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 4^th 1987 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.

Table 1 Analysis of factors significantly associated with accrual of damage in SLE patients either from no damage to damage (SLICC 0 to 1) or accrual in pre-existing damage (SLICC 1 to >1).

 *Standardised age, **increase in rate for each SLEDAI increase of 3