Mortality and CVD risk due to Use of Glucocorticosteroids among RA patients persists even after their cessation: Study

Glucocorticosteroid (GC) use is associated with increased mortality risk, especially from cardiovascular diseases (CVD) and infections, with dose and duration of use influencing risk. How long the impact lasts after stopping Glucocorticosteroid, and how this is influenced by duration of previous use, are not known. This study aims to estimate how the risk of mortality from CVD and infections is associated with i) cumulative duration of past Glucocorticosteroid use and ii) time since cessation of Glucocorticosteroid.

They conducted a longitudinal study of a population-based incident Rheumatoid arthritis cohort, using administrative health data in a universal health care system. All incident RA cases in British Columbia, Canada, who met Rheumatoid arthritis definition between 01/01/1996 and 12/31/2013, using a 5 yr look back period, were identified using physician billing data and followed until 12/31/2018. Oral Glucocorticosteroid exposure was measured as time-varying variables representing: current use, total cumulative duration of use, and time since discontinuation. Deaths with CVD or infections as the primary cause were identified from death certificates.

Each incident user of Glucocorticosteroid was followed from time of starting Glucocorticosteroid(if started after Rheumatoid arthritis index date) or of meeting Rheumatoid arthritis criteria (if Glucocorticosteroid started before Rheumatoid arthritis index date), using delayed entry to avoid immortal time bias, until death or censoring due to moving out of province or end of F/U. Multivariable conventional Cox PH model and its flexible extensions with non-linear effects were used to estimate the risk of death associated with cumulative duration of Glucocorticosteroid use, time since Glucocorticosteroid cessation and time varying interactions between the 2, adjusting for potential confounders (sociodemographic and comorbidities measured at index date and other Rheumatoid arthritis meds as time-varying covariates). Results: They identified 28,078 incident Glucocorticosteroid users (55.9% of cohort), with mean (SD) and median (25;75Q) Glucocorticosteroid use duration of 603 (1116) and 131(18;598) days. See Table 1 for sample characteristics.

They observed 2,489 CVD deaths and 387 from infections. In conventional Cox PHM risk of CVD / infection mortality increased by 7.5% / 6.8% for every year of Glucocorticosteroid use; and decreased by 1.3% / 4.9% for every year after stopping Glucocorticosteroid. Flexible extensions revealed non-linear relationships for both variables (Figure 1). Duration of previous use influenced risk after cessation (Figure 2). Risk decreased to that of someone prior to starting GC at 1.5, 3.5 and 10 years after cessation if Glucocorticosteroid had been used for 6,12, and 24 months for CVD deaths and at 2.5, 3.5, and 5.5 years, resp. for deaths from infections. Risk of death from CVD and infections never returned to pre-Glucocorticosteroid use risk in patients who used Glucocorticosteroid for > 2 years and > 3 years, respectively. Despite advances in Rheumatoid arthritis therapy Glucocorticosteroid are still commonly used and for long periods in some. The increased mortality risk from CVD and infections lasts for a substantial time after cessation, and never returns to that pre-GGlucocorticosteroid with prolonged use. These findings are of high clinical relevance to people with rheumatoid arthritis and physicians, inform shared decision-making for starting and stopping Glucocorticosteroid, and provide evidence supporting Rheumatoid arthritis guidelines recommending Glucocorticosteroid use at the lowest dose for shortest periods possible.

Reference:

Abstract Number: 2673 Changes in Mortality Risk After Stopping Glucocorticosteroids – a Population-based Study in Rheumatoid Arthritis Diane Lacaille1, Coraline Danieli 2, Kasra Moolooghy1 and Michal Abrahamowicz 3, 1 Arthritis Research Canada, University of British Columbia, Vancouver, BC, Canada, 2Research Institute of McGill University Health Center (RI-MUHC), Montreal, QC, Canada, 3McGill University, Verdun, Canada