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Background: Despite low-dose gluco-corticoid (GC) treatment, many patients with rheumatoid arthritis (RA) require additional flare therapy with GC at higher doses. Since low dose GC has been suggested to confer resistance to higher doses, we aimed to assess if resistance was detectable on the clinical level in patients with active RA., Methods: Eighty-nine patients with active RA (Disease Activity Score 28, DAS28>3.2; mean age 54.5 years, mean duration of RA 9.7 years) were consecutively enrolled into a one-week trial of a total of 250 mg prednisolone. We compared improvement of the DAS28 and the Simplified Disease Activity Index (SDAI) in groups of patients with (n=41) and without (n=48) low-dose GC at baseline (by t-test). In addition, we analyzed changes of all individual core set measures of disease activity using multivariate statistics., Results: All clinical, serological and functional measures improved significantly over one week (p<0.001). Baseline RA activity of patients with and without low-dose GC was on average +/- standard deviation similar among the two groups (DAS28: 4.8+/-1.2 and 4.9+/-1.1; mean SDAI: 26.1+/-14.0 and 25.9+/-13.0, respectively), and likewise there was no difference between the two groups in the final disease activity reached, for both the DAS28 (1.4+/-1.1 vs. 1.1+/-1.0; p=0.14) and the SDAI (11.1+/-13.4 vs. 11.1+/-11.4; p=0.99). Improvement in all individual measures was also not different using a multivariate model (p=0.26)., Conclusion: Pre-treatment with low-dose GC does not appear to portend GC resistance at least clinically, since the responsiveness to GC boosts is unaffected.

Rheumatoid arthritis is characterised by pain, swelling, and destruction of joints, with resultant disability. Only disease-modifying antirheumatic drugs can interfere with the disease process. In the past few years, biological agents, especially inhibitors of tumour necrosis factor, have allowed for hitherto unseen therapeutic benefit, although even with these drugs the frequency and degree of responses are restricted. Therefore, new agents are needed, and three novel biological compounds for treatment of rheumatoid arthritis have already been used in practice or are on the horizon: rituximab (anti-CD20), abatacept (cytotoxic T-lymphocyte antigen 4 immunoglobulin), and tocilizumab (anti-interleukin 6 receptor). We discuss the targets of these drugs, the roles of these targets in the pathogenesis of rheumatoid arthritis, and the efficacy and adverse effects of these agents from clinical trial data. Novel therapeutic strategies in conjunction with optimised disease assessment for better treatment of rheumatoid arthritis and an outlook into potential future targets are also presented.

Hormonal dysfunction involving the hypothalamic-pituitary-adrenal (HPA) axis, prolactin (PRL) secretion and sex hormone status has been supposed to contribute to the development or persistence of rheumatoid arthritis (RA). In addition, a reduced number of glucocorticoid receptors on circulating lymphocytes has been found in patients with RA. However, so far most studies have been performed in pre-treated patients. A combined test for total anterior pituitary reserve was performed in 10 patients with newly diagnosed untreated RA. Before and after stimulation with the respective hypothalamic releasing hormones, RA patients showed no difference in plasma concentrations of adrenocorticotrophic hormone (ACTH), cortisol, prolactin (PRL) and thyroid-stimulating hormone (TSH) when compared to healthy controls. In contrast, the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) was blunted in RA patients. The hypothalamic-pituitary-thyroid/gonadal and adrenal axes seem to be unaltered in RA. However, if one considers the presence of chronic inflammation, normal plasma ACTH and cortisol concentrations must be considered as inappropriately low. The observed blunted GH release could be mediated by cytokines (e.g. IL-1), which are known to be elevated in RA.