Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort

Abstract

Background and aimsWe studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients.MethodsThe Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort recruited patients within 15 months of developing four or more 1997 American College of Rheumatology (ACR) criteria for SLE; the SLICC/ACR damage index (SDI) was measured annually. We assessed relative rates of transition using maximum likelihood estimation in a multistate model. The Kaplan–Meier method estimated the probabilities for time to first increase in SDI score and Cox regression analysis was used to assess mortality.ResultsWe recruited 1722 patients; mean (SD) age 35.0 (13.4) years at cohort entry. Patients with damage at enrolment were more likely to have further worsening of SDI (SDI 0 vs ≥1; p<0.001). Age, USA African race/ethnicity, SLEDAI-2K score, steroid use and hypertension were associated with transition from no damage to damage, and increase(s) in pre-existing damage. Male gender (relative transition rates (95% CI) 1.48 (1.06 to 2.08)) and USA Caucasian race/ethnicity (1.63 (1.08 to 2.47)) were associated with SDI 0 to ≥1 transitions; Asian race/ethnicity patients had lower rates of new damage (0.60 (0.39 to 0.93)). Antimalarial use was associated with lower rates of increases in pre-existing damage (0.63 (0.44 to 0.89)). Damage was associated with future mortality (HR (95% CI) 1.46 (1.18 to 1.81) per SDI point).ConclusionsDamage in SLE predicts future damage accrual and mortality. We identified several potentially modifiable risk factors for damage accrual; an integrated strategy to address these may improve long-term outcomes.

Dr. Tselios, et al reply

“…Concerning the comment of Bachmeyer, et al 1 on the low level of antimalarial usage (80%) in our cohort, we state that similar levels have been reported in other large registries such as the RELESSER group with 83% in 4024 patients 7 , while lower numbers were described in inception cohorts, such as the Systemic Lupus International Collaborating Clinics cohort, with 67% in 1722 patients 8 . Ocular and gastrointestinal toxicity along with intolerance in a certain number of patients may account for this.…”

Soluble urokinase plasminogen activator receptor—A valuable biomarker in systemic lupus erythematosus?

“…Many studies have shown that it is not, at any single occasion, raised disease activity that associates with poor prognosis and mortality, 10 but rather the acquired organ damage which is a product of medication side effects, comorbidities and disease activity over time. Apart from increased mortality, organ damage also implies a reduced physical function, quality of life and productivity for the patient [17]. Biomarkers with the potential to early identify individuals who are at risk of developing severe disease with subsequent organ damage are thus highly warranted.…”

“…The disease course in SLE is unpredictable with episodes of flares and remissions, sometimes leading to permanent organ damage and to preterm mortality [17,131]. Many studies have shown that it is not, at any single occasion, raised disease activity that associates with poor prognosis and mortality, but rather the acquired organ damage which is a product of medication side effects, comorbidities and disease activity over time.…”

“…Furthermore, there were higher death rates among patients in the two groups with SDI increase (Figure 2). However, it is well known that present organ damage predicts further organ damage [17,100], and thus, adjustment for SDI at baseline should be performed to reduce the risk of bias. A stepwise linear multiple regression analysis was therefore performed to evaluate the impact of suPAR on future SDI increase.…”

“…SLE is a systemic rheumatic disease characterized by antinuclear antibody (ANA) production, increased expression of interferon alpha (IFNα) regulated genes, decrease in complement protein levels and deficient handling of dying cells which results in tissue deposition of immune complexes and subsequent inflammation and damage to organs [16,17]. The disease can affect almost any organ and has an extreme heterogeneity which constitutes a challenge in the diagnosis and treatment of the patients.…”