FRI0534 ORAL GLUCOCORTICOIDS AND NEWLY TREATED DIABETES MELLITUS, HYPERTENSION, AND THROMBOSIS IN CHILDREN WITH CHRONIC DISEASES
Authors: Daniel Horton, Fenglong Xie, Lang Chen, Melissa L. Mannion, Jeffrey Curtis, Brian Strom, Timothy Beukelman
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Systemic glucocorticoid use is associated with a well-known spectrum of toxicities. Nonetheless, the risks of cardiometabolic complications in children are poorly understood. <h3>Objectives</h3> We sought to quantify rates of newly treated diabetes mellitus, hypertension, and venous thromboembolism (VTE) associated with oral glucocorticoid exposure in children. We hypothesized that oral glucocorticoids were associated with each complication in a dose-dependent manner, most strongly with current or recent glucocorticoid exposure. <h3>Methods</h3> Using Medicaid claims data (2000-2010), we identified children ages 1-18 diagnosed with immune-mediated diseases (inflammatory bowel disease, juvenile idiopathic arthritis, or psoriasis) or a non-immune comparator condition (attention-deficit/hyperactivity disorder) based on diagnostic codes ± pharmacy claims. We studied time-varying oral glucocorticoid exposures using pharmacy claims after a ≥6-month glucocorticoid-free baseline period, categorizing dose as low (&lt;0.25 mg/kg/day), medium (0.25-0.99 mg/kg/day), or high (≥1 mg/kg/day) based on prescribed prednisone-equivalent dosage and age-/sex-imputed weights. Primary outcomes were incident treatment of diabetes (type 1 or 2), hypertension, and VTE. We used Cox regression and weighted cumulative exposure models<sup>1</sup> to estimate adjusted hazard ratios (aHRs) and number needed to harm (NNH) for varying patterns of glucocorticoid exposure. <h3>Results</h3> We followed 932,517 children (21.3% glucocorticoid-exposed) for 1.6 million person-years. Glucocorticoid usage varied by disease (Table). After adjusting for age, sex, race/ethnicity, calendar year, inclusion diagnosis, comorbidities, other medications, and healthcare usage, we found strong dose- and time-dependent relationships between glucocorticoid exposure and rates of newly treated diabetes, hypertension, and VTE (Figure 1). These effects increased with longer durations of exposure and declined within 6 months after stopping (Figure 2). Sustained low-dose exposures (e.g., 0.1 mg/kg/day) appeared relatively safe (aHR&lt;1.2), but risks increased even with brief high-dose exposures (2 mg/kg/day x7 days) (aHR 1.7-2.2). Risk differences were highest for hypertension (number needed to harm [NNH]: 2 mg/kg/day x7 days, 6,206-17,894; 2 mg/kg/day x30 days, 233-671) and lowest for VTE (NNH: 2 mg/kg/day x7 days, 54,886-612,350; 2 mg/kg/day x30 days, 1,977-22,045). Absolute risks were higher for children with immune-mediated diseases (e.g., diabetes, 2 mg/kg/day x30 days, NNH: 424-691) than for those with ADHD (NNH: 959). aHR, adjusted hazard ratio; CI, confidence interval Line plots show associations of daily glucocorticoid dose, duration, and recency with outcomes. <h3>Conclusion</h3> In children with various chronic conditions, current oral glucocorticoid use is strongly associated with newly treated diabetes, hypertension, and VTE in a dose- and duration-dependent fashion. Hypertension is a more common glucocorticoid-related complication than diabetes or VTE, but in absolute terms, all of these complications are uncommon in children. <h3>References</h3> [1] Sylvestre MP, Abrahamowicz M. Stat Med. 2009;28(27):3437-3453. <h3>Disclosure of Interests</h3> Daniel Horton Grant/research support from: Bristol-Myers Squibb, for unrelated research, Fenglong Xie: None declared, Lang Chen: None declared, Melissa L. Mannion: None declared, Jeffrey Curtis: None declared, Brian Strom: None declared, Timothy Beukelman Consultant for: Novartis, UCB