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

Objective Observational studies have reported an increased risk of infections associated with glucocorticoids in RA, not supported by evidence from randomized controlled trials. Inappropriately accommodating time-varying exposure and confounding in observational studies might explain the conflicting results. Therefore, we compared the incidence of serious infections between different oral glucocorticoid dose patterns over three years in a prospective inception cohort, adjusting for time-varying confounders in marginal structural models. Methods We included 9654 newly diagnosed RA patients from the Swedish Rheumatology Quality Register between 2007-2018 and followed them for three years after the first rheumatology visit. Follow-up was divided into 90-day periods. A mean oral prednisone daily dose was calculated for each period and categorized into 'no use', 'low' (<= 10 mg/day) and 'high' (>10 mg/day) doses. The incidence of serious infections (hospitalization for infection) over follow-up periods was modelled by pooled logistic regression allowing separate effects for recent and past exposure. Results An increased incidence of serious infections was associated with higher compared with lower doses and with more recent compared with past glucocorticoid exposure. Over 3 years of follow-up, the marginal structural models predicted one additional serious infection for every 83 individuals treated with low GC doses for the first 6 months, and for every 125 individuals treated with high GC doses for the first 3 months, compared with no GC use. Conclusion Our results broadly agree with previous observational studies showing a dose dependent increased risk of infection associated with (recent) use of oral glucocorticoids.

Automated summary

This study compared the incidence of serious infections between different oral glucocorticoid dose patterns in patients with rheumatoid arthritis. The results showed that higher doses and recent exposure to glucocorticoids are associated with an increased risk of serious infections. This study provides an explanation for the conflicting results in observational studies.