The paper presents the main provisions of the 2019 updated European League Against Rheumatism (EULAR)/European Renal Association (ERA) – European Dialysis and Transplant Association (EDTA) guidelines for the management of lupus nephritis. It discusses the technology of preparing recommendations by an international group of rheumatologists, nephrologists, morphologists, and pediatricians. The main part contains recommendations on the use of induction and maintenance therapy with immunosuppressants, glucocorticoids, and biological agents.
The issues relating to the management of pregnant patients with end-stage renal failure are considered.

Objective: to study risk factors for invasive aspergillosis (IA), its etiology, clinical manifestations, and treatment efficiency in patients with rheumatic diseases (RD).

Patients and methods. The first study of proven and probable IA (EORT/MSGERC, 2019) was conducted in 18 patients with RD, who accounted for 3% of all adult IA patients (n=699) included in the 1998–2020 registry of the Department of Clinical Mycology, Allergology, and Immunology, I.I. Mechnikov North-Western State Medical University (Group 1). This group comprised 56% women; the median age was 59 [21; 75] years. Group 2 (a comparison group) included 610 adult hematology patients with IA (median age, 45 [18; 79] years; 42% women). A prospective case-control study was conducted to identify risk factors for IA in patients with RD: 36 rheumatic patients without IA (median age, 58 (18–79) years; 61% women) (a control group).

Results and discussion. Patients with RD were found to often develop IA in the presence of anti-neutrophilic cytoplasmic antibody-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis) and systemic lupus erythematosus (50 and 16%, respectively). It was shown for the first time that the likelihood of IA in patients with RD increases with prolonged (median 14 days) lymphocytopenia during RD treatment (odds ratio 13.0; 95% confidence interval, 3.3–50.3). The main causative agents of IA were A. fumigatus (50%) and A. niger (29%). IA was more severe in Group 1 than in Group 2: in the resuscitation and intensive care units, there were 44 and 18%, respectively (p=0.01). Group 1 versus Group 2 more frequently had respiratory failure (61 and 37%, respectively; p=0.03), hemoptysis (28 and 7%; p=0.0001), chest pain (17 and 7%; p=0.04), and cardiac involvement (11 and 1%; p=0.0001), and less frequently had fever (67 and 85%; p=0.01). The common site of IA was the lung (83%); the characteristic feature detected by computed tomography (CT) is pulmonary cavitation (44%). Antifungal therapy was used in 89% of Group 1 patients; the overall 12-week survival was 69%.

Conclusion. In patients with RD, it is difficult to differentiate between the progression of the underlying disease, adverse drug reactions, infectious complications, or a combination of these disorders due to the similarity of their clinical manifestations. When RD patients with infectious syndrome and respiratory failure develop prolonged lymphocytopenia during combination therapy, AI should be suspected and lung CT, bronchoscopy, and mycological examination of the material obtained by bronchoalveolar lavage be done.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations. Numerous observations and surveys of patients have shown that the most common symptom of SLE is fatigue complaints in 51 to 90% of patients.

Objective: to determine the significance of fatigue in the general health status of RENAISSANCE cohort patients with SLE who were hospitalized in the Clinic, V.A. Nasonova Research Institute of Rheumatology.

Patients and methods. The investigation included SLE patients aged 18 years and older who met the 2012 SLICC criteria. The standard examination accepted in the management of patients with SLE was made. Disease activity was determined by SLEDAI-2K; irreversible lesions in various organs were identified using the SLICC damage index. The SF-36 and the LupusQoL questionnaires were used to assess health-related quality of life (HRQOL) and the FACIT-Fatigue scale was applied to measure fatigue.

Results and discussion. The investigation enrolled 328 patients, mainly women (91%); the mean age was 34.4±11.5 years; the duration of the disease was 106.3±97.9 months. In this group, moderate and high disease activities (SLEDAI-2K scores of 6–10 and 11–19, respectively) were observed at approximately the same frequency. At the time of inclusion, more than half (56.5%) of the patients already had various irreversible organ lesions. At Visit 1, the FACIT-Fatigue scale showed that fatigue was present in 148 (45%) of the 328 patients. According to the presence of fatigue, the patients were divided into two groups. Group 1 included 148 patients with fatigue; Group 2 consisted of 180 patients without fatigue. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and anti-DNA antibody levels were significantly higher in the fatigue group (p=0.01 and p=0.02, respectively); the patients also had decreased HRQOL according to 7 LupusQol domains (p<0.001). The patients with fatigue were significantly more likely to receive intravenous glucocorticoids and rituximab. At 12 months after the start of treatment, the patients with fatigue were found to have a statistically significant reduction in disease activity, as well as normalization of anti-DNA antibody levels, improvements in HRQOL according to the LupusQol domains, and less severity of fatigue according to the FACIT-Fatigue scale.

Conclusion. Fatigue was detected in almost half (45–53%) of SLE patients. It is associated with a higher disease activity by SLEDAI-2K and with a high anti-DNA antibody level. The patients with fatigue are observed to have an obvious worsening of HRQOL according to all LupusQol domains.

Objective: to determine the efficiency of sequential (combined) therapy with rituximab (RTM) and belimumab (BLM) in patients with active systemic lupus erythematosus (SLE).

Patients and methods. Twelve patients with true SLE having moderate-to-high activity were followed up. Six of them were noted to have skin and articular manifestations and 6 had kidney damage, vasculitis. The patients took RTM at 500–2000-mg doses, with 6-methylprednisolone as premedication, whereupon they were prescribed BLM according to the standard regimen of 10 mg/kg once monthly. The follow-up period was 1 year. At baseline and every three months after RTM administration, the efficiency and tolerability of therapy were evaluated, the concentrations of autoantibodies and complement components was estimated, and the dose of oral glucocorticoids (GCs) was recorded.

Results and discussion. During combined therapy with the biological agents (BAs), there was a considerable clinical and laboratory improvement: reductions in disease activity (median (Me) SLEDAI-2K scores were 12 [9.5; 17] at baseline and 2 [2; 6] at Visit 4), the Me concentrations of anti-double-stranded DNA (anti-ds-DNA) antibodies, 101 [39; 250] and 28 [6; 112] U/ml, respectively; those of complement component 3 (C3), 0.44 [0.39; 0.59] and 0.83 [0.81; 0.87] g/L, respectively; and those of complement C4, 0.06 [0.031; 0.1] and 0.16 [0.15; 0.18] g/l, respectively). Most patients received the medium and low doses of oral GCs as initiating therapy. During the year, the dose of GCs was reduced by more than a quarter and they could be completely discontinued.

evaluated, the concentrations of autoantibodies and complement components was estimated, and the dose of oral glucocorticoids (GCs) was recorded. Results and discussion. During combined therapy with the biological agents (BAs), there was a considerable clinical and laboratory improvement: reductions in disease activity (median (Me) SLEDAI-2K scores were 12 [9.5; 17] at baseline and 2 [2; 6] at Visit 4), the Me concentrations of anti-double-stranded DNA (anti-ds-DNA) antibodies, 101 [39; 250] and 28 [6; 112] U/ml, respectively; those of complement component 3 (C3), 0.44 [0.39; 0.59] and 0.83 [0.81; 0.87] g/L, respectively; and those of complement C4, 0.06 [0.031; 0.1] and 0.16 [0.15; 0.18] g/l, respectively). Most patients received the medium and low doses of oral GCs as initiating therapy. During the year, the dose of GCs was reduced by more than a quarter and they could be completely discontinued. Conclusion. Combined biological therapy with RTM and BLM is a promising treatment for active SLE. The use of this regimen promotes a rapid and effective reduction in disease activity, normalization of laboratory markers of SLE (anti-ds-DNA antibody and complement C3 and C4 levels), and decreases in the dose of oral GCs and, as a consequence, in the risk of irreversible organ damages.. Combined biological therapy with RTM and BLM is a promising treatment for active SLE. The use of this regimen promotes a rapid and effective reduction in disease activity, normalization of laboratory markers of SLE (anti-ds-DNA antibody and complement C3 and C4 levels), and decreases in the dose of oral GCs and, as a consequence, in the risk of irreversible organ damages.

Netakimab (NTK) is a humanized anti-interleukin-17A monoclonal antibody. To date, the drug has been approved to treat ankylosing spondylitis (AS), psoriatic arthritis, and plaque psoriasis. The paper gives the data obtained during 52-week follow-up of AS patients in the phase III ASTERA study.

Objective: to study the efficacy and safety of NTK when used long in patients with active AS.

Patients and methods. The investigation enrolled 228 patients with active AS, in whom nonsteroidal anti-inflammatory drugs or biological agents were ineffective. The patients were randomized in a 1:1 ratio to receive NTK 120 mg or placebo. The drug was administered subcutaneously at weeks 0, 1, 2, and then once every 2 weeks. Patients who received placebo and achieved a 20% improvement according to the ASAS criteria (ASAS20) were excluded from the study at week 16. At this week, patients who took placebo and did not achieve an ASAS20 response were switched to subcutaneous NTK at 120 mg dose once every two weeks. The follow-up period was 52 weeks.

Results and discussion. Patients with active AS who received NTK were more likely to respond to treatment than those who took placebo. The proportion of people who achieved 40% improvement (ASAS40) during treatment with NTK increased throughout the follow-up period and amounted to 80.7% at week 52. Positive changes were achieved in all used clinical and laboratory parameters of AS activity. There was also a decrease in inflammatory changes, as shown by magnetic resonance imaging (MRI). The adverse events (AEs) were mainly laboratory abnormalities and upper respiratory tract infections. Treatment-related AEs were recorded in no more than one third of patients and they were mild to moderate. Severe AEs were singular.

Conclusion. Response to NTK therapy generates in the first weeks of drug use and increases throughout a year. The safety profile of NTK when used long is generally favorable.

Objective: to study clinical and laboratory features in patients with anticentromere antibody (ACA)-positive SjЪgren's disease (SD), as well as the sensitivity of different methods for determination of ACA, and to elaborate an algorithm for differential diagnosis in ACA-positive patients.

Patients and methods. The V.A. Nasonova Research Institute of Rheumatology followed up 136 patients who were highly positive for ACA. The investigators used the 2001 Russian criteria for the diagnosis for SD; the 2013 ACR/European League Against Rheumatism (EULAR) criteria for that of scleroderma systematica (SDS); the guidelines of the American Association for the Study of Liver Diseases, the Russian Gastroenterological Association, and the Russian Society for the Study of the Liver for that of primary biliary cholangitis (PBC)/biliary duct epitheliitis in the presence of SD. Lymphomas were diagnosed by biopsies of affected organs according to the WHO classification. SD was diagnosed in 119 patients; SDS in 49 cases (37 with SDS concurrent with SD and 12 with isolated SDS), PBC/biliary duct epitheliitis in 23 (all cases with PBC/biliary duct epitheliitis concurrent with SD and/or SDS); 5 patients were excluded from the investigation. Further analysis included 131 ACA-positive patients. The patients were divided into three groups: SD (n=82 or 62.6%); SD+SDS (n=37 or 28.24%); SDS (n=12 or 9.16%).

Results and discussion. Autoantibodies to centromere peptide (CENP) A and CENP-B in the same titers were detected in all ACA-positive patients, regardless of diagnosis. Comparative analysis of three patient groups revealed no statistically significant differences in the frequency of laboratory deviations. The signs characteristic of classical SD (rheumatoid factor (RF)), anti-Ro and anti-La antibodies, leukopenia, higher ESR values, hypergammaglobulinemia, and elevated IgG/IgA levels) were found in a small proportion of patients. The frequency and severity of glandular manifestations did not differ in SD and SD + SDS. PBC/biliary duct epitheliitis was present in 17.5% of ACA-positive patients (in most antimitochondrial antibody-positive cases); no statistically significant differences in its frequency were found between the groups. Other extraglandular manifestations in SD and SD + SDS were identified in a smaller number of patients. All sclerodermic spectrum manifestations were more common in SD and SD + SDS than in BS. Pulmonary arterial hypertension was not diagnosed in any patient from the SD group. MALT lymphomas were detected in 19 ACA-positive patients. Those were present only in BS patients and absent in the SDS group. MALT lymphomas developed in the first 10 years after the onset of SD. The transformation of MALT lymphoma into diffuse large B-cell lymphoma was observed in 2 patients. The main signs of lymphomas in SD patients were persistent parotid salivary gland enlargement, decreased levels of complement C4 and peripheral blood CD19+ cells, as well as cryoglobulinemic vasculitis, serum monoclonal secretion, lymphoid infiltration in the minor salivary glands (a focus score of >4), and severe damage to the salivary and lacrimal glands.

Conclusion. ACA-associated SD is an independent disease subtype characterized by an increased risk for SDS, PBC, and MALT lymphomas and by a low frequency of the systemic manifestations and laboratory signs characteristic of classical SD. Regardless of the detected type of antibodies and the presence or absence of extraglandular manifestations, damage to the salivary and lacrimal glands progresses in SD, which often leads to lymphomas; therefore, the therapy that may prevent this complication should be initiated as soon as possible after SD diagnosis. The lymphoproliferation signs identified in this investigation should be taken into account in all ACA-positive patients with SD for the early diagnosis of lymphoid tumors before therapy is prescribed. An algorithm for differential diagnosis in seropositivity for ACA is presented. Determination of autoantibodies to CENP-A and CENP-B does not allow the differential diagnosis in ACA-positive patients.

Objective: to assess the time course of changes in the concentration of methotrexate (MTX) and its main metabolites in the red blood cells (RBC) and mononuclear cells (MNC) of patients with rheumatoid arthritis (RA), by taking into account individual characteristics (age, statin therapy, and smoking).

Patients and methods. The investigation enrolled 33 MTX-treated patients (mean age 53.2±11.7 years) with RA, who underwent therapeutic drug monitoring to measure the RBC and MNC concentrations of free MTX and MTX polyglutamates (MTXPGs) with 2, 3, and 4 glutamate residues (MTXPG 2–4) in using tandem chromatomass spectrometry after 4, 12, and 24 weeks of therapy.

Results and discussion. Following 12 weeks, the concentration of MTXPG4 in the MNC was higher in patients taking statins, while that of MTX and MTXPG2 in the RBC were significantly lower than in smokers. At 24 weeks, older patients were observed to have a higher MTX level and a lower MTXPG4 concentration in the RBC.

Conclusion. After 24 weeks of therapy, the RBC concentration of MTPG4 was lower and that of MTX was higher in older patients than in others, which confirms data on a slower MTX metabolism in the elderly. The use of statins is likely to have a positive impact on the accumulation of MTXPG. There is a statistically significantly lower RBC concentration of MTXPG in at 12 weeks of therapy.

In clinical practice, acute-phase protein measurements during inflammation are usually used to monitor the activity and severity of adult-onset Still's disease (AOSD).

Objective: to study the possibility of using the neutrophil-to-lymphocyte ratio (NLR) in complete blood cell count as a marker for the activity and severity of AOSD in clinical practice.

Patients and methods. The investigation enrolled 48 patients (29 females and 19 males; mean age, 32.8±12.5 years) with active AOSD, who met the criteria devised by M. Yamaguchi et al. Along with standard clinical and laboratory parameters and systemic scores, NLR was calculated in complete blood cell count.

Results and discussion. There was a statistically significant correlation of NLR with the level of CRP (r=0.532), ferritin (r=0.43), ESR (r=0.40), and the systemic score reflecting the severity of the disease (r=0.449), which allows NLR to be regarded as a tool that is convenient to assess the activity and severity of AOSD in clinical practice.

Conclusion. The findings have shown the good sensitivity and specificity of NLR, which indicates the possibility of using the latter as an available marker for assessing the activity and severity of AOSD in clinical practice.

Low compliance in patients with gout is one of the reasons for inadequate disease control.

Objective: to study treatment adherence in compliance with the national guidelines for the management of gout patients, which provide for the continuous use of urate-lowering drugs, a gradual increase in their dose until the target serum uric acid (UA) level is reached, prophylactic antiinflammatory therapy, and regular patient monitoring.

Patients and methods. This was a prospective single-center study. By now, 60 of the 80 enrolled gout patients had completed the study. The follow-up period was at least 24 weeks, during which allopurinol or febuxostat was used at the final dose.
During initiation of urate-lowering therapy, allopurinol 100 mg/day was prescribed, followed by dose titration to reach the target UA level (<360 μmol/L) for all patients or <300 μmol/L for those with severe tophaceous gout.
Patients with ineffective allopurinol and/or in the presence of its associated adverse reactions were prescribed febuxostat (Azurix®) 80 mg/day; the dose was increased up to 120 mg/day as needed.
To prevent acute arthritis attacks, all the patients received a nonsteroidal anti-inflammatory drug (NSAID) at minimal therapeutic doses or colchicine 0.5 mg/day, and in the presence of contraindications to their use, they took glucocorticoid (GC) 7.5 mg/day calculated with reference to prednisolone.
The four-item Morisky–Green questionnaire was used to assess patient adherence to therapy.

Results and discussion. At 24 weeks after the start of their follow-up, 53 (88%) of the 60 patients received urate-lowering therapy; 38 (72%) of these 53 patients achieved the target UA level.
The dose of allopurinol was titrated in 19 patients; and 10 (53%) of them achieved the target serum UA levels.
Due to its inefficacy, allopurinol was replaced by febuxostat in 24 patients. In this group, the target UA level was recorded in 16 (67%) patients.
Seventeen patients were immediately prescribed febuxostat that could achieve the target UA level in 12 (71%) of them.
All the patients enrolled in the study received prophylactic anti-inflammatory therapy: NSAIDs were used in 9 (15%) patients, colchicine and GC were given to 46 (77%) and 5 (8%), respectively.
Twenty-six (49%) patients who had completed the investigation were ascertained to have a high adherence therapy. Moderate and low adherence was observed in 9 (17%) and 18 (34%) patients, respectively. High therapy adherence was noted in more than half of cases in the febuxostat group and in 40% in the allopurinol one.

Conclusion. High compliance in gout patients can be achieved through the observance of the national guidelines for the treatment of this disease.

Objective: To evaluate foot disability both ultrasonographically and by using the Foot Function Index (FFI) in patients with axial spondyloarthritis (SpA) and to investigate its effects on patients' quality of life and functional capacity by determining the factors that may affect the level of disability.

Patients and methods. A total of 100 patients were included in the study. Enthesis sites in the feet were assessed for tenderness and swelling. Ultrasonographic examination of the Achilles tendon and plantar fascia was made and the findings were scored according to Glasgow Ultrasound Enthesitis Scoring System (GUESS). The Foot Function Index (FFI) was used to investigate the effects of foot disorders on disability and activity limitation. The correlation between GUESS and FFI scores, and relationship of GUESS and FFI scores with age, disease duration, body mass index (BMI), smoking and disease activity parameters were investigated.

Results and discussion. Physical examination revealed signs of enthesitis in 13 (13%) patients, while ultrasonographic (USG) evaluation – in 36 (36%) patients. A statistically significant correlation was found between all FFI and GUESS scores except between FFI for the right foot and GUESS for right Achilles tendon enthesitis. A positive correlation was found between age and BMI and FFI (p<0.05). There was no correlation between disease duration and smoking and FFI scores. While there was a statistically significant correlation between all scores of GUESS and age, disease duration, and BMI, no correlation was found between smoking and GUESS scores. No significant difference was found in either FFI or GUESS scores between patients with or without / diabetes and patients who were smokers or non-smokers. All FFI and GUESS scores significantly correlated with BASDAI, ASDAS, BASFI, and ASQoL (p<0.05).

Conclusion. Enthesitis may lead to decreased functional capacity and loss of quality of life in ax-SpA patients. Subclinical enthesitis in the feet of patients with SpA is not rare and may be detected by USG.

A combination of chondroitin and glucosamine is widely used in clinical practice as both a symptomatic and structure-modifying agent for the treatment of osteoarthritis (OA). The emergence of new drugs based on this combination substantially expands treatment options for OA therapy.

Objective: to evaluate the efficacy and safety of Artroflex® that is a combination of chondroitin sulfate 400 mg and glucosamine sulfate 500 mg (CS + GS) to support joint health in patients with knee and/or hip OA.

Patients and methods. When implementing an open observational research program, the results of using the CS + GS complex were assessed in 644 OA patients (74.7% women) (mean age, 58.0±14.6 years) who experienced moderate/severe pain and required to continuously take non-steroidal anti-inflammatory drugs (NSAIDs). The CS + GS complex was prescribed in a dose of 2 capsules per day for 3 months. The investigators estimated changes in pain on movement by a 0 to 10 verbal pain scale, general health (GH) by a 0–10 visual analogue scale), the Lequesne index, the need for NSAIDs, and patient satisfaction with treatment and its tolerance.

Results and discussion. After 3-month therapy, there were decreases in pain intensity by 49.2±16.8%, GH scores by 45.6±18.1%, the Lequesne index from 9.0 [6.0; 13.0] to 5.0 [3.0; 9.0]; less than half (45.2%) of the patients still needed for NSAIDs. 82.2% of patients were satisfied or completely satisfied with treatment results; 89.6% reported good treatment tolerance.
Adverse events (apparently associated with NSAID use) were recorded in 2.2% of cases. There were no serious complications that required CS + GS treatment discontinuation or hospitalization.

Conclusion. The findings have indicated that Artroflex® used to support joint health is an effective agent that controls OA symptoms and has a good safety level.

Diffuse cutaneous systemic sclerosis (SSc) characterized by an acute, rapidly progressive course and severe damage to the internal organs has an unfavorable prognosis, while the treatment of this often fatal type of the disease has not been sufficiently developed. This paper reviews an update on an autologous hematopoietic stem cell transplantation (auto-HSCT) procedure, transplantation stages, and conditioning modes in patients with SSc. It presents the characteristics of auto-HSCT studies conducted in 2005 to 2016. The inclusion and exclusion criteria used in these studies are described and their outcomes compared. The results of three randomized controlled trials concerning auto-HSCT are analyzed separately.
These findings confirm that auto-HSCT is currently more effective than standard immunosuppressive therapy. Auto-HSCT produces better results that can provide a more favorable long-term prognosis of SSc; it can prevent worsening of organ damages and improve skin scores and lung function. Patients with early diffuse SSc, a rapidly progressive course, and poor prognostic factors in the first 4–5 years of the disease before the development of functional insufficiency of the vital organs can be considered most promising for auto-HSCT.

Viral infections, hepatitis B and C and herpesvirus-induced infections in particular, are widespread in the population. Recent years have seen the emergence of new viral infections that were previously endemic. Understanding the role of viruses in the pathogenesis of rheumatic diseases (RDs) is of great importance. First, they cause the clinical manifestations characteristic of many RDs (systemic lupus erythematosus, rheumatoid arthritis, polymyositis, and Sjö gren's disease). The author discusses several possible mechanisms of the involvement of viruses in the development of autoimmune disorders: molecular mimicry; polyclonal B cell activation with overproduction of antibodies and immune complexes; T cell activation with cytokine overproduction. Secondly, viral infection can be reactivated during immunosuppressive therapy (also using biological agents), which is widely used to treat RDs.
The review presents data on both the most common viruses (hepatitis B and C viruses, HIV, and human herpesviruses types 1–6) and more rare ones (chikungunya virus and polyomavirus) in the Russian population.

The review considers the problem of comorbid infections (CIs) in ankylosing spondylitis and psoriatic arthritis (PsA) as the main nosological entities of spondyloarthritis (SpA). It analyzes the frequency of CIs during therapy with biological agents and targeted synthetic disease-modifying anti-rheumatic drugs. It is concluded that the problem of CI in SpA deserves the closest attention.
The review also shows the importance of preventive measures for CI in the treatment of SpA. It is in particular noted that in accordance with the updated guidelines of the European League Against Rheumatism and other rheumatology research associations, all patients with immunemediated inflammatory rheumatic diseases (including SpA) on immunosuppressive therapy are recommended to get influenza and pneumococcal vaccines due to the high risk of death from respiratory tract infections. Moreover, vaccination is indicated even for patients with an expected suboptimal response. The review gives the main points of the recommendations of the Medical Board of the National Psoriasis (Ps) Foundation on the use of recombinant Herpes zoster vaccine in patients with Ps/PsA.
There is a need for further investigations of the frequency and pattern of CIs and the impact of new therapy options on the prevalence of CIs in patients with SpA. Determination of the effectiveness and safety of vaccination in this patient population should become an important area for future investigations.

Injectable Alflutop® (the bioactive concentrate from small sea fish (BCSSF)) belongs to the pharmacological group of symptomatic slow-acting drugs for osteoarthritis. This drug has been widely used in our country for 25 years. During this time, 37 of its clinical trials (n=3676) have been conducted in Russia and post-Soviet countries, mainly in patients with knee osteoarthritis (OA) and nonspecific back pain. These are mainly open-label trials, a major portion of which has been performed at the good methodological level, by using active control and up-to-date methods to assess treatment results. Two works are double-blind placebo-controlled trials (DBPCTs) conducted in compliance with the modern requirements of evidence-based medicine – this is an evaluation of the efficacy of BCSSF in knee OA and vertebrogenic lumbar ischialgia. All the trials have shown a good therapeutic potential of BCSSF: on the average, after the cycle use of the agent, there is a 40–60% decrease in pain intensity as compared to the baseline level. A two-year DBPCT of the efficacy of BCSSF in knee OA has also confirmed that the concentrate has a structure-modifying effect. At the same time, all the trials have demonstrated that BCSSF is well tolerated and very rarely causes adverse reactions that require discontinuation of treatment.

Over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) contain a relatively low dose of their active ingredient and are intended for short-term use (for 3–5 days). They are effective and convenient in the treatment of musculoskeletal pain in many clinical situations in rheumatology practice. Over-the-counter naproxen 275 mg has a proven analgesic efficacy, with its action duration of up to 12–15 hours after single-dose administration, and a favorable safety profile. It can be used successfully for the management of exacerbations of osteoarthritis, short-term episodes of pain with a stable course of autoimmune inflammatory rheumatic diseases, with acute nonspecific back pain and at the onset of periarticular soft tissue pathology. With allowance made for the national guidelines for the use of NSAIDs, this drug can be prescribed for a short time as an analgesic therapy in patients at high risk for cardiovascular events. It is of particular value for outpatient practice, since the patients can freely purchase and use it in accordance with the principles of responsible self-medication.

The paper gives the current definition of osteoarthritis (OA), which reflects the pathogenetic and clinical characteristics of this disease, as well as general principles for choosing an OA treatment. It describes the effect of glucosamine and chondroitin on the key pathogenetic mechanisms of OA. It is noted that one of the promising areas of therapy for OA is the intra-articular administration of biopolymer-based hydrogels that provide not only an anti-inflammatory, but also regenerative effect that has been experimentally confirmed during their injection into the tendon sheaths.
There are data on the efficacy and safety of the Russian drug Sphero®gel, a biopolymer-based microheterogeneous collagen-containing hydrogel that belongs to a class of multicomponent biopolymer-based extracellular matrix mimetics. It consists of the cross-linked farm animal tissue-derived collagen microparticles placed in the gel base. The gel is not only a structural base for collagen microparticles; it also has its own therapeutic potential, since it is structurally similar to the natural extracellular matrix. The drug contains collagen, biologically active components of the extracellular matrix, such as proteoglycans, glycoproteins, uronic acids, growth factors, monosaccharides, and chondroitin sulfate. Extended-release symptomatic agents, Sphero®gel among them, are currently recommended for the treatment of OA. Application of Sphero®gel contributes to increased joint mobility and reduced pain, which allows the limited use of nonsteroidal anti-inflammatory drugs that cause adverse reactions, especially in the presence of comorbid diseases.

Effective pain relief in rheumatology practice is one of the most important criteria for the quality of medical care. Therefore, drugs with analgesic effects, primarily nonsteroidal anti-inflammatory drugs (NSAIDs), are among the most commonly used ones in the combination therapy of rheumatic diseases. All NSAIDs are capable of causing to one degree or another extent unwanted reactions that occur in the gastrointestinal tract (GIT), cardiovascular system (CVS), liver, kidneys, and allergic reactions. Considering the widespread use of NSAIDs, the problem of preventing these complications becomes not only medical, but also social.
In 2008, the European Union launched the international project SOS (Safety Of non-Steroidal anti-inflammatory drugs) to study the safety of NSAIDs. The results of this project have shown that aceclofenac is one of the most successful drugs in combining the safety for GIT and CVS. Compared with other NSAIDs, this drug has a minimal risk for GI bleeding (relative risk (RR) 1.43; 95% confidence interval (CI), 0.65–3.15); it does not increase the risk of hospitalization for heart failure (RR, 1.03; 95% CI, 0.91–1.15) or the risk of developing myocardial infarction (RR 1.04; 95% CI, 0.90–1.19) either. The risk of ischemic stroke during aceclofenac therapy was slightly increased (RR, 1.17); but statistically insignificant (95% CI, 0.98–1.39).
A large number of randomized clinical trials, meta-analyses, and observational programs have demonstrated that aceclofenac has pronounced analgesic and anti-inflammatory effects that are comparable to those of other NSAIDs and can be used in diseases accompanied by musculoskeletal pain, including that in older patients.

Gastrointestinal (GI) manifestations, such as abdominal pain, nausea, vomiting, and diarrhea, are common autoinflammatory disease (AID) symptoms. The abdominal symptomatology reflecting serositis is one of the most important classification and diagnostic criteria for the classic monogenic AID (MAID) – familial Mediterranean fever (FMF). Failure to timely diagnose FMF frequently leads to unjustified surgical interventions. Other periodic fevers may also present as abdominal symptoms; however, the latter are outside their diagnostic features. These diseases include, first of all, tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Interleukin 1 (IL1) inhibitors serve as the major targeted drugs for the treatment of TRAPS. Russia has registered the IL1 inhibitor canakinumab that prevents the development of organ damages, including those in the GI tract.
The paper describes a clinical case of the classic manifestations of TRAPS (fever, rash, periorbital edema, arthritis, and elevated levels of acutephase inflammatory markers) concurrent with severe abdominalgia during attacks and with the development of severe peritoneal adhesions, which led to bowel perforation and emergency surgical intervention. The prolonged persistence of inflammatory attacks before the initiation of therapy, as well as violation of the IL1 inhibitor administration regimen facilitated the development of an urgent exacerbation. Thus, TRAPS should be included in the differential diagnostic circle for patients with severe gastrointestinal manifestations characterized by an attack-like course. These patients need timely prescription of targeted therapy, strict adherence to the dosing and intervals between drug administrations, and careful monitoring to prevent serious complications with the visceral organs, including the gastrointestinal tract, and their immediate correction.

Axial skeletal injury is observed in 25–70% of patients with psoriatic arthritis (PsA). Spondylitis frequently occurs subclinically, which leads to serious structural and functional disorders over time. An update shows that axial skeleton involvement in PsA is characterized by a more severe clinical course: these patients are observed to have a greater severity of peripheral arthritis, enthesitis, and dactylitis, skin and nail psoriasis, a higher CRP level, and worse functional status. In addition, the disease is more severe according to the patients' subjective assessment, as evidenced by questionnaires. Synthetic disease-modifying antirheumatic drugs used to treat peripheral PsA are not recommended for axial injury. When nonsteroidal anti-inflammatory drugs are ineffective, biological drugs (tumor necrosis factor-α inhibitors or interleukin-17A (IL-17A) inhibitors) should be prescribed immediately to patients with psoriatic spondylitis.
The paper describes two clinical cases demonstrating the successful use of the IL-17A inhibitor secukinumab (SEC) in patients with axial PsA (axPsA). Given the positive experience with SEC in real clinical practice, it seems reasonable to prescribe it to patients at earlier stages of axPsA.

If standard therapy with nonsteroidal anti-inflammatory drugs is ineffective, biological drugs are usually prescribed for patients with active ankylosing spondylitis. These medicines are purchased in Russia not under their trade names, but under their international non-proprietary ones. This leads to the fact that either originator drugs or their biosimilars are purchased from time to time. For this reason, without a patient' and his/her attending physician's knowledge, the originator drug is switched to its biosimilar, or vice versa.
The paper describes two cases of multiple switches from an originator drug to its biosimilars, or vice versa, which are not clinically indicated. The results of analyzing these cases confirm the opinion that biosimilars may have a significantly different clinical efficacy from their originator drugs.

Nowadays, HIV infection is one of the leading health problems. Its clinical signs are extremely diverse and are associated with many diseases, including rheumatic diseases. This paper describes the course of articular syndrome in a patient with HIV infection.
In the patient given, asymmetric arthritis of the left wrist, first metacarpophalangeal, and knee joints with no damage to the skin and mucous membranes or enthesitis, a negative HLA-B27 test, and the whole clinical picture, as well as no convincing evidence of rheumatic diseases might suggest the presence of arthritis associated with HIV infection. The diagnosis of HIV infection was verified using enzyme immunoassay.
Today, knowledge continues to accumulate about the features of the course of joint damages and another rheumatic disease in the presence of HIV infection. The possibility of its existence to mask a rheumatic disease, as well as the mutual aggravation of any of the diseases and AIDS, should be taken into account in the practice of physicians of all specialties, especially in the inpatient setting where difficult and diagnostically difficult cases concentrate.

Psoriatic arthritis (PsA) is a chronic immune-mediated disease from a group of spondyloarthritis, which is characterized by damage to the musculoskeletal system with a wide range of different clinical manifestations and is usually associated with psoriasis. Activation of the interleukin (IL) 23/IL17 axis plays a key role in the pathogenesis of PsA and psoriasis. When non-steroidal and synthetic disease-modifying antirheumatic drugs are insufficiently effective, biological drugs are recommended. In recent years, there have been considerable advances in PsA treatment with tumor necrosis factor-α (IFN-α) inhibitors and IL-12/23 inhibitors. However, in some cases, this therapy fails to provide the desired effect and a search for new treatments for PsA seems to be an urgent task.
The paper desctibes a clinical case demonstrating the efficacy of the IL17A inhibitor ixekizumab in a patient with high PsA activity and recurrent uveitis in both eyes. Ixekizumab therapy resulted in positive changes as the reduced severity of articular syndrome and psoriasis and normalization of acute phase parameters. Assessing the activity of PsA over time when using ixekizumab during a year showed an average decrease in ESR from 72 to 19 mm/h, in CRP from 162.1 to 0 mg/L, BSA from 51 to 0.25%, PASI from 43. 6 to 0, DAPSA from 78.2 to 2, ASDAS-SRB from 5.11 to 1.12, BASDAI from 4.85 to 1, BASFI from 5.3 to 0.7, BASMI from 5.0 to 2.6, MASES from 6 to 0, LEI from 2 to 0, SPARCC from 6 to 0, and NAPSI from 28 to 8.
Thus, this clinical case is an example of successful treatment with the IL17 inhibitor ixekizumab for PsA with recurrent uveitis in the patient who has previously received three drugs from the TNFα group without any effect.