Glucocorticoid exposure and fracture risk in patients with new-onset rheumatoid arthritis.

Abstract

We evaluated the impact of systemic glucocorticoid exposure on fracture risk among relatively young patients with new-onset rheumatoid arthritis (RA). Using administrative data, we identified 42,127 RA patients diagnosed January 1, 2005-December 31, 2012, age 18-64years, with benefits coverage for ≥12months before RA diagnosis. Follow-up extended to clinical fracture, cancer diagnosis, or December 31, 2012. Glucocorticoid users were new to therapy. Fracture incidence rates (IR) were stratified by glucocorticoid exposure expressed as prednisone equivalent doses. Cox's proportional hazards models estimated fracture risk adjusted for demographics and baseline clinical characteristics to assess dose-response relationships with current (daily) and prior (cumulative) dose, and by time since discontinuation. Most patients (85%) had glucocorticoid exposure. Exposed and unexposed patients were demographically similar (74% female; mean age 49.7 and 48.8years); 1% had prior fracture. Fracture IRs (95% confidence intervals) were 5 to 9 per 1000 person-years at doses <15mg/day, 16.0 (11.0, 22.6) at doses ≥15mg/day, and 13.4 (10.7, 16.7) at cumulative doses ≥5400mg. Adjusted fracture risk was approximately 2-fold higher at highest dose levels compared with 0mg/day current daily dose and <675mg cumulative dose, respectively. Fracture risk was 29% lower at 60-182days post-discontinuation compared with ongoing use and was similar to unexposed patients by 12months. Findings were similar among patients age <50years. Among younger, new-onset RA patients, fracture risk was significantly elevated at high levels of daily and cumulative dose, and was similar to unexposed patients by 12months post-discontinuation.