Effective control of musculoskeletal pain (MSP) is one of the main tasks of medical care for the most common rheumatic diseases, such as osteoarthritis (OA) and non-specific back pain (NSBP). Epidemiological surveys have shown that a substantial proportion (about 40–50%) of patients consider their assigned treatment to be ineffective and are dissatisfied with its results. The reasons for this are a phenotypic diversity of MSP, individual responses to analgesic drugs, and comorbidities (particularly metabolic disorders and depression). Placebo-controlled trials have demonstrated that monotherapy with the most popular drugs (non-steroidal anti-inflammatory drugs (NSAIDs), opioids, local glucocorticoid injections, duloxetine, etc.) for the treatment of OA and NSBP provides significant pain relief (>50%) in only nearly one-half of patients. This necessitates comprehensive and individualized patient therapy aimed at different components of the pathogenesis of pain. The first step in the treatment of MSP should be the rational use of NSAIDs. Nimesulide that has a favorable combination of efficacy, good tolerability, and an acceptable cost may be considered as the drug of choice. The important element of treatment for chronic MSP is also the use of slow-acting anti-inflammatory drugs, such as diacerein.

This article presents results from two clinical trials of infliximab biosimilar, BCD-055, including comparative data on the pharmacokinetics (PK), efficacy and safety of BCD-055 and innovator infliximab (IFX) in patients with ankylosing spondylitis (AS).

Objective: The purpose of phase I clinical study ASART-1 was to evaluate the pharmacokinetic and safety profile of BCD-055 and to prove its equivalence with Remicade®, phase III study ASART-2 was conducted to evaluate the efficacy and tolerability of BCD-055 in comparison with Remicade® in patients with active AS.

Patients and methods: Both studies were conducted as international multi-center randomized double-blind studies in direct comparison with innovator IFX. Inclusion and exclusion criteria, main examination methods, and drug regimens were the same in both trials. A total of 199 patients were enrolled in the studies. After the screening, the patients were stratified by CRP and BASDAI score, randomized (1:1 ratio in ASART-1; 2:1 ratio in ASART-2) into 2 arms and received BCD-055 or innovator IFX at a dose 5 mg/kg IV at 0, 2, 6 and then every 8 weeks (up to week 54). The primary endpoint for PK profile evaluation was the area under the concentration-time curve (AUC(0-tau)), maximum serum concentration of infliximab at steady state Cmax,ss. Efficacy was assessed by achieving ASAS20 at week 30, the endpoints for safety profile were the incidence of adverse events and serious adverse events during the maintenance-dosing phase and withdrawals from the study due to the safety reasons.

Results: A total of 81 patients (ASART-1 study) were included in PK analysis, 199 patients were in efficacy and safety analysis. AUC(0-tau) value were 25,420,996.25±11,635,015.74 (ng/ml) Cmax,ss for BCD-055 and 26,114,705.71±12,102,376.9 (ng/ml)⋅h for INF innovator (p>0.05). Cmax,ss for BCD-055/Remicade® was 122,752 [99,401–151,553] ng/ml and 119,844 [98,120–132,772] ng/ml, respectively (p>0.05). ASAS20 was achieved at week 30 by 81.30% of the patients in the BCD-055 group, and 67.74% in the INF innovator group (p=0.061). The analysis of secondary endpoints (BASDAI, BASMI, BASFI, MASES, quality of life, chest excursion, and number of pathologically changed joints) showed no difference between the biosimilar and innovator groups. BCD-055 and innovator IFX showed highly similar safety profiles in both studies without cases of unexpected toxicity. The rates of AEs were equivalent for both drugs and were 48.48% and 58.21% of patients in the BCD-055 and Remicade®, respectively.

Conclusion: BCD-055 is found to be equivalent in terms of PK, and showed the similarity in efficacy and safety profile compared with innovator IFX in patients with active AS.

Kawasaki disease (KD) is acute systemic vasculitis of unknown etiology. Approximately 20–25% of untreated patients develop coronary artery changes with a range of severity from asymptomatic coronary artery dilatation to giant coronary artery aneurysms with thrombosis, myocardial infarction, and sudden death. To date there is no official data on the incidence of KD in Russia. In Russia, the disease is not enough known now to a wide circle of physicians and often masks other more common diseases. Since 2010, the detection rate of KD has dramatically increased in Saint-Petersburg.

Objective: to analyze the experience in diagnosing and treating KD in two largest hospitals of Saint Petersburg.

Patients and methods. The retrospective study included data on 30 children (18 boys, 12 girls) who were hospitalized with a diagnosis of KD in the Saint-Petersburg State Pediatric Medical University Clinic and Children’s Hospital One (Saint Petersburg) between January 2011 and September 2016. Data are represented by median and extreme values. The age of the children was 2.8 (0.2; 4.6) years; of them 5 (16.7%) patients were under the age of 1 year. The children were hospitalized on 5 (1; 14) days of disease onset; KD was diagnosed on 9 (3; 52) day of the disease.

Results. Immediately after diagnosis, 27 (90%) children received aspirin. In early stages (before 10 days of the disease), intravenous immunoglobulin (IVIG) therapy was performed in 15 (50%) children, one of them received IVIG before disease day 5 (on day 3), but without effect. On disease days 11-20 (immediately after diagnosis), 10 (33.3%) children were prescribed with IVIG; thereafter fever was abolished in all the patients. Their body temperature became normal on day 11 (6; 23). Ultrasonography revealed coronary artery lesions in 13 (43.3%) patients. Out of the 30 children followed up, one baby who fell ill at the age of 3 months and received IVIG died on day 30 of the disease.

Conclusion. Currently, there continues to be a delayed diagnosis of KD. IVIG therapy was effective, especially in cases of timely diagnosis. It is necessary to increase awareness of KD among clinicians and ultrasound diagnosticians.

Autoinflammatory diseases (AIDs) are being intensively studied. Molecular genetic testing of patients is of great importance for the diagnosis of AIDs since the basis for its development is pathological mutations that cause innate (antigen-nonspecific) immunity system disorders and the development of inflammation. This also applies to patients with systemic juvenile arthritis (SJA) that has been recently assigned to a group of AIDs due to the great similarity of symptoms. In this connection, the assumption that monogenic AIDs mask SJA in a number of patients was well founded. More than 25 genes, mutations in which lead to AIDs, are known; the NLRP3, TNFRSF1A, and MVK genes are most common and well investigated. These genes cause major monogenic AIDs, such as cryopyrin-associated periodic syndromes (CAPS), TNF receptor-associated periodic syndrome (TRAPS), and hyperimmunoglobulinemia D/deficit mevalonate kinase syndrome (HIDS).

Objective: to identify patients with monogenic AIDs among those with fever, arthralgias, and other manifestations of systemic inflammatory response, including among those with SJA, through molecular genetic testing.

Patients and methods. In 2012–2016, molecular genetic testing for mutations in the NLRP3, MVK, and TNFRSF1A genes was carried out within the framework of screening in 184 patients (94 women and 90 men). The investigation enrolled 117 patients with suspected AIDs (Group 1) and 67 patients with SJA (Group 2). The selection criteria were periodic or persistent fever, clinical manifestations of systemic inflammatory response (skin rashes, arthralgias/arthritis, lymphadenopathy, hepatolienal syndrome, serositis, etc.), acute-phase markers when excluding infectious, oncohematologic, and autoimmune causes. SJA was diagnosed based on the ILAR criteria (2001). The patients' age ranged from 6 months to 60 years (mean age, 9.0 years [5; 15]), disease duration, 2 months to 54 years (mean duration, 3.0 [1.0; 8.5])). To identify familial aggregation, genetic tests were also carried out in 18 relatives of the patients with genetically verified AIDs. Molecular genetic analysis was performed in the Laboratory of Hereditary Metabolic Diseases, Research Center of Medical Genetics, Moscow.

Results. 15 variants of pathogenic mutations in the studied genes were identified in 43 (23.4%) patients: 31 (16.8%) patients with those in NLRP3, 10 (5.4%) in TNFRSF1A (in a heterozygous state), and 2 (1.1%) in MVK (in a compound heterozygous state). In the AID group, the mutations were detected in 31 (26.5%) patients: 24 (20.5%) in NLRP3, 1 (0.9%) in MVK, and 6 (5.1%) in TNFRSF1A. In the SJA group, the mutations were present in 12 (17.9%) patients: 7 (10.4%) in NLRP3, 1 (1.5%) in MVK, and 4 (5.9%) in TNFRSF1A. The most common mutations in the NLRP3 gene were substitution-missense c. 1049C>T (p.T350M) in 7 (25.9%) patients and low-penetrance mutation c. 2113C>A (p. Q705K) in 13 (28.3%). Examinations established the genetic diagnoses of CAPS in 19 (10.3%) patients, TRAPS in 9 (4.9%), and HIDS in 2 (1.1%). In Group 1, CAPS was identified in 17 (14.5%) patients, of whom 15 had Muckle-Wells syndrome (MWS) and 2 had CINCA/NOMID (Chronic infantile neurologic, cutaneous articular syndrome (CINCA)/Neonatal onset multisystem inflammatory disorder (NOMID); TRAPS and HIDS were present in 6 (5.1%) and 1 (0.9%) patients, respectively. In Group 2, there was CAPS (MWS) in 2 (2.9%) patients, TRAPS in 3 (4.5%), and HIDS in 1 (1.5%). Eleven of the 18 relatives of the patients were ascertained to have mutations and 7 were diagnosed as having AIDs (CAPS in 4, TRAPS in 3).

Conclusion. About one-quarter of the patients who have an inflammatory phenotype, including the manifestations of SJA, suffer from monogenic AIDs. Half of them received therapy with the interleukin-1 inhibitor canakinumab, which had a pronounced positive effect. Interpretation of the diagnostic value of low-penetrance mutations is hampered and requires an individual approach. The diagnosis of AIDs should be established in patients having no mutations with great caution, in this case, there is a need for clinical and laboratory criteria for the disease and a thorough assessment of the data of medical history of the patient, and his/her family in particular. The decision to assign these patients to receive lifetime expensive targeted therapy should be well justified.

Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease (ARD) associated with the production of broad-spectrum antibodies, the detection of which is of important diagnostic and prognostic values. The problems of RA diagnosis are associated with the limited sensitivity of currently used serological markers.

Objective: to evaluate the diagnostic informative value of autoantibodies against different post-translationally modified (PTM) vimentin peptides in patients with RA and other ARDs.

Patients and methods. The frequency of autoantibodies against different isoforms of vimentin was estimated in 144 patients with RA, in 36 patients with other ARDs (ankylosing spondylitis and scleroderma systematica), and in 25 patients of a control group, who had no rheumatic diseases. Antibodies against different PTM vimentin peptides obtained using citrullination, carbamylation/homocitrullination, and acetylation were determined. Anti-citrullinated vimentin (anti-CitVim) peptide, anti-carbamylated vimentin (anti-CarVim) peptide, and anti-acetylated vimentin (anti-AcVim) peptide autoantibodies of IgG and IgA classes were estimated in the serum by enzyme immunoassay.

Results. The results of the study showed that IgG and IgA anti-CitVim had the maximum area under the ROC curve (AUC) (0.859 and 0.855, respectively). A slightly smaller AUC was seen in IgG anti-CarVim (0.85), IgG anti-AcVim (0.784), and IgA anti-AcVim (0.651). The diagnostic sensitivity and diagnostic specificity were 66.2 and 96.77% for IgG anti-CitVim, 60.56 and 91.94% for IgA anti-CitVim, 91.55 and 53.23% for IgG anti-CarVim, 63.38 and 93.55% for IgG anti-AcVim, and 49.3 and 70.97%, IgA anti-AcVim, respectively. Positivity for IgG anti-CitVim, IgG anti-CarVim, and IgG anti-AcVim, and anti-IgA CitVim was significantly more frequently detected in patients with RA than in those with other ARDs and in the control group (p<0.05). Thus, the identified autoantibodies against modified vimentin peptides proved to be diagnostically useful serological markers in RA. IgA anti-CarVim and IgA anti-AcVim can also be used in the diagnosis of RA in patients who are seronegative for rheumatoid factor and anti-cyclic citrullinated peptide antibodies.

Conclusion. When the upper reference limits are set for IgG anti-CitVim (20 U/ml), IgA anti-CitVim (8.95 U/ml), IgG anti-CarVim (6.25 U/ml), IgG anti-AcVim (17.1 U/ml), and IgA anti-AcVim (9.85 U/ml), antibodies against different isoforms of vimentin are recommended for use as additional laboratory tests to diagnose RA.

Diacerein (D) belongs to a class of symptomatic slow-acting agents, has an original mechanism of action, and is widely used as a diseasemodifying antirheumatic drug to treat osteoarthritis (OA) in Russia and many countries of the world. The ability of the drug to affect the main symptoms and progression of OA has been shown in a number of well-organized clinical trials.

Objective: to evaluate the efficacy and safety of D in patients with knee OA.

Patients and methods. An open-label trial evaluating the efficacy and safety of D (diaflex) in patients with knee OA was conducted in accordance with the multicenter program «Osteoarthrosis: Assessment of Progression in Real Clinical Practice». The trial included 80 patients of both sexes with Stage II–III knee OA; mean age, 60.8±6.8 years (47–75 years); mean body mass index, 31.8±5.9 kg/m2; disease duration, 10.3±5.7 years (2–30 years). The duration of the trial was 9 months (6 months of therapy and 3 months of follow-up).

Results. There was a statistically significant reduction in visual analog scale pain on walking just 1 month after therapy initiation (57.1±9.7 and 44.7±13.9 mm; p<0.0001) and a further significant improvement throughout the 6-month therapy. Pain did not increase after the drug was discontinued (the follow-up period was 3 months). The same pattern was observed in the assessment of the WOMAC index (pain during early therapy, 243.8±73.9; pain at the end of therapy, 137.5±78.9; stiffness, 97.8±41.1 and 57.7±38.6; functional failure, 875.8±250.4 and 525±305.7 respectively; p<0.0001). Statistically significantly improved quality of life indicators measured by EQ-5D were noted throughout the follow-up period: 0.43±0.23 at the beginning of therapy, 0.61±0.14 at its end, and 0.63±0.11 at 3 months following treatment completion (p<0.0001). By the time of therapy completion, 71.3% of the patients completely refused to take nonsteroidal anti-inflammatory drugs (NSAIDs). Both the patient and the physician evaluated the efficiency of treatment identically. By the end of therapy, 87.5% of the patients were observed to have improvement. Adverse reactions (ARs) were recorded in 10 (12.5%) patients and mainly associated with more frequent stools; ARs were not a cause of treatment interruptions or protocol deviations.

Conclusion. Diaflex has a good symptomatic and anti-inflammatory effect: the therapy statistically significantly reduces pain, stiffness, and the need for NSAIDs and improves quality of life and joint function. The drug has a good safety profile and after-effects, which is seen at least 3 months after therapy discontinuation.

Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular diseases. To determine their daily arterial stiffness (AS) as an indicator of cardiovascular risk is of unquestionable interest.

Objective: to evaluate the features of daily AS in RA patients with or without hypertension.

Patients and methods. Twenty-four hour AS monitoring (24-h ASM) was done in 75 women with a valid diagnosis of RA. The patients were randomized into 3 groups: 1) 39 RA patients with hypertension; 2) 24 RA patients without hypertension; 3) 12 RA patients with masked hypertension. A comparison group consisted of 30 hypertensive patients without RA and a control group included 22 apparently healthy women who were age-matched with the patients with RA and those from the comparison group. 24-h ASM readings were studied using a BPlab device with Vasotens software (Russia).

Results. All the patients with RA were found to have higher 24-h ASM readings than the controls; and, in the presence of hypertension, these changes were even more pronounced. Group 1 was noted to have higher ambulatory AS index than the comparison group; more than 70% of the patients in Group 2 were observed to
have increased aortic pulse wave velocity when reducing to a blood pressure (BP) of 100 mm Hg. The patients in Groups 1 and 2 had increases in augmentation index, in the latter normalized for a heart rate of 75 beats/min, in the propagation time of a reflected wave when reducing to a BP of 100 mm Hg, and in AS index at night. The patients with RA showed an association between daily AS and major cardiovascular risk factors (hypertension, age, body mass index, menopause duration), RA-specific risk factors (RA duration, erythrocyte sedimentation rate, and C-reactive protein), and psychoemotional status.

Conclusion. 24-h ASM revealed that the patients with RA had higher vascular wall stiffness than the individuals in the comparison and control groups. Taking into consideration the pronounced changes in AS not only during the daytime, but also during the night, it is appropriate to perform daily monitoring in patients with RA in order to obtain more objective data.

Angiotensin-converting enzyme (ACE) inhibitors have anti-inflammatory and antiproliferative properties and can affect the processes of angiogenesis, by reducing the effects of angiotensin II (ATII). The use of ACE inhibitors in the combination therapy of rheumatoid arthritis (RA) can be also effective for monitoring disease activity and for reducing a cardiovascular risk.

Objective: to evaluate the efficacy of an ACE inhibitor in the combination therapy of RA.

Patients and methods. Eighty-four patients with RA and endothelial dysfunction were examined; the mean age was 40.12±10.2 years; the mean disease duration was 4.22±3.43 years. All the patients had a blood level of ATII of >9 pg/ml. Enzyme immunoassay was used to measure the levels of tumor necrosis factor-α (TNF-α) (Vector-Best, Russia), intercellular adhesion molecules 1 (ICAM-1) (Diaclone, France), vascular endothelial growth factor (VEGF) and ATII (Diagnostic, Canada). Wrist ultrasonography using the Doppler ultrasound apparatus ESAOTE MyLAB40 was carried out to assess synovial vascularization. The patients were divided into two groups. Group 1 included 43 patients who were assigned to receive standard therapy for RA according to the rheumatic disease treatment protocols; Group 2 comprised 41 patients who received the standard therapy plus ACE inhibitors 2.5–5 mg/day.

Results. The use of ACE inhibitors in the 12-month combination therapy of RA patients led to an improvement in the endothelial regulation of vascular tone, to a decrease in the blood concentration of ICAM-1, to a reduction in the intensity of synovial angiogenesis and in the blood level of VEGF by 39%, and a more significant drop in the levels of CRP and TNF-? and in DAS28 by 1.2 scores as compared to those in the standard therapy.

Objective: to evaluate the efficiency of different chondroitin sulfate (CS) treatment regimens in patients with osteoarthritis (OA).

Patients and methods. The investigation enrolled 44 patients of both sexes aged 48.6±6.4 years with knee OA. 26 patients of a study group received step-by-step CS (chondrogard and structum)-containing therapy in combination with magnetic laser therapy (low-intensity laser radiation (LILR)) for the affected joints. 18 patients of a comparison group had traditional treatment with nonsteroidal anti-inflammatory drugs and physiotherapy.

Results. Step-by-step therapy with chondrogard in combination with LILR has an advantage over the traditional treatment regimen, because it is characterized by more pronounced long-acting analgesic and anti-inflammatory effects and by the absence of adverse reactions.

Objective: to evaluate the efficacy, tolerability, and safety of intra-articular hyaluronic acid (hyalurom) in patients with knee osteoarthritis (OA).

Patients and methods. A 6-month prospective trial enrolled 20 women aged 45–75 years (61±7 years) with primary knee OA of Kellgren–Lawrence grades II (85%) and III (15%) who needed nonsteroidal anti-inflammatory drugs (NSAIDs). The disease duration averaged 6.6±2.4 years. The mean body mass index was 33±5 kg/m2. Intra-articular administration of hyalurom was made; its cycle included 3 injections at a 1-week interval; a further follow-up was performed during 6 months. All the participants completed the trial.

Results. In the first month of therapy, its effect was developed in the majority (75%) of the patients. There was a substantial reduction in total WOMAC scores by an average of 29% at 1 month, by 27% at 3 and 6 months (p<0.01); pain by 35% at 1 month, by 32% at 3 months, and by 36% at 6 months (p<0.01); stiffness, by 37, 38, and 39% (p<0.01); and functional failure by 29, 25, and 23%, respectively (p<0.01). The effect of therapy in most (80%) patients persisted throughout the follow-up period; only 10% of patients continued to take NSAIDs with the same frequency at 6 months; 60% used them on-demand, and 30% did not need NSAID therapy. No adverse reactions associated with the therapy performed were detected during the follow-up period.

Conclusion. Hyalurom has a significant symptomatic effect and a good tolerability in the treatment of knee OA.

Gout is a chronic disease that frequently leads to disability if urate-lowering therapy is inefficient. The paper presents the positive experience with febuxostat, a novel non-purine xanthine oxidase inhibitor, in a young patient with disabling chronic tophaceous gout. Twelve-month therapy with daily 80-mg dose of febuxostat resulted in almost complete resorption of subcutaneous tophi and in a long-term lack of arthritis attacks with the persistent serum uric acid levels below target ones. This is the first experience in successfully switching from one to another xanthine oxidase inhibitor, which was described after febuxostat registration in the Russian Federation.

Interleukin-6 (IL-6) is one of the major proinflammatory cytokines, which, by interacting with hepatocytes, induces the synthesis of a broad spectrum of acute phase inflammatory proteins. IL-6 plays an important role in the development and progression of systemic lupus erythematosus (SLE), participates in the differentiation of CD4/CD8 regulatory T lymphocytes and in the production of autoantibodies by B lymphocytes, and increases the survival of plasmablasts. Tocilizumab (TCZ) is a humanized anti-IL-6 receptor antibody that neutralizes the pleiotropic effects of the cytokine. The use of this drug in SLE can have acceptable efficiency with the high inflammatory activity that is accompanied by fever, polyarthritis, polyserositis, skin lesions, and hemolytic anemia. The authors demonstrated the successful use of TCZ in a female patient with a documented diagnosis of SLE with a high activity (SLEDAI-2K-11). The use of the drug was justified by the prevalence of musculoarticular, constitutional (fever) disease, a high immunological activity (anti-DNA antibodies, 150 IU/ml; antinuclear factor, 1/1280 h; CRP, 88). This therapy could achieve complete relief of fever at day 2 after the first infusion of TCZ, a reduction, and subsequently complete relief of arthritis and normalization of laboratory blood parameters. TCZ has a satisfactory safety profile and may be considered as an alternative treatment for SLE when glucocorticoids, cytostatic agents, and rituximab are ineffective.

The article describes a wide spectrum of biological agents for treatment of Immune-mediated inflammatory rheumatic diseases in clinical practice in EU. Pharmacological classification, main characteristics of anti-TNF agents and biologics with another modes of action, as well as the most important results of clinical trials are provided. Authors focused on the use of biological agents in clinical practice in emerging market regions such as Central and Eastern Europe, particularly in Romania, were disparity due to economic and social factors provides challenges to achieving optimal monitoring and physician’s decision making. Such very important points as an adoption of «treat to target» recommendations to local practice, consensus guidelines on the criteria for biological treatment, patient education initiatives, the development of a national patients registry, are discussed.

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.

Treatment for chronic back pain (CBP) is a complex therapeutic challenge. The heterogeneity of the disease, different phenotypes of pain, comorbidities, and individual sensitivity to drugs require the use of a broad-spectrum of analgesics with different mechanisms of action. The present review briefly considers the evidence base of basic pharmacological groups that are used for the treatment of CBP in real clinical practice or in clinical trials: nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, tumor necrosis factor-α (TNF-α) inhibitors, nerve growth factor inhibitors, opioids, antidepressants, and muscle relaxants, as well as antibiotic therapy. It is shown that at the moment there are no existing or promising drugs that are able to completely solve the problem of CBP. Treatment should be initiated with NSAIDs. Although their efficacy in CBP is relatively low; nevertheless, the use of NSAIDs makes it possible to achieve a certain reduction in pain and to create conditions for the successful use of other drug classes and non-drug methods. The benefits of nimesulide that may be deemed to be a first-line drug among NSAIDs are considered in terms of its efficacy, relative safety, and availability.

Three main areas can be arbitrarily identified in the modern concept of treatment for osteoarthritis (OA); these are: 1) an impact on the progression of joint destruction; 2) suppression of peripheral pain mechanisms; and 3) inhibition of the central processes involved in the formation of pain sensation. Glucosamine and chondroitin sulfate (CS) have become the first agents that are able to retard the development of cartilage degeneration. They have been used in medical practice for more than 40 years. A number of clinical trials of these drugs have yielded favorable results during their use in patients with OA. Another agent containing amino sugars and CS – sea fish cartilage hydrolysate has more recently emerged. Clinical trials have demonstrated that it is able to significantly relieve OA-induced pain. To date, the main agent for the analgesic therapy of OA is considered to be nonsteroidal anti-inflammatory drugs (NSAIDs) that act on the peripheral mechanisms of pain and are widely used to treat diseases that are accompanied by chronic pain. However, a large-scale meta-analysis dealing with the experience with NSAIDs used to treat OA has shown that pain relief due to this therapy averaged only about 10 mm on a 100-mm visual analogue scale. To enhance the efficiency of therapy for OA, drug and non-drug treatments that affect the central mechanisms of pain in this disease are also used.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most prescribed drugs worldwide and, like any medication, can cause adverse drug reactions. Since NSAIDs belonging to the group of coxibs, are quite commonly used in clinical practice now, the study of the safety of this class of drugs is given the highest priority. The paper analyzes a largest-scale PRECISION study of the safety of NSAIDs, the aim of which was to assess the cardiovascular safety of celecoxib versus that of ibuprofen and naproxen in patients with osteoarthritis and rheumatoid arthritis