The immune response mediator genes polymorphic variants as predictors of the etanercept efficacy in juvenile idiopathic arthritis

Objective ― The aim of the study was to investigate the relationship of the alleles and genotypes of the immune response mediator genes polymorphic loci (rs1800629, rs909253, rs16944, rs6822844, rs2104286, rs1800795, rs1800872, rs3087243, rs755622 rs28362491, rs2240336, rs2476601) with the etanercept efficacy in juvenile idiopathic arthritis (JIA) patients. Material and Methods ― The study included 39 JIA patients from Bashkortostan, Russia. Achieving the American College of Rheumatology Pediatric 70 (ACR Pedi 70) response was regarded as the presence of the response to etanercept (otherwise – as the absence), while achieving clinical remission on medication – as the sufficient response (otherwise – as the insufficient). Genotyping was performed using real-time polymerase chain reaction method. Results ― The predictors of an increased risk of the non-response to etanercept were the IL1B rs16944*TT (pcor=0.023), NFKB1 rs28362491*II (pcor=0.042) genotypes, and of the increased risk of the insufficient response to etanercept – the IL2RA rs2104286*AA (pcor=0.010), NFKB1 rs28362491*II (pcor=0.026) genotypes. The markers of the decreased risk of the non-response to etanercept were the IL1B rs16944*C (pcor=0.046), NFKB1 rs28362491*D (pcor=0.029) alleles, and of the decreased risk of the insufficient response to etanercept – the IL2RA rs2104286*AG genotype (pcor=0.049), IL2RA rs2104286*G allele (pcor=0.005). Conclusion ― In this study the association of the alleles and genotypes of the IL1B rs16944, IL2RA rs2104286, NFKB1 rs28362491 polymorphic loci with the etanercept efficacy in JIA patients was established

sj-docx-1-jop-10.1177_02698811231166463 – Supplemental material for Behavioral profile of adult zebrafish acutely exposed to a selective dopamine uptake inhibitor, GBR 12909

Supplemental material, sj-docx-1-jop-10.1177_02698811231166463 for Behavioral profile of adult zebrafish acutely exposed to a selective dopamine uptake inhibitor, GBR 12909 by Konstantin N Zabegalov, Fabiano Costa, Yuliya A Viktorova, Gleb O Maslov, Tatiana O Kolesnikova, Elena V Gerasimova, Vladimir P Grinevich, Evgeny A Budygin and Allan V Kalueff in Journal of Psychopharmacology</p

Alirocumab and cardiovascular outcomes after acute coronary syndrome

BACKGROUN

Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

BACKGROUN

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk

Proceedings Of The 23Rd Paediatric Rheumatology European Society Congress: Part Two

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