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ObjectivesPatients with advanced ankylosing spondylitis (AS) experience disability because of reduced spinal mobility and pulmonary function impairment. This placebo-controlled study evaluated the effect of etanercept (ETN) in patients with advanced AS.MethodsA multicentre randomised double-blind placebo-controlled trial of 12 weeks' duration was performed. Patients had definite (modified New York criteria), active (Bath AS Disease Activity Index (BASDAI) ≥40), severe (radiological intervertebral bridges) AS refractory to non-steroidal anti-inflammatory drugs and were antitumour necrosis factor naive. They were treated with ETN 50 mg once weekly or identical placebo (PBO).ResultsOf the 95 patients screened, 82 were randomised to receive ETN (n=39) or PBO (n=43). At baseline the disease was active (mean BASDAI 61.0±13.4, C reactive protein (CRP) 20.7±25.5 mg/l) and severe (mean Bath AS Metrology Index (BASMI) 5.7±1.3, mSASSS 36.5±20.5); forced pulmonary vital capacity (FVC) was 3.3±0.7 l. Improvement in BASDAI (normalised net incremental area under the curve between baseline and week 12, primary end point) was significantly greater in the ETN group than in the PBO group (−19.8±16.5 vs −11.0±16.4, p=0.019). Moreover, at week 12, ETN gave better results than PBO for the BASDAI (−26.4±19.7 vs −14.4±19.7; p=0.008), total back pain (−29.2±24.0 vs −14.9±24.0; p=0.010), BASFI (−21.7±17.6 vs −10.1±17.6; p=0.004), BASMI (−0.6±0.6 vs −0.2±0.6; p=0.011), CRP level (−15.7±14.2 vs −1.3±14.2; p<0.001) and FVC (+160±280 ml vs −20±280 ml; p=0.006).ConclusionsETN has short-term efficacy for patients with advanced AS, as was previously reported for less advanced disease. The efficacy is observed for the main symptoms (pain) and on markers of inflammation (CRP), as well as disease severity in terms of spinal mobility and pulmonary function.

This trial is the first randomised placebo-controlled study of an anti-tumour necrosis factor (TNF) agent in refractory heel enthesitis in patients with SpA. It demonstrates that etanercept has a statistically significant and clinically relevant benefit in such patients. ClinicalTrials.gov identifier NCT00420303.

Osteoarthritis (OA), a disease affecting different patient phenotypes, appears as an optimal candidate for personalized healthcare. The aim of the discussions of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group was to explore the value of markers of different sources in defining different phenotypes of patients with OA. The ESCEO organized a series of meetings to explore the possibility of identifying patients who would most benefit from treatment for OA, on the basis of recent data and expert opinion. In the first meeting, patient phenotypes were identified according to the number of affected joints, biomechanical factors, and the presence of lesions in the subchondral bone. In the second meeting, summarized in the present article, the working group explored other markers involved in OA. Profiles of patients may be defined according to their level of pain, functional limitation, and presence of coexistent chronic conditions including frailty status. A considerable amount of data suggests that magnetic resonance imaging may also assist in delineating different phenotypes of patients with OA. Among multiple biochemical biomarkers identified, none is sufficiently validated and recognized to identify patients who should be treated. Considerable efforts are also being made to identify genetic and epigenetic factors involved in OA, but results are still limited. The many potential biomarkers that could be used as potential stratifiers are promising, but more research is needed to characterize and qualify the existing biomarkers and to identify new candidates.

The growing attention that non-coding RNAs have attracted in the field of cancer research in recent years is undeniable. Whether investigated as prospective therapeutic targets or prognostic indicators or diagnostic biomarkers, the clinical relevance of these molecules is starting to emerge. In addition, identification of non-coding RNAs in a plethora of body fluids has further positioned these molecules as attractive non-invasive biomarkers. This review will first provide an overview of the synthetic cascade that leads to the production of the small non-coding RNAs microRNAs (miRNAs) and presents their strengths as biomarkers of disease. Our interest will next be directed at exploring the diagnostic utility of miRNAs in two types of cancer: the brain tumor glioblastoma multiforme (GBM) and breast cancer. Finally, we will discuss additional clinical implications associated with miRNA detection as well as introduce other non-coding RNAs that have generated recent interest in the cancer research community.

Objective. To evaluate the interest of the Assessment of SpondyloArthritis international Society (ASAS) nonsteroidal antiinflammatory drug (NSAID) score as a quality indicator and a potential outcome measure in clinical studies. Methods. We used data from patients with active, advanced, axial ankylosing spondylitis refractory to NSAIDs. The study design was a 12-week, randomized, placebo-controlled period followed by a 12-week open-label extension. The ASAS-NSAID score was collected during 3 periods of interest (i.e., the 12 weeks preceding baseline, the 12 weeks of the placebo-controlled trial, and the 12 weeks of the open-label trial). Results. For the 82 enrolled patients, the mean ؎ SD ASAS-NSAID score at baseline was similar between the 2 groups: 93 ؎ 76 and 74 ؎ 54 in the etanercept and placebo groups, respectively. There was no significant change in the ASAS-NSAID score during the first part of the trial, as recommended by the protocol. There was a statistically significant decrease in the ASAS-NSAID score during the second part of the trial with a relevant effect size (؊0.56) in the placebo to etanercept group. Conclusion. This study confirms the feasibility and simplicity of the ASAS-NSAID score and suggests that such a score be integrated in all studies in spondylarthritis either to check the quality of the observed data (i.e., intergroup baseline characteristics) or to evaluate the NSAID-sparing effect of other therapies.

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Despite the improvements in symptoms and inflammatory markers observed shortly after initiation of once-weekly etanercept, there was no notable plateauing effect on patient-reported outcomes. Indeed, signs and symptoms of severe and advanced active AS continued to improve after up to 24 weeks, treatment with etanercept.