Current evidence for the management of rheumatoid arthritis with glucocorticoids: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis.
ABSTRACT Glucocorticoids (GCs) rapidly reduce disease activity in early and advanced rheumatoid arthritis (RA). This systematic review on behalf of the task force on recommendations for the management of RA addresses the efficacy of GCs in RA. A literature search was performed in Medline, Embase, the Cochrane database, and the ACR/EULAR abstracts 2007 and 2008 on a set of questions relating to the use of GCs in RA. Eleven publications (including three Cochrane reviews comprising 33 trials) that met the criteria for detailed assessment were found. Robust evidence that GCs are effective as bridging therapy was obtained. The addition of GCs, to either standard synthetic disease-modifying antirheumatic drug (DMARD) monotherapy or combinations of synthetic DMARDs, yields clinical benefits and inhibition of radiographic progression that may extend over many years. In early RA, the addition of low-dose GCs (<7.5 mg/day) to DMARDs leads to a reduction in radiographic progression; in longstanding RA, GCs (up to 15 mg/day) improve disease activity. There is some evidence that appropriate timing of GC administration may result in less morning stiffness. Only indirect information was found on the best tapering strategy, supporting the general view that GCs should be tapered slowly in order to avoid clinical relapses. GCs are effective in relieving signs and symptoms and inhibiting radiographic progression, either as monotherapy or in combination with synthetic DMARD monotherapy or combination therapy.
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ABSTRACT: T helper 2 (Th2) cells regulate helminth infections, allergic disorders, tumor immunity, and pregnancy by secreting various cytokines. It is likely that there are undiscovered Th2 signaling molecules. Although steroids are known to be immunoregulators, de novo steroid production from immune cells has not been previously characterized. Here, we demonstrate production of the steroid pregnenolone by Th2 cells in vitro and in vivo in a helminth infection model. Single-cell RNA sequencing and quantitative PCR analysis suggest that pregnenolone synthesis in Th2 cells is related to immunosuppression. In support of this, we show that pregnenolone inhibits Th cell proliferation and B cell immunoglobulin class switching. We also show that steroidogenic Th2 cells inhibit Th cell proliferation in a Cyp11a1 enzyme-dependent manner. We propose pregnenolone as a "lymphosteroid," a steroid produced by lymphocytes. We speculate that this de novo steroid production may be an intrinsic phenomenon of Th2-mediated immune responses to actively restore immune homeostasis.Cell Reports 05/2014; · 7.21 Impact Factor
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ABSTRACT: Glucocorticosteroids (GCs) have been employed extensively for the treatment of rheumatoid arthritis (RA) and other autoimmune and systemic inflammatory disorders. Their use is supported by extensive literature and their utility is reflected in their incorporation into current treatment guidelines for RA and other conditions. Nevertheless, there is still some concern regarding the long-term use of GCs because of their potential for clinically important adverse events, particularly with an extended duration of treatment and the use of high doses. This article systematically reviews the efficacy for radiological and clinical outcomes for low-dose GCs (defined as ≤10 mg/day prednisone equivalent) in the treatment of RA. Results reviewed indicated that low-dose GCs, usually administered in combination with synthetic DMARDs, most often MTX, significantly improve structural outcomes and decrease symptom severity in patients with RA. Safety data indicate that GC-associated adverse events are dose related, but still occur in patients receiving low doses of these agents. Concerns about side effects associated with GCs have prompted the development of new strategies aimed at improving safety without compromising efficacy. These include altering the structure of existing GCs and the development of delayed-release GC formulations so that drug delivery is timed to match greatest symptom severity. Optimal use of low-dose GCs has the potential to improve long-term outcomes for patients with RA.Rheumatology (Oxford, England) 04/2014; · 4.24 Impact Factor
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ABSTRACT: Glucocorticoids are widely used in rheumatoid arthritis (RA); however, their effectiveness and safety is still a subject of debate. In particular, when to introduce glucocorticoids, but also when and how to taper them, are important questions for clinicians. In this paper, we will discuss the place of glucocorticoids in the European League Against Rheumatism (EULAR) recommendations for the management of RA and review the literature that was the basis for these recommendations. The recommendations cover the introduction of glucocorticoids (and for whom they are recommended), doses and duration of treatment, and tapering strategies. Items still on the research agenda include more data on safety, particularly for long-term use, and small doses of glucocorticoids.Annals of the New York Academy of Sciences 05/2014; · 4.38 Impact Factor