Despite great advances in the diagnosis and treatment of Immune-mediated inflammatory diseases (IMIDs), which have led to a significant improvement in the prognosis in many patients, the central medical problems of this pathology – restoring the quality of life and reducing mortality to the population level – are far from being resolved. This served as a powerful stimulus for the study of new approaches to the pharmacotherapy of IMIDs, one of which is associated with the discovery of targets for small-molecule therapeutics that inhibit intracellular “signaling” molecules JAKs (Janus kinases). The current achievements, trends and recommendations regarding the use of JAK inhibitors in the treatment of IMIDs and also in the hyper-response phase of COVID-19 are reviewed.

The prescribing of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (iJAK) during the COVID-19 pandemic requires a balanced approach and tight monitoring of the patients.

The aim of the study was to study the effect of bDMARDs and iJAK inhibitors on the condition of patients with rheumatoid arthritis (RA), taking the patients reported outcomes, as well as the incidence of COVID-19 in these patients.

Materials and methods. A telephone survey was conducted of 254 patients with RA (average age – 49.8±13.7 years; 64.4% of patients are positive for rheumatoid factor; women – 83.5%; DAS28 score – 5.4±1.6 points), who in the period from January 2020 to June 2021 were prescribed bDMARDs or iJAK for the first time: 148 (58.3%) – rituximab; 57 (22.4%) – tumor necrosis factor α inhibitors; 20 (7.9%) – iJAK; 17 (6.7%) – interleukin 6 inhibitors; 12 (4.7%) – abatacept.

Results. At the time of the survey, 204 (80.3%) patients continued taking prescribed medications. The main reason for the interruption of treatment was administrative problems. Synthetic DMARDs (mainly methotrexate and leflunomide) were received by 68.0%, glucocorticoids – 45.3%, nonsteroidal anti-inflammatory drugs – 44.5% of respondents. Among patients treated with bDMARDs or iJAK, 68.1% noted «the state of symptoms acceptable to the patient», the absence of frequent joint pain – 65.3%, the absence of increased fatigue – 14.3%. The incidence of COVID-19 and hospitalization associated with this disease did not differ in individuals who continued and stopped using bDMARDs or iJAK: 41.2% and 44.6%, 13.7% and 14.0%, respectively (p=0.80884). There were no statistically significant differences in the incidence of COVID-19 and hospitalization associated with this disease in patients taking various bDMARDs or iJAK.

Conclusion. Despite the COVID-19 pandemic, rituximab remains one of the most popular bDMARDs. About a third of patients receiving bDMARDs or iJAK are not satisfied with their condition. More than 40% of patients who received these drugs suffered COVID-19; 14.0% required hospitalization.

To date, there are numerous studies on the effect of COVID-19 on the course of autoimmune rheumatic diseases and the value of vaccination in preventing this dangerous viral infection.

Objective: to assess the effect of coronavirus infection on the course of rheumatoid arthritis (RA), the severity of infection, the effect of current baseline therapy on infection outcomes, and the role of vaccination against COVID-19.

Patients and methods. 134 patients with a reliable diagnosis of RA were interviewed and their outpatient records analysed during the pandemic period from January 2020 to July 2021.

Results. Most of the patients were in the older age group (62.7 years on average), had an average disease duration of 13 years, low to moderate RA activity, comorbidities including arterial hypertension, excess body weight, type 2 diabetes mellitus, etc. All patients received synthetic basic anti-inflammatory drugs (BАID) and glucocorticoids (GC). Thirtyseven (27.6%) patients were vaccinated with the Sputnik V vaccine. Their adverse events were represented by soreness at the injection site (n=6) and transient flu-like syndrome (n=6). Worsening of joint syndrome was reported by 1 patient. COVID-19 was suffered by 43 patients, none of whom were vaccinated. 7 patients were hospitalized, 3 patients died (all had severe comorbidities). In the post-infection period, weakness (64%), memory impairment (48.7%), reduced ability to work (38.5%) persisted for a long time (42 days on average), which was due to the long withdrawal of BАID.

Conclusion. No exacerbations of the disease were noted in those vaccinated with Sputnik V. COVID-19 was detected in 43 (32.1%) patients, 7 of whom required hospitalization and 3 died. Exacerbation of RA in the post-infection period was associated with prolonged withdrawal of BАID.

Actual problems of rheumatology include the possibility of developing a wide range of long-term consequences of COVID-19, so-called post-COVID syndrome (PCS). The results of our own research are presented, during which among 45 patients over 18 years with rheumatic diseases (RD) PCS was detected in 20% cases: 6 of them had ANCAassociated vasculitis (AAV) and one each for rheumatoid arthritis, juvenile arthritis and osteoarthritis. In AAV cases PCS was more severe and varied than in other RD: lung lesions according to computed tomography (up to the damage 75% of the lung parenchyma), skin an d nervous (Guillain–Barré syndrome) lesions, myalgias, arthralgias were present. In most patients PCS ended in recovery, sudden death occurred only in the patient with AAV. The frequency of RD’s relapses in patients with PCS was 9%. Relapses were not noted in AAV, against the background of anti-B cell therapy with rituximab. Our own results and literature data indicate that patients with RD after COVID-19 need careful continuous monitoring to detect long-term complications of coronavirus infection and early diagnosis of relapses of the underlying disease.

The main statements of the recommendations of the American College of Rheumatology and the Vasculitis Foundation on the treatment of patients with systemic vasculitis of large vessels, published in August 2021, are discussed. As a result of a detailed review of current data, a group of experts proposed 22 recommendations and 2 ungraded position statements for giant cell arteritis (GCA), as well as 20 recommendations and 1 ungraded position statement for Takayasu arteritis (AT), on the basis of which algorithms for the treatment of patients with these diseases are presented. An expansion of the value of genetically engineered biological therapy, primarily tocilizumab in GCA and tumour necrosis factor alpha inhibitors in AT, has been recorded. The new recommendations should not be considered as final standards, but are intended to become the basis for choosing a personalized treatment strategy for patients with large vessels vasculitis and serve as a starting point for further research.

Objective. Assessment of clinical manifestations and ultrasonographic signs of enthesitis (En) in patients with psoriasis (PsO) and psoriatic arthritis (PsA).

Subjects and methods. The study is based on the analysis of survey data from 106 patients with PsO for the period 2018–2021, which were firstly sent by dermatologists for a consultation with a rheumatologist due to musculoskeletal pain. The duration of the period of musculoskeletal pain in the observed patients did not exceed 12 months. In addition to general clinical and laboratory examination, all patients underwent ultrasonography of painful and/or swollen joints, tendons and ligaments using a linear sensor (frequency – 12–18 MHz) of MyLab 50 (Esaote, Italy) apparatus and supplemented by Doppler energy study with a pulse frequency of 6.6 MHz. The OMERACT definitions were used to identify En, synovitis and tenosynovitis.

Results and discussion. The diagnosis of PsA was established in 73.6%, osteoarthritis – in 13.2%, gout – in 8.4%, fibromyalgia – in 17.9%. Ultrasonographic signs of En were found in 67.9% of patients: signs of an active inflammatory process in enthesises (decreased echogenicity, thickening and appearance of Doppler signals) were observed in 48.7%, signs of structural damage to enthesial zones (calcifications, enthesophytes and bone erosions) in 25,6% of patients. Isolated En was found in 24.4% of patients, a combination of En and synovitis – in 32.1% of patients, a combination of En and tenosynovitis – in 20.5% of patients. The correlation between the inflammatory domain values of the ultrasoundographic enthesial index MASEI (Madrid Sonographic Enthesitis Index) and the clinical enthesial index LEI (Leeds Enthesitis Index) was 0.71 [0.58; 0.77]. There were less pronounced clinical indicators of enthesial inflammation (lower LEI index values), functional disorders of the joints (lower values of the HAQ-DI index) and laboratory signs of systemic inflammation (lower CRP values) in patients with isolated En in comparison with combination of En and synovitis. Ultrasonographic signs of structural damage of enthesises were observed in 15.4% of patients without clinical and ultrasonographic signs of active En, which may indicate the possibility of a subclinical course of enthesial inflammation in patients with PsO.

Conclusion. It was demonstrated that ultrasonography has diagnostic capabilities to identify the site of the inflammatory process in patients with PsA and differentiate patients with isolated En and a combination of En and synovitis in order to select a method of differentiated anti-inflammatory therapy.

Objective – to find a potential relationship between ACPA and disease activity, bone destruction, and ACPAs responses to various therapeutic regimens.

Materials and methods. The study included 232 patients with rheumatoid arthritis (RA); 90 patients had early RA; 142 patients had advanced stage of the disease.

Results. 77 (85.6%) patients with early RA were high positive for anti-CCP, and 29 (70.7%) patients – high positive for anti-MCV. A positive correlation was found between anti-MCV and DAS28 (r=0.4; p=0.04). As for advanced RA, 78 (80.4%) patients were high positive for anti-CCP, and 70 (79.5%) – for anti-MCV. There was a positive correlation between anti-MCV concentration and SDAI (r=0.4; p=0.02), as well as CDAI (r=0.4; p=0.02). No significant correlations were found between the anti-CCP levels and activity indices, anti-CCP and acute-phase parameters in both early and advanced RA groups. Higher total Sharp scores (96.5 (65.0–122.0)) were found in pts high positive for anti-MCV (n=79), compared to low-positive/negative (n=27) patients (57.0 (31.0–88.0); p<0.05). Anti-MCV levels dropped significantly in pts on rituximab and tocilizumab therapy at weeks 12 and 24 after initiation of treatment, while high anti-CCP concentration persisted throughout the treatment.

Conclusion. Anti-MCV levels correlated with inflammatory activity and development of bone destruction, and were decreasing in pts on treatment. Anti-CCP was less responsive, showed minor changes during treatment, therefore its’ thorough monitoring was not feasible.

Objective – validation of the Russian-language version of the PsAID-12 questionnaire in patients with psoriatic arthritis

Materials and methods. The study included 187 patients, mostly men (50.2%), with a reliable diagnosis of psoriatic arthritis (PsA) according to the CASPAR criteria (2006), who consistently sought medical help at the V.A. Nasonova Research Institute of Rheumatology and those who signed informed consent to participate in the study. Average age was 45.6±11.7 years, duration of PsA – 113.8±76.7 months, duration of psoriasis – 241±144 months, disease activity according to DAPSA (Disease Activity in Psoriatic Arthritis) – 29.1±22.6. At the initial visit and after 12 months of therapy, all patients underwent a standard rheumatologic examination and assessment of the quality of life. The number of tender joint count (TJC 68), the number of swollen joint count (SJC 66), PGA (patient global assessments) were assessed using a visual analogue scale (VAS) (0–10 cm), VAS pain (0–10 cm), BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), PsAID-12 (Psoriatic Arthritis Impact of Disease-12) and EQ-5D (EuroQoL-5D). The EQ-5D was considered the “gold standard” for assessing quality of life. The reliability of the PsAID-12 questionnaire was studied on the basis of its reproducibility by test-retest analysis and internal constancy by calculating the Cronbach’s alpha for each scale. We assessed the validity, i. e., the ability of the PsAID-12 questionnaire to reliably measure its characteristics based on criterional and constructive validity. The criterion validity was calculated by assessing the relationship between PsAID-12 and “external criteria”| reflecting the activity of PsA and interchangeability with the EQ-5D questionnaire using correlation analysis. A moderate and strong bond was considered r≥0.30. Constructive validity was assessed by the method of “known groups” and factor analysis. The study of the reliability of the PsAID-12 questionnaire was carried out in 30 PsA patients. Sensitivity – in 172 patients in dynamics after 12 months of various PsA therapy regimens.

Results. The study of the reliability of the PsAID-12 questionnaire included 30 patients. According to the results of the test-retest analysis, it was revealed that there were no statistically significant differences between the initial and repeated assessments on all 12 PsAID-12 scales (p>0.05). To assess the internal constancy, the Cronbach’s alpha was calculated for each of the 12 scales of the questionnaire. The value of this coefficient ranged from 0.8 to 0.9 and was quite high. Validity was assessed in 187 patients with PsA. The analysis of the criterion validity of the PsAID-12 questionnaire was studied by assessing the relationship of its scales with the scales of the EQ-5D questionnaire, where it demonstrated a close correlation (r>0.3). That testifies to the good interchangeability of this questionnaire. Also, the criterion validity was carried out by assessing the “external criteria” (TJC 68, SJC 66, DAPSA, VAS global assessments, VAS global pain, BASDAI). Where were identified direct correlations of external criteria with all scales of the questionnaire. The highest correlation coefficient (r=0.8) was found between the BASDAI index and the “Physical performance” scale. When assessing constructive validity by the “known groups” method, patients were divided into 2 groups according to disease activity: with DAPSA index ≥5 and DAPSA index ≤4. Significant differences were revealed between the group of patients with active PsA and the absence of PsA activity on all scales of the questionnaire (p<0.001). Factor analysis revealed two main factors – physical and emotional health; a high level of correlation of the scales with their factor was also shown. To assess the sensitivity of the questionnaire, its changes were analyzed depending on the achieved effect on therapy after 12 months: group I of patients in whom MDA was achieved – 50 patients; group II – 43 patients REM/LDA; group III – 79 patients with no effect on therapy. It was revealed that in groups I and II there was a statistically significant difference on all scales of questionnaires, in group III, “non-responders” to therapy, there were no statistically significant improvements in the scales “Pain” (p=0.37), “Fatigue” (p=0.15), “Skin problems” (p=0.23), “Work and/or leisure activities” (p=0.056), “Functional capacity” (p=0.44). Thus, during treatment, it was noted that the PsAID-12 questionnaire may reflect the dynamics depending on the activity of the disease during treatment, which proves its good sensitivity.

Conclusion. The Russian version of the PsAID-12 has good psychometric properties and is able to reflect changes in the patient’s health status over time, along with disease activity and laboratory manifestations.

Immune-mediated rheumatic diseases (IMRDs), based on the leading mechanisms of pathogenesis, are conditionally classified into autoimmune, autoinflammatory, and «mixed pattern». In the spectrum of cytokines involved in the development of the immunopathological process in IMRDs, the “pro-inflammatory” cytokine interleukin (IL) 18, a member of the IL-1 family, plays an important role in the regulation of T-helper (Th) 1-, Th2- and Th17- types of immune response that induces the synthesis of interferon (IFN) γ, other pro-inflammatory cytokines and chemokines. The possibility of determining the concentration of IL-18 in IMRDs is discussed to improve diagnosis, identify subtypes of diseases, and predict the effectiveness of pharmacotherapy. IL-18 is a promising target for anticytokine therapy, primarily in patients with high activity of inflammation associated with hyperactivation of innate immunity.

The article provides an overview of new and promising drugs aimed at anti-inflammatory and urate-lowering therapy of gout, both already registered and used in clinical practice, and at the stages of implementation or clinical research and demonstrating their high efficacy and safety. Modern views and approaches to the treatment of gout, reflected in foreign and domestic clinical recommendations, are shown. Emphasis is placed on the safety and efficacy of colchicine in gouty arthritis and its cardioprotective properties in comorbid patients suffering from gout in combination with cardiovascular pathology. Information is provided on the effectiveness of new anti-inflammatory drugs for symptomatic therapy of gout: kanakinumab, according to the experience of which our country occupies a leading position in Europe. The efficacy and safety of anakinra allows us to consider the drug as an effective alternative to the traditional approach to antiinflammatory therapy of gout. Rilonacept provides doctors with more potential treatment algorithms in a population of patients with gout that is difficult to treat with traditional treatment. The historical data on the use of adrenocorticotropic hormone as an anti-inflammatory agent in gout are given. Information on reserve, new and promising urate-lowering drugs is provided. The focus is on the safety and efficacy of febuxostat, based on the results of recent large randomized clinical trials. Other drugs that reduce the level of uric acid in the blood plasma are considered: uricosuric agents (probenecid, benzbromarone, sulfinpyrazone, lezinurad, verinurad, dotinurad and archalophenate), xanthine oxidase inhibitors (allopurinol and topiroxostat), pegylated uricase preparations (pegloticase and rasburicase), which can be considered in the future as reserve drugs with the possibility of combined applications with the main means for urate-lowering therapy.

The article provides a literature review on the current understanding of respiratory tract damage in primary Sjögren’s syndrome (pSS) with an emphasis on interstitial lung disease (ILD), as well as approaches to the differential diagnosis, treatment, and screening of pSS-ILD.

The purpose of this study: to evaluate the results of conservative treatment of isolated grade II and III PCL rupture in athletes.

Materials and methods. The study included 36 patients who were athletes at a professional level, with isolated PCL rupture, and have been treated non-operative in the period from 2012 to 2020. The non-operative protocol of isolated lesions of the PCL involve, bracing with posterior leg support, rehabilitation program determined by the symptoms and physical signs.

Results. After 2 years from injury, the average score on the Tegner scale was 9 (5–10) (p=0.42). 32 (89%) patients returned to the previous level of sports activity, the average score on the Tegner scale was 9 (7–10). The mean time to return to sports-specific training was 10.6 (4–27) weeks, and the mean time to return to full competitive sport was 16.4 (10–40) weeks. Conclusion. The non-operative management of isolated, Hughston grade II and III PCL injuries gives excellent functional outcomes with a high proportion returning to the same level of sport.

Objective – to assess the effect of patient-specific parameters (age, body mass index (BMI), stage of the knee osteoarthritis (KOA), the osteotomy gap size, concomitant medial opening angle high tibial osteotomy (MOWHTO) arthroscopic plastic (AP) and open chondroplasty (OCHP) on the development of complications and the outcome of the operation.

Materials and methods. The study included 76 patients who underwent MOWHTO. To study the influence of each of the parameters, comparison groups were created: 1) by age: patients younger and older than 60 years (45 versus 31); 2) by BMI: patients with BMI<30 kg/m² versus patients with a BMI from 30 to 40 kg/m² (35 versus 41); 3) by the osteotomy gap size: ≤10 mm and >10 mm (29 versus 47); 4) by stages of KOA: patients with stage I and II versus patients with stage III (43 versus 33); 5) patients with MOWHTO + AP of the knee or OCHP versus patients who underwent only MOWHTO (34 versus 42). To assess the result, we studied the change in pain intensity according to the visual analogue scale (VAS), as well as the state of the knee joint according to the Knee Society Score (KSS) scale before surgery and 1 year after MOWHTO.

Results. The development of complications had a weak direct relationship with stage III of the KOA (r=–0.24) and moderate strength a direct relationship with the osteotomy gap size >10 mm (r=–0.42). Age, BMI, the presence of concomitant AP of the knee or OCHP did not affect the development of complications. However, the number of complications was statistically significantly higher among patients with stage III and osteotomy gap size >10 mm relative to patients with stage II of the KOA (p=0.03) and patients with deformity correction ≤10 mm (p=0.0002). Age over 60 years and BMI<30 kg/m² had a direct weak relationship (r=0.27 and r=0.23) with the achievement of a satisfactory result. An excellent result had a direct weak relationship with a BMI<30 kg/m² and stages I–II of the KOA (r=0.34 and r=0.31), as well as a direct moderate strength relationship with an osteotomy gap size ≤10 mm (r=0.46). At the age of patients over 60 years, a satisfactory result was significantly more frequent compared with patients of young and middle age (p=0.016). 71.1% of excellent results were obtained in patients with a BMI<30 kg/m² (p=0.002), and there were significantly more good and satisfactory results in the group of patients with a BMI>30 kg/m² (p=0.08 and p=0.04). At stage III, an excellent result was obtained 3 times less frequently than in patients with stages I and II of the KOA (p=0.004). In patients with gap size ≤10 mm, excellent results were 1.5 times greater than in patients with a gap size >10 mm (p=0.00006). There were no differences in the results in patients who underwent MOWHTO in isolation and in patients in whom MOWHTO was supplemented with AP of the knee or OCHP.

Conclusions. The development of complications is associated with stage III of the KOA and the need for correction (the osteotomy gap size) >10 mm. The best result of MOWHTO can be obtained in patients under the age of 60 years, with a BMI <30 kg/m² at stages I–II of the KOA and deformity correction within 10 mm. Concomitant AP of the knee or OCHP don’t affect the development of complications and the outcome of the operation.

Study of the interleukin 6 (IL-6) role in chronic autoimmune inflammation has led to the development of innovative treatments for various autoimmune inflammatory rheumatic diseases, including Takayasu’s arteritis (TAK). Given the important role of IL-6 in the pathogenesis of TAK and its association with high clinical and laboratory activity of the disease, tocilizumab (TCZ) is recommended as a second-line drug if both glucocorticoids and basic antiinflammatory drugs are inefficient, and previous therapy with tumor necrosis factor-α (alpha) inhibitors. The article presents our own observation of the successful use of TCZ in a patient with refractory TAK.

Oncogenic osteomalacia is an orphan disease caused by the overproduction of fibroblast growth factor 23 (FGF23) in tumors, which leads to impaired bone matrix mineralization. Typical laboratory changes are hypophosphatemia, increased alkaline phosphatase, hyperphosphaturia, and decreased tubular phosphate reabsorption index. Surgery is the treatment of choice to eliminate an excessive production of FGF23. If surgical intervention is ineffective or impossible, preparations of phosphorus, calcium, vitamin D are prescribed. We present a clinical case of the stage-bystage diagnosis and treatment of the patient with chronic pain syndrome in the bones and multiple fractures.