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Clinical response to methotrexate (MT) therapy in rheumatoid arthritis (RA) can be predicted on the basis of some single nucleotide polymorphisms (SNPs) of genes, involved in folate metabolism. One of these SNPs is the rs1801394 (A66G) polymorphism of the methionine synthase reductase gene (MTRR). We investigated the association of this polymorphism with the clinical characteristics of RA patients after 6 months of MT therapy. Studies of the relationship between the response to MT therapy and the rs1801394 polymorphism have not been carried out in Russia previously.Objective: to study the possible association of the rs1801394 polymorphism with the clinical characteristics of patients with RA after 6 months of MT therapy.Patients and methods. The study included 60 patients with RA who met the ACR / EULAR criteria (2010) and received≥20 mg MT per week continuously. Based on the EULAR criteria, patients were divided into two groups: group 1 (n=30) with a good (DAS28>1.2) and group 2 (n=30) with an unsatisfactory (DAS28

In clinical practice, acute-phase protein measurements during inflammation are usually used to monitor the activity and severity of adult-onset Still's disease (AOSD).Objective: to study the possibility of using the neutrophil-to-lymphocyte ratio (NLR) in complete blood cell count as a marker for the activity and severity of AOSD in clinical practice.Patients and methods. The investigation enrolled 48 patients (29 females and 19 males; mean age, 32.8±12.5 years) with active AOSD, who met the criteria devised by M. Yamaguchi et al. Along with standard clinical and laboratory parameters and systemic scores, NLR was calculated in complete blood cell count.Results and discussion. There was a statistically significant correlation of NLR with the level of CRP (r=0.532), ferritin (r=0.43), ESR (r=0.40), and the systemic score reflecting the severity of the disease (r=0.449), which allows NLR to be regarded as a tool that is convenient to assess the activity and severity of AOSD in clinical practice.Conclusion. The findings have shown the good sensitivity and specificity of NLR, which indicates the possibility of using the latter as an available marker for assessing the activity and severity of AOSD in clinical practice.

Objective: to assess the time course of changes in the concentration of methotrexate (MTX) and its main metabolites in the red blood cells (RBC) and mononuclear cells (MNC) of patients with rheumatoid arthritis (RA), by taking into account individual characteristics (age, statin therapy, and smoking).Patients and methods. The investigation enrolled 33 MTX-treated patients (mean age 53.2±11.7 years) with RA, who underwent therapeutic drug monitoring to measure the RBC and MNC concentrations of free MTX and MTX polyglutamates (MTXPGs) with 2, 3, and 4 glutamate residues (MTXPG 2–4) in using tandem chromatomass spectrometry after 4, 12, and 24 weeks of therapy.Results and discussion. Following 12 weeks, the concentration of MTXPG4 in the MNC was higher in patients taking statins, while that of MTX and MTXPG2 in the RBC were significantly lower than in smokers. At 24 weeks, older patients were observed to have a higher MTX level and a lower MTXPG4 concentration in the RBC.Conclusion. After 24 weeks of therapy, the RBC concentration of MTPG4 was lower and that of MTX was higher in older patients than in others, which confirms data on a slower MTX metabolism in the elderly. The use of statins is likely to have a positive impact on the accumulation of MTXPG. There is a statistically significantly lower RBC concentration of MTXPG in at 12 weeks of therapy.

The paper discusses prospects for prescribing tumor necrosis factor-α (TNF-α) inhibitor biosimilars, their interchangeability with original drugs for inflammatory joint diseases. It describes clinical cases when original infliximab is replaced with its biosimilar Flammagis for ankylosing spondylitis. The authors emphasize that it is difficult to predict the interchangeability of original TNF-α inhibitors and biosimilars in rheumatology, and this is confirmed by the above clinical cases. They also indicate that the optimal use of biosimilars requires a constant cooperation of rheumatologists, pharmacologists, and regulatory authorities, which is aimed at protecting the rights of a patient in order to ensure safe, effective and high-quality care. It is concluded that it is advisable to conduct further investigations to develop a special pharmacovigilance system in this area.

Objective: to assess whether the modified combined glucocorticoid (GC) toxicity index (MCGTI) can be used to analyze adverse reactions (ARs) to GCs administered in the management of rheumatoid arthritis (RA).Subjects and methods. The investigation enrolled 71 RA patients (57 females, 14 males; mean age, 51.7+15.2 years). All the patients met the ACR/EULAR classification criteria and took GCs (the median duration of GC treatment duration was 7.1 [0.9; 12.0] years). In addition to the standard clinical, laboratory, and instrumental indicators, the daily and cumulative doses of GCs (in prednisolone equivalent) and MCGTI were analyzed.Results and discussion. The value of MCGTI statistically significantly correlated with treatment duration (r=0.411), age (r=0.384), and the cumulative dose of GCs (r=0.361), but did not correlate with their maximum dose (r=0.06). A ROC analysis showed that the critical level of the cumulative dose of GCs in relation to MCGTI was 17,337.5 mg.Conclusion. MCGTI correlates with cumulative dose (making it possible to establish its critical level), treatment duration, and age, which is the basis for further study of whether this can be applied in clinical practice to evaluate, predict, and prevent ARs.

Therapeutic control of the methotrexate (MT) polyglutamates (MTPG) level in erythrocytes can be an objective marker of the effective dose of MT prescribed for rheumatoid arthritis (RA).Objective: to assess the relationship between the level of MTPG in red blood cells and efficacy of the MT dose used by RA patients.Subjects and methods. The study included 60 patients with RA (44 women and 16 men over 18 years) who met the criteria of the American College of Rheumatology and the European League Against Rheumatism (ACR/EULAR) 2010 and received MT ≥20 mg/week subcutaneously for ≥12 weeks. The patients were divided into two groups of comparable age, sex, alcohol intake, number of smokers, body mass index (BMI), depending on the presence (group 1; n=30) or absence (group 2; n=30) of the effect of MT, according to the EULAR efficacy criteria (DAS28). The concentration of MTPG (total MTPG and metabolites of MTPG 1, 2, 3, 4, 5) was determined in erythrocytes by high-performance liquid chromatography with mass spectrometric detection.Results and discussion. It was found that the levels of total MTPG and MTPG1, 2, 3, 5 in erythrocytes did not differ in groups of responders and nonresponders, and the dose of MT was comparable in both groups. At the same time, the level of MTPG4 in the first group was significantly higher (26.4±6.1 nmol/l; p=0.023) than in the second one (22.1±6.8 nmol/l). Analysis of the ROC curve showed that the values of MTPG4

The paper discusses data on the high frequency of non-indicated use of proton pump inhibitors and on the manifestations of potential harms of their use.

The paper discusses the problem of laboratory monitoring in therapy with disease-modifying antirheumatic drugs (DMARDs) and biological agents (BAs) in patients with rheumatoid arthritis (RA). Due to the risk of adverse reactions, in particular to that of cardiovascular diseases, hepatotoxicity, hematological disorders, deterioration of renal function, infections, and bleeding caused by the use of DMARDs and BAs, recommendations are needed to have a list of tests for laboratory monitoring during this therapy and the frequency of their implementation in patients with RA.

The review gives an update on adult-onset Still’s disease: on its causes, the specific features of its pathogenesis, diagnosis, clinical presentations (with identification of subtypes), and treatment with consideration for the nature of the course of the disease and life-threatening complications.

The paper discusses the appearance of unusual – paradoxical – adverse reactions that occur as a result of treatment of rheumatic diseases with biological agents.

Rheumatoid arthritis (RA) is an immune inflammatory (autoimmune) rheumatic disease of unknown etiology, which is characterized by chronic erosive arthritis and systemic damage to the viscera, and leads to early disability and reduced survival in patients. For its diagnosis, it is currently recommended to use the 2010 ACR/EULAR classification criteria for RA, which should be applied in clinical trials to identify at least one swollen joint, i.e. the presence of arthritis; therefore, the problem of extra-articular manifestations of RA is apparent to stay in the background.

The paper discusses the possible causes of the problems related to pharmacovigilance.

The article presents the provisions of the Erice Declaration on the safety of medicines and discusses the need for their transformation into the XXI century.

The lecture gives an update on adult-onset Still's disease, including that on the specific features of the clinical picture and treatment of this disease.

Objective: to evaluate the safety and efficiency of monotherapy with methotrexate (MTX) solution for subcutaneous injection (SC MTX), by using the estimated dosing, in patients with rheumatoid arthritis (RA).Subjects and methods. A 12-month prospective controlled study enrolled 106 patients with early RA who were given SC MTX was conducted at the V.A. Nasonova Research Institute of Rheumatology in the framework of the REMARCA (Russian invEstigation of MethotrexAte and biologicals for eaRly aCtive Arthritis) program.Results and discussion. 12-month SC MTX monotherapy could achieve the treatment goal (remission or low disease activity) in 68% of the patients with active RA who did not need biological agents (BAs). In 36% of the patients, the treatment caused adverse reactions (ARs) that were the basis for its complete discontinuation in 8%. The therapeutic effect of SC MTX depended on body mass index (BMI) and was more pronounced in patients with its normal values (≤25 kg/m2) than in those with overweight or obesity. The incidence of ARs did not depend on the duration of the disease and the weight of a patient receiving SC MTX. Addition of BAs to SC MTX monotherapy did not lead to an increase in the frequency of ARs. In early RA, the effect was better when SC MTX was used in combination with lowdose oral glucocorticoids. The findings showed the expediency of intensively using SC MTX at the doses calculated per 1 m2 of the body surface, the dependence of therapeutic action and the independence of the frequency and severity of ARs from the patient’s BMI.

There are virtually no diagnostic tests that can diagnose diseases of the musculoskeletal system and connective tissue with 100% sensitivity and 100% specificity, which was the reason for making both diagnostic and classification criteria to help practitioners and investigators. The application of these criteria is discussed in the article.

The paper discusses the issues of imperfect 1987 American College of Rheumatology (ACR) and the 2010 ACR/European League Against Rheumatology (EULAR) rheumatoid arthritis classification criteria and justifies the need for their correction.

Objective: to investigate the immunogenicity, safety, and clinical efficacy of 23-valent polysaccharide pneumococcal vaccine in patients with rheumatoid arthritis (RA) during a two-year follow-up study.Subjects and methods. The prospective open-label comparative study enrolled 110 people, of them there were 81 (73.6%) women and 29 (26.4%) men at the age of 23 to 76 years, including 79 patients with RA, as well as 31 subjects without systemic inflammatory rheumatic diseases (RD) (a control group). The group of RA patients exhibited a predominance of middle-aged women who had > 3 years’ disease duration and a moderate inflammatory activity (the mean value of DAS28, 4.32). 52 patients received methotrexate (MTX), 14 had Leflunomide (LEF), and 13 were treated with tumor necrosis factor-α (TNF-α) inhibitors + MTX.The 23-valent polysaccharide pneumococcal vaccine Pneumo-23 (Sanofi Pasteur, France) was administered in a single dose of 0.5 ml subcutaneously during continuous MTX or LEF therapy for the underlying disease or 3–4 weeks before the use of TNF-α inhibitors. Clinical examinations of the patient and conventional clinical and laboratory studies were performed during control visits (1, 3, 12, and 24 months after vaccination). Clinical effectiveness and safety were evaluated in all the patients included in the study. The serum levels of anti-pneumococcal capsular polysaccharide antibodies (Ab) were measured in 72 patients with RA and in 30 individuals in the control group during a 12-month follow-up study, including in 25 patients with RA for a 24-month follow-up study by enzyme immunoassay using commercial VaccZymeTM Anti-PCP IgG Enzyme Immunoassay kits (The Binding Site Group Ltd, Birmingham, United Kingdom). Along with this, the post-immunization response coefficient was calculated for each patient as the ratio of postvaccination Ab levels during Visits 2, 3, 4, and 5 to the baseline Ab level.Results and discussion. No clinical and radiological symptoms of pneumonia were recorded in any case during the follow-up period. The patients with RA and the control group showed a more than double significant increase of anti-pneumococcal Ab level during 3 months following vaccination. Despite the decrease in their concentration by month 12, the latter remained at the appropriate level and significantly increased at 24-month follow-up. Vaccination was well tolerated. A favorable course of the postvaccinal period was noted in all cases. There were no adverse reactions to vaccination in 72 (65%) patients; 38 (35%) patients were noted to have pain, skin swelling and hyperemia up to 2 cm in diameter at the site of injection, as well as 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 during the two-year follow-up period.

Russian and international clinical recommendations postulate the possibility of withdrawal of biological agents in patients with rheumatoid arthritis (RA) after the achievement of clinical remission. But it is not clear what would be the results of implementation of these recommendations in clinical practice.Patients and methods. In REMARCA (Russian invEstigation of MethotrexAte and biologicals for eaRly aCtive Arthritis) trial 78 patients (66 females, 12 males, median age 53 years, duration of disease 7 months at inclusion), who were resistant to high doses of subcutaneous (SC) methotrexate (MTX), were treated by combination therapy with SC MT and biologics (adalimumab, certolizumab or abatacept). Patients were investigated every 3 months using DAS28-ESR, SDAI, CDAI indices as disease activity measures.Results. 30 (38.5%) patients (from 78) continued combination therapy. In 47 (60.3%) after achievement of remission or low disease activity (LDA) the therapy was modified to one of two options: 1) in 21 (26.9%) patients doses of biologics were tapered, in some cases to zero; 2) in 26 (33.3%) patients single-step discontinuation of biologics was performed. After 6 months among 47 patients with modification of therapy 27 (57.4%) maintained remission or LDA, in 20 (42.6%) deterioration observed, including 6 (12.8%) patients who lost remission but remained in LDA, and 14 (29.8%) flared (activity increased to moderate or high levels). First modification option was significantly superior to second option regarding the maintaining remission or LDA.Conclusion. In terms of maximum preservation of the results, optimal modification of treatment strategy is the tapering of the dose by the gradual increase in the period between injections of biologics, at least 12 months after reaching the state LDA or clinical remission.

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 paper reports the development of the adverse events of the skin and its appendages due to subcutaneous methotrexate, which serve as a manifestation of its toxicity in patients with rheumatoid arthritis. It discusses the possible mechanisms of their occurrence, although both clinical presentations and histological changes are not specific.

The early administration of methotrexate (MTX) and the use of its high (by the rheumatology practice standards) doses contribute to the enhanced efficiency of therapy and the reduced severity of rheumatoid arthritis (RA). One of the important merits of MTX in the treatment of RA is the possibility of adjusting its dose and choosing its (oral or subcutaneous) administration routes, which makes it possible to individualize treatment. Particular emphasis has been recently placed just on a subcutaneous MTX formulation that creates prerequisites for substantially improving the efficiency of RA therapy. The paper gives the data of the REMARCA (Russian investigation of methotrexate and biologicals for early active arthritis) trial assessing the results of RA treatment in the use of the subcutaneous MTX dosage form as a first-line drug and in the elaboration of management tactics for this disease.Subjects and methods. The investigation included 191 patients (34 men and 157 women) with active RA; of whom 51.8% had very early RA (< 6 months' disease duration). 115 patients with RA completed a 24-month follow-up period; and their data were analyzed in more detail.Results and discussion. The findings may substantiate treatment policy based on the prescription of subcutaneous MTX (without previously administering its oral formulation) in patients with early RA and high disease activity, starting the drug at 15 mg/week and rapidly escalating with the highest tolerable doses during 4-8 weeks, which allows remission (or low disease activity) in the majority of patients without using glucocorticoids and biological agents.

Objective: to evaluate of the efficacy of methotrexate (MTX) as a concentrated solution (50 mg/ml) for subcutaneous administration versus coated tablets at equal oral doses of 15 mg/week for rheumatoid arthritis (RA).Subjects and methods. The study was conducted at two centers: the V.A. Nasonova Research Institute of Rheumatology and the Saint Petersburg Medical Academy of Postgraduate Education, Federal Agency for Healthcare and Social Development. At each center, the patients were randomized into two groups: a study group and a control group. In the study group, MTX was used as a concentrated solution (50 mg/ml) for subcutaneous administration at a dose of 15 mg/week. The controls were patients with RA who took MTX as coated tablets once weekly at the same dose as used in the study group. A trend in the 28-joint disease activity score (DAS28) was a main criterion for evaluating therapy efficiency. For efficiency evaluation, other criteria were additionally used; these included disease activity assessment by a physician; functional status assessment (Health Assessment Questionnaire); C-reactive protein level. The safety of the used MTX formulations was evaluated during each visit: the patients' subjective sensations and examination and laboratory findings were kept in mind.Results and discussion. After randomization (totally at the two centers), the study group included 42 patients and the control group comprised 23. Based on 95% confidence interval for the mean, it may be concluded that the efficiency of MTX as a solution for subcutaneous administration (the study group) is no less than that of MTX as tablets (the control group). Subcutaneous MTX was shown to be associated with the lower rate of therapy correction than oral MTX; and did not differ from it in toxicity. In addition, subcutaneous MTX may noticeably reduce the need for biological agents.The final DAS28 value in the study group does not exceed that in the control group (t-test). Remission was observed only after subcutaneous administration of the drug.Conclusion. Based on the findings, it can be concluded that MTX as a concentrated (50 mg/ml) solution for subcutaneous administration may be the drug of choice for the treatment of patients with active RA.

The past two decades have been marked by the design of a great variety of innovative biological agents, the clinical introduction of which could substantially improve the results of treatment for rheumatic diseases. At the same time, there are a larger number of reports on their administration-associated adverse events, often paradoxical ones (these drugs indicated in many autoimmune processes may induce similar autoimmune processes).

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.

The paper describes a case of infliximab-induced lupus-like syndrome in a female patient with rheumatoid arthritis and discusses the possible causes of this pathology.

The paper discusses whether patients' spontaneous reporting on adverse drug reactions is appropriate and possible.

The paper discusses the results of the long-term PRECISION study specially designed for the prospective comparative evaluation primarily of the cardiovascular safety of celecoxib, ibuprofen, and naproxen, which are long used for the treatment of pain in patients with arthritis.

The discussion provides evidence for the long-felt need to standardize the terms reflecting the harm of drugs.

The paper discusses the use of the recommended methotrexate doses for the treatment of rheumatoid arthritis in the randomized clinical comparative trials with biological agents.

The authors comment on the discussion article «Definition of the term “rheumatology”: do we need this and how do the EULAR and the ACR look at this?» by Sh. Erdes.

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.

When treating rheumatoid arthritis (RA), it is important not only to suppress inflammation, but also to prevent local and generalized bone loss, particularly in patients receiving glucocorticoids (GC). Denosumab is a fully human monoclonal antibody that binds receptor activator of nuclear factor kappa B ligand (RANKL), prevents its interaction with receptor on osteoclasts, reduces their activity, and inhibits bone resorption.Objective: to evaluate the effect of 12-month therapy with denosumab on bone mineral density (BMD) of the axialand peripheral skeleton and destructive changes in the hand and foot joints of RA patients receiving GC.Subjects and methods. Fifty-two postmenopausal women with RA concurrent with osteoporosis received subcutaneous denosumab 60 mg twice: at baseline and 6 months later. BMD was measured before drug administration and after 12 months of a follow-up, by applying dual-energy X-ray absorptiometry of three sections: the lumbar spine (LI–IV), femoral neck (FN), and distal forearm (DF). Radiographic changes in the hand and foot joints were assessed using the Sharp method modified by van der Heijde (SVH) at baseline and 12 months later.Results and discussion. The patients’ mean age was 58.4±6.4 years; the mean RA duration – 19.0±10.9 years. Antiinflammatorytherapy was performed in all the patients, including 30 (57.7%) who received GC. The mean BMD during follow-up increased from 0.814±0.101 to 0.848±0.103 g/cm2 in LI–IV (p

Objective: to evaluate the safety of treatment with methotrexate (MT) solution for subcutaneous injections in patients with rheumatoid arthritis (RA).Subjects and methods. 237 RA patients enrolled in the study within the REMARCA protocol were given MT solution for subcutaneous injections (Metoject) to assess the standard parameters of therapy safety.Results. Overall, adverse events (AE) were noted in 49 (21%) patients. In 30 (30%) of them RA duration was less than 6 months (Group 1) and in 19 (14%) – more than 6 months (Group 2), in most cases average MT dose was 20.9±3.45 mg/week. Elevation of alanine aminotransferase and aspartate aminotransferase levels, nausea, postinjection reactions, alopecia, rash, infections, and leukopenia, were common (> 1%, but

The paper describes a long-term observation and discusses the possible mechanism of leflunomide-induced clinical and morphological regression of AA-amyloidosis diagnosed at a nephrotic stage in the presence of adult-onset Still's disease.

The review deals with the prediction of the therapeutic effect of methotrexate in rheumatoid arthritis, by determining its level in the red blood cells.

The paper discusses whether it is expedient to use the standards approved by the editorial staff of a number of medical journals for original articles on the therapeutic effect of drugs, including antirheumatic agents since this is of importance for the analysis of their safety.

Objective: to study the clinical efficacy, immunogenicity, and safety of a 23-valent pneumococcal vaccine in patients with rheumatoid arthritis (RA).Subjects and methods. The investigation enrolled 102 patients (78 women and 24 men, aged 23 – 70 years), including 72 patients with RA and 30 people without systemic inflammatory rheumatic diseases (a control group) who had a recent history of 2 and more cases of lower respiratory tract infections (bronchitis, pneumonia). When included, all the patients received anti-inflammatory therapy with methotrexate (MT) (n = 52), leflunomide (LEF) (n = 10), or MT + tumor necrosis factor-α (TNF-α ) inhibitors (n = 10). A single 0.5-ml dose of the 23-valent pneumococcal vaccine was administered subcutaneously during continuous MT or LEF therapy for the underlying disease or 3 – 4 weeks before the use of a TNF-α inhibitor. During control visits (1 and 3 months and 1 year after administration of the vaccine), the patients underwent physical examination and routine clinical and laboratory studies.Results. No clinical and radiological symptoms of pneumonia were recorded in any case during a 12-month follow-up. The RA and control groups showed a more than 2-fold increase in anti-pneumococcal antibody levels 1 year after vaccination. The vaccine was well tolerated by 67 patients. 27 patients were observed to have pain, cutaneous swelling and hyperemia and 8 patients had subfebrility. There were neither episodes of RA exacerbation nor new autoimmune disorders during the follow-up.Conclusion. The findings suggest that 23-valent pneumococcal vaccine shows a good clinical efficacy, adequate immunogenicity, and good tolerability in the patients with RA.

Objective: to study the clinical efficacy, immunogenicity, and safety of a 23-valent pneumococcal vaccine in patients with rheumatoid arthritis (RA). Subjects and methods. The investigation enrolled 70 patients (55 women and 15 men) aged 23–70 years, including 40 patients with RA and 30 people without systemic inflammatory rheumatic diseases (a control group) who had a recent history of 2 and more cases of lower respiratory tract infections (bronchitis, pneumonia). When included, all the patients received anti-inflammatory therapy with methotrexate (MT) (n = 24), leflunomide (LEF) (n = 6), or MT + tumor necrosis factor-α (TNF-α) inhibitors (n = 10). A single 0.5-ml dose of the 23-valent pneumococcal vaccine Pneumo-23 (Sanofi Pasteur) was administered subcutaneously or intramuscularly during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of a TNF-α inhibitor. During control visits (1 and 3 months and 1 year after administration of the vaccine), the patients underwent physical examination and routine clinical and laboratory studies. Results. No clinical and radiological symptoms of pneumonia were recorded in any case during a 12-month follow-up. The RA and control groups showed a more than 2-fold increase in anti-pneumococcal antibody levels 1 year after vaccination. The vaccine was well tolerated by 50 patients. Sixteen patients were observed to have pain, cutaneous swelling and hyperemia and 4 had subfebrility. There were neither episodes of RA exacerbation nor new autoimmune disorders during the follow-up. Conclusion. The findings suggest that 23-valent pneumococcal vaccine shows a good clinical efficacy, adequate immunogenicity, and good tolerability in the patients with RA.

The paper historically considers whether it is appropriate to use the term (concept) “drug-induced disease”.

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

The paper considers discussion ideas about the possible causes of medicine uncertainty that arose in the era of digital technologies and information flooding.

Objective: to estimate the advantages and disadvantages of using the injectable formulation of methotrexate (MT) (Methoject (MTJ)) in rheumatoid arthritis (RA) in clinical practice. Subjects and methods. A 24-week open-label controlled randomized comparative study evaluated the therapeutic and side effects of MTJ and methotrexate tablets in RA and clarified whether MTJ treatment might be continued if its tabletted formulation was discontinued because of adverse reactions. Results and discussion. MTJ was found to be more effective than the tabletted formulation of MT and as a whole; and following 3-month therapy, more patients receiving MTJ achieved an ACR20 response. The advantage of MTJ was also retained 6 months after therapy. Higher transaminase levels were noted in 2 patients, one in each group. Switching from MT to MTJ noticeably reduced the number of adverse reactions in the majority of patients from an additional group. Conclusion. As compared to MT, MTJ used in RA patients is more effective when given in an equivalent dose, exerts a therapeutic effect more rapidly, and induces adverse gastrointestinal reactions less frequently.

Ingibitory faktora nekroza opukholi α (FNO α) – infliksimab, adalimumab i etanertsept – k aprelyu 2009 g. poluchili bolee 2 mln bol'nykh vo vsem mire. Vse eti preparaty okazalis' odinakovo effektivny (okolo 60% bol'nykh otvetili na lechenie) pri revmatoidnom artrite (RA), ankiloziruyushchem spondilite (AS), psoriaze, psoriaticheskom artrite i odobreny dlya lecheniya etikh boleznei [1, 2]. Odnako ikh ispol'zovanie mozhet byt' svyazano s tselym ryadom neblagopriyatnykh reaktsii, odnoi iz kotorykh yavlyaetsya obostrenie ili razvitie novykh sluchaev psoriaza [3].