Search

Objective: to study the efficiency and tolerance of rituximab (RTM) treatment in patients with scleroderma systematica (SDS) with interstitial lung injury (ILI).Subjects and methods. The trial included 27 patients (26 women and 1 man) (mean age 45.7±13.0 years), with diffuse (n=13) and circumscribed (n = 14) forms and a disease duration of > 5 years in 63%. All the patients underwent chestcomputed tomography; examination of external respiratory function, including forced vital capacity (FVC) and diffusing capacity of the lung (DCL), as well as echocardiographic study. The efficiency of the treatment was evaluated from changes in FVC, skin score, and disease activity index. The indicators were compared prior to the treatment and one year after the first administration of RTM. The latter was injected with premedication (125–500 mg of methylprednisolone intravenously) 500–1000 mg per administration. The mean dose of RTM was low and amounted to 1.3 g per year.Results. As estimated by the physician, good, satisfactory, no effects were seen in 81.5, 14.8, and 3.7% of the patients, respectively. There was a significant increase in mean FVC one year after the first administration of RTM and a reduction in the total activity of the disease, including skin syndrome. DCL was substantially unchanged in the entire group. In the diffuse and circumscribed forms of the disease, FVC increased significantly and to the same extent. A clinically significant increase in FVC (by 11%) was achieved in patients with a disease duration of ≤5 years and mild lung injury. In people with a more than 5-year disease duration, FVC was initially decreased to a greater extent and the treatment-induced increase was only 3.7%. A significant and permanent decline in peripheral blood B lymphocytes was noted when both the standard dose (2 g) of RTM and its lower doses (0.5–1 g) were administered. RTM treatment was well tolerated, but complicated by mild intercurrent infections in 11% of cases within the first 2 months after RTM administration.Conclusion. The findings substantiate the indications for RTM use primarily in the early stage of the disease. The admittedly low doses of RTM have an inadequate effect if the disease is long-lasting. Further study of dosage regimensfor RTM is required within the framework of controlled trials.

Objective: to study the association of ultrasound (US) remission criteria with the clinical and laboratory indicators of inflammatory activity, functional status, and X-ray changes in patients with rheumatoid arthritis (RA) during tocilizumab (TCZ) therapy.Subjects and methods. The trial included 36 patients with RA (meeting the 1987 American College of Rheumatology (ACR) criteria) who had received TCZ for 6 months. The authors made a clinical and laboratory assessment of RA activity (DAS28-CRP, and SDAI), functional impairments (HAQ index) and US verification of wrist joint synovitis (a Voluson-i device, GE, 4-13-MHz linear transducer) at baseline and 6 months after therapy. No signs of grey-scale (B-mode) and power Doppler (PD) synovitis (B = 0; PD = 0) or minimal B-mode synovitis, and not more one PD hypervascular signal (В ≤1; PD ≤1) were arbitrarily taken as US remission criteria. Destruction changes were evaluated by hand and foot X-ray using the Sharp method modified by van der Heijde (SHS).Results. After 6 months of therapy, about 80% of the patients in clinical remission retained moderate or significant synovitis, as evidenced by US studies. There were no clinical differences in clinical activity indices and functional impairments between the patients who were and were not in US remission (p > 0.05). The 12-month follow-up SHS score was significantly higher with the preservation of 6-month therapy signs of B-mode synovitis and PD hypervascularization (of not more than one signal) than that in US remission (p < 0.05). There was no relationship of X-ray progression to the clinical and functional statuses (p > 0.05).Conclusion. Subclinical synovitis is observed even in clinical remission of RA. Destruction progression is significantlyrelated to synovitis persistence, as shown by ultrasonography.

The diagnosis of enthesitis can help in differentiating early psoriatic arthritis (ePsA) from early rheumatoid arthritis (eRA).Objective. To estimate the diagnostic value of detecting enthesitis during clinical examination and ultrasound in ePsA and eRA.Subjects and methods. The trial included 36 patients with ePsA and 33 with eRA. Entheses were evaluated using the Leeds Enthesitis Index (LEI): lateral humeral epicondyle and medial femoral condyle (MFC), Achilles tendon insertion site (ATAP), and plantar fascia (PF) point on the right and on the left. Enthesitis (on ultrasound) presented with thickening, reduced echo density, and vascularization at Doppler energy imaging. DAS, DAS28, SDAI, CDAI, M±SD, Me [25th, 75th percentile], t-test, Fisher's exact test, χ2test, U test, and Spearman correlation coefficients (R) were calculated; the value p < 0.05 was considered statistically significant.Results. Clinical examination revealed enthesitis in 41.6% of the patients with ePsA and in 39.4% of those with eRA (p >0.05). No significant differences were found between ePsA and eRA according to LEI (0.5 [0; 2] and 1 [0; 2] and to LEI+PF (1 [0; 2] and 1 [0; 2], respectively). Enthesitis of MFC and PF was significantly more frequently detected in ePsA than in eRA – 12 (33.3%)/2 (6.1%) and 10 (27.8%)/2 (6.1%) patients, respectively. In eRA versus ePsA, enthesitis of MFC was more frequently found (16 (48.4%) and 8 (22.2%) patients), respectively. Ultrasound revealed no significant differences between the groups in enthesitis. In ePsA, there was a significant correlation between DAS, DAS28, SDAI, CDAI, LEI, and LEI+PF.Conclusion. Enthesis ultrasound cannot differentiate ePsA from eRA. Clinical examination more frequently detects enthesitis in the knee joints in eRA and in the calcaneal region in ePsA.

Objective: to estimate the value of simplified ultrasound (US) indices of synovitis in the most commonly involved joints of the dominant hand, which are studied using the grey scale mode while monitoring the efficiency of tocilizumab (TCZ) therapy in patients with rheumatoid arthritis (RA). Subjects and methods. Forty-six patients with RA confirmed by the 1987 American College of Rheumatology (ACR) criteria who had been ineffectively treated received TCZ infusions for 6 months. The patients were stratified into two groups: 1) 11 patients with early (2-year) RA (PRA). Disease activity and therapy efficiency were determined by DAS28-CRP, SDAI, and US study of the dominant hand joints most commonly involved in the pathological process. Results. The evaluation of TCZ therapy from the simplified US indices reflected synovitis regression in the dominant hand joints of patients with ERA. The highly significant correlations between the changes in US parameters and RA activity the indices ^US-wrist/iDAS28-CRP: r = 0.75; p = 0.01; ΔUS-S8/ΔDAS28-CRP and ΔUS-S5/ΔSDAI: r = 0.65; p < 0.05) confirm the validity of the above changes. No reduction in the joint indices was observed in the patients with PRA. Conclusion. The simplified grey-scale US indices of synovitis in the joints of the dominant hand (including one wrist joint) is an accessible noninvasive method for evaluating the efficiency of the therapy performed in patients with ERA.

Objective: to estimate the contribution of arthrosonography to the diagnosis of metatarsophalangeal joint (MTPJ) injury and to reveal predictors for functional impairments in patients with rheumatoid arthritis (RA). Subjects and methods. The investigation enrolled 50 patients with the RA diagnosis meeting to the American College of Rheumatology 1987 criteria. According to disease duration, the patients were divided into two groups: 1) 9 patients with an early RA history of less than 2 years (ERA); 2) 41 patients with a RA history of over 2 years (LRA). All the patients underwent clinical joint evaluation, laboratory and instrumental examination, including joint X-ray and ultrasonography (USG). Results. An inflammatory process in the foot joints is significantly more frequently detected on ultrasound than clinically (p < 0.0001). The detection rate of erosions, as evidenced by USG, was significantly higher than that by X-ray, in ERA in particular (p = 0.01). Comparison analysis of patients with low and high HAQ scores showed the relationship between functional status, age, pain degree, and inflammatory process in the fifth MTPJ, as shown by USG. There were no associations with disease duration, traditional clinical and laboratory parameters of RA activity, and erosive changes in the feet. Conclusion. Joint USG in daily clinical practice makes it possible to objectively evaluate pathological changes in the feet and the probability of work disability due to RA.

Objective: to estimate the informative value and reproducibility of ultrasound study (USS) in interstitial lung disease (ILD) in patients with scleroderma systematica (SDS) and to compare ultrasound lung comet (ULC) scores with the data of multislice spiral computed tomography (MSCT) of the lung and its function tests. Subjects and methods. Forty patients with SSD and ILD were examined. According to the extent of lung injury, the patients were divided into two groups: 1) 12 patients with significantly pronounced changes (>20% lung involvement, as evidenced by MSCT); 2) 28 patients with just noticeable changes (

The international recommendations «Treat to target» (T2T) underline the greatest importance of treatment strategy for the success of treating rheumatoid arthritis (RA). Evaluation of the efficiency of this approach obviously requires special strategic studies with an adaptive design, which substantially differ from classical randomized clinical trials and are much closer to clinical practice. To date, there are only single publications on the practical application of the T2T recommendations, there is a problem in the choice of effectiveness criteria and there are a number of other important problems associated with the introduction of these recommendations. The Russian study REMARCA is to answer these questions. Its design focuses on the practical adaptation of the T2T strategy to treat patients with earlyand extended-stage active RA who have poor prognostic factors, by using subcutaneous methotrexate and genetically engineered biological agents (GEBA). Preliminary analysis shows that therapy according to the REMARCA protocol is successful in the majority of patients. The high rate of low RA activity and remission has been achieved during subcutaneous methotrexate monotherapy. The patients who need GEBA to be incorporated may be initially more resistant to therapy. The patients with early RA have better chances of successful T2T therapy than those with extended-stage RA.

Objective: to define the significance of ultrasonography (USG) in the diagnosis of early destructive changes in the hand joints and the rates of rheumatoid arthritis (RA) progression in patients at different ages of disease onset. Subjects and methods. 100 patients with a valid RA diagnosis (American College of Rheumatology (ACR) 1987 criteria were examined. They were divided into 2 groups: 1) 11 patients with an early RA history of less than 2 years (ERA); 2) 35 patients with a RA history of over 2 years (LRA). Hand USG (Voluson-i GE; a 4-13-MHz linear probe; gray scale mode) was carried out at baseline and after 6-month follow-up. A sonographic index (US-Er-10) based on the bilateral evaluation of 5 articular areas, such as wrinkles, second-to-third metacarpophalangeal (MCP) and second-to-third proximal interphalangeal (PIP) joints, was proposed to evaluate the progression of destruction. According to US-Er-10 changes, the rates of development of the destructive process were arbitrarily separated into three categories: 1) slow progression rate; 2) moderate progression rate; 3) a rapidly progressive course. The X-ray parameters of structural progression were estimated at 12-month follow-up, by employing the Sharp method modified by van der Heide (SHS). Results. The USG versus X-ray detection rate of erosions was significantly higher in both ERA and LRA (p < 0.05). The ERA patients who had fallen ill after 55 years of age were found to have more significant baseline and final destructive changes according to a total SHS score (p < 0.05) and US-Er-10 index (p < 0.005) than those with RA onset at a younger age. In the ERA patients in whom US-Er-10 increased by three points or more at 6-month follow-up, the rates of X-ray progression at 12 months were significantly higher than those with less pronounced negative changes in this index (Δ total SHS score of 13.5 [3-23] and 0 [0-0], respectively; p < 0.05). The LRA group displayed no statistically relationships between the USG rate of erosion progression and the time course of X-ray changes and laboratory evidence. Conclusion. Hand USG reveals early erosive joint changes significantly more frequently than X-ray study and the high progression rate of destruction according to USG and the disease with onset after 55 years of age are associated with its severer course and poor prognosis in patients with ERA.

Objective: to estimate the time course of changes in the ultrasound signs of wrist joint synovitis in patients with rheumatoid arthritis (RA) during tocilizumab (TCZ) treatment and to determine whether the progression of joint X-ray changes can be predicted by ultrasonography (USG). Subjects and methods. The investigation enrolled 46 patients with the diagnosis of RA that met the American College of Rheumatology 1987 criteria. All the patients were given TCZ during insufficiently effective previous therapy (median DAS28 was 6.7 [range 5.9—7.2]). They were divided into 2 groups: 1) early RA (ERA) with a disease history of less than 2 years (n = 11); 2) RA with a history of over 2 years (n = 35). Hand USG (Voluson-i GE, USA) with a 4—13-MHz linear probe using an energy Doppler (ED) was carried out before and 6 months after therapy. Structural changes were evaluated by hand and foot X-ray study (before and at 12-month follow-up) according to the Sharp method modified by van der Heide. Results. Dynamic evaluation of the ultrasound signs of inflammation indicated a significant reduction in the magnitude of synovitis in accordance with the gray-scale data in both groups and only in the patients with ERA in the ED mode. There was a clear association of the annual increment in joint X-ray changes with the result of estimation of the magnitude of synovitis according to the ED data (r = 0.669; p < 0.01). Conclusion. Wrist joint sonography allows evaluation of the efficiency of the performed therapy in patients with RA and the presence of moderate or severe synovitis, as evidenced by ED, is a predictor for the progression of joint destruction.

Objective — to evaluate potential input of different factors in the development of left ventricular hypertrophy (LVH) in patients with gout. Material and methods. 57 male patients with gout were included into the study. Echocardiography was performed in M- and B-modes and left ventricular myocardial mass index (LVMMI) was calculated for each patient. LVH was defined as LVMMI >115 g/m 2. Results. LVH was detected in 23 (40,4%) out of 57 patients. LVH was associated with advanced age, arterial hypertension, obesity, hyperuricemia and increased C-reactive protein levels.

Erosive osteoarthritis (EOA) of the hand is an osteoarthritis (OA) phenotype that is characterized by central and marginal erosions of the articular surfaces in the distal and proximal interphalangeal (DIP and PIP) joints and in some cases by a fairly aggressive course with obvious pain syndrome and a high level of functional impairment. Diagnostic criteria and management tactics for EOA patients are still under investigation.Objective: to evaluate the nature of the changes detected by hand joint magnetic resonance imaging (MRI) in patients with EOA and non-erosive OA (NEOA) of the hand.Subjects and methods. Examinations were made in 61 females meeting the American College of Rheumatology (ACR) diagnostic criteria for hand OA; the patients' mean age was 66.34+5.79 years; the median age at disease onset was 50 [45; 56] years; the duration of pain was 15 [11; 20] years. All the patients underwent MRI of the second-fifth DIP, PIP, and metacarpophalangeal (MCP) joints of the right hand. The patients also filled out the AUSCAN questionnaire. EOA and NEOA were detected in 30 and 31 patients, respectively.Results and discussion. The patients with EOA and those with NEOA were matched for gender, age, and disease duration. The DIP joints in patients with EOA were found to have significantly more frequently and a greater number of large osteophytes (OPs), (53 and 16%, respectively), joint space narrowing (JSN) (73 and 35%), degenerative collateral ligament changes (DCLCs) (93 and 55%), subluxations (47 and 13%), and bone marrow edema (BME) (57 and 19%) than in those with NEOA. Synovitides and subchondral cysts occurred with approximately the same frequency in EOA and NEOA. The PIP joints in patients with EOA significantly more frequently showed BME (37%) and DCLCs (97%) than in those with NEOA. Subluxations in the PIP joint of the right hand were encountered exclusively in patients with EOA. Their incidence was 17%. Degenerative symptoms (small, less often moderate sizes of OPs, JSN, and DCLCs) were identified with approximately the same frequency in both groups (p>0.05). The PIP joints in patients with EOA were significantly more often found to have BME (53 and 26%, respectively; (p0.05). Large OPs in the PIP joint were found relatively rarely. Subluxations in the PIP joints were undetected in both groups.Conclusion. The symptoms of active inflammation are predominant and degenerative changes are more pronounced in patients with EOA unlike those with NEOA. Articular surface defects in the PIP joints in patients with hand OA differ from erosions in those with rheumatoid arthritis. These CDs in EOA are much more common than those in NEOA; however, the nature of their occurrence is unclear; therefore, the patients in whom they have been found need dynamic monitoring.

Standard radiography in direct projection is the “gold standard” in the diagnosis of hand osteoarthritis (HOA). However, the currently clinically most severe “erosive” or “inflammatory” phenotype of HOA is characterized by the presence of inflammatory symptoms such as bone marrow lession (BML), synovitis and tenosinovitis, which are not visible on the radiograph by the nature of the study due to the low optical density. In addition, X-ray examination is planar and has no possibility of multiplanar visualization. This dictated the need to search for a more informative visualization technique in HOA.Aim – to compare the sensitivity and specificity of standard radiography and magnetic resonance imaging (MRI) techniques in determining the symptoms of osteoarthritis (OA) of the distal interphalangeal (DIP), proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints of the right hand; to determine the indications for the appointment of MRI in patients with HOA.Materials and methods. The study included 64 women with clinically verified diagnosis of HOA according to ask criteria. For the first time, X-rays of the joints of the right hand in the anterior-posterior projection and MRI were performed for each of them. Each patient completed the AUSCAN questionnaire. X-rays were described according to the Kellgren and Lawrence systems, magnetic resonance imaging was analyzed according to the modified OHOA system. The sensitivity and specificity of the methods were compared based on the detection of 4 symptoms detected by radiography and MRI: joint space narrowing (JSN), osteophytes (OP), erosions and subluxations. The average age of the patients was 65.28±6.82 years, the age of onset was 48.81±7.73 years, the duration of the disease was 15.0 (10.0–19.5) years.Results. Both methods showed approximately equal identification JSN symptom in DIP and PIP, 95% definition JSN in MCP. OP were detected in 88% of patients in DIP according to radiography and in 95% – using MRI (p>0.05). In PIP OP were observed in 70% of patients on radiographs and in 86% on magnetic resonance imaging, in MCP – in 45% and 66% of cases, respectively. Erosion in DIP were found in 41% of patients according to MRI and 34% as a result of X-ray examination, in PIP – in 27% and 13% of cases, in MCP – in 60% and 8% of cases, respectively. Subluxations were determined in DIP 23% on radiographs in 31% of cases by MRI, in PIP – in 8% and 6% (p>0.05), in MCP subluxations almost never met – in 3% of cases by conventional radiography.Conclusions. MRI in HOA can be used in the detection of erosive process, differential diagnosis with other diseases of the joints, determination of inflammatory changes in the hands and assessment of their severity, but has no significant advantages over standard radiography in determining the symptoms of degenerative-dystrophic nature (JSN and OP). Subluxations of the MCP joints are not typical for the HOA.

Osteoarthritis (OA) is one of the most common diseases of the musculoskeletal system in the world. Some researchers call the small joints of the hands as being one of the most common sites of involvement in OA. Its most severe phenotype is considered to be inflammatory, or erosive, OA (EOA). Nevertheless, the radiographic pattern of this disease has not yet been sufficiently studied, and whether EOA is an independent form of OA, a regular later stage of the disease or an individual nosological entity, has not yet been resolved.Objective: to assess the location, frequency, and severity of radiographic symptoms and pain in patients with EOA and non-erosive OA (NEOA), to study the involvement of carpometacarpal (CMC), wrist, metacarpophalangeal (MCP) and radiocarpal (RC) joints in the pathological process in patients with EOA and NEOA of the hands.Subjects and methods. The investigation enrolled 64 women with hand OA who met the American College of Rheumatology (ACR) OA criteria. Hand joint images in the anteroposterior projection were first performed in all the patients. Each patient completed the AUSCAN questionnaire. The images were described according to the Kellgren and Lawrence classification. The mean age of the patients was 65.28+6.82 years; the age at onset of the disease was 48.81+7.73 years; its median OA duration was 15.0 [10.0; 19.5] years. According to the presence of erosions in the interphalangeal joints (IPJ) of the hand, the patients were divided into two groups: 1) EOA (n=23); 2) NEOA (n=37). Both groups were matched for age and disease duration (the mean age of patients with EOA was 68+6.15 years, the mean disease duration was 18.34+7.11 years; these in the NEOA group were 65.13+5.43 and 16.56+8.4 years, respectively). For age matching, 4 patients were excluded from Group 2.Results and discussion. Kellgren and Lawrence Stage II hand OA was detected most frequently (49%) and the most common radiographic symptoms of OA in the distal IPJ (DIPJ), proximal IPJ (PIPJ) and MCP joints were joint space narrowing (JSN) (100%, 100%, and 95%, respectively) and osteophytes (OPs) (88%, 70%, and 45% respectively). The least common conditions were subchondral osteosclerosis (SCOS) (5%), erosions (8%), and subluxations (3%) in the MCP joints, as well as subluxations in the PIPJ (6%). In the wrist, the most frequent sites of involvement was first CMCJ and scaphoid-trapezium-trapezoid joint (STTJ); their JSN was identified in 86 and 69% of patients, respectively; OPs were found respectively in 81 and 50% of cases. Changes in the RC joint (RCJ) were least common.EOA of the DIPJ and PIPJ was found in 15 (23%) patients with radiographic changes corresponding to Stages III—IV OA of the hand and in 8 (12%) patients with Stage II according to the Kellgren and Lawrence classification. The DIPJ in EOA versus NEOA showed significantly higher frequency of OPs (100 and 78%), SCOS (74 and 11%), cysts (61 and 24%), and subluxations (43 and 14%); the PIPJ — SCOS (43 and 5%), cysts (52 and 27%), and subluxations (17 and 0%; p

The choice of drugs for the treatment of interstitial lung disease (ILD) associated with systemic sclerosis (SS) is currently very limited. Data from a number of studies show that rituximab (RTM) can improve lung function and reduce the severity of skin fibrosis in patients with SS.Objective: to evaluate the efficiency of RTM in a cohort of patients with SS-associated ILD after one-year follow-up. The indications for prescribing RTM were: 1) the inefficiency of standard therapy with glucocorticoids and immunosuppressants (ISs) or the impossibility of their use; 2) the early stage (first 3 years of the disease) with signs of poor prognosis, such as diffuse form, high skin scores (>14), male gender, rapid progression with a significant initial decline in forced vital capacity (FVC) and/or diffusion lung capacity (DLC), and a high anti-Scl-70 antibody positivity.Subjects and methods. The investigators selected a group of patients who had at least two assessment points at a 12-to-18 month interval (the mean follow-up period of 13±2 months) and took at least 1 g of RTM during this period. The investigation included 71 patients with a valid diagnosis of SS. Multi-slice spiral computed tomography (MSCT) revealed ILD in 90% of patients. The disease duration was 5.6±4.4 years. The presence of anti-Scl-70 antibodies was detected in 73% of patients. The mean cumulative dose of RTM was 1.43±0.6 g; 48 patients in Group 1 received ≤2 g of RTM (the mean dose, 1.1±0.1 g) and 23 patients in Group 2 took ≥2 g of RTM (mean dose, 2±0.6 g). Before starting treatment with RTM, all the patients received concomitant therapy with prednisone and 45% - with immunosuppressants.Results and discussion. The results assessed by a physician showed that good and moderate effects of the therapy were observed in 52 (73.2%) and 16 (22.6%) patients, respectively; no effect was seen in 3 (4.2%) patients. Overall, 95.8% of patients reported various degrees of improvement. There were significant changes as reductions in the disease activity index, skin scores, C-reactive protein and IgG levels, the number of patients with a high antinuclear antibody level, and the mean dose of prednisolone as well as increases in an oral aperture size, left ventricular ejection fraction, and 6-minute walk test scores. There were no changes in pulmonary artery systolic pressure and the HAQ DI. FVC increased from 77.35±19.9 to 82.6±20.7% (p=0.001). A minimal clinically significant increase in FVC ≥5% was noted in 41 (57.7%) people. The overall improvement in FVC (ΔFVC) reached 5.24%, while the changes were more significant in Group 2 (ΔFVC 8.98%) than in Group 1 (ΔFVC 3.75%; p=0.01). DLC remained stable, but there were significant group differences: ΔDLC was 3.75% in Group 2 and, conversely, decreased in Group 1 (1.6%; p=0005). The safety profile of the therapy was regarded as good and quite comparable with both the safety profile of ISs and the use of RTM in other trials. Infectious complications were recorded to be most common in 11 (15%) people. Of these, upper respiratory tract infections developed in 7 patients; plantar phlegmon occurred in one case; urinary tract infection and herpes zoster were detected in two and one cases, respectively.The results of this study confirm data from other studies that have demonstrated that RTM exerts a positive effect on SS-associated ILD. We were the first to show the association of positive changes in the measures of pulmonary function tests with the dose of RTM.

Pulmonary arterial hypertension (PAH) is a complex, multidisciplinary problem of modern medicine. The basis for the disease is a microcirculatory lesion in the vessels, which leads to a decrease in their blood flow, to increased pulmonary vascular resistance and, as an outcome, right ventricular failure, and death. PAH may also be associated with systemic connective tissue diseases (SCTDs), in particular with systemic sclerosis (SS), as one of the manifestations of the disease. As well as idiopathic pulmonary hypertension, PAH-SCTDs is an orphan disease: according to the data of the V.A. Nasonova Research Institute of Rheumatology, the incidence of PAH is 5.2% in SS, 0.3% in systemic lupus erythematosus, and 7.4% in mixed connective tissue disease. Low prevalence is responsible for late diagnosis, which is always associated with a poor therapy response and poor prognosis. The purpose of the lecture is to acquaint rheumatologists with the possibilities of diagnosis and treatment of this rare, but prognostic severe manifestation of SCTDs.

Rheumatoid arthritis (RA) is a disease with a high cardiovascular risk. The results of works on the impact of antirheumatic therapy on carotid artery (CA) intima-media thickness (IMT) are contradictory. Objective: to assess the time course of changes in CA IMT and CA atherosclerosis (CAA) in patients with early RA during treatment to target at a 18-month follow-up. Subjects and methods. The investigation enrolled patients with early RA (disease duration of less than 12 months), who had not previously taken disease-modifying antirheumatic drugs and glucocorticoids. Duplex scanning (DS) of the CA was performed with IMT measurement at baseline and at 18 months after treatment. Vascular atherosclerotic lesion was recorded when atherosclerotic plaque (ASP) was detected. Starting methotrexate (MTX) monotherapy was prescribed to all the patients, when it showed an insufficient effect at 3 months, a biological agent (BA), such as a tumor necrosis factor-α inhibitor or abatacept, was added. RA remission was noted in 31 (42%) patients at 18 months of treatment. Results and discussion. The investigation included 74 patients with early RA; whose median (Me) age was 56 years, all the patients had moderate or high disease activity (Me DAS28-ESR, 5.4). At baseline, there was increased CA IMT in 51.4% of cases and CAA in 55.4%. At 18 months of treatment, there were no significant IMT changes. New CA ASPs were recorded in 8 (24.2%) patients who had no CAA at the time of inclusion in the investigation (p < 0.05). Nineteen (46.3%) patients were recorded to have the progression that had been identified when including CAA as a considerable increase in the number of ASPs (p < 0.05). The risk of CAA progression was correlated inversely with the mean 18-month level of high-density lipoprotein cholesterol (HDL-Cmean) and directly with the mean concentration of C-reactive protein (CRPmean). There was no significant correlation between HDL-Cmean and CRPmean. The changes of CAA were unassociated with the value of DAS28-ESR, the achievement of RA remission, and antirheumatic therapy (MTX monotherapy, MTX + BA). Conclusion. CAA shows progress in patients with early RA despite they are treated to target. DAS28-ESR remission in RA and ongoing RA treatment option had no substantial impact on the course of CAA. HDL-Cmean and CRPmean are independent risk factors for progression of CAA.

Objective: to investigate the impact of antirheumatic therapy carried out according to the treat-to-target (T2T) principle on the time course of changes in NT-proBNP levels in patients with early rheumatoid arthritis (RA) over an 18- month follow-up period.Subjects and methods. The investigation enrolled 74 patients, comprising 56 (74%) women (median age, 54 years) with a reliable diagnosis of RA (ACR/AULAR criteria (2010)) (disease duration, 7 months); who were seropositive for IgM rheumatoid factor (87%) and/or anti-cyclic citrullinated peptide antibodies (100%) and had not previously taken disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids. All the patients started therapy with subcutaneous methotrexate (MTX), with escalation of the dose to 25-30 mg/week; in the absence of any effect after 3 months, biological agents (BAs) were added in 47 (71%) patients. Following 18 months, 44% of patients achieved RA remission; 51 patients (77%) received cardioprotective therapy. NT-proBNP levels were measured in 66 patients with early RA before and 18 months after treatment. The NT-proBNP value

Pulmonary arterial hypertension (PAH) is a progressive and irreversible disease characterized by a steady increase in pulmonary vascular resistance (PVR) and death. Introduction of current PAH-specific drugs has not solved the problem of follow-up of critical patients with PAH associated with systemic sclerosis (SSc). Clinical trials have shown that 1-, 2- and 3-year survival rates are 77, 46, and 33%, respectively. Arguments in favor of starting triple PAH-specific therapy that substantially improves the prognosis of this critical group of patients are being accumulated. The paper describes Russia’s first clinical case of successful up-front triple combination therapy (iloprost, bosentan and sildenafil) in a 40 year old female with SSc and diagnosed functional class (FC) IV PAH. There were clinical, laboratory, and hemodynamic improvements already at 2 weeks after therapy initiation. Thirty-month therapy resulted in a reversal of FC from IV to II, relieved the signs of right ventricular failure, complete right ventricular reverse remodeling and subnormalization of hemodynamic parameters. Hemodynamic improvement including reductions in right atrial pressure to 4 mm Hg, mean pulmonary arterial pressure to 26 mm Hg, and PVR to 2.2 Wood units and an increase in cardiac output up to 7.4 l/min, despite preserved elevated uric acid levels (432 μmol/l). The intriguing feature of this case is critically low values of % predicted/carbon monoxide lung diffusion capacity, which rose from 17% to only 22%, in the presence of positive changes. This clinical case demonstrates the predictive capabilities of up-front triple combination therapy for severe PAH associated with SSc.

Objective: to determine the level of the N-terminal fragment of brain natriuretic peptide progenitor (NT-proBNP) in patients with systemic lupus erythematous (SLE) prior to immunosuppressive therapy and its possible association with inflammatory markers, traditional risk factors (TRFs) for cardiovascular diseases (CVD), and transthoracic echocardiographic (EchoCG) parameters.Subjects and methods. The investigation enrolled 28 SLE patients fulfilled the 1997 ACR criteria, including 23 (82%) women (median age, 28.5 [25.0; 32.0] years), who had no clinical signs of CVD and received no immunosuppressive therapy. A control group consisted of 27 age-and sex-matched healthy donors. Disease activity was assessed by SLEDAI-2K; irreversible damages were measured using SLICC. The median duration of SLE was 21.0 [5.0; 60.0] months, the scores of SLEDAI-2K and SLICC/DI were 11 [8; 19] and 0 [0; 0], respectively. The investigators estimated the concentration of Creactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), carried out EchoCG, and assessed TRFs. The serum concentration of NT-proBNP was determined by electrochemiluminescence (Roche Diagnostics, Switzerland). The normal range for NT-proBNP was ≤125.0 pg/ml. Results and discussion. The patients with SLE had elevated levels of NT-proBNP compared with the controls: 160.7 [88.6; 335.4] and 55.2 [36.6; 70.3] pg/ml, respectively (p < 0.001). The patients were divided into two groups: 1) 18 (64%) patients had a NT-proBNP concentration of > 125.0 pg/ml; 2) 10 (36%) patients had no more than this level. As compared with Group 2, Group 1 had the elevated values of IgG anti-cardiolipin (aCL) antibodies (p < 0.01), creatinine (p < 0.05), left ventricular (LV) end-systolic dimension (ESD) (p < 0.05) and decreases in LV ejection fraction (EF) (p 125.0 pg/ml). The higher level of NT-proBNP is associated with the immunological parameters of SLE activity (elevated values of IgG aCL, anti-dsDNA, and ANA as well as C4 hypocomplementemia) and with the markers that reflect deterioration in renal and myocardial functions. There was no relationship of NT-proBNP levels to the clinical manifestations of SLE and the markers of inflammation (CRP, IL-6, and TNF-α) and TRFs.

Objective: to estimate heart rate variability (HRV) in patients with systemic sclerosis (SS) and to investigate their relationship to echocardiographic structural and functional changes in the heart.Subjects and methods. The investigation enrolled 125 patients with SS and 50 gender- and age-matched apparently healthy individuals who made up a control group. In addition to clinical examinations, 73 patients underwent HRV assessment from 24-hour Holter electrocardiogram (ECG) monitoring results and 121 patients had echocardiography (EchoCG). 24-hour Holter ECG monitoring was carried out in all control individuals.Results and discussion. Examination of the main parameters of time-domain HRV in patients with SS revealed a significant decline in all temporal and spectral indices, except for the mean R–R interval duration (meanNN), as compared with the control group. EchoCG detected a variety of changes, primarily the induration and calcification of aortic and mitral valves in most patients. Left ventricular diastolic dysfunction was encountered in almost half of the patients with SS. Eight patients had a lower left ventricular ejection fraction (LVEF), which was

To introduce treat-to-target recommendations is an important task of modern rheumatology; however, there is still a diversity of serious problems relating to a scientific rationale and a clinical one for this strategy and to the possibilitiesof its implementation in real clinical practice, in the rheumatology service of the Russian Federation in particular, by taking into account the specific features of funding for high-tech medical care.Objective: to determine the efficiency and safety of combined therapy with subcutaneous methotrexate (MT) and biological agents (BA) when using the treat-to-target strategy in patients with active early and extended-stage rheumatoid arthritis (RA) who have risk factors for a poor prognosis.Subjects and methods. The results of the REMARCA (Russian InvEstigation of MethotrexAte and biologicals in eaRly aCtive inflammatory Arthritis) trial of 130 patients followed up for 12 months or more were given. There was a female preponderance; mean age 48.9±13.9 years, rheumatoid factor positivity (86.9%); anti-cyclic citrullinated peptide anti body positivity (89.2%). Seventy patients formed a subgroup of early RA (disease duration ≤6 months (mean 4.17±1.39 months)); 60 patients were a subgroup of advanced-stage RA (disease duration >6 months (mean 30.8±32.7 months)). In all the patients, therapy was initiated by using subcutaneous MT with its rapid dose escalation up to 20–30 mg/week and the achievement of the treatment goal (low disease activity or remission) was checked every 3 months and depending on the result a decision had been taken to add or not to add a biological agent (BA) (a tumor necrosis factor inhibitor or abatacept). If the former was insufficientlyeffective, it was substituted for a BA from another class.Results. Subcutaneous MT monotherapy provided remission or low disease activity in 49 (37.7%) patients; a BA was given to 81 (62.3%) patients. Following 6 and 12 months, low activity or remission according to SDAI was observed significantly more frequently in the patients who continued ubcutaneous MT monotherapy than in those who received combined therapy with MT and BA. The similar results were obtained by using DAS28 and CDAI to assess a trend in disease activity. After 6- and 12-month follow-up, there was a significantly more marked decline of tender joint count, SDAI and CDAI in early RA than in advanced-stage RA; at 12 months, SDAI remission rate was45.7% and 28.3%, respectively (p=0.047).Conclusion. The treat-to-target strategy should be used in real clinical practiceand can yield spectacular results. Active therapy with subcutaneous MT with its rapid dose escalation to the maximally tolerable dose allows identification of a considerable group of patients (38%) with a good response to MT monotherapy.

The mechanisms for lowering a cardiovascular risk (CVR) in patients with early rheumatoid arthritis (RA) when implementing the treat-to-target strategy remain inadequately investigated.Objective: to estimate the time course of changes in blood lipid parameters in patients with early RA during Treat-totarget antirheumatic therapy at an 18-month follow-up.Subjects and methods. Seventy-four patients (73% women; median age, 56 years) with early RA meeting the respective 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria and moderate or high activity (median DAS28-ESR score of 5.4) were examined within the framework of the REMARCA trial. After 6-month treatment, RA activity significantly reduced (p < 0.05). At months 6 to 18, no significant change in RA activity was recorded. After 18 months, remission was observed in 31 (42%) patients: in 17 (55%) on methotrexate (MTX) monotherapy and in 14 (45%) on combined therapy with MTX and a biological agent. Blood lipid levels were determined at inclusion in the investigation, 6 and 18 months later. The values of lipid parameters were estimated in terms of the total CVR. 67.6% of the patients were classified as at very high CVR. At 18 months of treatment, 34 (46%) patients were treated with statins (median atorvastatin and rosuvastatin doses were 10 mg/day each).Results and discussion. Only 12% of the patients had optimal baseline values of just all lipid parameters. The concentration of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) correlated negatively with C-reactive protein (CRP) levels, DAS28-ESR, DAS28-CRP, and HAQ (p < 0.05). After 6-month treatment, there were increases in TC by 7%, LDL-C by 12.5%, and HDL-C by 19.7%, and a decrease in the atherogenic index by 16% (p < 0.05). ΔCRP negatively correlated with ΔTC, ΔLDL-C, and ΔHDL-C (r = -0.3; p < 0.05). A correlation of TC and LDL-C with inflammation markers broke off in the presence of lower RA activity; the investigators began recording a relationship of these lipid parameters to traditional CVR factors. Between 6th and 18th month of treatment, there was no significant change in lipid parameters. Statin therapy resulted in no considerable change in lipid concentrations.Conclusion. The level of lipids negatively correlates with disease activity in the patients with early RA. During antirheumatic treatment, the lipid concentrations are more elevated with a more intensive decrease in CRP levels. With lowered RA activity, the level of lipids correlates with traditional CVR factors more strongly than with inflammation markers.

Rheumatoid arthritis (RA) is a chronic inflammatory disease causing joint destructive changes and disability.Objective: to investigate the association between the ultrasound signs of active inflammation and destruction of the joints, as evidenced by radiography, in RA patients treated with a treat-to-target strategy and to study whether ultrasound study (USS) of the joints can be used to predict the occurrence of their destructive changes.Subjects and methods. The investigation included 81 patients (medium age 56 [46; 62] years) with RA, who had been followed up at the V.A. Nasonova Research Institute of Rheumatology within the first Russian strategic study of pharmacotherapy for RA – REMARCA (Russian invEstigation of MethotrexAte and biologicals for eaRly aCtive Arthritis). In all the patients, methotrexate (Metoject, MEDAS, Germany) as the first disease-modifying anti-rheumatic drug was subcutaneously injected at an initial dose of 10 mg/week with its rapid escalation up to 20–25 mg/week. Then the therapy was added by biologicals as the need arose. Clinical and laboratory parameters were analyzed immediately before and then after 12, 24, 36, and 48 weeks. Efficacy was assessed using the European League Against Rheumatism (EULAR) criteria, CDAI, and SDAI. USS of eight articular areas (the wrist, second and third metacarpophalangeal, second and third proximal interphalangeal, second and fifth metatarsophalangeal joints) in the hand and foot of the clinically dominant side was carried out in all the patients before treatment and then after 12, 24, 36, and 48 weeks. Semiquantitative gray-scale (GS) assessment and power Doppler (PD) were performed. Radiographic examination was done before and after 48 weeks of therapy. The Sharp method modified by van der Heijde was employed to estimate X-ray changes.Results and discussion. In the group of patients with radiographic progression, the activity of inflammation, as evidenced by PD USS, was significantly higher at 48 weeks of the follow-up; at the same time, the median PD score was 0 in the absence of progression. At 48 weeks, radiographic progression was significantly more common in the group of patients with persistently active synovitis than in the group without inflammation (odds ratio (OR) 4.76; 95% confidence interval (CI) 1.2–18.9; р = 0.018). At 48 weeks of therapy, the PD score of 0 (complete lack of vascularization in the study joints) had satisfactory sensitivity (77%) and satisfactory specificity (59%) (the area under the curve was 0.698; p < 0.024; 95% CI 0.544–0.852). Multivariate analysis showed that GS USS scores after 24 weeks of therapy proved to be significant predictors of progressive erosive joint changes at 48 weeks of therapy (OR = 0.15; 95% CI, 0.023–0.207; p = 0.015). At the same time, the PD score following 24 weeks of therapy could not predict joint destruction (OR = 0.104; 95% CI, -0.043 to 0.251; р = 0.16). Clinical disease activity indices and baseline PD and GS scores were of no significant prognostic value.Conclusion. We found a significant association of radiographic progression with active synovitis, as evidenced by PD USS at 48 weeks of therapy; however, we did not obtain any convincing evidence for the prognostic value of the baseline ultrasound signs of inflammation.

Rheumatoid arthritis (RA) is a systemic autoimmune rheumatic disease characterized by chronic inflammation of the synovial membrane and a wide range of extra-articular (systemic) manifestations. The main goal of RA therapy is to achieve low disease activity or clinical remission. Power Doppler (PD) ultrasonography (USG) can significantly distinguish between active synovitis (hypervascularization of the synovial membrane) and inactive synovial proliferation.Objective: to investigate the association between the ultrasonic signs of active inflammation and the clinical and laboratory parameters of disease activity in patients with RA.Subjects and methods. The investigation included RA patients followed up at the V.A. Nasonova Research Institute of Rheumatology within the first Russian strategic study of pharmacotherapy for RA – REMARCA (Russian invEstigation of MethotrexAte and biologicals for eaRly aCtive Arthritis). A total of 105 RA patients (mean age 51 years), among whom 80% were rheumatoid factor (RF)-positive and 75% were anti-cyclic citrullinated peptide (ACCP)-positive, were examined. In all the patients, methotrexate (metoject, MEDAC, Germany) as the first diseasemodifying anti-rheumatic drug was subcutaneously injected in an initial dose of 10 mg/week with its rapid escalation up to 20–25 mg/week. Then the therapy was added by biologicals as the need arose. The clinical and laboratory parameters were analyzed immediately before and then 12, 24, 36, and 48 weeks following treatment. Therapeutic efficacy was evaluated using the European League Against Rheumatism (EULAR) criteria and activity indices (DAS28, CDAI, and SDAI). USG of eight articular areas (the wrist, second and third metacarpophalangeal, second and third proximal interphalangeal, second and fifth metatarsophalangeal articulations) in the hand and foot of the clinically dominant side was carried out in all the patients prior to treatment and at 12, 24, 36, and 48 weeks after its initiation. Semiquantitative gray-scale (GS) assessment and PD USG were performed according to the OMERACT criteria.Results and discussion. Weak correlations were found between USG parameters and DAS28, SDAI, and CDAI. After 48-week therapy, the signs of active synovitis were absent in 54 patients and persisted in 51, as evidenced by PD USG. The differences in clinical, laboratory, and ultrasonic parameters were analyzed in relation to USG evidence for active inflammation following 48 weeks of treatment. There were significant differences in GS and PD scores throughout the follow-up period; there were also differences in C-reactive protein levels at 12 and 48 weeks of therapy. No differences were found in clinical activity indices.Conclusion. The investigation provides support for the important role of USG in assessing the activity of synovitis in RA.

Pulmonary arterial hypertension (PAH) associated with systemic connective tissue diseases (SCTD) is a poor prognostic manifestation of the latter that result in death if untreated. The invasive determination of hemodynamic parameters is prominent in diagnosing the disease and determining its treatment policy and prognosis.Objective: to analyze the results of catheterization in PAH-SCTD patients admitted to the V.A. Nasonova Research Institute of Rheumatology.Subjects and methods. The investigation included 59 patients admitted to the V.A. Nasonova Research Institute of Rheumatology from September 2009 to September 2014. PAH was diagnosed in accordance with the conventional guidelines. All the patients underwent right heart and pulmonary artery (PA) catheterization at the diagnosis and over time during treatment.Results and discussion. All the patients included in the trial met the pre-capillary pulmonary hypertension (PH) criteria: mean pulmonary artery pressure (MPAP) ≥25 mm Hg; and PA wedge pressure (PAWP) 15 mm Hg and pulmonary vascular resistance (PVR) >3 Wood units could diagnose PAH in all our patients. There was a statistically highly significant association between pathological hemodynamic changes and functional class (FC). FC was found to be most closely correlated with right atrial pressure (RAP), cardiac output (CO), PVR, and cardiac index (CI). Among the most common manifestations of heart failure, only the presence of peripheral edemas was associated with worse hemodynamic parameters in PAH. It should be noted that out of two biomarkers (N-terminal pro-brain natriuretic peptide and uric acid), the former is largely related to the magnitude of changes in hemodynamic factors. The critical values of hemodynamic parameters were due to extreme edema – anasarca (RAP >17 mm Hg, PVR >20 Wood units, CI

Objective: to investigate the immunogenicity and safety of 23-valent polysaccharide pneumococcal vaccine in patients with rheumatic diseases (RD).Subjects and methods. The prospective open-label comparative study enrolled 133 people (102 (76.7%) women and 31 (23.3%) men) aged 23 to 76 years, including 79 patients with rheumatoid arthritis (RA), 16 with systemic sclerosis, and 7 with dermatomyositis/polymyositis, as well as 31 subjects without systemic inflammatory RD (a control group), who had a recent history of at least two cases of lower respiratory tract infections (bronchitis, pneumonia). At their inclusion, all the patients with RD were receiving ant-inflammatory therapy, including 52 taking methotrexate (MT), 14 – leflunomide (LEF), and 13 – MT + tumor necrosis factor-α (TNF-α) inhibitors. The 23-valent polysaccharide pneumococcal vaccine Pneumo-23 (Sanofi Pasteur, France) was administered in a single dose of 0.5 ml subcutaneously during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of TNF-α inhibitors. Clinical examinations of the patients and conventional laboratory studies were performed during control visits (1, 3, and 12 months after vaccination). The serum levels of anti-pneumococcal capsular polysaccharide antibodies were measured in 102 patients by enzyme immunoassay using commercial VaccZymeTM Anti-PCP IgG Enzyme Immunoassay kits (The Binding Site Group Ltd, United Kingdom).Results and discussion. No clinical and radiological symptoms of pneumonia were recorded in any case during the follow-up period of 12 months. The patients with RD and the control group showed a significant, more than double increase in anti-pneumococcal antibodies 12 months following vaccination. Vaccination was well tolerated: 90 (68%) patients displayed no adverse events; 37 (28%) had pain, cutaneous swelling and hyperemia up to 2 cm in diameter at the site of injection for vaccination;6 (4%) had low-grade fever. There were no episodes of a RD exacerbation or any new autoimmune disorders during the follow-up period.Conclusion. The findings were suggestive of the sufficient immunogenicity and good tolerability of 23-valent pneumococcal vaccine in patients with RD.

Subclinical inflammation detected by ultrasonography (USG) promotes the progression of joint injury in patients with rheumatoid arthritis (RA). Performed studies ambiguously assess the association of disease activity indices with the Doppler ultrasonic signs of synovitis and the serum concentration of cytokines in patents with RA.Subjects and methods. Thirty-eight patients with early RA, who were followed up within the framework of the REMARCA program, were examined. All the patients' therapy was started with subcutaneous methotrexate (MTX) with its rapid dose escalation up to 20–30 mg/week and assessment of the achievement of the treatment goal (low disease activity or remission) every 3 months according to the reason why a decision had been made to add biological agents to the therapy. Clinical and standard laboratory parameters with calculated disease activity indices (DAS28, CDAI, SDAI) were analyzed immediately before and 12, 24, and 48 weeks after treatment. Blood cytokine concentrations were determined by the xMAP multiplex technology before and then 12 and 24 weeks after therapy. USG of 8 joint areas of the hands and feet was undertaken prior to and then 12, 24, and 48 weeks following treatment. Gray-scale synovial hypertrophy and synovial power Doppler (PD) signals were rated for each joint area (0 to 3 scores).Results and discussion. During the drug therapy, all the patients showed improvement with a reduction in activity indices (DAS28, SDAI, CDAI; p < 0.001) and PD signals (p < 0.05). After 12 months of therapy, the ultrasonic signs of remission were found in 4 (21%) patients with clinical remission, amounting to 11% of all the patients included in the study. In a group of patients with active inflammation persisting after 48 weeks of therapy, the basal concentration of interleukin-6 (IL-6) was significantly higher than that in a group without signs of inflammation (p = 0.025). There was a trend for higher tumor necrosis factor-α (TNF-α) levels in the persistent inflammation group (p = 0.06); however, following 24 weeks, the concentration of TNF-α in the patients with persistent synovitis was significantly higher than in those without the latter (p = 0.045). The baseline level of IL-6 as a prognostic factor showed satisfactory sensitivity (71%) and specificity (67%) for a cut-off value of 46.02 pg/ml (p < 0.025). The TNF-α level of ≤51.79 pg/mg achieved after 6 months was associated with the absence of active inflammation, as evidenced by PD with 64% sensitivity and 62.5% specificity (p < 0.046). The predictive value of DAS28 following 24 weeks (3.26) was lower than that of IL-6. Thus, PD USG of hand and foot joints is a sensitive and specific method to assess RA activity. The association of the basal level of IL-6 (and TNF-α to a lesser extent) with ultrasonic changes after 48 weeks of therapy may suggest that PD USG can more accurately characterize inflammation activity than can the disease activity indices.

To introduce treat-to-target recommendations is an important task of modern rheumatology; however, there is still a diversity of serious problems relating to a scientific rationale and a clinical one for this strategy and to the possibilities of its implementation in real clinical practice, in the rheumatology service of the Russian Federation in particular, by taking into account the specific features of funding for high-tech medical care. Objective: to determine the efficiency and safety of combined therapy with subcutaneous methotrexate (MT) and biological agents (BA) when using the treat-to-target strategy in patients with active early and extended-stage rheumatoid arthritis (RA) who have risk factors for a poor prognosis. Subjects and methods. The results of the REMARCA (Russian InvEstigation of MethotrexAte and biologicals in eaRly aCtive inflammatory Arthritis) trial of 130 patients followed up for 12 months or more were given. There was a female preponderance; mean age 48.9±13.9 years, rheumatoid factor positivity (86.9%); anti-cyclic citrullinated peptide antibody positivity (89.2%). Seventy patients formed a subgroup of early RA (disease duration ≤6 months (mean 4.17±1.39 months)); 60 patients were a subgroup of advanced-stage RA (disease duration >6 months (mean 30.8±32.7 months)). In all the patients, therapy was initiated by using subcutaneous MT with its rapid dose escalation up to 20–30 mg/week and the achievement of the treatment goal (low disease activity or remission) was checked every 3 months and depending on the result a decision had been taken to add or not to add a biological agent (BA) (a tumor necrosis factor inhibitor or abatacept). If the former was insufficiently effective, it was substituted for a BA from another class. Results. Subcutaneous MT monotherapy provided remission or low disease activity in 49 (37.7%) patients; a BA was given to 81 (62.3%) patients. Following 6 and 12 months, low activity or remission according to SDAI was observed significantly more frequently in the patients who continued subcutaneous MT monotherapy than in those who received combined therapy with MT and BA. The similar results were obtained by using DAS28 and CDAI to assess a trend in disease activity. After 6and 12-month follow-up, there was a significantly more marked decline of tender joint count, SDAI and CDAI in early RA than in advanced-stage RA; at 12 months, SDAI remission rate was 45.7% and 28.3%, respectively (p=0.047). Conclusion. The treat-to-target strategy should be used in real clinical practice and can yield spectacular results. Active therapy with subcutaneous MT with its rapid dose escalation to the maximally tolerable dose allows identification of a considerable group of patients (38%) with a good response to MT monotherapy.

Most patients with early rheumatoid arthritis (RA) have a high or very high cardiovascular risk (CVR) before therapy with disease-modifying antirheumatic drugs (DMARDs). Objective: to evaluate the impact of antirheumatic therapy performed in accordance with the Treat-to-Target strategy on the progression of atherosclerosis and CVR in patients with early RA. Subjects and methods. This investigation enrolled 74 patients (72% women; median age, 56 years) with early RA having moderate to high activity (median DAS28, 5.6) who had not previously received DMARDs and glucocorticoids (GCs). All patients were anticyclic citrullinated peptide antibody-positive and 87% of the patients were rheumatoid factor-positive. All patients received methotrexate (MT) subcutaneously with dose escalation up to 25–30 mg/week, in case of its inefficiency at 3 months a biological agent (BA) was added. After 6 months, 39% of the patients achieved remission; 19% had low; 35 and 7% had moderate and high disease activity, respectively. The majority (n = 20 (69%)) who achieved remission received MT monotherapy; 9 (31%) – MT + BA whereas among the patients who did not achieve remission 15 (33%) and 30 (67%) respectively. At baseline and after 6 months of treatment, traditional CVR factors were assessed in all patients, by determining the total coronary risk by the SCORE scale, including that modified by EULAR (mSCORE), carotid artery atherosclerosis (CAA) by duplex scanning data, coronary calcification (CC) by multislice spiral computed tomography and by estimating the degree of CVR.Results and discussion. The rates of hypertension, overweight, abdominal obesity, low activity, smoking, and type 2 diabetes mellitus did not change significantly after 6 months. There were increases in the levels of total cholesterol by 7% (p < 0.05), low-density lipoprotein cholesterol by 9% (p

The lecture considers the problem of one of the rare manifestations of systemic diseases (pulmonary arterial hypertension) and shows the need for early diagnosis, careful differential diagnosis, and verification of diagnosis, by applying invasive procedures to evaluate central hemodynamics. It gives a model for screening patients with systemic sclerosis, which simplifies the determination of indications for the use of diagnostic verification methods. Current approaches to drug therapy are described and the issues of better survival of patients with poor prognosis of this disorder are discussed.

Objective: to assess the significance of noninvasive estimation of pulmonary artery pressure (PAP) using Doppler echocardiography (echoCG) as compared to invasive measurements of this parameter in patients with systemic connective tissue diseases (SCTD). Subjects and methods. The invasively measured hemodynamic parameters versus those estimated at echoCG were analyzed. The analysis included 156 paired studies of 61 patients with pulmonary hypertension (PH) in the presence of SCTD and 26 patients, in whom PH was not verified by catheterization. Forty-five patients were found to have PH; PH was caused by left heart involvement in 7 patients and by hypoxemia in 9. Results and discussion. Systolic PAP (SPAP) measured by echoCG averaged 72.4±33.7 mm Hg and that by right heart catheterization did 63.3±25.1 mm Hg. The correlation of the values of this measure, which were obtained by the two methods, was highly significant (r = 0.83; p < 0.00001). Right atrial pressure (RAP) measured by echoCG and catheterization was 8.4±4.1 and 6.7±5.2 mm Hg, respectively. The echoCG and catheterization RAP correlation was highly significant (r = 0.57; p < 0.0001). Despite the high correlation coefficients, echoCG failed to detect higher SPAP in 7 patients with PH verified by catheterization; EchoCG could not detect higher SPAP; false-positive results were absent. EchoCG demonstrated good sensitivity (94%) and specificity (100%) for a threshold SPAP of 40.1 mm Hg (the area under the curve was 0.99 (p < 0.0001) with 95% CI 0.98–1.01. The echoCG determination of RAP by the existing methods showed good sensitivity (79%) and specificity (69%) for its threshold of 5 mm Hg (the area under the curve was 0.79 (p < 0.0001) with 95% CI 0.70–0.95. The patients with low level of mean PAP (PAPmean) measured by catheterization showed a difference of > 10 mm Hg as compared with the echoCG levels in 5% of the cases; > 20 mm Hg discrepancy was not noted. In patients with high PAPmean, the differences of > 10 and > 20 mm Hg were observed in 28.9 and 34.2% of the cases, respectively. Analysis of the Bland–Altman agreement showed deviations of +8.22 mm Hg for SPAP (95% CI 6.6–12.8) and +1.56 mm Hg for RAP (95% CI 0.85–2.27). The standard deviation of differences was 18.4 for SPAP and 4.5 for RAP. There was a relationship between the differences from their mean value, which is more significant for SPAP. The correlation coefficient for SPAP was 0.43 (p < 0.001) and that for RAP was 0.31 (p < 0.05). Thus, the Bland–Altman analysis revealed a systematic disparity, suggesting a weak agreement of the results of the two methods determining SPAP and RAP. Conclusion. Our investigation demonstrated that echoCG proved to be a valid and reliable screening method for PH in patients with SCTD. More accurate estimation of SPAP and RAP measurement requires the application of invasive diagnostic methods.

To introduce treat-to-target recommendations is an important task of modern rheumatology; however, there is still a diversity of serious problems relating to a scientific rationale and a clinical one for this strategy and to the possibilities of its implementation in real clinical practice, in the rheumatology service of the Russian Federation in particular, by taking into account the specific features of funding for high-tech medical care.Objective: to determine the efficiency and safety of combined therapy with subcutaneous methotrexate (MT) and biological agents (BA) when using the treat-to-target strategy in patients with active early and extended-stage rheumatoid arthritis (RA) who have risk factors for a poor prognosis.Subjects and methods.The results of the REMARCA (Russian InvEstigation of MethotrexAte and biologicals in eaRly aCtive inflammatory Arthritis) trial of 130 patients followed up for 12 months or more were given. There was a female preponderance; mean age 48.9±13.9 years, rheumatoid factor positivity (86.9%); anti-cyclic citrullinated peptide antibody positivity (89.2%). Seventy patients formed a subgroup of early RA (disease duration ≤6 months (mean 4.17±1.39 months)); 60 patients were a subgroup of advanced-stage RA (disease duration >6 months (mean 30.8±32.7 months)). In all the patients, therapy was initiated by using subcutaneous MT with its rapid dose escalation up to 20–30 mg/week and the achievement of the treatment goal (low disease activity or remission) was checked every 3 months and depending on the result a decision had been taken to add or not to add a biological agent (BA) (a tumor necrosis factor inhibitor or abatacept). If the former was insufficiently effective, it was substituted for a BA from another class.Results. Subcutaneous MT monotherapy provided remission or low disease activity in 49 (37.7%) patients; a BA was given to 81 (62.3%) patients. Following 6 and 12 months, low activity or remission according to SDAI was observed significantly more frequently in the patients who continued subcutaneous MT monotherapy than in those who received combined therapy with MT and BA. The similar results were obtained by using DAS28 and CDAI to assess a trend in disease activity. After 6- and 12-month follow-up, there was a significantly more marked decline of tender joint count, SDAI and CDAI in early RA than in advanced-stage RA; at 12 months, SDAI remission rate was 45.7% and 28.3%, respectively (p=0.047).Conclusion. The treat-to-target strategy should be used in real clinical practice and can yield spectacular results. Active therapy with subcutaneous MT with its rapid dose escalation to the maximally tolerable dose allows identification of a considerable group of patients (38%) with a good response to MT monotherapy

Objective: to assess the efficacy and tolerability of Rituximab treatment in patients with serious immune inflammatory rheumatic diseases (IRD) like systemic lupus erythematosus (SLE), systemic sclerosis (SS), systemic vasculitis (SV), Sjogren syndrome (SjS), dermatomyositis/polymyositis (DM/PM).Subjects and methods. The clinical efficacy has been analyzed in 229 patients with IRD: SLE (n=97), SV (n=50), SS (n=40), SjS (n=23) and DM/PM (n=19). Rituximab treatment was accompanied by administration of glucocorticoids and/or immunosuppressive drugs. Most patients demonstrated resistance to or low tolerability of standard therapy. Efficacy of treatment was analyzed in each group with the criteria relevant for each disease. To compare clinical response to the treatment between the groups we used gradations accepted by international registries: complete (good) response, partial response, no response. Average duration of monitoring comprised 72 (1–288) weeks after the first introduction of Rituximab. Average Rituximab dose administered to patients over the period of monitoring was low and varied from 1.6±0.84 in DM/PM to 3.1±1.75 in SV. About 80% of patients received one or two courses of Rituximab except for patients with SS (half of them received three and more courses).Results. «Complete response» was observed in 50.6%, «partial response» – in 35% of patients. Rituximab courses provided positive dynamics in clinical scores and allowed to reduce supportive dose of glucocorticoids and to lower the dose or withdraw of immune-stimulating drugs. Multiple Rituximab courses provided stable and longlasting effect. Recurrences were observed less frequently, whereas efficacy of the therapy increased during a year and longer. Occurrence of adverse events and mortality rate were comparable to data of other national Rituximab registries.Conclusion. The results of the study may prove administration of Rituximab in patients with resistance to standard therapy

Objective: to provide the clinical characteristics of joint injury in patients with calcium pyrophosphate crystal (CPC) deposition disease.Subjects and methods. The trial enrolled 68 patients (43 women, 25 men) with a verified diagnosis of CPC deposition disease. Their mean age was 60.2±11.8 years and disease duration was 7.5±6.4 years. Examination revealed the presence of arthritis and arthralgias. Polarizing microscopy with an Olympus CX31-P compensator was used to detectcrystals in synovial fluid. X-ray study of the knee joints was performed in the anteroposterior and lateral projections and that of the hand joints was in the frontal projection, Ultrasonography (USG) of the knee and wrist joints was done using a GE Voluson-I transducer.Results. A concurrence of arthritis and arthralgias was noted in 37 (54%) patients; 24 (36%) patients had arthralgias only; 7 (10%) had arthritis only. Arthritis affecting the knee, wrist, ankle, and first metacarpophalangeal joints was observed in 53, 15, 12, and 6% of cases, respectively. There was acute arthritis in 18% of the patients and chronic arthritis in 39%; the rate of CPC osteoarthrosis was 43%. Joint USG diagnosed knee and wrist joint chondrocalcinosis in 94 and 56% of the patients, respectively. USG could reveal asymptomatic wrist joint chondrocalcinosis significantly more often (in 56 and 17% of the patients, respectively; p = 0.008). Besides, USG could visualize synovitis in the knee joints in 88% of the patients with isolated arthralgias in them and synovitis in the wrinkle joints in 52% of the patients without clinical signs of inflammation in them.Conclusion. Osteoarthrosis is the most common form of CPC deposition disease. Knee joints in this disease are most frequently involved. Joint USG is of more informative value in detecting chondrocalcinosis than X-ray study; USG can also identify synovitis in the intact joints.

Antifosfolipidnyi sindrom (AFS) – simptomo- kompleks, proyavlyayushchiisya trombozom sosudov razlichnoi lokalizatsii i kalibra pri obyazatel'nom nalichii v krovi antifosfolipidnykh antitel (aFL) [1]. K serologicheskim markeram AFS, soglasno mezhdunarodnym diagnosticheskim kriteriyam, otneseny: antitela k kardiolipinu (aKL) i/ili volchanochnyi antikoagulyant (VA), i/ili antitela k β2-glikoproteinu 1 (anti-β2-GP 1). V zavisimosti ot pozitivnosti po aFL rekomendovano stratifitsirovat' bol'nykh AFS po sleduyushchim kategoriyam: I – vyyavlenie bolee odnogo laboratornogo markera (v lyuboi kombinatsii); IIa – tol'ko VA; IIb – tol'ko aKL; IIc – tol'ko anti-β2-GP 1 [2]

Pulmonary pathology is diagnosed in patients with rheumatoid arthritis (RA). The external respiratory function (ERF) examination is widely used to assess the functional capacity of the lungs. Objective. To evaluate ERF in patients with RA. Material and methods. The study included 155 patients with RA. A MasterScreen Body plethysmograph (Erich Jaeger) was used to determine the ERF parameters (diffusing lung capacity, DLC; forced inspiratory vital capacity, FIVC; forced expiratory volume in 1 second, FEV1; total lung capacity, TLC; the FEV1/FIVC ratio, and the modified Tiffeneau index). DLC was measured by the single-breath method. ERF parameters were represented as a percentage of the appropriate value for a given gender, age, and height of the patient. Results. Of the 155 examined patients with RA, a decrease in the DLC parameter was detected in 107 (69%), while in 87 (81%) patients, the decrease was less than 10% of the proper values. An analysis of the state of the ERF parameters revealed a decrease in FEV1 in 48 (31%) patients, FIVC in 41 (27%) patients, and TLC in 36 (23%) patients. The restrictive type of lung ventilation was determined in 27% of patients, bronchial obstruction in 31% of patients, an iso- lated decrease in DLC in 12% of patients with RA. In 31% of cases, no deviations of the ERF parameters from normal values were found. A statistically significant negative correlation between the clinical activity of RA and the DLC level (r = -0.59; p

Objective. Rertrospective analysis of clinical and laboratory features of primary (PAPS) and secondary (SAPS) antiphospholipid syndrome (APS) in systemic lupus erythematosus (SLE). Material and methods. 280 pts (96 male, 184 female) with SLE were included. 142 had SAPS and 84 (24 male, 60 female) - PAPS. Mean age was 31,2±ll,l years and mean disease duration - 8.6+7,2 years. PAPS pts mean age was 35,6±9,9 years and mean disease duration - 1 1,9±8,5 years. Peripheral vessels USDG and echocardiography (EchoCG) were performed to verify vascular complications. Anticardiolipin antibodies (АСА) and lupus anticoagulant (LA) served as serological markers of APS. Results. In 75% of pts the disease began with SLE signs, in 17% - with ARS signs and in 8% - with thrombocytopenia. 5 from 138 SLE pts without APS showed LA and APS clinical signs during follow- up. In 54% from 142 SAPS pts the disease began with an SLE sign, in 34% - with an APS sign and in 12% - with thrombocytopenia. At the onset of PAPS thrombocytopenia was much more seldom - in 5 from 84 pts. The rest had other APS signs at presentation. 8 pts showed PAPS transformation into SLE, Thrombotic complications frequency among SLE pts was 42%. They were significantly more frequent in APS (76% in PAPS and 90% in SAPS) than in SLE without APS (6%), x 2=I3I, p