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Glucocorticoids (prednisone) are essential in the treatment of RA and other autoimmune diseases. They are widely used, but treatment guidelines advise against. This viewpoint article explains why and suggests a way forward. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to assess the safety and efficacy of long-term low-dose glucocorticoids (GCs) in RA. Methods A protocolised systematic review and meta-analysis (PROSPERO No. CRD42021252528) of double-blind, placebo-controlled randomised trials (RCTs) comparing a low dose of GCs (≤ 7.5mg/day prednisone) to placebo over at least 2 years was performed. The primary outcome investigated was adverse events (AEs). We performed random-effects meta-analyses and used the Cochrane RoB tool and GRADE to assess risk of bias and quality of evidence (QoE). Results Six trials with 1078 participants were included. There was no evidence of an increased risk of AEs (incidence rate ratio 1.08; 95% CI 0.86, 1.34; P  = 0.52); however, the QoE was low. The risks of death, serious AEs, withdrawals due to AEs, and AEs of special interest did not differ from placebo (very low to moderate QoE). Infections occurred more frequently with GCs (risk ratio 1.4; 1.19–1.65; moderate QoE). Concerning benefit, we found moderate to high quality evidence of improvement in disease activity (DAS28: −0.23; −0.43 to −0.03), function (HAQ −0.09; −0.18 to 0.00), and Larsen scores (–4.61; −7.52 to −1.69). In other efficacy outcomes, including Sharp van der Heijde scores, there was no evidence of benefits with GCs. Conclusion There is very low to moderate QoE for no harm with long-term low dose GCs in RA, except for an increased risk of infections in GC users. The benefit-risk ratio might be reasonable forusing low-dose long-term GCs considering the moderate to high quality evidence for disease-modifying properties. [ABSTRACT FROM AUTHOR]

Objective To develop prediction models for individual patient harm and benefit outcomes in elderly patients with RA and comorbidities treated with chronic low-dose glucocorticoid therapy or placebo. Methods In the Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis (GLORIA) study, 451 RA patients ≥65 years of age were randomized to 2 years 5 mg/day prednisolone or placebo. Eight prediction models were developed from the dataset in a stepwise procedure based on prior knowledge. The first set of four models disregarded study treatment and examined general predictive factors. The second set of four models was similar but examined the additional role of low-dose prednisolone. In each set, two models focused on harm [the occurrence of one or more adverse events of special interest (AESIs) and the number of AESIs per year) and two on benefit (early clinical response/disease activity and a lack of joint damage progression). Linear and logistic multivariable regression methods with backward selection were used to develop the models. The final models were assessed and internally validated with bootstrapping techniques. Results A few variables were slightly predictive for one of the outcomes in the models, but none were of immediate clinical value. The quality of the prediction models was sufficient and the performance was low to moderate (explained variance 12–15%, area under the curve 0.67–0.69). Conclusion Baseline factors are not helpful in selecting elderly RA patients for treatment with low-dose prednisolone given their low power to predict the chance of benefit or harm. Trial registration https://clinicaltrials.gov ; NCT02585258. [ABSTRACT FROM AUTHOR]

The article reports a response after switching from prednisole to dexamethasone in three D2T-RA patients with active disease despite prednisolone. Topics discussed include possible mechanisms why response to different glucocorticoids (GCs) may vary, pharmacodynamic differences between GCs, and characteristics of 3 ACPA-positive patients switched from prednisolone to dexamethasone.

Objective. To investigate the effect of two different high-dose, step-down prednisolone regimens on body composition in early RA patients after 26 weeks of treatment. Methods. Prednisolone-naive patients with recent-onset RA (n = 108) were randomized to either COBRA (prednisolone 60 mg/day, tapered to 7.5 mg/day in 6 weeks; MTX and SSZ) or COBRA-light therapy (prednisolone 30 mg/day, tapered to 7.5 mg/day in 8 weeks and MTX). Body composition was assessed at baseline (before or soon after start of treatment) and after 26 weeks with DXA, and recorded as total body mass (TBM), total fat mass (FM), total lean mass (LM) and trunk/peripheral fat ratio. Log-ratio analyses assessed the proportional distribution of TBM (between LM, FM and bone mass) and FM (between trunk, extremities and head). The subgroup of patients with a DXA before start of treatment (n = 38) was analysed separately. Results. In the subgroup of patients with a DXA before start of treatment, TBM increased by 1.6 kg (P < 0.001) and total FM by 1.3 kg (P < 0.001). The trunk/peripheral fat ratio and the proportional distribution of TBM and FM remained stable over time. There were no differences between the treatment groups. Similar results were obtained in the study population as a whole. Conclusion. Both high-dose, step-down prednisolone regimens caused increases in TBM, mainly caused by an increase in FM, but we found no fat redistribution from peripheral to central tissues. This absence in fat redistribution contradicts the widely held assumption of rapid adverse effects of prednisolone on body composition in RA. Trial registration: ISRCTNregistry, http://www.isrctn.com, ISRCTN55552928 [ABSTRACT FROM AUTHOR]

Objective. The effects of a 12-week treatment with modified-release prednisone (MR-pred) on the costs of drug treatment of RA were modelled.Methods. With the results of a recent randomized trial as source data, we expressed the effect of treatment (MR-pred vs placebo) on the decrease in the proportion of RA patients meeting disease activity thresholds for reimbursement of biologic treatment.Results. The results showed 11–13% more patients on MR-pred than on placebo dropped below reimbursement thresholds for the Netherlands, Belgium and the UK. Assuming 1 year of biologics cost €15 000 and MR-pred costs €1/day, €396 are saved in each patient delaying biologic treatment by 12 weeks.Conclusion. Despite a considerably higher cost than conventional prednisone, MR-pred is a cost-effective option for RA patients not on glucocorticoids who are eligible for therapy with biologic agents. [ABSTRACT FROM PUBLISHER]