Search

Baricitinib, an oral Janus kinase (JAK) 1-2 inhibitor, is currently used along biologic DMARDs (bDMARDs) after the failure of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated the efficacy and safety of baricitinib in real life.We prospectively enrolled 446 RA patients treated with baricitinib from 11 Italian centres. Patients were evaluated at baseline and after 3, 6, and 12 months. They were arrayed based on previous treatments as bDMARD-naïve and bDMARD-insufficient responders (IR) after the failure or intolerance to bDMARDs. A sub-analysis differentiated the effects of methotrexate (MTX) and the use of oral glucocorticoids (OGC).Our cohort included 150 (34%) bDMARD-naïve and 296 (66%) bDMARD-IR patients, with 217 (49%) using baricitinib as monotherapy. Considering DAS-28-CRP as the primary outcome, at 3 and 6 months, 114/314 (36%) and 149/289 (51.6%) patients achieved remission, while those in low disease activity (LDA) were 62/314 (20%) and 46/289 (15.9%), respectively; finally at 12 months 81/126 (64%) were in remission and 21/126 (17%) in LDA. At all-timepoints up to 12 months, bDMARDs-naïve patients demonstrated a better clinical response, independently of MTX. A significant reduction in the OGC dose was observed at 3 and 12 months in all groups. The serum positivity for both rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPA) conferred a lower risk of stopping baricitinib due to inefficacy. Fifty-eight (13%) patients discontinued baricitinib due to adverse events, including thrombotic events and herpes zoster reactivation.Real-life data confirm the efficacy and safety profiles of baricitinib in patients with RA and provide evidence that drug survival is higher in bDMARDs-naïve and seropositive patients.

Carbamylation is an irreversible post-translational modification of proteins. The presence of anti-carbamylated protein antibodies (anti-CarP) has been observed in rheumatoid arthritis (RA). This study was focused to verify whether anti-CarP antibodies can be used as a predictive factor of clinical response to abatacept (CTLA4-Ig) in RA patients.Sixty RA patients treated with abatacept were enrolled. A home-made ELISA for anti-CarP and a commercial anti-CCP3.1 kit for anti-citrullinated proteins antibodies (anti-CCP) were applied to determine serum levels every six months of therapy. Rheumatoid factor (RF) was also tested.Anti-CarP positive patients (n=18) were younger (p=0.01) and with a longer disease duration (p=0.05) when compared to anti-CarP negative patients (n=42) at baseline. Considering the entire cohort, a significant reduction of anti-CarP titre after twelve-months of treatment was shown (p0.01). A significant reduction of Disease Activity Score (DAS) 28-C-reactive protein (CRP) in the first six months of therapy was found in the subgroup of anti-CarP positive patients in comparison with the negative ones (p=0.003). No significant results were found by dividing the cohort using the positivity to anti-CCP and/or RF.Earlier onset and a longer disease duration in anti-CarP positive patients might suggest they are specific risk factors for RA in this subgroup of patients. The correlation between the anti-CarP positivity at baseline and the reduction of disease activity during the first six months of treatment with abatacept allowed us to hypothesise that anti-CarP antibodies, but not anti-CCP and/or RF, could be used as a good clinical response predictor.

We aimed to provide data on golimumab real-life use in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) from a multicentre observational registry of Northern Italy.We extracted data of patients who started treatment with golimumab from October 2010, and who had at least one follow-up visit. Data were analysed until a maximum follow-up of 24 months. The two-year retention rate in the three diseases was assessed with Kaplan-Meier estimators. To compare crude survival between diagnoses and lines of treatment we used the log-rank test, while Cox proportional hazard models were used to adjust for confounders.Overall, 410 subjects were included: 180 patients with RA, 110 with PsA and 120 with AS. The two-year retention rate of patients with RA was 47.3%, 48% for PsA, and 62.8% for AS. Crude survival on treatment of patients with AS was significantly higher than that of RA patients (p=0.032), while no significant difference was found between AS and PsA and between RA and PsA. In patients with RA, subjects treated with concomitant sDMARDs showed a lower discontinuation rate than those receiving golimumab alone. The comparison between first and second line of treatment groups did not show any significant difference in mean survival time in patients with RA, PsA and AS.This is the first report of real-life data on two-year survival on treatment with golimumab in RA, PsA and AS. Golimumab showed a similar retention rate when given as first or second line of treatment.

This article presents an analysis of the evolution of illicit crops in Colombia through the National Accounts System, which provides a basis for the study of transactions and the use of the product in an economy. Through the input-output methodology it is shown that, thanks to the drug policy action developed by the national government, its importance in generation of value added has been changing and decreasing over time.

Several emerging portable applications require high-efficiency LED drivers [1-4]. An LED driver is basically a current source that forces the current required for achieving the desired light emission into the LED. In order to increase the LED driver efficiency, besides controlling the LED current, it is necessary to regulate the voltage applied to the LED itself, to minimize the voltage drop across the driver current source and, hence, the power consumption. Depending on the kind of LED and on the current forced through the LED itself (0.1 to 2A in this design) and, hence, on the desired light emission, the voltage required to drive the LED, while maintaining the voltage headroom across the driver current source to the minimum, varies over a wide range (0 to 5V). Starting from a standard voltage supply in the range 2.7 to 5.5V, a buck-boost DC-DC converter is then required (Fig. 16.4.1). The buck-boost DC-DC converter includes the LED in the control feedback loop and has to provide fast turn-on and load transients (on the order of 20μs), in order to allow pulsed operation of the LED itself.