624.