Safety of low‐ to medium‐dose glucocorticoid treatment in rheumatoid arthritis: myths and reality over the years

Abstract

Low-to medium-dose glucocorticoids have been shown to have not only anti-inflammatory but also diseasemodifying properties in rheumatoid arthritis. The evidence for the benefit of its early use in combination with disease-modifying antirheumatic drugs underlines the need for a close evaluation of their risk-benefit ratio. Over time, numerous myths and fears about glucocorticoid toxicity in rheumatoid arthritis have arisen from observational studies, and many concerns have been unduly extrapolated from observations with higher-dose treatment. Furthermore, we cannot exclude the possibility of a powerful effect of bias by indication in these studies. Low-to medium-dose glucocorticoid regimens continued to be evaluated in randomized clinical trials, particularly in early disease, but these studies also have relevant methodological limitations in assessing safety, particularly due to small size and/or short duration. At present, the evidence on which to support clear recommendations about glucocorticoid toxicity remains remarkably weak. A large prospective pragmatic trial dedicated to the toxicity of low-dose glucocorticoids is dearly needed. Meanwhile, adherence to recommendations on standardized methodologies for registration and report of glucocorticoid adverse events is essential for improving our knowledge and competence in the best management of these important medications.

A Retrospective Analysis of Corticosteroid Utilization Before Initiation of Biologic DMARDs Among Patients with Rheumatoid Arthritis in the United States

“…The issue of corticosteroid safety in RA treatment is further complicated by this study's dosage findings, in which medium dose (defined in this study as 2.5 to\7.5 mg/day) was associated with reduced number of adverse events compared to low dose. This seemingly contradicts recent studies of corticosteroids in RA treatment suggesting that low dosage (even in the long-term) may result in non-significant, limited or mild adverse events [5,6,31]. However, without full access to the medical record of individual patients, it is difficult to fully explain defined low dose as\7.5 mg compared to medium dose of C 7.5 mg, and found that longterm use of medium-dose corticosteroid therapy was associated with an increased prevalence of hypertension in RA patients compared to low dose and no use groups [32].…”

“…In particular, understanding corticosteroid treatment patterns and associated burden prior to biologic DMARD initiation can inform clinical and policy decision-makers on the appropriate use of these two drug classes in RA management. Santiago and da Silva noted limitations in the knowledge base regarding adverse events associated with corticosteroid use in RA treatment [6]. These investigators encourage that the ''risk and benefit'' of corticosteroid use in RA should be ''regularly revisited [6]''.…”

“…Santiago and da Silva noted limitations in the knowledge base regarding adverse events associated with corticosteroid use in RA treatment [6]. These investigators encourage that the ''risk and benefit'' of corticosteroid use in RA should be ''regularly revisited [6]''. Therefore, the objectives of this study were to test whether: (1) corticosteroid utilization was associated with a delay in the initiation of biologic DMARDs among patients with RA; (2) corticosteroid utilization was associated with more adverse events before the initiation of biologic DMARDs among patients with RA; and (3) corticosteroid use was associated with higher healthcare utilization and costs before the initiation of biologic DMARDs among patients with RA.…”

“…The most recent guidelines by the European League Against Rheumatism (EULAR) have similar recommendations regarding the use of only short-term corticosteroids [2]. Harmful side effects of corticosteroid use have been reported (e.g., weight gain, worsening of diabetes, increased risk of infection), thus the decision to initiate therapy should be balanced by the lack of long-term corticosteroid safety studies in the RA population [1,5,6].…”

“…Researchers have thus explored the relationship between corticosteroid and biologic DMARD use in clinical practice [6][7][8][9][10]. For example, it was found that corticosteroids are often used as RA treatment prior to initiating DMARDs despite recommendations that all patients should be managed with a DMARD [6].…”