In modern rheumatology, the problem of rheumatoid arthritis (RA) treatment remains highly relevant. This is demonstrated by the numerous clinical trials of new drugs with an expanding range of mechanisms of action and studies of optimal treatment strategies using currently available medications conducted worldwide. This review analyzes materials prepared by EULAR experts on the efficacy of current disease-modifying antirheumatic drugs and glucocorticoids in the treatment of RA.

A characteristic feature of rheumatic diseases (RD) is a chronic inflammatory process, which contribute to their pathogenesis, and determines the formation of a persistent pain syndrome. Therefore, in current recommendations for the treatment of RD, the main attention is paid to the correction of disorders that induce pain caused by inflammation. Meanwhile, more and more data are accumulating on the participation of noninflammatory mechanisms in the development of pain in RD. In some cases, the clinical picture of RD is determined by the simultaneous participation of several mechanisms. At the same time, the symptoms associated with the inflammatory process can eventually transform into a different pain phenotype, which persists even after the suppression of inflammatory changes. In such a situation, a correct assessment of the patient's status can cause serious difficulties. The results of the studies show that in everyday clinical practice, when assessing the status of a patient, in addition to the disorders characteristic of each disease, it is necessary to take into account the possibility of the presence of symptoms due to the mechanisms of central sensitization common to various joint diseases.

The problem of comorbidity is widely discussed in modern medical literature. Its role in rheumatic diseases is of particular interest due to their multifactorial nature and the involvement of a wide range of pathogenetic mechanisms. For many years, researchers around the world have noted correlations between the presence of active autoimmune disorders and the complicated course of cardiovascular diseases. A deeper understanding of the pathogenetic mechanisms at the present stage of development of rheumatology allows us to take a fresh look at the relationship between atherosclerosis and rheumatoid arthritis. The definition of multimorbidity developed in recent years and the results of recent scientific studies may contribute to a more correct choice of tactics for managing patients with a combination of these two diseases.

Objective: to compare the course of the disease and therapy in rheumatoid arthritis (RA) patients who meet and do not meet the criteria for difficult- to-treat RA (D2T).Patients and methods. The study included RA patients who met the 2010 ACR/EULAR criteria and who were hospitalized in the V.A. Nasonova Research Institute of Rheumatology from March to October 2021. All patients underwent a conventional clinical and laboratory examination, radiography of the hands and distal feet, and the radiological stage of RA according to Steinbroker was assessed. To determine the inflammatory activity, the DAS28-ESR and DAS28-CRP indices were calculated.Results and discussion. The study included 303 patients with RA, 25 (8.4%) of them had D2T RA. The duration of RA in the D2T group was significantly longer than in other patients (15.9±11.8 and 11.9±9 years, respectively; p=0.04). X-ray changes in the joints in D2T were more pronounced. Patients with D2T had higher inflammatory activity at the time of hospitalization than patients who had continued prior therapy with biologic/targeted synthetic DMARDs. The dose of glucocorticoids (GC) in patients with D2T RA was higher compared to patients of other groups: on average 8.3±5.1 and 6.4±2.9 mg/day, respectively (p=0.02).Conclusion. The results of this study suggest that in Russia, as well as abroad, the treat-to-target principle has not yet become widespread, and the selection of adequate therapy takes too much time. At the same time, Russian rheumatologists primarily use GC to suppress inflammatory activity. The introduction of modern recommendations for the management of patients with RA into routine clinical practice, could possibly restrain the formation of D2T RA.

Local methods are widely used in the treatment of osteoarthritis (OA) and play a significant role in the complex therapy of this disease. A special place among them belongs to intra-articular (i/a) administration of drugs. The most widely used for this purpose are glucocorticoids (GC) and hyaluronic acid (HA) drugs. When comparing the effectiveness of these drugs, it was shown that during the 1st month, HA had more favorable results, after 3 months the results did not differ significantly, and after 6 months, the effectiveness of HA was higher. Some authors believe that the optimal result can be obtained with the combined use of HA and GC.The efficacy and tolerability of HA drugs in patients with OA have been studied in numerous randomized controlled trials (RCTs), and the data obtained in these studies have been summarized in a number of meta-analyses. At the same time, both in RCTs and in meta-analyses, the results of such treatment were assessed differently. However, when summarizing the materials of various meta-analyses within the framework of a systematic review, it was shown that i/a injections of HA are an effective and safe method of local treatment of OA. However, there are no generally accepted recommendations for the use of HA in the treatment of OA, and the question of their administration in each case is decided individually, taking into account the history, clinical picture, OA phenotype, and tolerability of therapy. The Russian Association of Rheumatologists recommends the use of i/a HA injections in knee OA with synovitis and the use of HA injections to reduce pain and improve joint function.

The aim of the study was to assess the efficacy of intra-articular injection of lornoxicam (xefocam, Nycomed) in patients with rheumatoid arthritis. Xefocam was injected into knee joints of 15 patients with rheumatoid arthritis, 8 mg once a week for the period of 3 weeks. The following parameters were assessed: pronouncement of arthralgia, joint tenderness at palpation, circumference of knee joint on the level of the upper patellar margin. Prior and post treatment ultrasonography and thermography were used. Significant clinical improvement was observed in 11 patients. In 3 cases the dynamics was less positive and in 1 patients the effect of single dose drug injection was preserved for less than one week. Arthralgia manifestation (p0.01), joint tenderness at palpation (p0.01) and joint circumference (p0.05) showed reliable decrease. Ultrasonography showed reliable decrease the synovial membrane thickness. Xefocam injection could be successfully used to suppress moderate inflammatory joint changes in patients with rheumatoid arthritis when there are no strict indications to local steroid therapy.

Back pain can be caused by various etiological factors, and its development is mediated by various pathogenetic mechanisms. Anatomical structures that can participate in the formation of pain include muscles, fascia, ligaments, tendons, facet joints, intervertebral discs and vertebrae. Changes in the central pain modulation system are an important factor in the development of chronic low back pain (LBP). Accumulating evidence allows us to consider LBP not as a series of isolated unrelated episodes, but as a long-term condition with a variable course. In the practice of a rheumatologist, LBP can occur as a manifestation of the underlying disease or as a comorbid pathology on the background of rheumatic pathology. In this case, it may be difficult to determine the activity of the underlying disease and the effectiveness of the therapy.

Currently, a biosimilar (BS) of rituximab (RTM) Acellbia® is widely used in Russia for the treatment of rheumatoid arthritis (RA), however, a systematic study of this drug in routine clinical practice has not been conducted.Objective: to compare the results of the use of RTM BS (Acellbia®) and the original rituximab (oRTM) in the daily clinical practice of a large rheumatology center.Patients and methods. The study involved 127 patients predominantly with seropositive RA, who were divided into four groups. Groups 1 and 2 included 66 bionaive patients with active RA and ineffectiveness of previous therapy. 31 patients of the 1st group received 2 infusions of oRTM at a dose of 500 mg intravenously (IV) 2 weeks apart; 35 patients of the 2nd group – 2 infusions of RTM BS at a dose of 500 mg IV 2 weeks apart. Groups 3 and 4 included 61 patients who had previously received oRTM therapy. These patients received 4 courses of oRTM treatment on average before being included in the study. 30 patients of the 3rd group continued oRTM therapy: they received 2 infusions at a dose of 500 mg IV 2 weeks apart; 31 patients of the 4th group received 2 infusions of RTM BS at a dose of 500 mg IV 2 weeks apart.Results and discussion. During the observation period, the dynamics of the main indicators of RA activity in the 1st and 2nd groups did not differ significantly. Although the indication for rehospitalization was an exacerbation of the disease, 64.5% of patients in the 1st and 77.1% of patients in the 2nd group, preserved a 20% improvement according to the ACR criteria on re-examination. The condition of patients of the 3rd and 4th groups remained generally stable during the observation period. The change in the DAS28 index in most cases was clinically insignificant. There were no significant differences in the dynamics of inflammatory activity among patients who continued oRTM treatment and who received RTM BS.Conclusion. The results of the study show that both the prescription of RTM to bionaive RA patients and repeated courses of treatment with RTM BS and oRTM are comparable in terms of efficacy and tolerability.

Current trends in the development of personalized medicine dictate the need to interpret chronic pain as a multifactorial biopsychosocial phenomenon. A comprehensive integrated approach to the management of patients with chronic pain includes nosological diagnostics, assessment of factors that determine the persistence of pain and comorbid pathology, and the use of necessary pharmacological and non-pharmacological methods of treatment. Currently, primarily non-steroidal anti-inflammatory drugs are used for the pharmacotherapy of chronic pain, which is predominantly nociceptive in nature. Meloxicam (Movalis®), along with high efficacy, has a favorable safety profile and has proven itself in the treatment of chronic musculoskeletal pain. For chronic pain associated predominantly with neuropathy and central sensitization, the drugs of choice are tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitor duloxetine, the α2δ ligands pregabalin and gabapentin.

The widespread introduction into clinical practice of modern approaches to the treatment of rheumatoid arthritis (RA), the rational use of traditional and targeted antirheumatic drugs can effectively suppress inflammatory activity, restrain the progression of the disease and improve the quality of life of patients. At the same time, in some patients, even after the repeated change of targeted drugs, it is not possible to achieve the target level of RA activity. Serious difficulties arising in the management of such patients raised the question of identifying a special variant of the disease – difficult-to-treat (D2T) RA. The presence of various variants of D2T RA and the need to use a personalized approach to therapy justify the creation of special recommendations for the management of this category of patients. The first step in preparing these recommendations was the definition of D2T RA recently presented by the EULAR working group. It includes three criteria: 1) insufficient effectiveness of the therapy; 2) the presence of an active symptomatic disease; 3) clinical perception.

Objective: to study of the relationship between psychological factors and indicators of rheumatoid arthritis (RA) disease activity in patients who have been followed up for a long time after initiation of treat-to-target therapy.Patients and methods. The investigation enrolled 38 RA patients (29 women and 9 men) aged 33 to 80 years (mean age, 56.5±12.5 years) with a mean disease duration of 6.0±0.9 years. All the patients underwent clinical examination; the following parameters were recorded: patient global assessment; physician’s global assessment; pain visual analogue scale (VAS), by measuring in millimeters; number of painful joints (NPJ), and number of swollen joints (NSJ). The investigators determined functional status with the Health Assessment Questionnaire (HAQ), quality of life with the 36-Item Short Form Health Survey questionnaire (SF-36), the nature of pain by the painDETECT questionnaire (PDQ), and the presence of anxiety and depression with the Hospital Anxiety and Depression Scale (HADS). The patients also filled out the Resilience (Res) Questionnaire (RQ) and the General Self-Efficacy ((GSE) Scale. Disease activity was evaluated by DAS28, CDAI, and RAPID3 scores. Results and discussion. RA disease activity was high in 4 patients, moderate in 21, and low in 9, and 4 patients had DAS28 remission. The average scores of RQ, its individual components, and GSE scale were comparable with the corresponding population scores for this age group. The patients who had RQ scores below the average group ones were noted to have significantly higher scores of patient global assessment; physician’s global assessment, NPJ, NSJ, CDAI, and RAPID3 than in those who had moderate and higher RQ scores. The similar trend was traced for individual Res components, such as involvement (INV), control (CONT), and risk acceptance (RA). However, the revealed differences in these indicators failed to reach statistical significance. There was no correlation between the measures of inflammatory activity and the result of GSE. The patients with subclinical and clinical anxiety and depression had significantly lower RQ, INV, and CONT scores than those who did not have anxiety or depression, whereas RA and GSE did not differ significantly in these groups. There was a significant positive correlation of Res, INV, and CONT with the quality of life, as assessed by SF-36. The findings suggest that low RQ scores can decrease the efficiency of the therapy performed (due to the patient’s poor compliance), on the one hand, and can corrupt the result of inflammatory activity assessment (due to the impact on a patient’s perception of his/her illness), on the other hand.Conclusion. The findings may suggest that there is a need to assess the psychological status of a patient when determining the level of RA disease activity.

Assessing the status of a patient with rheumatoid arthritis allows one to obtain information necessary to choose appropriate management tactics for the patient. The use of quantitative methods in routine practice to determine inflammatory activity is the basis for the development of standardized patient management recommendations and provides a substantial improvement in the quality of health care. At the same time, the accumulated experience suggests that the existing summary indices do not always allow one to correctly determine disease activity. The paper discusses factors that can corrupt the result of assessment of inflammatory activity, as well as approaches to eliminating possible errors.

The World Health Organization assigns cardiovascular diseases, cancers, chronic respiratory diseases, as well as diabetes mellitus and some other nosological entities, including mental and musculoskeletal disorders, to main non-communicable diseases. These are considered to be a major public health challenge of the 21st century. In this case, one patient frequently has a set of several age-related chronic diseases that develop simultaneously or sequentially. The management of these patients requires an integrated approach based on the multimorbid nature of pathology. Unlike the definition of comorbidities, which assumes to identify the underlying and related diseases, the concept of multimorbidity of such gradations fails to provide and interprets a patient's chronic diseases as equivalent.

In a number of cases, systemic therapy for rheumatoid arthritis (RA), including disease-modifying anti-rheumatic drugs, biological agents, glucocorticoids (GCs), and nonsteroidal anti-inflammatory drugs, fails to completely suppress joint inflammatory changes in the patients. Therefore, local methods are widely used in the combination therapy of RA. Intra-articular injection of hyaluronic acid (HA) is a highly local treatment modality. HA can be used as initial therapy when it is necessary to achieve rapid clinical improvement, or at a later stage of the disease, in exacerbation of arthritis. However, in some patients the effect of intra-articular HA can be short-lasting, and a favorable result can be obtained with local radiotherapy. It is based on powerful irradiation of the inflamed synovium, which is provided by intra-articular injection of radioactive isotope colloids. In Russia, RA was successfully treated with colloidal Au-198, but its production was ceased in the 1990s, and agents for radioisotope synovectomy have been long unavailable.Tungsten-188/Rhenium-188generator has been recently designed in Russia, which allows Rhenium-188 to be obtained in clinics. Preclinical trials have shown that intra-articular injection ensures good fixation of the drug in the knee joint with its insignificant accumulation in the liver and other non-target organs and tissues. Introduction of this drug into routine clinical practice can markedly improve the efficiency of treatment in patients with chronic arthritis.

The chief complaint of patients with rheumatoid arthritis (RA) is pain. The latter is one of the main signs of chronic inflammation, which holds a central position in the clinical picture of the disease. Pain is not among the baseline parameters that are used to calculate total disease activity indices. Nevertheless, pain greatly influences the result of RA activity determination using the total indices. However, this assessment system can take into account only the intensity of pain, whereas the clinical significance of pain syndrome is largely determined by its nature. The causes of pain in RA can be different in different patients and even in one patient at early and late stages of the disease, during the periods of exacerbation and attenuation of the inflammatory activity. Pain in RA is not always associated with the active inflammatory process. At the same time, intense non-inflammatory pain can significantly affect the traditional indicators of inflammatory activity, by distorting the result of quantitative determination of disease activity. In turn, an erroneous activity assessment may cause an incorrect choice of treatment policy. Therefore, the clinical use of tools that reliably determine the nature of pain, can contribute to a significant improvement in the quality of care for RA patients. In most cases pain in RA is associated with inflammatory changes in joints or periarticular soft tissues. Therefore along with disease-modifying anti-rheumatic drugs, nonstreroidal anti-inflammatory drugs (NSAIDs) are widely used in the combination therapy of RA. However, their use is limited by a risk of adverse reactions. Etoricoxib is one of the highly effective drugs with a good safety profile. Currently, there are no recommendations for the treatment of neuropathic pain in patients with RA. Investigating the efficacy of tricyclic antidepressants and cannabinoids in RA has failed to prove their advantages over placebo.

The high anti-inflammatory activity and pronounced analgesic effect of nonsteroidal anti-inflammatory drugs ((NSAIDs) allow successful treatment for pain syndrome associated with many diseases, primarily rheumatic diseases. NSAIDs are the main agents used to relieve pain in osteoarthritis, lower back pain, and periarticular soft tissue diseases. They are also an essential component of combination pharmacotherapy for chronic arthritis. The therapeutic effect of NSAIDs is determined by the suppressed activity of the cyclooxygenase (COX) isoenzymes COX- 1 and COX-2. The widely use of NSAIDs in clinical practice is considerably limited by the risk of adverse reactions (ARs) in the gastrointestinal tract (GIT), which are characteristic for this class of drugs. Medications that are able to selectively inhibit the activity of COX-2 while maintaining that of COX-1 less rarely cause ARs in GIT. This selective effect is produced by aceclofenac. A number of clinical trials have demonstrated the high efficacy of this drug in treating various locomotor diseases. The drug has been also noted to be well tolerated: the risk for aceclofenac- induced ARs in GIT is substantially lower than that due to the use of the majority of other NSAIDs. Высокая противовоспалительная активность и выраженный анальгетический эффект НПВП позволяют с успехом использовать их при лечении болевого синдрома, связанного со многими заболеваниями, прежде всего ревматическими. НПВП являются основным средством купирования боли при остеоартрите, боли в нижней части спины, заболеваниях околосуставных мягких тканей. Они также представляют собой важнейший компонент комплексной фармакотерапии хронических артритов. Терапевтический эффект НПВП определяется подавлением активности изоферментов циклооксигеназы (ЦОГ) – ЦОГ1 и ЦОГ2. Возможности применения НПВП в широкой клинической практике существенно ограничены из-за риска характерных для препаратов этого класса неблагоприятных реакций (НР) со стороны желудочно-кишечного тракта (ЖКТ). Препараты, способные избирательно блокировать активность ЦОГ2 при сохранении активности ЦОГ1, реже вызывают НР со стороны ЖКТ. Таким избирательным действием характеризуется ацеклофенак. В ряде клинических исследований была продемонстрирована высокая эффективность этого препарата в лечении различных заболеваний опорно-двигательного аппарата. Отмечалась также его хорошая переносимость: при терапии ацеклофенаком риск возникновения НР со стороны ЖКТ был значительно ниже, чем при использовании большинства других НПВП.

Chronic pain in the spine is one of the most urgent medical problems. Clinical and instrumental studies fail to reveal that most patients with back pain have any structural changes that may contribute to its occurrence. It is considered that the pain may be caused by the strain of muscles and ligaments located in the lower back, by the overload of these segments, and by detraining. If the cause of the pain syndrome cannot be established, the pain in the spine is regarded as nonspecific. It is believed that behavioral, psychological, and social factors can play an important role in the development of pain. Therefore, current guidelines propose to apply a biopsychosocial approach in patients with back pain. At the same time, much attention is paid to patient self-treatment, exercise therapy, psychotherapy, and some other auxiliary methods. When nonpharmacological interventions are insufficiently effective, drug therapy is indicated. Nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, opioid analgesics, and muscle relaxants are used to treat nonspecific spinal pain. Pharmacotherapy is usually initiated with the use of NSAIDs. They can effectively relieve pain sndrome, but the possibilities of their use in a large proportion of patients are significantly limited due to adverse reactions (ARs). Gastrointestinal and cardiovascular ARs most commonly occur. The likelihood of ARs can be substantially reduced by the use of aceclofenac (AirtalR) that is characterized by a favorable gastrointestinal and cardiovascular safety profile. Paracetamol, opioid analgesics, and muscle relaxants are also used in the combination treatment of these patients.

Guidelines for the management of patients with rheumatoid arthritis (RA) envisage that its therapy should be intensified if it is insufficiently effective; at the same time, reduction of its intensity of treatment may be discussed when the set goal has been successfully achieved. The EULAR guidelines allow for dose reduction and even discontinuation of biological agents (BAs), especially when performing combination therapy with BAs and disease-modifying antirheumatic drugs (DMARDs). However, the strategy for this therapy change has not yet been sufficiently clearly defined. In this review, we would like to raise an issue regarding frank rather than early RA in patients with irreversible changes of the locomotor apparatus, who have received DMARDs and/or BAs for a long time. When remission is achieved, it is more difficult to reduce the dose of the drug or discontinue the latter in these cases than in early RA.

Rheumatoid arthritis (RA) is an immunoinflammatory (autoimmune) rheumatic disease of unknown etiology, which is characterized by chronic erosive arthritis and systemic visceral organ damage that results in early disability and shorter patient survival. Despite RA treatment advances associated with the design of novel drugs and the improvement of treatment strategies to achieve remission in many patients, there are still many theoretical and clinical problems concerning both the definition of the concept of remission, its characteristics and types and approaches to the optimum policy of symptomatic and pathogenetic drug therapy at different stages of the disease, the use of which will be able to rapidly induce and maintain remission in the long-term. Further investigations are needed to study the nature of heterogeneity of pathogenetic mechanisms of RA and approaches to early diagnosis, to improve methods for monitoring disease activity and biomarkers for the efficiency of and resistance to therapy and, finally, to develop differentiation therapy, including those related to a search for new therapeutic targets.

The high anti-inflammatory activity and pronounced analgesic effect of nonsteroidal anti-inflammatory drugs ((NSAIDs) allow successful treatment for pain syndrome associated with many diseases, primarily rheumatic diseases. NSAIDs are the main agents used to relieve pain in osteoarthritis, lower back pain, and periarticular soft tissue diseases. They are also an essential component of combination pharmacotherapy for chronic arthritis. The therapeutic effect of NSAIDs is determined by the suppressed activity of the cyclooxygenase (COX) isoenzymes COX- 1 and COX-2. The widely use of NSAIDs in clinical practice is considerably limited by the risk of adverse reactions (ARs) in the gastrointestinal tract (GIT), which are characteristic for this class of drugs. Medications that are able to selectively inhibit the activity of COX-2 while maintaining that of COX-1 less rarely cause ARs in GIT. This selective effect is produced by aceclofenac. A number of clinical trials have demonstrated the high efficacy of this drug in treating various locomotor diseases. The drug has been also noted to be well tolerated: the risk for aceclofenac- induced ARs in GIT is substantially lower than that due to the use of the majority of other NSAIDs.