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A recent analysis of retrospective clinical data on patients with systemic lupus erythematosus (SLE) at 14 Canadian centers found that a surprisingly high proportion—at least one-third—had active disease at any point over five years of data collection.1
It has been a longstanding belief among clinicians that SLE becomes less active over time, although its accumulation of inflammatory organ damage is permanent, says lead author Christine A. Peschken, MD, MSc, FRCPC, head of the Section of Rheumatology and associate professor of medicine and community health sciences in the Rady Faculty of Health Sciences at the University of Manitoba, Winnipeg, Canada. “But our analysis found a higher level of disease activity at the study entry point was the single major independent predictor of higher disease activity over time.”
Lupus is a chronic, debilitating, autoimmune disease that leads to irreversible loss of function in a number of organs. It is known to present fluctuating levels of inflammation, and persistent disease activity is associated with high levels of morbidity and mortality, Dr. Peschken says. “You see some lupus patients and they don’t have any evidence of disease—no skin rash, no swollen, tender, painful joints, no signs of lung, kidney or neurologic inflammation.” That could mean remission, or it could mean adequate control from treatment, she says. But a few months later, all of the symptoms return.
The disease is also heterogeneous, which has hampered efforts to develop new drug therapies.2 Only one new medication, belimumab, has been approved for SLE since 1955 (with the approval of hydroxychloroquine), and current research emphasizes the development of biomarkers that may help target treatments based on disease subgroups.
The Study
The 1000 Canadian Faces of Lupus is a prospective, multi-center study of patients who had a clinical diagnosis of SLE from 2005–2008 at sites across Canada.3 The researchers enrolled 2,019 patients, with declining follow-up over the course of the study. Ninety percent were female, with an average age of 42 and an average disease duration of 11 years. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K). Clinical manifestations, treatment, damage accrual and autoantibody status were also recorded.
Data documenting clinical disease manifestations from all available medical records were abstracted using a comprehensive standardized form and entered into a database at enrollment. Study subjects were divided into four groups based on their scores on the SLEDAI-2K: low, moderate, moderately high and very high. Multi-variable linear and longitudinal mixed linear regression models were used to identify predictors of change over time in SLEDAI-2K scores for these four categories.
Findings show that for patients who started at a low level of disease on enrollment in the study, 71% still had low activity a year later. But those with very high disease activity at the start had a smaller chance of achieving low disease activity in subsequent years, and a higher chance of continuing to have very high disease activity.
Only one new medication, belimumab, has been approved for SLE in recent years, & current research emphasizes the development of biomarkers that might help target treatments based on disease subgroups.
Prednisone, a Double-Edged Sword
Forty-two percent of enrolled patients with inactive disease were taking prednisone, compared with 64% with very high disease activity. “This suggests that some ongoing treatment is required to maintain even a relatively low level of disease activity. The probability of disease flare-up at some time during the following year was substantial,” Dr. Peschken says.
Does measurable disease activity suggest the patient is not getting enough treatment, or the wrong treatment? “Generally speaking, rheumatologists keep going back to prednisone when they see disease activity, because they feel they have to do something,” she says. “The SLE patient can’t just be left untreated with active disease.”
But Dr. Peschken expresses surprise so many patients were receiving prednisone. Because of the side effects of long-term steroid treatment, the risk of organ damage from the disease must be balanced with damage caused by treatment. Rheumatologists are always looking for any other treatment options that might be out there. Lupologists (i.e., SLE medical experts) recognize the importance of working to reduce prednisone treatments to the greatest extent possible, but other physicians may not always appreciate the long-term importance of reducing prednisone use.
“[We know] control of this disease is suboptimal,” Dr. Peschken says. But it can be hard to find the right balance. “Our study finds a surprising number of patients where we’re not doing a good job managing their lupus, which underscores the need to keep looking for better treatment options.”
In other findings, there was no difference in the prescribing of recommended anti-malarial therapies across the different disease activity groups. And Dr. Peschken wonders about a possible relationship between income and disease activity levels. Canada has universal healthcare coverage, but not universal drug coverage, she says. Does income affect which medications get prescribed, with an emphasis on lower cost prednisone for those who can’t afford other drugs?
Bottom Line
A surprisingly high proportion of the study’s patients had active disease at any given time. The amount of disease activity dictates treatment strategies, Dr. Peschken says.
The next analysis target of the 1000 Canadian Faces of Lupus database is to identify and quantify the impact of disease activity on organ damage.
Larry Beresford is a medical journalist in Oakland, Calif.
References
- Peschken CA, Wang Y, Abrahamowicz M, et al. Persistent disease activity remains a burden for patients with systemic lupus erythematosus. J Rheumatol. 2019 Feb;46(2):166–175.
- Dall’Era M, Bruce IN, Gordon C, et al. Current challenges in the development of new treatments for lupus. Ann Rheum Dis. 2019 Jun;78(6):729–735.
- Peschken CA, Katz SJ, Silverman E, et al. The 1000 Canadian faces of lupus: Determinants of disease outcome in a large multiethnic cohort. J Rheumatol. 2009 Jun; 36(6):1200–1208.
