Ten-year analysis of the risk of severe outcomes related to low-dose glucocorticoids in early rheumatoid arthritis

Rheumatology (Oxford). 2021 Aug 2;60(8):3738-3746. doi: 10.1093/rheumatology/keaa850.


Objectives: To explore the 10-year tolerability profile of glucocorticoids (GC) use in patients with early RA.

Methods: Analysis of 10-year outcome from the early arthritis ESPOIR cohort. Patients were stratified in two groups, without or with GC treatment at least once during their follow-up. The primary outcome was a composite of deaths, cardiovascular diseases (CVD), severe infections and fractures. The weighted Cox time-dependent analysis model was used with inverse probability of treatment weighting (IPTW) propensity score method.

Results: Among the 608 patients [480 women, mean age of 47.5 (12.1) years], 397 (65%) received low-dose GC [median 1.9 mg/day (IQR 0.6-4.2), mean cumulative prednisone dose 8468 mg (8376), mean duration 44.6 months (40.1)]. In univariate analysis, over 95 total events (10 deaths, 18 CVDs, 32 fractures and 35 severe infections), patients taking GC experienced more events (n = 71) than those without GC (n = 24) (P =0.035). Highest cumulative exposure of GC (≥8.4 g) was associated with highest risk of occurrence of the primary outcome (24.3%, P =0.007), CVDs (7.9%, P =0.001) and severe infections (9.9%, P =0.024). The risk of events over time was significantly associated with GC, age, hypertension and ESR. The risk associated with GC treatment increased between the first follow-up visit [hazard ratio (HR) at 1 year = 0.46, 95% CI: 0.23, 0.90] and 10 years (HR = 6.83, 95% CI: 2.29, 20.35).

Conclusion: The 10-year analysis of this prospective early RA cohort supports a dose and time-dependent impact of low-dose GC treatment, with a long-term high risk of severe outcomes.

Trial registration: (ClinicalTrials.gov Identifier: NCT03666091).

Keywords: early arthritis; glucocorticoids; rheumatoid arthritis; safety outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / drug therapy*
  • Blood Sedimentation
  • Cardiovascular Diseases / epidemiology*
  • Female
  • Fractures, Bone / epidemiology*
  • Glucocorticoids / therapeutic use*
  • Humans
  • Hypertension / epidemiology
  • Infections / epidemiology*
  • Male
  • Middle Aged
  • Mortality*
  • Prednisone / therapeutic use
  • Propensity Score
  • Proportional Hazards Models
  • Risk


  • Glucocorticoids
  • Prednisone

Associated data

  • ClinicalTrials.gov/NCT03666091