Objective: Corticosteroids are a mainstay of SLE treatment; however, cumulative steroid exposure may lead to organ damage. This study aimed to quantify the risk of new diabetes, hypertension, cataracts, osteoporosis and avascular necrosis that is attributable to cumulative corticosteroid exposure in SLE. Methods: Using data from the Hopkins Lupus Cohort, a longitudinal study of lupus activity, organ damage and quality of life in patients with SLE, five matched case-control analyses nested within a prospectively enrolled SLE cohort were performed. Two randomly selected controls were matched to each case using incidence-density sampling from defined risk sets. Attributable risk was calculated for steroid exposure (dose and duration, separately). Cumulative steroid dose was modelled as a four-level categorical variable using clinically relevant thresholds: 0 g (no exposure); >0 and <3.65 g (<10 mg/day for a year); ≥3.65 g and <18.25 g (1-5 years at 10 mg/day); and ≥18.25 g (>5 years at 10 mg/day). Results: Eligible cases were identified for diabetes (n=42), hypertension (n=79), cataract (n=132), osteoporosis (n=118) and avascular necrosis (n=38). The unadjusted OR for a one-category increase in cumulative steroid exposure ranged from 1.157 (cataract (0.889 to 1.506); p=0.2779) to 2.183 (avascular necrosis (1.162 to 4.103); p=0.0153). After adjusting for confounding variables, a one-category increase in the cumulative steroid dose was significantly associated with risk of cataract (OR (95% CI) 1.855 (1.190 to 2.892); p=0.0064) and osteoporosis (OR (95% CI) 1.604 (1.067 to 2.412); p=0.0232). ORs for avascular necrosis, diabetes and hypertension suggested a moderately increased risk (not significant). Duration of steroid exposure was not associated with any of the outcomes. The proportion of risk attributable to steroid exposure after adjustment for covariates was 0.711 for cataract and 0.540 for osteoporosis. Conclusions: Cumulative steroid exposure was associated with an increased risk of cataract and osteoporosis in patients with SLE.
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