New Findings Show Damage Resulting From Lupus Is a Potentially Modifiable Outcome

Newswise — SAN DIEGO –According to research presented this week at the American College of Rheumatology Annual Meeting in San Diego, researchers have identified three potentially modifiable risk factors and one protective medication that may improve the health of people living with lupus.

Systemic lupus erythematosus, also called SLE or lupus, is a chronic inflammatory disease that can affect the skin, joints, kidneys, lungs, nervous system, and/or other organs of the body. The most common symptoms include skin rashes and arthritis, often accompanied by fatigue and fever. Lupus occurs mostly in women, typically developing in individuals in their twenties and thirties – prime child- bearing age.

“Early tissue and organ damage in people with lupus can predict the likelihood of future damage and death due to the disease,” says Ian N Bruce, MD, FRCP; professor of rheumatology at the University of Manchester, UK; current chair of the SLICC Inception Cohort; and lead investigator in the study. Dr. Bruce’s team recently studied factors that might contribute to the development and progression of tissue and organ damage as well as the relationship between that damage and long-term survival rates. They found that increased disease activity, high blood pressure, and steroid use were associated with worsening damage, and the use of antimalarials protected against worsening damage from SLE.

Using the SLICC Inception Cohort Study – which includes patients from 31 centers in 11 countries in North America, Europe, and Asia – The SLICC group recruited 1,722 patients between 2000 and 2011 and enrolled them in the study within 15 months of meeting their fourth 1997 ACR criteria for having lupus. The average age of participants in the study was 35 years old and they averaged 4.25 follow-up visits throughout the duration of the study. All patients had a careful annual follow-up that included details of their lupus and its treatment as well as details other conditions they may have and other treatments they were taking.

1,502 patients – including 1,337 females – were analyzed for changes in the amount of irreversible damage they experienced over the study period. Damage was measured using the ACR/SLICC Damage Index (called SDI), which is an accepted standard measure of damage in SLE patients. Over the duration of the study, damage rates steadily increased so that by six years of follow-up, 51.1 percent had at least one item of damage recorded.

The researchers found that patients with initial damage were more likely to increase their SDI at each follow-up visit. They also found several factors that were associated with an increased risk of developing or increasing damage. These included older age, being of African ancestry within the USA, higher levels of inflammation (measured by the SLEDAI score), steroid use and high blood pressure.

They also found that men and Caucasians living in the United States were most likely to experience new damage and those who were from an Asian background had lower rates of new damage. In addition, taking antimalarial drugs reduced the rate of damage developing in patients with pre-existing damage. Finally, they found that each point increase in SDI score was associated with a moderate increased risk of death.

“This study shows that irreversible damage develops steadily over time in lupus patients and starts early in the course of the disease,” says Dr. Bruce. “Many of the risk factors we have identified, such as high blood pressure, use of steroids and ongoing disease activity could potentially be modified. Clinical trials should test whether we can improve the long-term health of SLE patients by specifically targeting these risk factors in our patients.”

The American College of Rheumatology is an international professional medical society that represents more than 9,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. For more information about the meeting, visit http://www.acrannualmeeting.org/ or join the conversation on Twitter by using the official hashtag: #ACR13.

Editor’s Notes: Dr. Bruce will present this research during the ACR Annual Meeting at the San Diego Convention Center at 11:00 AM on Wednesday, October 30 in Room 33 A. Dr. Bruce will be available for media questions and briefing at 1:30 PM Tuesday, October 29 in the on-site press conference room, 27 AB.

Abstract Number: 2896

Damage In Systemic Lupus Erythematosus Is a Potentially Modifiable Outcome: Results From The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort

Ian N. Bruce1, Aidan O'Keefe2, Li Su3, Vernon Farewell3, John G. Hanly4, Susan Manzi5, Murray B. Urowitz6 and Systemic Lupus International Collaborating Clinics (SLICC)7, 1Arthritis Research UK Epidemiology Unit and NIHR Manchester Musculoskeletal Biomedical Research Unit, The University of Manchester, Manchester, United Kingdom, 2University of Cambridge, Cambridge, United Kingdom, 3MRC Biostatistics Unit, Cambridge, United Kingdom, 4Dalhousie University and Capital Health, Halifax, NS, 5West Penn Allegheny Health System, Pittsburgh, PA, 6University of Toronto, Toronto Western Hospital, Toronto,ON, 7Toronto Western Hospital, Toronto, ON

Background/Purpose:Irreversible damage is an important outcome in patients with SLE. We aimed to study damage accrual in early SLE. We examined the rate of accrual and factors that determine the development and progression of damage as well as the relationship between damage and survival.

Methods:The SLICC Inception Cohort Study includes patients from 31 centres in 11 countries in North America, Europe, and Asia. The cohort was recruited from 2000-2011 and enrolled within 15 months of their 4th1987 ACR criteria. Damage was measured annually by the SLICC/ACR damage index (SDI). A multi-state model for transitions among damage states was used. Initial modelling was based on a proportional hazards analysis and assumed common explanatory variables effects across selected transition rates. We assessed the relative rates of transition using maximum likelihood estimation. The Kaplan-Meier method was used to estimate the probabilities relating to time until first worsening of SDI score. Cox regression analysis was performed with patient survival as the outcome against damage scores over time.

Results:We recruited 1722 patients. The mean (SD) age at cohort entry and number of visits was 35.0(13.4) years and 4.25(2.72) respectively. At baseline, 600 (34.8%) patients had at least one item of damage rising to 51.1% (178/348) by 6 years follow-up. 1502 patients, including 1337 (89%) females were analysed for SDI change over time. Patients with initial damage were more likely to increase their SDI at each follow-up visit [SDI 0 vs ≥1 (p<0.01)].

Multivariate models for transitions from no damage to damage and increase(s) in pre-existing damage were comparable; age, USA African race/ethnicity, SLEDAI score, steroid use and hypertension were all associated with increasing damage (Table 1). For transition from SDI 0 to >=1, male gender (Relative Transition Rates [95%CI]: 1.48 [1.06, 2.07]) and USA Caucasian race/ethnicity (1.68 [1.08, 2.46]) were associated new damage and Asian race/ethnicity with lower rates of new damage (0.60 [0.39, 0.93]). Increase in pre-existing damage was reduced in patients taking antimalarials (0.63 [0.44, 0.89]). Each point increase in SDI score was associated with an increased risk of death (HR [95%CI]: 1.46 [1.18, 1.81]).

Conclusion:Early damage in SLE is an important stratification factor that predicts future damage and mortality. We found a number of modifiable risk factors for damage (disease activity, hypertension, steroid use and a protective effect of antimalarial use). An integrated intervention strategy to address these may improve long-term outcomes in SLE patients.

Disclosures: I. N. Bruce, Glaxo Smith Kline, 2, Roche Pharmaceuticals, 2, UCB, 5, BMS, 5 A. O'Keefe, Glaxo Smith Kline, 2 L. Su, Glaxo Smith Kline, 2 V. Farewell, Glaxo Smith Kline, 2 J. G. Hanly, None. S. Manzi, None.M. B. Urowitz, None.S. L. I. C. C. (SLICC), GlaxoSmithKline, 2, Bristol-Myers Squibb, 2, Human Genome Sciences, Inc., 2