In this issue of The Journal, Best, et al1 report from their retrospective observational cohort study the associations between the usage of oral glucocorticoids (GC) and the incidence and cost of potential adverse effects (AE) of this medication in rheumatoid arthritis (RA). They included 84,357 patients from a US medical database. The highest cumulative oral GC dose (> 1.8 g prednisone equivalent) during a “baseline period” of 1 year (so on average, > 5 mg of prednisone daily during that year) was associated with an increased risk of any potentially GC-associated AE during the directly following “evaluation period” of 1 year, compared to no GC exposure. In their view, these results suggest that all efforts (such as earlier implementation of GC-sparing treatment) should be made to avoid high-dose and chronic oral GC therapy.
This study adds to the longstanding debate on risks and benefits of GC in RA. North American publications tend to underscore the risks, whereas many European researchers plead that the toxicity of low-dose GC therapy in RA is frequently overestimated, while its benefits are downplayed. This transatlantic divide does not have a parallel in clinical practice: on both sides of the Atlantic, GC therapy is frequently applied. The CORRONA registry, a US-based longitudinal registry of patients with RA (n = 25,000), shows that about 30% of its patients with RA use a GC2. In an older US study, 35.5% of 12,749 patients with RA were currently using GC, and the lifetime exposure was 65.5%3.
Observational studies on AE of GC, like this one by Best, et al1, intrinsically are associated with a number of methodological issues, obscuring interpretation of results. Here, we will address 3 issues:
Are all negative events that occur during GC therapy due to GC?
May …
Address correspondence to Dr. J.W. Jacobs, University Medical Center Utrecht, G02.228, Box 85500, Utrecht 3508 GA, the Netherlands. E-mail: j.w.g.jacobs{at}umcutrecht.nl