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Glucocorticoid exposure and the risk of serious infections in rheumatoid arthritis: a marginal structural model

Andrei Barbulescu1, Arvid Sjölander2, Bénédicte Delcoigne1

  • 1Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Rheumatology (Oxford, England)
|February 23, 2023
PubMed
Abstract

Insights

Higher doses and recent use of oral glucocorticoids increase serious infection risk in rheumatoid arthritis (RA) patients. This study quantifies the infection risk associated with different glucocorticoid dosing patterns over three years.

Area of Science:

  • Rheumatology
  • Infectious Disease Epidemiology
  • Pharmacovigilance

Background:

  • Observational studies suggest increased infection risk with glucocorticoids in rheumatoid arthritis (RA), but randomized controlled trials (RCTs) lack this support.
  • Conflicting results may stem from challenges in accounting for time-varying exposures and confounders in observational data.

Purpose of the Study:

  • To compare the incidence of serious infections in RA patients based on different oral glucocorticoid dose patterns.
  • To adjust for time-varying confounders using marginal structural models in a prospective inception cohort.

Main Methods:

  • A prospective inception cohort of 9654 newly diagnosed RA patients was followed for three years.
  • Oral prednisone doses were categorized (no use, low ≤10 mg/day, high >10 mg/day) over 90-day periods.
  • Pooled logistic regression and marginal structural models analyzed serious infection incidence, considering recent and past exposure.

Main Results:

  • Higher doses and more recent exposure to oral glucocorticoids were associated with an increased incidence of serious infections.
  • Marginal structural models predicted one additional serious infection for every 83 individuals on low-dose GCs (first 6 months) and 125 on high-dose GCs (first 3 months) versus no GC use.

Conclusions:

  • Results align with observational studies indicating a dose-dependent increase in infection risk with recent oral glucocorticoid use in RA.
  • The findings highlight the importance of considering glucocorticoid dose and timing in managing infection risk in RA patients.
Keywords:
RAglucocorticoidsinfectionsmarginal structural models

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