Background/Purpose:

Glucocorticosteroids (GC) are frequently used in the management of rheumatoid arthritis (RA). Due to their metabolic and immunosuppressive effects, they could increase the risk of mortality, yet suppression of disease activity, a known predictor of premature mortality, could also reduce the risk of mortality in RA. We evaluated the association between exposure to GC and risk of mortality in RA, using a population-based incident RA cohort with administrative health data. 

Methods:

Using administrative billing data, we assembled a population-based cohort including all incident RA cases between 01/1996 and 03/2006, followed until 03/2010. Cases with GC use prior to RA onset were excluded. Administrative data were obtained on all medications since 09/1995; MD visits, hospitalizations, and tests since 01/1990. The Cox proportional hazard model (PHM) was used to estimate risk of death associated with GC exposure. Time analyzed was from index RA date to death or end of follow-up. GC exposure was defined as any dispensed prescription for oral GC during follow up, and was measured using three time-dependent exposure variables, in separate models, representing current dose (in mg prednisone equivalent), past cumulative dose and past cumulative duration of exposure . We used propensity scores (PS) to control for the observed differences between GC users and non-users, calculated at the time of initiating GC, using markers of RA severity, as well as co-morbidities increasing risk of death. Variables for which there was residual imbalance across PS quintiles were also included as covariates in the model.  PHM analyses were also adjusted for age, gender, calendar year of inclusion, PS, as well as time-dependent variables representing exposure to RA medications that could influence mortality risk (MTX, biologics and NSAIDs).

Results:

Our sample includes 18,215 incident RA cases (mean (SD) age: 57.2(17.1), 66.5% females) providing a mean of 7.1 years and a total of 128,799 person-years of follow-up, with 5,326 RA cases (29.2%) exposed to GC. We observed 2,881 deaths. Exposure to GC was associated with an increased risk of death in all models (Table 1). Female gender, current MTX and biologic use, and later calendar year of inclusion were associated with a reduced risk of death; whereas age, smoking, Charlson comorbidity score and markers of RA severity were associated with an increased risk of death. Limitations of our study are those inherent to observational study, including possible effect of residual or unmeasured confounding, and selection bias from non-random allocation of treatment. 

Conclusion:

In a population-based cohort, exposure to GC was associated with a significant increase in mortality. Given the increased mortality risk of RA, this has important implications for health care providers and people with arthritis.

Table 1: