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This review presents the latest data on the long-term use of the selective Janus kinase inhibitor (JAKi) baricitinib (BARI) in patients with rheumatoid arthritis (RA) in real-world clinical practice. The results of long-term use (up to 9.5 years) of BARI in RA suggest that its efficacy is comparable or even superior to that of biologic disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib, while the drug is more effective in patients who have not previously received bDMARDs or JAKi. It has been shown that the BARI dose can be reduced to 2 mg/day once the treatment goal has been reached in most patients without a decrease in efficacy, and that exacerbations that have occurred after reduction of the dosage (or treatment interruption) are relieved when returning to the full dose of the drug. According to data from registries from many countries and open observational studies, BARI is well tolerated during long-term use, even in elderly patients with ≥1 risk factor for cardiovascular disease. A high survival rate with BARI therapy has also been observed, which according to some registries exceeds that of tumor necrosis factor α inhibitors. Against the background of BARI therapy, a rapid (within 1 to 3 months) statistically significant reduction in pain has been demonstrated, regardless of the degree of suppression of disease activity, which correlates with an improvement in the functional status and general condition of patients. The possibility of suppressing the progression of structural damage in patients with RA was also demonstrated, allowing the choice of individualized tactics for the management of such patients.

Background. According to epidemiological studies, chronic musculoskeletal pain affects more than 30% of people worldwide, causing a huge personal and social burden. Nonsteroidal anti-inflammatory drugs are widely used to treat musculoskeletal pain. The drug etoricoxib, highly selective for COX-2, is characterized by linear pharmacodynamics, that is, its effect directly depends on the dose, and the wide range of doses registered for use (from 30 to 120 mg per day) makes it possible to effectively suppress both acute and chronic pain with various diseases.Results. This review provides information on the use of etoricoxib in osteoarthritis, particularly of the knee or hip, including in elderly patients; in the treatment of low back pain, one of the most common causes of decreased productivity worldwide; in the treatment of rheumatoid arthritis and ankylosing spondylitis, as well as gout. It has been shown that the selective COX-2 inhibitor etoricoxib has pronounced anti-inflammatory and analgesic activity and has a number of undeniable advantages not only over non-selective COX-1 and COX-2 inhibitors, but also over selective COX-2 inhibitors, being the most highly selective among them. The drug has the same pharmacokinetic parameters in both young patients and the elderly, which simplifies its administration to patients in older age groups, and, in addition, etoricoxib is rapidly absorbed when taken orally. Important characteristics of etoricoxib include its safety in relation to the gastrointestinal tract. The availability of a range of therapeutic doses of etoricoxib makes it possible to effectively treat acute and chronic pain in various diseases affecting the structures of the musculoskeletal system and perioperative pain.

Local injection therapy (LIT) is an important component of the complex treatment of musculoskeletal disorders (MSD), which is widely used in real clinical practice. Glucocorticoids, hyaluronic acid drugs (HA), autologous cell drugs, botulinum toxin type A, radioactive isotopes, etc. are used for LIT. LIT makes it possible to achieve a pronounced symptomatic effect, while in some cases, for example, repeated HA treatments in patients with osteoarthritis, the possibility of slowing the progression of the disease and reducing the need for surgical treatment is discussed.The performance of LIT requires special skills and abilities of the physician, careful compliance with the rules of asepsis and antisepsis, and instrumental visualization. LIT can be associated with serious complications and therefore must be performed according to strict indications.The Expert Council was devoted to defining the basic principles of LIT. The indications for the use of certain types of this therapies, the evidence base for its efficacy and safety, the order of application of different drugs, and the need to combine LIT with other drug and non-drug treatments of MSD were reviewed.

The present study considers a care of a 42-year old female patient with a severe variant of rheumatoid arthritis and extra-articular manifestations. The debut clinical symptoms included polyarthritis, fever, and anemia. On selection of a basic therapy, intolerance (leucopenia, flu-like syndrome) and inefficiency of treatment regimen have been revealed. Administration of a genetically engineered biological drug resulted in the development of tuberculosis and the patient required a long break in the biotherapy for a specific treatment course. The use of anti-TNF agents is associated with an increased risk to tuberculosis and anti-TNF agents are stopped when active tuberculosis develops. However, discontinuation of treatment results in a flare of the underlying disease. The rituximab therapy was initiated because the clinicolaboratory activity was high. Due to the strategy “Treat to Target”, the patient reached improvement by classification criteria and clinical and laboratory remission. The use of high doses of glucocorticoids during the patient’s planning pregnancy led to the development of secondary osteoporosis with spontaneous fractures of pelvic bones and ribs, expressed progression of erosive process, deformations of small and large joints. Specific features of the course of disease with formation of a severe progressing form of rheumatoid arthritis and the conducted treatment were considered from the point of view of difficulty in the selection of therapy when rheumatologists had a limited arsenal of drugs. The risk of re-onset of tuberculosis infection mandates careful follow-up.

Osteoarthritis (OA) is the most common joint disease due to the increasing life expectancy of the world's population. Every 2nd patient over the age of 50 suffers from knee or hip OA, and this is directly related to the increased burden on healthcare. Accumulated data on the comorbid profile of patients with OA dictate the need to identify disease phenotypes in order to provide personalized care. Individual clinical manifestations of OA also require a differential approach: the pain treatment requires consideration of the patient's psycho-emotional profile and the possibility of involving nociceptive pathways in the process. However, due to the ambiguity of existing clinical guidelines, most experts note a number of difficulties in prescribing treatment for patients with OA.The resolution presents an agreed opinion of experts on the algorithms for managing patients with OA, starting from the primary level, with the gradual involvement of related specialists. Some issues of a personalized approach are considered depending on the presence of comorbid pathology and the severity of individual symptoms of the disease. The prospects of the combined use of pharmacological and non-drug methods of treatment are noted; emphasis was placed on the importance of rehabilitation measures at the first level of medical care, provided to patients with OA, long before the development of structural changes.The proposed algorithms for managing patients can be considered as the basis for future recommendations for managing patients with this pathology.

The article presents modern recommendations for the use of systemic administration of glucocorticoids. It is indicated that there is a clear tendency to minimize the doses and timing of the appointment of systemic glucocorticoids in rheumatoid arthritis, and in seronegative spondyloarthropathies (ankylosing spondylitis, psoriatic arthritis), in accordance with both foreign and domestic recommendations, systemic therapy with glucocorticoids is not carried out. It is emphasized that at the present stage, the role of local administration of glucocorticoids will increase as an effective way to reduce the activity of arthritis in any nosologically form. The mechanisms of action of locally administered glucocorticoids leading to anti-inflammatory and analgesic effects are described. The comparative characteristics of locally administered glucocorticoids with different duration of action according to their effectiveness and safety are presented. Predictors of the effectiveness of local therapy with glucocorticoids are described. The data on the evaluation of the duration of the anti-inflammatory and analgesic effects of various local glucocorticoids, including in comparison with the intra-articular administration of hyaluronic acid preparations, which showed the advantages of betamethasone over triamcinolone acetate, are presented. The differences in the crystal structure of betamethasone and triamcinolone acetate are described. It is indicated that the 2.5-fold smaller size of betamethasone crystals compared to triamcinolone acetate crystals and the absence of betamethasone crystals makes it possible to use betamethasone in the treatment of inflammatory processes in periarticular tissues, as well as in crystalline arthritis (gout, pseudogout). The data on the safety of the use of intra-articular injection of glucocorticoids are presented. It is indicated that the registration in the Russian Federation of a new form of betamethasone in pre-filled syringes makes it even more possible to avoid infectious complications of this type of therapy. Rare cases of complications of local therapy with glucocorticoids are described.

The article discusses various options for the management of patients with rheumatoid arthritis (RA) in accordance with modern foreign and domestic recommendations. Data on the possibility of achieving an effect on the background of monotherapy with methotrexate (MT) are presented and options for more active therapy are discussed. The authors compare the effectiveness of sequential change of basic anti-inflammatory drugs (DMARDs), sequential addition of DMARDs to MT, treatment with a triple combination of DMARDs with an inadequate response to MT or in the debut of therapy, combination of DMARDs and biological drugs. According to the study data, in cohorts of patients with equal clinical effectiveness of the triple combination of DMARDs and the combination of DMARDs with biological drugs, however, the severity of the progression of destruction in the joints of the hands and feet is less when using biological agents. It was noted that the evaluation of the effectiveness of the double / triple combination of DMARDs was carried out in open observational studies, which has less evidence value than randomized controlled double-blind placebo-controlled trials (RCTs) for the assessment of biological drugs. Despite the importance of implementing biological drugs in clinical practice, their high cost limits their use by patients. Registration in the Russian Federation of the first biosimilar of etanercept (ETN) - the drug Erelzi is important for the treatment of patients with RA. The article describes the advantages of original ETN (tumor necrosis factor ainhibitor - iFNO a) over other iFNO a, which are monoclonal antibodies to this cytokine. The article presents data on the equivalence of the ETN biosimilar registered in the Russian Federation (Erelzi) with the original ETN in terms of clinical efficacy, safety and immunogenicity. The comparability of drugs in terms of the frequency of adverse events was demonstrated. It is shown that switching from the original ETN to its biosimilar allows you to maintain the effect, not accompanied by an increase in the frequency of intolerance or immunogenicity. It is indicated that Erelzi is registered in the Russian Federation for the treatment of RA, various variants of axial spondylitis, psoriatic arthritis, psoriasis and juvenile idiopathic arthritis.

The article provides data on the place of methotrexate in accordance with international and national recommendations 2019– 2020 in the management of patients with rheumatoid and psoriatic arthritis. Data on the prevalence of these diseases, the effectiveness and tolerability of methotrexate according to randomized controlled and cohort studies are presented. The advantages of the subcutaneous form of methotrexate in terms of efficacy and tolerability for both rheumatoid and psoriatic arthritis are discussed. Data on the tolerance of the subcutaneous form of methotrexate from various manufacturers are presented.Analysis of literature data and the results of our own research indicate the need for early prescription of methotrexate in patients with rheumatoid arthritis and patients with peripheral joint lesions in psoriatic arthritis.Numerous studies confirm the effectiveness of methotrexate in rheumatoid arthritis in relation to the symptoms of the disease, both articular and non-articular, structural damage (slowing down X-ray progression), which is accompanied by an improvement in the patient’s functional abilities. With psoriatic arthritis, methotrexate is able to reduce the activity of arthritis, enthesitis, reduce skin manifestations, and improve the functional state of the patient. Treatment with methotrexate, when the clinical effect is achieved, is accompanied by a decrease in cardiovascular complications in inflammatory lesions of the joints.

Objective: to evaluate the efficacy and safety of glycosaminoglycan-peptide complex (GPC, Rumalon) used in patients with knee osteoarthritis (OA) and comorbidities (hypertension and/or type 2 diabetes mellitus (T2DM).Patients and methods: A 10-month multicenter (13 centers from 10 subjects of the Russian Federation) prospective study included 179 patients with Stages II–III primary tibiofemoral knee OA and comorbidity, a walking pain intensity of ≥40 mm on a visual analogue scale (VAS), and a need for nonsteroidal anti-inflammatory drugs (for at least 30 days in the previous 3 months). The efficiency of treatment was evaluated from the changes in VAS scores for knee pain intensity during walking, the overall WOMAC score and scores of its individual indicators, laboratory parameters, and ultrasound data. All the patients received 2 cycles of GPC treatment with 25 injections, by following the manufacturer's instructions.Results and discussion. Even at 2 months after starting the treatment, there was a statistically significant reduction in pain during walking from 60 (50–69) to 40 (27–53.5) mm on the VAS (p< 0.05), which persisted during the follow-up period. A similar pattern was found when assessing the WOMAC index and its components. The drug demonstrated an anti-inflammatory effect: a decrease in the number of patients with synovitis from 55.7 to 39.2% (p=0.02), the level of high-sensitivity C-reactive protein (hsCRP) from 3.2 (1.3–6.2) to 2.6 (1.2–5.7) mg/l (p< 0.05). GPC was ascertained to have a safety profile.Conclusion. The data of this study confirm the good therapeutic effect and safety of GPC Rumalon in knee OA patients with hypertension and/or T2DM. The drug is shown to have a rapid analgesic and anti-inflammatory effect, as well as a positive influence on all clinical manifestations of OA.

The article discusses the social significance of osteoarthritis as a widespread disease that develops mainly in older people, which makes it difficult to carry out anti-inflammatory and analgesic therapy due to the frequent combination of osteoarthritis with other diseases at this age, the need to treat comorbid conditions, which is often poorly combined with systemic therapy with non-steroidal anti-inflammatory drugs. It is noted that osteoarthritis not only worsens the quality of life of patients, but also leads to a decrease in the length of their life, which emphasizes the medical and social importance of conducting the safest possible therapy for this disease. Data on the negative impact of the presence of chronic pain on the progression of osteoarthritis are presented. The negative aspects of the use of oral forms of non-steroidal anti-inflammatory drugs are discussed: the development of adverse events primarily from the gastrointestinal tract and cardiovascular system, the negative effect on the synthesis of glycoaminoglycans («chondronegative effect»). Discusses the place of topical forms of NSAIDs in the treatment of patients with osteoarthritis in accordance with the recommendations of the International society for the use of topical forms of NSAIDs in the management of patients with osteoarthritis of large and small joints. Data on transdermal transport of the topical form of diclofenac, a small molecule with lipophilic properties, are presented. Data on the effectiveness of topical forms of diclofenac in comparison with oral forms are presented according to numerous randomized controlled trials, and the comparable effectiveness of both forms of diclofenac is demonstrated, with maximum safety of the topical form. A special structure of Voltaren® Emulgel (Voltaren® Emulgel), combining the properties of a gel and cream, which provides rapid transdermal penetration and longer retention of the active substance in the area of inflammation, is described, as well as a special prolonged form of Voltaren® Emulgel), which creates additional convenience for use.

The data given in the article is in accordance with the latest recommendations of ESCEO years 2016, 2019 in regard to possibilities of the sympthom-modifying and structure-modifying action of chondroitin sulfate in the treatment of patients with osteoarthritis. There is the data on the therapy effect when treating patients with osteoarthritis and with periarticular tissues damage with chondroitin sulfate injections (Alflutop, Biotehnos) having strong evidence base, including randomized placebo-controlled studies. In the randomized study it is shown reliably high effectiveness of Alflutop against placebo in regard to main clinical manifestations of the desease as well as possibility to slow down progress of the destructive processes at osteoarthritis of the knee-joint. The data given on estimation of effectiveness and safety of alternate introduction of Alflutop at osteoarthritis 2 ml intramuscularly every other day (10 injections) compared with a standard mode of use of Alflutop 1 ml intramuscularly every day for 20 days. Equal effectiveness of the two modes of Alflutop introduction is demonstrated subject to good tolerance of the drug. Ability of Alflutop to supress the mediators of inflammation, such as interleukins 6 and 8, and degradations at osteoarthritis, as well as to stimulate the proliferation and renewal of chondrocytes is shown according to the results of an international experimental study, explaining its ability to cause a quick analgesic and anti-inflammatory effect. Alflutop inhibits in vitro extracellular release of the pro-inflammatory cytokine interleukin 6 (IL-6) for 16 per cent and chemokine IL-8 for 35 per cent, inhibits pro-angiogenic factor VEGF for 56 per cent, has an antioxidant effect, which contributes to the synthesis of cartilage macromolecules, a decrease in the activity of matrix metalloproteases (MMPs), a decrease in the concentration of prostaglandins and leukotrienes, and a decrease in chondrocyte apoptosis. The data on the effectiveness of the Alflutop injection course in case of damage to the periaticular tissues in the shoulder, elbow, knee joint is given. The data on the gastroprotective effect of the drug, demonstrated in experimental and clinical studies is given.

The lecture covers main approaches to differential diagnosis in rheumatic diseases. It highlights the key questions that should be answered at the primary examination of the patient. The most important signs that can identify severe, sometimes urgent nonrheumatic diseases are presented. The author describes pain of different patterns and intensity and the most common variants of acute or chronic onset of mono-, oligo-, or polyarthritis. The 2016 European League Against Rheumatism (EULAR) definition of arthralgia suspicious for the development of rheumatoid arthritis is given. The lecture presents the signs indicating the inflammatory nature of back pain in cases of suspected spondyloarthritis (SpA), as well as a two-step diagnostic strategy for axial SpA. Attention is paid to the semiotics of joint damage and extra-articular manifestations in various rheumatic diseases. A brief algorithm for a differential diagnostic search for joint pain is given.

The question about the peculiarities of the course of rheumatoid arthritis in different age periods was raised in the literature repeatedly and the answer depended on the period of development of rheumatology and was not unambiguous. The course of age-specific features of the initial stages of disease development has also been studied (although less frequently). At the same time, the issues of age-related features of as yet untreated early rheumatoid arthritis have not been previously presented in the literature studied by the authors. This article gives a brief overview of the problem and discusses the findings.The aim of the present study was the comparative study of the characteristics of untreated early rheumatoid arthritis with early (18–49 years) and late (50 years and older) onset.The material was represented by 292 patients with rheumatoid arthritis with disease duration from 1 to 12 months from the disease onset, entered into the All-Russian Register of Patients with Inflammatory Arthritis “OREL” in the period from January 01, 2012 to December 31, 2018 with the results of examination at the time of the first examination. All patients were naïve to treatment with basal (synthetic, biological or other targeted) drugs and systemic glucocorticoid therapy. In 141 patients, the disease started at a younger age, group 1 (18–49 years), and in 151, at an older age (50 years or older), group 2.Methods. Disease activity (according to DAS-28 index), radiological stage – (according to Steinbroker, modified), functional disorders – according to functional class, immunological characteristic and additional immunological characteristic (rheumatoid factor, cyclic citrullinated peptide antibodies) and other parameters were estimated in accordance to requirements of current national rheumatoid arthritis classification. The results of the study indicate that the disease in older age is characterized by more pronounced inflammatory, destructive changes in relation to the joint apparatus and functional disorders than the onset of rheumatoid arthritis at a young age.

According to modern ideas, pain is a multidisciplinary problem with serious medical and socio-economic importance. The most common pain occurs in various structures of the musculoskeletal system. It is noted that the universal mechanism of acute and chronic pain is inflammation, which requires therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). Data on the effectiveness and good tolerability of local NSAIDs are presented. The latest recommendations of the international Committee ESCEO 2019 on the management of patients with osteoarthritis (OA), which confirms the effectiveness and safety of local forms of NSAIDs, in connection with which, ESCEO recommends their use in elderly patients, in patients with comorbid conditions and at high risk of adverse reactions. It is also envisaged to use these drugs for the treatment of OA before the appointment of systemic NSAIDs. The results of randomized clinical trials (RCTS) and meta-analyses confirming clinical efficacy and safety in the treatment of acute and chronic pain by one of the representatives of local NSAIDs-diclofenac sodium gel are presented. Diclofenac sodium gel has been shown to be more effective than placebo in the treatment of acute and chronic pain. Good tolerability of the drug was observed in patients in different age groups, including patients older than 65 years, and in patients with comorbid conditions. The results obtained indicate the effectiveness and good tolerability of diclofenac sodium gel, including long-term, and allow the drug to be widely used as symptomatic therapy for the treatment of acute and chronic pain, including in elderly patients and patients with comorbid conditions.

The paper presents the results of the Osteoarthritis (OA) Expert Council held on September 8, 2019, which was attended by Russian and foreign specialists. The experts considered pharmacological treatment options for OA. The expert meeting resolution states that the treatment of patients with OA should be based on an individual assessment of the patient and on a modern evidence base of therapy efficacy.Treatment of patients with OA is based on the principles of evidence-based medicine that requires an integrated approach and the need of SYSADOAs prescription. Combined drugs with therapeutic dosages of chondroitin sulfate and glucosamine in the early stages of the disease are available as basic agents. The place of paracetamol in the anesthetic therapy algorithm in OA needs to be clarified. It is also noted that when choosing nonsteroidal anti-inflammatory drugs for OA treatment, it is important to take into account individual patient characteristics and the presence of comorbidities.

Objective: to analyze therapy with rituximab (RTM) in real clinical practice according to the data available in OREL registry of patients with active rheumatoid arthritis (RA).Subjects and methods. The analysis included 349 patients. All the patients received RTM: 340 – the original drug (MabThera®) and 9 – the biosimilar Acellbia®. 263 patients (75.4%) received RTM in combination with disease-modifying anti-rheumatic drugs (DMARDs) and 86 (24.6%) – RTM as monotherapy.Results and discussion. Of the 349 patients included in the analysis, 272 (77.9%) patients received RTM as the first biologic agent (BA) (263 patients were treated with the original drug and 9 – with the biosimilar) and 77 (22.1%) patients had previously used the BA. The majority of patients (n=205 (58.7%)) received three or more; 109 (31.2%) patients – one, and 35 (10%) – two RTM courses of RTM therapy. RTM caused a significant reduction in disease activity just after the first therapy course and in the levels of acute-phase reactants (C-reactive protein (CRP) and ESR); after the fifth therapy course, median CRP concentration decreased by 1.4 times and amounted to 7 [1.2; 17.9] mg/l and that of ESR reduced by 1.8 times and was 10 [5; 20] mm/hr (p

The article presents the data of international and domestic controlled studies, in which the effectiveness of topacitinib in the period of 6-24 months is evaluated in respect of clinical and laboratory manifestations of RA activity, progression of destructive arthritis and functional ability of rheumatoid arthritis patients. Also the data of efficiency and safety of tofacitinib in long terms - up to 96 months - are given. According to the results of short- and long-term studies, tofacitinib is a highly effective drug for the treatment of patients with active RA who have not responded to standard therapy with UCVD and GIBP. Tofacitinib is also highly effective in monotherapy. Tolerability of the drug is comparable with other variants of RA treatment.

Objective: to evaluate the clinical efficacy of the rituximab biosimilar Acellbia® at a dose of 600 mg intravenously at a 2-week interval in patients with active rheumatoid arthritis (RA) 12 and 24 weeks after initiation of treatment.Subjects and methods. Examinations were made in 20 active seropositive RA patients who had not been previously treated with biological agents (BAs), but received two infusions of the rituximab biosimilar Acellbia® at a dose of 600 mg intravenously at a 2-week interval during stable therapy with methotrexate (MT) and glucocorticoids (GCs). The European League Against Rheumatism (EULAR) response criteria (Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index) and the American College of Rheumatology (ACR) criteria were used to evaluate the efficiency of Acellbia® therapy. Disease remission was identified by DAS28 and 2011 ACR/EULAR criteria. The safety profile (the frequency of all reported adverse events) corresponds to the data on the safety of rituximab (MabThera®).Results and discussion. At the time of inclusion, median DAS28 was 5.6 [4.9; 6.8], SDAI – 27.1 [23.0; 39.9], and CDAI – 26.6 [22.2; 37.0]. At week 12 after initiation of Acellbia® therapy, they decreased to 4.2 [3.24; 4.75], 14.4 [8.5; 20.7], and 13.2 [7.9; 19.0] respectively, which remained at 24-week follow-up (p

The paper gives data on the efficacy and safety of tumor necrosis factor-α(TNF-α) inhibitors used in first- and second-line therapy. It describes options to optimize treatment with TNF-αinhibitors in first-line therapy, by increasing the dose, which is accompanied by the greater effect only with infliximab; by changing the dose of concomitant disease-modifying antirheumatic drugs, primarily methotrexate (MTX), the use of which increases the probability of achieving the effect of TNF-αinhibitors, the magnitude of the effect rises with the larger doses of MTX or with its parenteral formulation. There are data on the effectiveness of switching from the first TNF-αinhibitor to the second TNF-αinhibitor or to a biologic agent with another mechanism of action.

The possibilities of rheumatoid arthritis therapy have been significantly expanded today. In addition to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologic agents (BAs), and a targeted synthetic DMARD, a control treatment strategy has been put into practice.The paper demonstrates successes in the early prescription of csDMARD and the implementation of treat-to-target principles – to achieve the goal after 6 months in 50% of patients receiving subcutaneous methotrexate and 45% of those using a Leflunomide generic. During this therapy, there is a lower need for BAs and targeted synthetic DMARDs. The priority problem is to train general practitioners in methods for the early detection of RA and to set up schools for these patients.

In accordance with international and Russian guidelines for the management of patients with rheumatoid arthritis (RA), after its diagnosis, a synthetic disease-modifying antirheumatic drug is prescribed, among these drugs, methotrexate is anchor and, when the latter is impossible to use, leflunomide is commonly administered. Objective: to evaluate the efficacy and safety of a leflunomide generic (Elafra) during a multicenter follow-up. Subjects and methods. The investigation enrolled 347 patients aged over 18 years who met the 2010 ACR/EULAR criteria for RA, had its duration of less and more than 2 years, signed informed consent, and followed up in 29 centers of Russia. Elafra was prescribed at a saturating dose of 100 mg for the first 3 days, then 20 mg/day. There might be a temporary two-fold reduction in the dose when adverse events (AE) occurred. The patients were examined before and 4, 12 and 24 weeks after beginning leflunomide treatment. The treatment efficiency was evaluated with DAS28 and CDAI and by the physician global assessment. Results and discussion. The patients were divided into two groups: 1) 125 patients with RA of less than 2 years’ duration and 2) 222 patients with RA of more than 2 years’ duration. The mean age of patients in Group 1 was 48.7±12.9 years; that in Group 2 was 52.5±11.95 years; the mean disease duration was 11.9±7.8 and 90.99±54.28 months, respectively. During 24-week treatment, there was a highly significant decrease in all assessed clinical, laboratory parameters and indices of RA activity in both groups. At 4 weeks of treatment, the effect was observed in 91.8% of the patients in Group 1 and in 84.6% in Group 2, whereas at 12 weeks the effect was noted in almost all patients (99.1% and 96.9% in Groups 1 and 2, respectively). The highest rate of AE during Elafra therapy was recorded in the early periods: at 4 weeks, AE were noted in 6.5% of the patients in Group 1 and in 9.9% in Group 2, without needing to discontinue the drug. Treatment continuation decreased the rate of AE. Because of its intolerance, Elafra was discontinued due to in one case in Group 1 (diarrhea at 24 weeks of treatment) and in 6 cases in Group 2 (at 12 and 24 weeks of treatment). Conclusion. Treatment with leflunomide (Elafra) leads to the rapid development of its effect in early and late RA in most patients and is characterized by a good tolerability.

The clinical picture of the symptomatic phase of antineutrophil cytoplasmic antibody-associated systemic vasculitis (ANCA-SV) can vary widely and be accompanied by joint damage, which complicates the early diagnosis of the disease. The paper presents a case of ANCA-SV with acute kidney injury, the manifestations of the symptomatic phase of which were confined to joint damage, myalgia, and Raynaud's syndrome, which led to delayed diagnosis at the stage of renal failure requiring hemodialysis (HD). Urgent adequate induction therapy could preserve kidney function, despite 10-day anuria and 5-week HD.The paper discusses the need for a systematic detailed examination of patients with the onset of a joint inflammatory lesion, especially in those with its systemic manifestations, and the inclusion of serum ANCA tests in the standards of diagnosis in early arthritis.

In 2015, the experts from various medical associations of Russia elaborated the clinical guidelines “Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in clinical practice”. These guidelines were drawn up to improve the use of NSAIDs, our country’s most popular agents to treat pain in acute and chronic diseases. The main purpose of this paper was to reduce the frequency of potentially dangerous class-specific adverse events (AE) that may arise from the use of NSAIDs. To do this, the authors proposed a NSAID choice algorithm based on the assessment of risk factors for AE, the individual characteristics of various representatives of this drug group, and the possibility of prevention of AE.Since then, new data on the efficacy and safety of NSAIDs have been obtained. This has necessitated the revision and addition of a number of provisions in the 2015 guidelines. It seems that the new version of the guidelines, which has been drawn up based on the analysis of a large number of clinical and epidemiological studies, their meta-analysis, by taking into account the clinical experience and opinion of the world’s leading experts, presents more fully the main aspects of the use of NSAIDs in real clinical practice.The guidelines are intended for physicians of all specialties.

Glycosaminoglycan-peptide complex (GPC) (Rumalon®) is an injectable slow-release anti-inflammatory agent (SRIA) that has complex anti-inflammatory and metabolic effects. GPC has been successfully used in the treatment of osteoarthritis (OA) for several decades. The agent now returns again to Russian clinical practice. Objective: to evaluate the efficacy and tolerability of GPC in patients with knee OA, in whom other SRIAs have been previously ineffective.Subjects and methods. A study group consisted of 104 patients (92.3% women) (mean age, 63.2±8.5 years; body mass index (BMI), 28.5±5.4 kg/m2) with severe joint pain (≥40 mm on a 100-mm visual analogue scale (VAS)) and/or the need to regularly use nonsteroidal anti-inflammatory drugs (NSAIDs). All the patients received oral SRIAs in the last 6 months and had no improvement. At baseline, VAS pain intensity was 59.4±13.1 mm; the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain was 227.3±90.8; WOMAC stiffness, 97.9±42.1; WOMAC function, 769.2±326.1; total WOMAC scores, 1095.1±426.6. GPC was used by the standard scheme: 25 intramuscular injections every other day per treatment cycle; the results of treatment were assessed at 8 and 12 weeks by VAS and WOMAC pain scores, needs for NSAIDs, satisfaction with treatment (measured on a 1- to 5-pont scale where 1 = no improvement or deterioration and 5 = the best result).Results and discussion. At 8 and 12 weeks, VAS pain scores decreased by 30.1±18.3% and 36.9±16.9%, respectively; the reductions in WOMAC pain scores were 29.8±16.3 and 38.2±23.4%; WOMAC stiffness scores, 29.2±15.4 and 31.6±17.4%; WOMAC function scores, 27.7±14.7 and 30.6±18.4%; and total WOMAC scores, 27.2±13.5 and 33.6±18.0%. The changes in pain intensity and WOMAC scores were statistically significant in both followup periods (p

The article presents the current international and domestic guidelines for the management of patients with osteoarthritis. We discuss the possibilities of pain reduction in OA, the effects of slow drugs on the structures of the joint, the place the combination of chondroitin sulfate and glucosamine in treating OA.

The article discusses experimental data that demonstrated the ability of Aflutop to stimulate proliferation and regeneration of chondrocytes, to inhibate in vitro extracellular release of IL-6 cytokine and IL-8 chemokine compared to control cells, to inhibit VEGF, a proangiogenic factor, a biochemical proactive factor in destructive processes of OA, as well as the proven existence of the antioxidant activity of Alflutop. The data of numerous clinical studies (including the double blind placebo-controlled) show that it has an expressed analgesic effect, developing in the first weeks after administration in osteoarthritis patients, including with periarthrites, osteochondrosis, with back pain of different genesis, and the existence of the anti-inflammatory effect and a positive impact on the quality of life of osteoarthritis patients. At a high evidentiary level, the structural modifying effect of Alflutop and its safety is confirmed.

The paper highlights data on the mechanisms of action and efficacy of aceclofenac in chronic inflammatory diseases of the joint and spine (rheumatoid arthritis, spondyloarthritis) and osteoarthritis (OA). It shows the comparable efficacy of aceclofenac and nonselective nonsteroidal anti-inflammatory drugs in different rheumatic diseases. Randomized controlled trials and meta-analyses have revealed the high gastrointestinal safety of aceclofenac, which is comparable with that of celecoxib, including the low risk of gastrointestinal bleeding. Since aceclofenac has no negative effect on the articular cartilage and has a good tolerability, it may be given to persons of any age, including long-term use, which does not affect the safety of treatment.

The paper discusses whether the effect of different biological agents (BAs) can be achieved in patients with active rheumatoid arthritis (RA) when they inadequately respond to therapy with tumor necrosis factor-α (TNF-α) inhibitors. It gives data on the efficacy of BAs with another mechanism of action (abatacept, tocilizumab, and rituximab) and on the comparable efficacy of golimumab (GLM) in this group of patients. It is shown that the effect of GLM therapy does not depend on the reasons for discontinuation of a previously used TNF-α inhibitors (inefficacy, adverse events, etc.). It is conclusion that GLM is effective after failure of one or two TNF-α inhibitors.

The most common reason for a patient to contact a doctor is the pain accompanying about 70% of all known diseases. The article introduces the basic principles for treating acute and chronic pain. The role of inflammation in pathogenesis of acute and chronic pain is shown. It provides information on the effectiveness and safety of a non-steroid anti-inflammatory drug (NSAIDs) Nimesulide in the treatment of acute and chronic pain. Information is provided on the variety of Nimesulide mechanisms that allow it to be used in various rheumatic diseases as well as in other areas of medicine. The results of clinical research and analyses are presented that confirm the high efficiency and good tolerability of Nimesulide. The years of experience in the application of the granular form of Nimesulide (Nimesil®) by domestic clinicians indicate a high rate of development and a expressed anagesic, anti-inflammatory effects combined with good tolerability, which makes it possible to use the drug successfully in treating acute and chronic pain.

Widespread osteoarthritis (OA) and high related disability rates determine not only the medical, but also socioeconomic significance of this disease. In recent years there has been a tendency to increase the incidence of OA. According to the current concepts, inflammation plays a leading role in the development of chronic pain in OA, which requires adequate anti-inflammatory therapy. There are data on the diverse mechanisms of action of the nonsteroidal anti-inflammatory drug (NSAID) nimesulide and results from clinical trials and metaanalyses, which confirm its efficacy and good tolerability. Several clinical trials covering 22,938 patients with OA have indicated that the overall frequency of adverse reactions (AR) from nimesulide is 8.2%. There is evidence on the efficacy and good tolerability of topical NSAIDs, as well as combination drugs containing glucosamine sulfate and chondroitin sulfate, the use of which together with oral drugs enhances the efficiency of treatment without increasing the risk of ARs.

The detection of anti-cyclic citrullinated peptide (anti-CCP) antibodies plays a diagnostic and statistical predictive role in rheumatoid arthritis (RA). The decreased concentration of anti-CCP antibodies or their seroconversion is observed for not all groups of anti-inflammatory drugs. Seropositivity for anti-CCP antibodies is a predictor of the higher efficacy of abatacept (ABC). The possibility of seroconversion of anti-CCP antibodies, like rheumatoid factor, during treatment with ABC is associated with the more pronounced suppression of clinical symptoms of RA activity and progressive joint destruction, with remission achievement in a large proportion of patients.

The paper presents the materials of the Russian Arthritis Registry (OREL) that includes 3276 patients from 11 Russian Federation's largest research-and-practical centers situated in Moscow, Saint Petersburg, Novosibirsk, Kazan, Tula, Yaroslavl, Tyumen. It discusses the main goals of setting up registries, compares the results of an analysis of the data available in the Russian Registry OREL and registries of European countries and the USA. The findings suggest that there is non-uniform information on clinical, laboratory, and instrumental parameters in the national registers of a number of European countries and the USA. According to its basic characteristics, the Russian Registry OREL compares favorably with a number of other registries in the completeness of data collection, which allows a general idea of rheumatoidarthritis (RA) patients in Russia. For further development of the OREL Registry, it is necessary to concentrate our attention on the following main areas: to improve the quality of filling out documents; to follow-up patients receiving different RA therapy regimens according to the guidelines of the Association of Rheumatologists of Russia for the treatment of RA; to conduct in-depth studies of comorbidity, primarily depressive disorders; to analyze adverse reactions that make RA therapy difficult; to actively use modules for patients' self-rating of their condition; to develop nursing care, etc.

The main manifestation of joint and spine diseases, such as osteoarthritis, nonspecific back pain, and soft tissue rheumatic disorders, is musculoskeletal pain (MSP). It leads to considerable morbidity as well as temporary and permanent disability in millions of people of our country. These people need adequate medical care and most significantly a prompt and maximally complete analgesia. Unfortunately, serious problems are being faced in this field of medicine. The lack of a unified approach or continuity in the therapeutic process, inadequate knowledge of the pathogenesis of MSP and of the possibilities of its therapy may substantially hamper the work of practitioners.The meeting of Russian experts who were represented in different medical specialties and discussed the optimization of MSP treatment policy was held in Moscow on 20 June 2015. According to the results of the meeting, the authors identified the main points regarding the theoretical and practical aspects of MSP and also proposed an algorithm for the treatment of this pathology. It seems that the use of this algorithm will be able to facilitate the work of practitioners and to enhance the efficiency and safety of analgesic therapy.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of acquired systemic diseases mainly involving skeletal muscles. The main representatives of IIM are polymyositis (PM) and dermatomyositis (DM). Epidemiological surveys demonstrate that there is a relationship between PM/DM and malignant neoplasms (MNs), the detection risk of which is higher than that in the population of respective age groups. The rate of MNs in PM/DM ranges from 9 to 50%. The relationship to MNs is described in each subtype of IIM; however, these are most common in DM. The patients suffering from PM/DM associated with MNs have a worse prognosis than those without MNs. The early detection of MNs could improve the prognosis in these patients. The investigations published identify demographic, clinical, and laboratory factors increasing MN detection risks in patients with PM/DM. Just the same, they all cover small patient groups; the findings are heterogeneous and not well convincing, which calls for a further larger-scale study of this problem.Objective: to reveal and identify the specific features of paraneoplastic myositis (PnM).Subjects and methods. The investigation included 320 patients with a valid diagnosis of IIM, who had been followed up in the period of 1996 to 2016. The patients underwent laboratory tests, manual proximal muscle strength testing using a 10-point scale and electromyographic examination with needle electrodes.Results and discussion. PnM was detected in 32 (10%) of the 320 patients with IIM. Among the patients with PnM, there were 6 (19%) men and 26 (81%) women. The mean age at the onset of PnM was 55.4 years. PnM manifested with characteristic musculocutaneous syndrome in 19 (59%) patients; 18 (41%) of them were found to have MNs within the first year after disease onset. The manifestation of MNs was preliminary to the picture of PM/DM in 13 (41%) patients. The most commonly detected conditions were ovarian cancer (37.5%), MNs of the lung and breast (15%); next were MNs of the intestine (12.5%), blood (6.3%), uterus (6%), and stomach (3.1%). The median survival was 5 years in patients with PnM.

The review gives data on the safety of nimesulide used for the treatment of chronic joint diseases. The first-line treatment at its any stage for joint diseases is nonsteroidal anti-inflammatory drugs (NSAIDs). Questions have recently arisen of the safety of nimesulide; however, epidemiological findings and clinical experience confirm a positive benefit/risk profile of nimesulide in the treatment of acute pain. The International Consensus Meeting (Vienna, 2014) noted that the risk of severe adverse hepatic NSAID reactions was low and the rate of liver damage associated with nimesulide was completely similar to that observed with other NSAIDs. There are data available in the literature on the rate of serious adverse liver reactions to different NSAIDs and paracetamol. The rate of such reactions to all NSAIDs per million patientyears was 1.55 and that to nimesulide was 1.88. The members of the International Consensus Group concluded that nimesulide, if properly used, remained a valuable and safe drug for the treatment of various conditions, characterized by the presence of acute inflammatory pain, by virtue of the rapid onset of analgesic action and an evidence-based positive benefit/risk profile. The long successful experience with nimesulide in our country suggests that the agent may be successfully used to treat chronic and acute pain (including dysmenorrhea) in a daily dose of 200 mg/day. The safety profile of the drug is quite satisfactorily for all adverse reactions typical of NSAIDs, including its negative effect on the liver.

The goal of therapy for rheumatoid arthritis (RA) is to suppress inflammation, to prevent or delay destructive changes in the joints, and to normalize functions during the longest monitoring of the course of RA. The data of randomized controlled trials and national registries are of great importance to a clinician. The paper reviews the literature data characterizing the long-term results of RA therapy with the tumor necrosis factor-α inhibitor golimumab (GLM) and patient compliance with the therapy. Treatment with GLM at the registered subcutaneous dose of 50 mg once every 4 weeks gives rise to an effect in the vast majority of patients regardless of the type of previous ineffective therapy, the dose of concurrently administered methotrexate, the number of previous ineffective disease-modifying antirheumatic drugs, and the use and nonuse of glucocorticoids. GLM is characterized by a long-term (as long as 5 years) effect with suppressed progression of destruction, functional recovery, and satisfactory tolerability with no additional risk for adverse events as the therapy is continued.

The paper gives data on the prevalence of osteoarthritis (OA) and the rate of comorbidities in this disease. It discusses problems of adequate and safe therapy in these patients. The basic provisions of the 2015 clinical guidelines for the rational use of nonsteroidal antiinflammatory drugs (NSAIDs), as well as assessment of risk factors for NSAID-related complications are presented. The place of symptomatic slow-acting drugs for OA (SYSАDOA) and a clash of opinions as to their efficacy among different national or international communities of specialists are discussed. The 2014 ESCEO International Committee guidelines for the management of OA patients, which confirm the necessity of prescribing SYSDOA as initial treatment, are presented. The properties and function of synovial fluid in health and OA are depicted. Clinical and experimental findings have shown that, by improving the lubricating properties of synovial fluid, exogenous hyaluronon has many anticatabolic and anabolic effects and affects pathogenetically significant factors in OA. The results of randomized clinical trials (RCTs) comparing hyaluronans of different molecular weight are given. There are data of RCTs on the clinical efficacy and structuremodifying activity of hylan G-F 20 and on its significant pain relief in OA patients. The paper demonstrates benefits in surviving the analgesic effect of hylan G-F 20 versus intraarticular administration of glucocorticoids.

Immunogenicity, the characteristic property of proteins affecting an immune response, shows up in the formation of anti-drug antibodies (ADA) and/or immune complexes. The paper discusses whether immunogenicity has an impact on the efficacy and safety of TNF-α inhibitors (TNF-αI) in different rheumatic diseases. It provides evidence that immunogenicity has an impact and no impact on the pharmacodynamics and pharmacokinetics of the drugs. It also demonstrates the detection rate of ADA when using different biological agents (BAs) in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, and Crohn's disease. The impact of TNF-αI change, concurrent methotrexate (MT) therapy, and treatment intervals on immunogenicity is characterized. A combination of TNF-αI and MT versus BA monotherapy is shown to diminish immunogenicity; moreover, the use of therapeutic doses of MT as compared to its low weekly doses (2.5–5 mg) could reduce to a greater degree the rate of anti-TNF-αI antibody formation. Randomized controlled trials have demonstrated that the presence or absence of ADA affects the rate of adverse reactions (ARs) (due to infusion or injectable therapy) than the change in TNF-αI efficacy. This is confirmed by the data of real clinical practice (BA registers from different countries), which show that there is no significant difference in the duration of treatment with different TNF-αI; therapy with the latter in the presence of ADA was shorter mainly because of ARs rather than its inefficiency. ADA detecting methods and the complexity of their interpretation are depicted.

As the period of use of genetically engineered biologic drugs (GEBD) in clinical practice is growing, clinicians are faced with new questions: how to switch from one GEBD to another in case of primary or secondary inefficacy, intolerance to previous GEBD therapy; what should be done after low disease activity or remission is achieved. The article highlights the recent findings that are relevant for healthcare practitioners.

The paper presents the materials of the Russian Arthritis Registry (OREL) that includes 3276 patients from 11 Russian Federation's largest research-and-practical centers situated in Moscow, Saint Petersburg, Novosibirsk, Kazan, Tula, Yaroslavl, Tyumen. It discusses the main goals of setting up registries, compares the results of an analysis of the data available in the Russian Registry OREL and registries of European countries and the USA. The findings suggest that there is non-uniform information on clinical, laboratory, and instrumental parameters in the national registers of a numberof European countries and the USA. According to its basic characteristics, the Russian Registry OREL compares favorably with a number of other registries in the completeness of data collection, which allows a general idea of rheumatoid arthritis (RA) patients in Russia. For further development of the OREL Registry, it is necessary to concentrate our attention on the following main areas: to improve the quality of filling out documents; to follow-up patients receiving different RA therapy regimens according to the guidelines of the Association of Rheumatologists of Russia for the treatment of RA; to conduct in-depth studies of comorbidity, primarily depressive disorders; to analyze adverse reactions that make RA therapy difficult; to actively use modules for patients' self-rating of their condition; to develop nursing care, etc.

There has been significant progress in research focused on rheumatoid arthritis (RA) over the past decade. Nine innovative biologics agents – monoclonal antibodies and recombinant proteins inhibiting activity of the key proinflammatory cytokines and pathological activation of T and B cells involved in the development of the immune-inflammatory process – have been designed to treat RA. However, the radical improvement of prognosis in RA patients depends both on launching innovative drugs and refining the treatment strategy. This strategy is based on early diagnosis, which makes it possible to initiate the very early («window of opportunity drug») active and tightly controlled anti-inflammatory therapy aimed at achieving remission as soon as possible (the «Treat to Target» conception). The «Treat to Target» conception formulated by EULAR in 2010 has been widely incorporated in national guidelines on management of RA elaborated in many countries, including Russia. A new edition of EULAR recommendations was prepared in 2013; it has accumulated the scientific progress and clinical experience over the past three years. The publication is aimed at providing the general characteristics of the key provisions in the new recommendations and discussing some disputable problems that have not been solved yet and require further research.

The main goal of osteoarthritis (OA) treatment is to perform rational analgesic and anti-inflammatory therapy, to slow down the progression of the disease, and to preserve quality of life in patients. The performance of analgesic therapy in the elderly is impeded by the presence of a concomitant disease, primarily that of the cardiovascular system and gastrointestinal tract. A group of experts has elaborated the algorithm for managing OA patients, which tracks a careful approach to using nonsteroidal anti-inflammatory drugs and confirms the efficacy of slow-acting agents (chondroitin sulfate (CS) and glucosamine) and intraarticular hyaluronate. The experts have concluded that the use of symptomatic slow-acting drugs for the treatment of OA (SYSADOA), if need be, in combination with short-term paracetanol cycles as basic therapy for this condition is safer and more effective. The 2003 EULAR guidelines identify CS and glucosamine as chondroprotectors. Many studies have shown that CS and glucosamine have a moderate or significant effect on joint pain syndrome and functional mobility in OA; they are safe and characterized by minimal side effects. Long-term qualitative randomized controlled trials have demonstrated that CS and glucosamine are able to slow down the progression of joint space narrowing in OA. It is also shown that the use of a combination of glucosamine and CS allows cartilage loss to be prevented.

The paper reviews the literature on the treatment of chronic diseases of the locomotor apparatus. In arthrological diseases, pain is most commonly chronic and has a different genesis, mainly inflammatory, as well as mechanical, vascular, neurogenic, and psychosomatic, which requires continuous, at times long-term, therapy to improve quality of life in patients. Requirements for long-term drug therapy that can reduce the degree of inflammation and pain are determined by the magnitude of the analgesic and anti-inflammatory effect and safety of drugs. Mostly elderly age, the presence of comorbidities, and the need for attendant treatment complicate anti-inflammatory and analgesic therapy in these patients. It is shown that the representative of a class of selective cyclooxygenase-2 inhibitors meloxicam is as effective as classical nonsteroidal anti-inflammatory drugs (NSAIDs), but it is much well tolerated by elderly patients in particular. There is information on the efficacy and safety of meloxicam, as evidenced by researches and real clinical practice. The paper shows the higher safety of meloxicam having an efficacy equal to that of nonselective NSAIDs, its low frequency of gastrointestinal complications, which is comparable with that of celecoxib, and no cardiotoxicity. It also gives clinical and experimental findings suggesting that meloxicam has no negative effect on the cartilage.

The paper presents the new version of the clinical guidelines «Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in clinical practice » prepared by the Association of Rheumatologists of Russia, the Russian Pain Society, the Russian Gastroenterological Association, the Russian Society of Cardiology, the Association of Traumatologists and Orthopedists of Russia, the Association of Interdisciplinary Medicine, and the Russian Association of Palliative Medicine.In our country, NSAIDs are the most important and most popular class of analgesics. Unlike global practice, Russian physicians rather rarely recommend paracetamol as a first-line drug to relieve moderate or severe pain, by giving preference to NSAIDs; the use of opioid analgesics for noncancers is minimized because of tight legal restrictions.NSAIDs are effective and easy-to-use; however, they are far from safe; the administration of these medications may lead to serious gastrointestinal, cardiovascular, renal, and other complications in a number of cases. So the use of NSAIDs should be compulsorily monitored for adverse reactions and the choice of a specific drug for each clinical case should be based on the objective estimation of a ratio of its efficacy to safety.In recent years, there have been fresh data on the use of NSAIDs for different diseases and a few novel representatives of this drug group have appeared on the Russian pharmacological market.This all has necessitated a new version of the guidelines on the rational use of NSAIDs. These are based on the provisions that have high validity and have been confirmed by the results of well-organized clinical and large-scale population-based studies, as well as by their meta-analysis.The guidelines are intended for physicians of all specialties.

The annual incidence of adult-onset Still's disease (AOSD) worldwide is 0.16 cases per 100,000 persons. Its leading symptoms are joint involvement, fever, skin rash, and neutrophilic leukocytosis in the absence of rheumatoid factor and anticyclic citrullinated peptide antibodies in serum and synovial fluid. In its initial stage, there may be monoarthritis more commonly of the wrist, hip, or knee. Then the lesion assumes the pattern of oligo- or polyarthritis. Musculoskeletal involvement appearing as arthralgia, arthritis, and myalgia is noted in all patients. In the majority of patients, articular involvement progresses and destructive polyarthritis develops. Symmetric involvement of the carpophalangeal and distal interphalangeal joints is frequently detected. Skin lesion manifests itself as maculopapular or roseolous rashes on the chest, back, shoulders, occasionally on the legs, or in the areas of mechanical irritation. A sore throat with the signs of pharyngitis is a characteristic early symptom of the disease. There may be involvements of the liver, cardiovascular system, lung, as well as lymphadenopathy, or splenomegaly. The chronic course of the disease is more frequently noted.The paper describes two cases of AOSD. One case demonstrates that the physician has no experience in diagnosing and managing patients with AOSD, resulting in the misinterpretation of the increase in disease activity when the subclinical doses of methotrexate (MT) are used, which has been regarded as a therapeutic complication. The use of the adequate dose of MT could achieve a clinical and laboratory remission and discontinue glucocorticoids (GC).In the other case of recurrent AOSD and mild clinical symptoms, the unreasonable use of high GC doses gave rise to adverse reactions.

Currently, the use of drugs which can modify metabolic processes in the cartilage attracts increasing attention, primarily because of their high safety profile. The article presents data on the use of combined drugs Theraflex and Theraflex Advance in the treatment of patients with degenerative-dystrophic diseases of the joints and spine.

Objective. To evaluate the symptom- and structure-modifying effect of Alflutop compared to placebo (PL) in patients with knee osteoarthritis (OA). Material and methods. The study included 90 patients with knee OA (according to the criteria of the Russian Association of Rheumatologists) at the stage 2–3 (according to the Kellgren-Lawrence scale); pain score when walk- ing ≥ 40 mm (assessed using the visual analog scale). All the patients provided an informed consent. The patients were randomly divided into two groups: group 1 (n=45) received an intramuscular injection of 1 mL Alflutop for 20 days with 6-month intervals for 2 years (a total of 4 courses for 2 years); group 2 (n=45) received an injection of PL (iso- tonic sodium chloride solution) in the same way. Ibuprofen at a dose of 600–1200 mg/day was administered as concomitant therapy. To evaluate the structure-modifying effect of Alflutop, X-ray of the knee joint was performed at the beginning and end of the study; the level of biochemical markers (CTX-II and COMP) was determined at the beginning, after 3 months, and at the end of the study. A statistical analysis was performed using the Statistica 10 software package.Results. After the 2-year follow-up, a statistically significant negative trend was detected less frequently in the group of patients treated with Alflutop compared to the PL group (6.1 and 38.4%, respectively). The statistically significant delay in joint space narrowing was observed in patients who received Alflutop in contrast to patients who received PL (the numerical score of the joint space, the Wilcoxon test; p=0.0003). An increase in osteo- phyte size was observed in 72% of the patients receiving PL, and only in 27% of the patients receiving Alflutop (medial and lateral osteophytes of the femoral bone, the Wilcoxon test; p=0.0078; medial and lateral osteophytes of the shin bone, the Wilcoxon test; p=0.0001 and p=0.0039, respective- ly). Augmentation of subchondral osteosclerosis was determined more often in the PL group (the McNemar's test; p=0.0313). The level of the marker of cartilage degradation CTX-II tended to decrease after 3 months of Alflutop therapy, which has persisted until the end of the study. This indicates a decrease in the articular cartilage degradation. In the PL group, the CTX-II level remained unchanged. A tendency to an increase in the level of the marker of cartilage degradation COMP was found in the PL group. Conclusion. Based on double-blind, placebo-controlled, randomized study, the structure-modifying effect of Alflutop in knee OA has been proved. Alflutop delays the radiographic progression of knee OA, joint space narrowing and osteophyte growth, and reduces the degradation of the articular cartilage matrix.

The results of multicenter, open-label trial aimed at assessing the effectiveness, safety, and compliance of medication Ketonal Duo in 602 patients with osteoarthritis (OA) are presented. The trial duration was 28 days. The medication demonstrated a reliable analgesic effect and good tolerance; adverse events were observed in 4.7% of patients. The effect was observed in 97.9% of patients with OA according to the physician's opinion and in 99.1% as reported by the patients. Most patients and physicians consider the medication to have maximal convenience.