Tapering of Etanercept is feasible in patients with Rheumatoid Arthritis in sustained remission: a pragmatic randomized controlled trial.

OBJECTIVE: In patients with rheumatoid arthritis (RA) in sustained remission, tapering of biological disease-modifying anti-rheumatic drugs can be considered. Tapering has already been investigated, but its feasibility remains to be determined. Therefore, we explored the feasibility of tapering etanercept in RA in a setting close to practice. METHOD: Patients with RA in 28-joint Disease Activity Score (DAS28) remission (≥ 6 months) and treated with etanercept 50 mg weekly (≥ 1 year) were included in the pragmatic 1 year open-label multicentre randomized controlled TapERA (Tapering Etanercept in Rheumatoid Arthritis) trial. Patients were assigned to continue etanercept weekly or to taper to every other week (EOW). Patients who lost remission [DAS28-C-reactive protein (CRP) ≥ 2.6] were re-escalated to etanercept weekly. The primary outcome was the proportion of patients maintaining DAS28-CRP remission for 6 months. RESULTS: Sixty-six patients were randomized to etanercept weekly (n = 34) or EOW (n = 32). After 6 months, 26/34 patients (76%) in the weekly and 19/32 (59%) in the EOW group maintained disease control (p = 0.136). In the EOW group, 20/32 patients (63%) remained on their tapered treatment during the trial. Two patients reintroduced weekly etanercept themselves. Ten patients were re-escalated to etanercept weekly by the rheumatologist, after a median (interquartile range) interval of 3.0 (2.0-6.0) months. Among these patients, 7/10 regained remission after re-escalation, four of them at the next study visit. CONCLUSIONS: Although non-inferiority could not be demonstrated, tapering of etanercept to EOW appeared feasible in patients in sustained remission.

Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16†weeks of treatment: the CareRA trial.

OBJECTIVES: To compare the efficacy and safety of intensive combination strategies with glucocorticoids (GCs) in the first 16 weeks (W) of early rheumatoid arthritis (eRA) treatment, focusing on high-risk patients, in the Care in early RA trial. METHODS: 400 disease-modifying antirheumatic drugs (DMARD)-naive patients with eRA were recruited and stratified into high risk or low risk according to classical prognostic markers. High-risk patients (n=290) were randomised to 1/3 treatment strategies: combination therapy for early rheumatoid arthritis (COBRA) Classic (methotrexate (MTX)+ sulfasalazine+60 mg prednisone tapered to 7.5 mg daily from W7), COBRA Slim (MTX+30 mg prednisone tapered to 5 mg from W6) and COBRA Avant-Garde (MTX+leflunomide+30 mg prednisone tapered to 5 mg from W6). Treatment modifications to target low-disease activity were mandatory from W8, if desirable and feasible according to the rheumatologist. The primary outcome was remission (28 joint disease activity score calculated with C-reactive protein <2.6) at W16 (intention-to-treat analysis). Secondary endpoints were good European League Against Rheumatism response, clinically meaningful health assessment questionnaire (HAQ) response and HAQ equal to zero. Adverse events (AEs) were registered. RESULTS: Data from 98 Classic, 98 Slim and 94 Avant-Garde patients were analysed. At W16, remission was reached in 70.4% Classic, 73.6% Slim and 68.1% Avant-Garde patients (p=0.713). Likewise, no significant differences were shown in other secondary endpoints. However, therapy-related AEs were reported in 61.2% of Classic, in 46.9% of Slim and in 69.1% of Avant-Garde patients (p=0.006). CONCLUSIONS: For high-risk eRA, MTX associated with a moderate step-down dose of GCs was as effective in inducing remission at W16 as DMARD combination therapies with moderate or high step-down GC doses and it showed a more favourable short-term safety profile. EUDRACT NUMBER: 2008-007225-39.

Xath2, a bHLH gene expressed during a late transition stage of neurogenesis in the forebrain of Xenopus embryos.

We have identified a Xenopus bHLH gene, Xath2, which is the homologue of the murine MATH-2/NEX-1 gene, using a functional expression screening approach. Overexpression of this gene in neurula embryos induces the expression of the N-tubulin neuronal marker but does not stimulate the expression of the X-ngnr-1 and NeuroD proneural genes. Expression of Xath2 begins in stage 32 embryos and is restricted to the dorsal telencephalon. Within the neuroepithelium of the dorsal telencephalon, Xath2 expression is detected in postmitotic cells located more laterally than those expressing several other related bHLH neuronal regulators.

Body composition in rheumatoid arthritis.

The objectives were to assess bone mineral density (BMD) at different body sites in rheumatoid arthritis (RA) patients related to disease severity parameters, disease duration and corticosteroid intake, and to look for body composition measurements as lean body mass (LBM) and per cent fat as possible prognostic factors in RA. Body composition values were measured cross-sectionally in 89 RA patients and compared with 157 controls. Patients were divided into males and postmenopausal females, ever steroid treated and never steroid treated. BMD values of all body sites were significantly lower compared to normals in all subgroups, except for the lumbar spine (L2 L4) in all postmenopausal women and males never treated with steroids. There was also no clear BMD decrease in the arms of male RA patients. LBM was significantly lower in all body parts compared to controls, whereas the fat distribution ratio (FDR) showed a clear shift to abdominal in all patients. These are parameters of chronic illness and a predictor of cardiovascular disease, respectively. BMD data confirm our previous data in different patient groups (low at appendicular sites, normal lumbar BMD), but no clear influence of disease severity and steroid intake could be found. Body composition data, as LBM and FDR, are also altered in RA patients: decreased LMB and more central FDR. Their usefulness as prognostic markers in early RA patients needs to be clarified prospectively in these patient groups.