Objective: To compare the efficacy, serum drug concentrations, immunogenicity, and safety of FKB327 with the adalimumab reference product (RP) in combination with methotrexate in patients with moderate-to-severe, active rheumatoid arthritis (RA). Methods: Patients were randomized 1:1 in a double-blind study (NCT02260791), received 40 mg of FKB327 or RP by subcutaneous injection every other week for 24 weeks (Period I), then re-randomized 2:1, remaining on the same study drug or switching to the other up to week 54 in an open-label extension (Period II, NCT02405780). Efficacy was evaluated using American College of Rheumatology (ACR20) response rate difference at week 24 with equivalence margins of ± 13% and − 12% to + 15% using 95% and 90% confidence intervals (CIs), respectively. Efficacy, serum drug concentrations, immunogenicity, and safety were compared at week 54. Results: A total of 730 patients were randomized in Period I (n = 367 FKB327, n = 363 RP), and 645 transitioned to Period II (n = 216 FKB327–FKB327, n = 108 FKB327–RP, n = 108 RP–FKB327, n = 213 RP–RP). At week 24, ACR20 response rates were 74.1% with FKB327 versus 75.7% with RP. 95% and 90% CI of the response rate difference were − 7.9 to 4.7% and − 7.3 to 3.6%, respectively, meeting predefined equivalence margins. The ACR20 response rate remained over 70% of patients to week 54 with all treatment sequences. In Period I, mean trough serum drug concentrations were slightly higher for patients receiving FKB327 than those receiving RP. Mean concentrations were stable over time and reflected steady state in Period II. The proportions of patients with samples positive for neutralizing antidrug antibodies (ADAs) were comparable (57.7% with FKB327 vs. 55.5% with RP) at week 24, and no consistent difference in ADA were seen between continuous and switched treatments in Period II. Efficacy was slightly reduced in the small proportion of patients with high ADA titers in all treatment groups. No clinically significant differences were observed in the incidence of commonly reported treatment-emergent adverse events between the treatments across Periods I and II. Conclusion: FKB327 was equivalent to RP in clinical efficacy and demonstrated comparable safety and immunogenicity in patients with moderate-to-severe RA. No effect of switching between FKB327 and RP was observed. Trial registration: ClinicalTrials.gov, NCT02260791, Registered 29 July 2014. ClinicalTrials.gov, NCT02405780, Registered 17 July 2015.

Меморандум экспертов Российского кардиологического общества по рекомендациям Европейского общества кардиологов/Европейского общества по артериальной гипертензии по лечению артериальной гипертензии 2018г

Фибрилляция предсердий в когорте амбулаторных пациентов Санкт-Петербурга: встречаемость, факторы риска, антиаритмическая терапия и профилактика тромбоэмболических осложнений

The aim of this study was to determine the concentration of galectin-3, PINP and PIIINP in patients with metabolic syndrome (MS) and atrial fibrillation (AF) with an assessment of the relationship with severity of left atrium fibrosis. A total of 480 subjects were included in the case-control study: MS patients (n = 337), 176 of whom had AF, 72 patients with AF without MS and 71 healthy subjects. Galectin-3, PINP and PIIINP blood concentrations and metabolic parameters were compared with the severity of left atrium fibrosis, measured by CARTO3. Galectin-3 in AF and MS patients is higher than in MS without AF and in healthy subjects (10.3 (4.8–15.4), 5.1 (4.3–8.8), 3.2 (2.4–4.2) ng/mL, p < 0.0001). Galectin-3 serum concentration in AF patients with MS is higher than in patients without MS: 10.3 (4.8–15.4), 6.8 (5.2–8.1) ng/mL, p = 0.0001. PINP and PIIINP concentration were higher in patients with AF and MS than in MS without AF: 3499.1 (2299.2–4567.3), 2130.9 (1425.3–2861.8) pg/mL, p < 0.0001, 94.9 (64.8–123.5), 57.6 (40.5–86.9) ng/mL, p < 0.0001. Galectin-3 correlates with PINP (r = 0.496, p < 0.001) and PIIINP concentration (r = 0.451, p < 0.0001). The correlation between galectin-3, PINP and the severity of left atrium fibrosis was found (r = 0.410, p < 0.001; r = 0.623, p < 0.001). Galectin-3 higher than 12.6 ng/mL increased the risk of AF more than five-fold. High galectin-3, PINP and PIIINP concentrations were associated with heart remodeling in MS patients and increased the risk of AF.

The article provides modern data on the prevalence of cardiovascular diseases and mortality in Europe and Russia. Groups of high-risk patients requiring special attention when conducting measures to reduce cardiovascular mortality are discussed: patients with hypertension, including resistant, patients with severe dyslipidemia, heart failure, and atrial fibrillation. Particular attention is paid to the problem of effective and safe treatment and reducing cardiovascular mortality in patients with atrial fibrillation and a high risk of stroke. The treatment of these patients may be most successful due to the availability of effective medications that reduce cardiovascular mortality. The article outlines the major paradigms of modern healthcare: focus on results and patient, integration of inpatient and outpatient health care units and accelerating the innovation in the diagnosis and treatment of patients with cardiovascular diseases.

Cardiovascular diseases are widespread and are the leading death cause in most countries, despite the creation and improvement of strategies to reduce cardiovascular risk. A significant role in the development and evolution of cardiovascular diseases belongs to sympathetic nervous system hyperactivity, and therefore the methods of effecting it are relevant for the prevention and treatment of cardiovascular pathology. The article discusses modern approaches to interventional and conservative regulation of the autonomic nervous system and neuromodulation in the prevention and treatment of hypertension, heart failure, tachyarrhythmias, as well as reflects a conjoint expert judgment on these issues.