IntroductionThe purpose of this study was to determine whether maraviroc, a human CC chemokine receptor 5 (CCR5) antagonist, is safe and effective in the treatment of active rheumatoid arthritis (RA) in patients on background methotrexate (MTX).MethodsThis phase IIa study comprised two distinct components: an open-label safety study of the pharmacokinetics (PK) of MTX in the presence of maraviroc, and a randomized, double-blind, placebo-controlled, proof-of-concept (POC) component. In the PK component, patients were randomized 1:1 to receive maraviroc 150 or 300 mg twice daily (BID) for four weeks. In the POC component, patients were randomized 2:1 to receive maraviroc 300 mg BID or placebo for 12 weeks. Patients were not eligible for inclusion in both components.ResultsSixteen patients were treated in the safety/PK component. Maraviroc was well tolerated and there was no evidence of drug-drug interaction with MTX. One hundred ten patients were treated in the POC component. The study was terminated after the planned interim futility analysis due to lack of efficacy, at which time 59 patients (38 maraviroc; 21 placebo) had completed their week 12 visit. There was no significant difference in the number of ACR20 responders between the maraviroc (23.7%) and placebo (23.8%) groups (treatment difference -0.13%; 90% CI -20.45, 17.70; P = 0.504). The most common all-causality treatment-emergent adverse events in the maraviroc group were constipation (7.8%), nausea (5.2%), and fatigue (3.9%).ConclusionsMaraviroc was generally well tolerated over 12 weeks; however, selective antagonism of CCR5 with maraviroc 300 mg BID failed to improve signs and symptoms in patients with active RA on background MTX.Trial RegistrationClinicalTrials.gov: NCT00427934

Objective: to study the clinical characteristics of PsA and working capacity in patients included in the All-Russian PsA Registry.Patients and methods. The investigation enrolled 614 patients aged 19–84 years with psoriasis from 39 subjects the Russian Federation, who were followed up in the All-Russian PsA Registry. On the basis of the assessment of demographic data, the spectrum of comorbidities, the degree of activity of the underlying disease according to Disease Activity Index for PsA (DAPSA) and Disease Activity in 28 joints (DAS28), clinical, functional, and social indicators were analyzed in the patients. The investigators studied information on the patients employment, working capacity, and disability, by assessing the group of the latter. The health status and the presence and severity of functional impairment in the patients were analyzed using the Health Assessment Questionnaire (HAQ), while their working efficiency was estimated according to the Workers Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP questionnaire), by calculating the following parameters: absenteeism, presenteeism, an overall decrease in labor productivity, and impairment in daily functional activity.Results and discussion. The analysis of the All-Russian PsA Registry showed that most of them were of working age (30 to 59 years); 48.4% had concomitant diseases. Data on DAPSA changes were obtained in 349 patients, who were recorded to have mainly moderate (34.7%) or high (42.7%) disease activity, multiple dactylitides and enthesitides, and limited joint function. The registry reflects information on the social status of 521 patients: employed (61.2%) and unemployed (22.1%) persons, pensioners (15.2%), and students (1.5%). More than one third (37.1%) of patients with PsA had disability, mainly of Group III. The changes in the HAQ disability index were assessed in 326 patients; mild, moderate, and severe functional impairments were observed in 36, 26.4, and 3.7%, respectively. Absenteeism was detected in less than one third of patients with PsA, presenteeism was found in about half; there was an overall decrease in labor productivity in more than 60% and daily activity impairment in 68.8%. Statistically significant direct moderate correlations were established between the indicators of PsA activity (DAPSA and DAS28) and the level of productivity impairment in the patients; this was mostly related to an overall decline in labor productivity and to a decrease in daily activity.Conclusion. The data obtained from real clinical practice suggest that half of the PsA patients had high disease activity and a third had severe functional impairment, which led to a lower quality of life and to disability. The overall decrease in labor productivity and daily activity, which was detected in more than half of the patients, was associated with high PsA activity. The follow-up in the All-Russian PsA Registry, regular anti-inflammatory therapy with disease-modifying antirheumatic drugs and biological agents can improve the clinical and functional status and, consequently, working capacity in patients with PsA.

A combination of chondroitin and glucosamine is widely used in clinical practice as both a symptomatic and structure-modifying agent for the treatment of osteoarthritis (OA). The emergence of new drugs based on this combination substantially expands treatment options for OA therapy.Objective: to evaluate the efficacy and safety of Artroflex® that is a combination of chondroitin sulfate 400 mg and glucosamine sulfate 500 mg (CS + GS) to support joint health in patients with knee and/or hip OA.Patients and methods. When implementing an open observational research program, the results of using the CS + GS complex were assessed in 644 OA patients (74.7% women) (mean age, 58.0±14.6 years) who experienced moderate/severe pain and required to continuously take non-steroidal anti-inflammatory drugs (NSAIDs). The CS + GS complex was prescribed in a dose of 2 capsules per day for 3 months. The investigators estimated changes in pain on movement by a 0 to 10 verbal pain scale, general health (GH) by a 0–10 visual analogue scale), the Lequesne index, the need for NSAIDs, and patient satisfaction with treatment and its tolerance.Results and discussion. After 3-month therapy, there were decreases in pain intensity by 49.2±16.8%, GH scores by 45.6±18.1%, the Lequesne index from 9.0 [6.0; 13.0] to 5.0 [3.0; 9.0]; less than half (45.2%) of the patients still needed for NSAIDs. 82.2% of patients were satisfied or completely satisfied with treatment results; 89.6% reported good treatment tolerance.Adverse events (apparently associated with NSAID use) were recorded in 2.2% of cases. There were no serious complications that required CS + GS treatment discontinuation or hospitalization.Conclusion. The findings have indicated that Artroflex® used to support joint health is an effective agent that controls OA symptoms and has a good safety level.

The aimof the study was to assess the relationship between the detection of hyperechogenic deposits (HD) in the hyaline cartilage of the knee joints (KJ) at ultrasonography in patients with osteoarthritis (OA), clinical manifestations and structural changes according to KJ ultrasonography and radiography.Material and methods.A prospective analysis of clinical, radiological and ultrasonographic data of 114 patients with knee OA was conducted. The patients were divided into two groups: 32 patients with HD detected in at least one of the KJ, and 82 patients without HD; 32 patients of the 1st group and 34 patients of the 2nd group were observed for 2 years. A comparative assessment of initial clinical manifestations (WOMAC index), x-ray data and ultrasonographic parameters of the subchondral bone, hyaline cartilage and the degree of synovial inflammation in the groups of patients at the beginning of the study and after 2 years was carried out. The exclusion criteria were other joint diseases; paroxysmal course of the inflammatory process in KJ; trauma and history of operations on KJ; ESR >20 mm/h, uric acid level >360 μmol/l and C-reactive protein >5 mg/l.Results and discussion.HD in hyaline cartilage was found in 28.1% of patients with knee OA. After 2 years HD remained in all patients having them at inclusion, and in 5.6% of the patients they were found for the first time. In 13 patients with HD in hyaline cartilage, synovial fluid was studied and in all cases calcium pyrophosphate crystals were identified by phase-contrast microscopy. The presence of HD in the hyaline cartilage of patients with knee OA was accompanied by more pronounced ultrasonographic signs of synovitis and was associated with a higher rate of osteophytes growth in the absence of the changes of the hyaline cartilage thickness according to the ultrasonography and the width of the joint space according to x-ray.Conclusion.The presence of HD in the hyaline cartilage of patients with knee OA according to ultrasound examination may be associated with the deposition of calcium pyrophosphate crystals and is associated with persistent synovitis and accelerated growth of osteophytes.

Цель исследования -оценить динамику качества жизни (КЖ) больных РА при инициации терапии генно-инженерными биологическими препаратами (ГИБП) в реальной клинической практике.

Objective. Assessment of clinical manifestations and ultrasonographic signs of enthesitis (En) in patients with psoriasis (PsO) and psoriatic arthritis (PsA).Subjects and methods. The study is based on the analysis of survey data from 106 patients with PsO for the period 2018–2021, which were firstly sent by dermatologists for a consultation with a rheumatologist due to musculoskeletal pain. The duration of the period of musculoskeletal pain in the observed patients did not exceed 12 months. In addition to general clinical and laboratory examination, all patients underwent ultrasonography of painful and/or swollen joints, tendons and ligaments using a linear sensor (frequency – 12–18 MHz) of MyLab 50 (Esaote, Italy) apparatus and supplemented by Doppler energy study with a pulse frequency of 6.6 MHz. The OMERACT definitions were used to identify En, synovitis and tenosynovitis.Results and discussion. The diagnosis of PsA was established in 73.6%, osteoarthritis – in 13.2%, gout – in 8.4%, fibromyalgia – in 17.9%. Ultrasonographic signs of En were found in 67.9% of patients: signs of an active inflammatory process in enthesises (decreased echogenicity, thickening and appearance of Doppler signals) were observed in 48.7%, signs of structural damage to enthesial zones (calcifications, enthesophytes and bone erosions) in 25,6% of patients. Isolated En was found in 24.4% of patients, a combination of En and synovitis – in 32.1% of patients, a combination of En and tenosynovitis – in 20.5% of patients. The correlation between the inflammatory domain values of the ultrasoundographic enthesial index MASEI (Madrid Sonographic Enthesitis Index) and the clinical enthesial index LEI (Leeds Enthesitis Index) was 0.71 [0.58; 0.77]. There were less pronounced clinical indicators of enthesial inflammation (lower LEI index values), functional disorders of the joints (lower values of the HAQ-DI index) and laboratory signs of systemic inflammation (lower CRP values) in patients with isolated En in comparison with combination of En and synovitis. Ultrasonographic signs of structural damage of enthesises were observed in 15.4% of patients without clinical and ultrasonographic signs of active En, which may indicate the possibility of a subclinical course of enthesial inflammation in patients with PsO.Conclusion. It was demonstrated that ultrasonography has diagnostic capabilities to identify the site of the inflammatory process in patients with PsA and differentiate patients with isolated En and a combination of En and synovitis in order to select a method of differentiated anti-inflammatory therapy.

ЦЕЛЬ: изучить параметры компенсации углеводного обмена и связанные с ними факторы у пациентов, проходивших обучение в школах диабета и иных образовательных мероприятиях РООИ «Нижегородская диабетическая лига». МАТЕРИАЛЫ И МЕТОДЫ: проведено анкетирование и оценка гликированного гемоглобина (НвА1с) у 121 пациента с сахарным диабетом 2 типа, обучавшихся в школе диабета или участвовавших в одноднев- ных образовательных мероприятиях РООИ «Нижегородская диабетическая лига». Оценивался анамнез сахарного диабета и его терапии, самоконтроль. Данные приведены в формате M±SD, уровень статисти- ческой значимости принят как р<0.05 РЕЗУЛЬТАТЫ: из 121 обследованного пациента 89% составили женщины, средний возраст 65±11,5 лет; средняя длительность диабета 9±7,0 лет. 68% пациентов получали терапию метформином; 24% - препара- тами сульфонилмочевины; 10% - глиптинами; 7,4% (9 чел.) – глифлозинами; 22% - препаратами инсулина. Тест на гликированный гемоглобин был выполнен у 84 пациентов (69% обследованных), средний уро- вень составил 7,6±1,94%. Доля пациентов с НвА1с >8% была равна 32%, эти пациенты не имели достовер- ных отличий по возрасту (68±10,6 пр.63±13,5 лет, р=0,09) и, закономерно, отличались большей длительно- стью диабета (12±6,7 пр. 7±6,6 лет, р=0,002). Из 11 мужчин НвА1с более 8% отмечался у 9 (82%), тогда как среди женщин такое повышение было зарегистрировано в меньшинстве случаев (26%, р=0,0003). Среди пациентов с уровнем НвА1с более 8% 30% получали инсулинотерапию, тогда как в группе с меньшими значениями инсулинотерапия проводилась достоверно реже (7%, р=0,006). По результатам опросника регулярный самоконтроль не менее 1 дня в неделю проводили 70% паци- ентов, среди них 63% измеряли уровень гликемии как натощак, так и в течение дня. 57 пациентов (69%), проводивших регулярный самоконтроль, сообщили при анкетировании данные о средних показателях гликемии. В наибольшей степени с уровнем НвА1с коррелировал средний показатель гликемии при са- моконтроле в течение дня (R=0.75 p<0.0001), для средней гликемии натощак коэффициент корреляции был меньше (R=0.57 p<0.0001). Доля пациентов, проводивших регулярный самоконтроль, не отличалась существенно между группами, разделенными по уровню НвА1с 8%. При этом у пациентов с высокими уровнями НвА1с при самоконтроле регистрировались высокие значения гликемии – натощак 9,1±2,6 пр. 6,4±1,1 ммоль/л, р<0,0001; в течение дня 12,5±2,4 пр. 8,6±1,1 ммоль/л, р<0,0001. ВЫВОДЫ: среди людей с диабетом 2 типа, принимавших участие в образовательных мероприятиях региональной общественной организации пациентов с сахарным диабетом, плохой гликемический кон- троль отмечался не менее чем в 1/3 случаев. Мужчины с сахарным диабетом в большей степени страдают от низкого уровня знаний и мотивации в отношении сохранения здоровья, при этом имея низкий уровень участия в обучении. Активное привлечение мужчин с сахарным диабетом 2го типа может являться одним из приоритетов в организации обучения. Значительная доля пациентов не осуществляет регулярного самоконтроля гликемии, однако даже при его проведении сохраняется риск плохого управления гликемией, связанный, по-видимому, с инерцией в интенсификации сахароснижающей терапии и игнорированием высоких показателей гликемии по дан- ным самоконтроля.

Aim. To study the prognostic value of cell-mediated immunity changes in patients with type II diabetes mellitus undergoing simultaneous operations for treatment of cholelithiasis and postoperative ventral hernias. Methods. Two groups of female patients with cholelithiasis and postoperative ventral hernias who underwent planned simultaneous surgical treatment were examined. The firs group included 48 patients with type II diabetes mellitus and abdominal obesity. The second group included 48 patients without diabetes mellitus and metabolic syndrome. Mononuclear leukocytes of peripheral blood were isolated by density gradient centrifugation on Ficoll-verografin. Relative and absolute number of lymphocyte populations and subpopulations and FAS-receptor expression were studied by indirect immunofluorescence using specific monoclonal antibodies. Apoptotic cells were determined by fluorescent microscopy after exposure of separated mononuclear leukocytes to DNA dye Hoechst 33342. Results. Patients with type II diabetes mellitus had higher incidence of purulent complications after laparoscopic cholecystectomy and surgical treatment of ventral hernias (14.6% vs. 2.0%, p 0.01), which was associated with absolute and relative decrease of CD4+ and CD16+ lymphocyte levels and immunoregulatory index and increased spontaneous and FAS-induced apoptosis of mononuclear leukocytes. In patients who developed purulent complications, more significant reduction of the absolute number of CD16+ lymphocytes (34.5±3.8×106/L vs. 76.72±5.16×106/L, p 0.01) and increased spontaneous apoptosis (7.9%±1.1% vs. 2.7±0.3% compared to patients without complications, p 0.01) was determined. Conclusion. Immunological predictors for developing postoperative purulent complications after simultaneous abdominal surgeries in patients with type II diabetes include decreased indicators of spontaneous apoptosis and decreased number of NK-cells.