GLORIA trial findings show the safety and tolerability of tapering glucocorticoids in elderly RA patients

A recent study published in the journal Annals of the Rheumatic Diseases has indicated that discontinuing long-term, low-dose glucocorticoid use after three months is both feasible and safe for elderly patients with rheumatoid arthritis (RA).   

The GLORIA trial, a randomized placebo-controlled study, examined the effects of adding prednisolone 5 mg/day to standard therapy for two years in RA patients aged 65 and older. According to Mr. Almayali, the tapering of prednisolone demonstrated a slight increase in the risk of flaring, without any signs of adrenal insufficiency, and led to a mild elevation in disease activity levels comparable to the placebo group. The trial included a total of 191 eligible patients, with 36 of them participating only in the flare analysis due to meeting treatment-related flare criteria. In the prednisolone group (n=76), the mean change in the 28-joint Disease Activity Score (DAS-28) at follow-up was 0.2 (1.0), while in the placebo group (n=79), it was 0.0 (1.2). After adjusting for baseline, the between-group difference in DAS-28 progression was calculated at 0.16 (P =0.12). The prednisolone users experienced flares at a rate of 45%, compared to 33% in the placebo group, resulting in a relative risk of 1.37 (P =0.12). Importantly, no evidence of adrenal insufficiency was detected. This suggests that the use of low-dose prednisolone can be safely discontinued after a two-year duration. 

In another recent systematic review (2023), the safety and effectiveness of long-term, low-dose glucocorticoid use in patients with RA were assessed. The results indicated a low to moderate quality of evidence (QoE) showing improvements in disease activity (DAS28: -0.23; -0.43 to –0.03), function (Health Assessment Questionnaire: -0.09; -0.18 to 0.00), and Larsen scores (-4.61; -7.52 to -1.69) with the use of long-term, low-dose glucocorticoids in RA patients. Considering the moderate to high-quality data related to disease-modifying effects, the benefit-risk ratio for using low-dose, long-term glucocorticoids appears to be reasonable. Despite the low QoE, no evidence of an increased risk of adverse events was observed (incidence rate ratio: 1.08; P = 0.52). The risks associated with death, severe adverse events (AEs), withdrawals due to AEs, and AEs of specific concern were comparable to those of the placebo group (with QoE ranging from very low to moderate). However, infections occurred more frequently with glucocorticoid use (risk ratio: 1.4; range: 1.19–1.65; moderate QoE). Consequently, the study suggests a generally low to moderate quality of evidence for the effectiveness of long-term, low-dose glucocorticoid use in RA, with the exception of an increased risk of infections among glucocorticoid users. 

The collective evidence suggests that discontinuing long-term, low-dose glucocorticoid use after a certain duration in elderly patients with RA is safe, with minor increases in disease flares. Moreover, while the effectiveness of such glucocorticoid therapy is supported by moderate evidence, concerns regarding an increased risk of infections should be taken into consideration. As with any medical decision, individual patient factors and considerations should guide the approach to glucocorticoid treatment in RA. 

References 

  1. Almayali AA, Boers M, Hartman L, Opris D, Bos R, Kok MR, et al. Three-month tapering and discontinuation of long-term, low-dose glucocorticoids in senior patients with rheumatoid arthritis is feasible and safe: placebo-controlled double blind tapering after the GLORIA trial. Annals of the Rheumatic Diseases. 2023 Aug 4. 
  2. Palmowski A, Nielsen SM, Boyadzhieva Z, Schneider A, Pankow A, Hartman L, et al. Safety and efficacy associated with long-term low-dose glucocorticoids in rheumatoid arthritis: a systematic review and meta-analysis. Rheumatology. 2023 Feb 22:kead088. 

 

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