Introduction: The advent of anti-tumor necrosis factor alpha (anti-TNFα) drugs has considerably improved medical management in rheumatoid arthritis (RA) patients, although it has been reported to be ineffective in a fraction of them. MicroRNAs (miRNAs) are small, non-coding RNAs that act as fine-tuning regulators of gene expression. Targeting miRNAs by gain or loss of function approaches have brought therapeutic effects in various disease models. The aim of this study was to investigate serum miRNA levels as predictive biomarkers of response to anti-TNFα therapy in RA patients. Methods: In total, 95 RA patients undergoing anti-TNFα/disease-modifying antirheumatic drugs (anti-TNFα/DMARDs) combined treatments were enrolled. Serum samples were obtained at 0 and 6 months and therapeutic efficacy was assessed. miRNAs were isolated from the serum of 10 patients before and after anti-TNFα/DMARDs combination therapy, cDNA transcribed and pooled, and human serum miRNA polymerase chain reaction (PCR) arrays were performed. Subsequently, selected miRNAs were analyzed in a validation cohort consisting of 85 RA patients. Correlation studies with clinical and serological variables were also performed. Results: Ninety percent of RA patients responded to anti-TNFα/DMARDs combination therapy according to European League Against Rheumatism (EULAR) criteria. Array analysis showed that 91% of miRNAS were overexpressed and 9% downregulated after therapy. Functional classification revealed a preponderance of target mRNAs involved in reduction of cells maturation - especially on chondrocytes - as well as in immune and inflammatory response, cardiovascular disease, connective tissue and musculoskeletal system. Six out of ten miRNAs selected for validation were found significantly upregulated by anti-TNFα/DMARDs combination therapy (miR-16-5p, miR-23-3p, miR125b-5p, miR-126-3p, miRN-146a-5p, miR-223-3p). Only responder patients showed an increase in those miRNAs after therapy, and paralleled the reduction of TNFα, interleukin (IL)-6, IL-17, rheumatoid factor (RF), and C-reactive protein (CRP). Correlation studies demonstrated associations between validated miRNAs and clinical and inflammatory parameters. Further, we identified a specific plasma miRNA signature (miR-23 and miR-223) that may serve both as predictor and biomarker of response to anti-TNFα/DMARDs combination therapy. Conclusions: miRNA levels in the serum of RA patients before and after anti-TNFα/DMARDs combination therapy are potential novel biomarkers for predicting and monitoring therapy outcome.

Background Prolonged anticoagulation is the treatment of choice for patients with thrombosis and the antiphospholipid syndrome. However, there is still debate about the optimum intensity of anticoagulation. Methods The study included 66 patients with antiphospholipid syndrome (Sapporo criteria) and previous thrombosis. All were receiving oral anticoagulation to a target international normalized ratio of 3.5. Every patient was individually interviewed to recall major bleeding and thrombotic episodes during the previous 12 months. Results Patients were mainly women and white. The rate of major bleeding was 6 cases per 100 patient-years (95% confidence interval [CI] 1.6-15.0). The rate of intracranial bleed was 1.5 per 100 patient-years (95% CI, 0.04-8.4). None of the bleeding episodes was fatal. The rate of thrombotic recurrences was 9.1 cases per 100 patient-years (95% CI, 3.3-19.6). Most recurrences took place in the same vascular bed as the original thrombosis. Age, time receiving anticoagulant therapy, primary vs secondary antiphospholipid syndrome, positivity for anticardiolipin antibodies, positivity for lupus anticoagulant, previous arterial thrombosis, previous stroke, previous venous thrombosis, and previous thrombocytopenia were not predictive of bleeding events. However, the risk of thrombotic recurrences was independently higher in patients who were receiving anticoagulation for longer periods. Conclusions The risk of intracranial and fatal bleeding in patients with definite antiphospholipid syndrome and previous thrombosis treated with oral anticoagulation to a target international normalized ratio of 3.5 is similar than in groups of patients treated to lower target ratios. The risk of thrombotic recurrences, even during anticoagulation, was high. Most recurrences took place in the same territory as original thromboses.

Objective. To determine the first signs and symptoms, and the clinical, biological and radiological characteristics of patients with early SpA. Methods. A total of 150 SpA patients were selected from 2367 listed in REGISPONSER (Registro Español de Espondiloartritis de la Sociedad Española de Reumatología). The inclusion criterion was a disease course of ⩽2 yrs from the onset of symptoms or the appearance of the first sign of disease. Results. Forty-six patients had AS, 51 psoriatic SpA (Ps-SpA), 43 uSpA, 5 ReA, 4 IBD arthropathy and 1 JCA. The mean age at onset of symptoms and at diagnosis was higher in Ps-SpA group (48.1 ± 13.6 and 48.5 ± 13.6 yrs) than in AS group (38.1 ± 12.8 and 38.9 ± 12.7 yrs) and uSpA group (36.3 ± 11.5 and 36.9 ± 11.4 yrs). The most frequent signs or symptoms were back pain: 72% AS group and 56% uSpA group. Lower limb arthritis was the first symptom in 57% Ps-SpA patients, 35% uSpA patients and 20% AS patients; upper limb arthritis was the first symptom in 53% Ps-SpA group and <16% of the remainder. Compared with longer duration disease, at onset, AS patients report upper limb arthritis more frequently and uSpA patients report more of enthesitis. Early radiological sacroiliitis was observed in all AS patients, of whom 54% had Grade II, 39% had Grade III and 7% had Grade IV. Conclusions. In our population, the first manifestations of SpA were low back pain and SI syndrome in AS and uSpA patients and peripheral arthritis in the Ps-SpA group. We can find early SI joint affectation in AS patients.