Abstract

Previous studies of glucocorticoid (GC) therapy and mortality have had inconsistent results and have not considered possible perimortal bias—a type of protopathic bias where illness in the latter stages of life influences GC exposure, and might affect the observed relationship between GC use and death. This study aimed to investigate all-cause and cause-specific mortality in association with GC therapy in patients with rheumatoid arthritis (RA), and explore possible perimortal bias. A retrospective cohort study using the primary care electronic medical records. Oral GC exposure was identified from prescriptions. Mortality data were obtained from the UK Office for National Statistics. Multivariable Cox proportional hazards regression models assessed the association between GC use models and death. Several methods to explore perimortal bias were examined. The cohort included 16,762 patients. For ever GC use there was an adjusted hazard ratio for all-cause mortality of 1.97 (95 % CI 1.81–2.15). Current GC dose of below 5 mg per day (prednisolone equivalent dose) was not associated with an increased risk of death, but a dose–response association was seen for higher dose categories. The association between ever GC use and all-cause mortality was partly explained by perimortal bias. GC therapy was associated with an increased risk of mortality for all specific causes considered, albeit to a lesser extent for cardiovascular causes. GC use was associated with an increased risk of death in RA, at least partially explained by perimortal bias. Importantly, GC doses below 5 mg were not associated with an increased risk of death.Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-016-0167-1) contains supplementary material, which is available to authorized users.

Highlights

  • Rheumatoid arthritis (RA) is a chronic inflammatory disease which affects between 0.5 and 1 % of the adult population worldwide [1,2,3]

  • There were 8367 (50 %) patients who received at least one prescription for oral GCs. These patients were on average 4 years older, more likely to have received GCs in the 1 year prior to rheumatoid arthritis (RA) (44 vs. 6 %, respectively) and had higher disease-modifying anti-rheumatic drug (DMARD) use during follow-up compared to nonusers

  • This study examined the association between oral GC therapy and mortality rates in a cohort of patients with RA in the UK

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Summary

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory disease which affects between 0.5 and 1 % of the adult population worldwide [1,2,3]. Previous studies have investigated the association between GC therapy and mortality, mostly focusing on allcause mortality, though some have investigated CV mortality [5, 12,13,14,15,16]. GCs have been associated with an increased risk of all-cause mortality in some [12,13,14,15, 17, 18] but not all studies [16, 19, 20], with similar inconsistency for CV mortality [12, 14, 16]. In studies that consider dose, some have suggested no association with doses \5 mg prednisolone equivalent [12, 13], reflecting either a lack of significant side effects at this dose or perhaps a favourable balance between side effects and positive antiinflammatory properties

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