The coronavirus 2019 pandemic (coronavirus disease, COVID-19), etiologically related to the SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus-2), has once again reawakened healthcare professionals’ interest towards new clinical and conceptual issues of human immunology and immunopathology. An unprecedented number of clinical trials and fundamental studies of epidemiology, virology, immunology and molecular biology, of the COVID-19 clinical course polymorphism and pharmacotherapy have been conducted within one year since the outbreak of 2019 pandemic, bringing together scientists of almost all biological and physicians of almost all medical specialties. Their joint efforts have resulted in elaboration of several types of vaccines against SARS-CoV-2 infection and, in general, fashioning of more rational approaches to patient management. Also important for COVID-19 management were all clinical trials of biologics and “targeted” anti-inflammatory drugs modulating intracellular cytokine signaling, which have been specifically developed for treatment immune-mediated inflammatory rheumatic disease (IMIRDs) over the past 20 years. It became obvious after a comprehensive analysis of the entire spectrum of clinical manifestations and immunopathological disorders in COVID-19 is accompanied by a wide range of extrapulmonary clinical and laboratory disorders, some of which are characteristic of IMIRDs and other autoimmune and auto-in-flammatory human diseases. All these phenomena substantiated the practice of anti-inflammatory drugs repurposing with off-label use of specific antirheumatic agents for treatment of COVID-19. This paper discusses potential use of glucocorticoids, biologics, JAK inhibitors, etc., blocking the effects of pro-inflammatory cytokines for treatment of COVID-19.

An enormous body of evidence on various aspects of the coronavirus disease 2019, COVID-19 associated with the SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus-2) has been accumulated over the past year. Meanwhile, investigated relationship between COVID-19 and rheumatic immune-mediated inflammatory diseases (IMIDs) and certain identified similarities were of paramount importance. It was shown that the incidence of COVID-19 in patients with rheumatic diseases does not significantly differ from that in general population. The risk of severe course and unfavorable COVID-19 outcomes in patients with rheumatic IMIDs is significantly associated with older age and comorbidities – as in general population, and is not aggravated by preceding use of the majority of antirheumatic drugs. Gaining better insights into pathogenesis of COVID-19 provided sound prerequisites for anti-rheumatic drugs repurposing and substantiated their use for treatment of COVID-19 infection. Under current COVID-19 pandemic circumstances, accelerated development and invention of various COVID-19 vaccines offers a great hope to curb the tide of pandemic. However, the efficacy, immunogenicity, and safety of these vaccines in patients with rheumatic IMIDs must be studied in controlled clinical trials. Generally speaking, there are still numerous blind spots in our knowledge of rheumatological aspects of such a versatile and polymorphous condition as COVID-19 infection.

Objective. Currently, the issues of the effect of anti-B cell therapy or inhibitor of interleukin 5 on the risk of COVID-19 infecting and outcomes in patients with ANCA-associated vasculitis (AAV) has not been completely studied. We present an analysis of the COVID-19 course and outcomes in AAV patients treated with rituximab or mepolizumab from one rheumatology center registry.

Methods. From November 11 to November 15, 2020, a cross-sectional study was conducted using telephone and online surveys, and information was collected from all 128 AAV patients treated with rituximab in V.A. Nasonova Research Institute of Rheumatology. Patients mean age was 51 (20–81) years, 61.7% were women. Granulomatosis with polyangiitis (GPA) was diagnosed in 58 patients, microscopic polyangiitis (MPA) – in 38, eosinophilic granulomatosis with polyangiitis (EGPA) – in 24 (including 54.2% of ANCA-negative cases), and AAV with uncertain nosological affiliation – in 8 patients. Due to the disease activity or a high risk of AAV recurrence during the pandemic rituximab was prescribed in 60/126 (47.6%) patients, and mepolizumab – in 6 cases.

Results. In the spring of the pandemic (until May 2020), the incidence of COVID-19 in AAV patients treated with rituximab was 4.3%, the disease course was relatively favorable. All patients recovered. At month 3–6, antibodies to SARS-CoV-2 IgG persisted in only 1 out of 4 patients. Since September 2020, the incidence has increased 3-fold, with a more severe course of COVID-19. In total, in the period until November 11, 2020, COVID-19 was diagnosed in 17.2% (22/128); the mean age of patients was 55 (25–81) years; 54.5% were women. 21/22 patients were on rituximab therapy, 2 patients had mepolizumab therapy (including 1 case after previous rituximab therapy). COVID-19 incidence was lower in patients with GPA (15.5%) vs MPA and EGPA (21.1% and 20.8% respectively). The mortality rate was 13.6%, including 2 patients with MPA and 1 patient with GPA. When analyzing the 5-year survival rate according to the registry of AAV patients treated with rituximab, prognosis worsening was noted; in 2020 there were 3 deaths due to COVID-19, in the previous 5 years – only 2 deaths.

Discussion. Taking into account the fact the mechanisms of AAV and severe COVID-19 are largely synergistic (primarily in the context of microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome as manifestation of the acute inflammatory syndrome), the activity of AAV can potentially contribute to the disease onset and a severe course of COVID-19. Given the previously published information on the use of rituximab during the COVID-19 pandemic for various diseases, it seems that B cell depletion, without reducing the risk of infection, may have a protective effect with regard to the risk of severe/catastrophic COVID-19, which, however, can be insufficient in AAV patients. Further analysis of COVID-19 cases in patients with AAV and other immuno-inflammatory rheumatic diseases is exceptionally important.

Netakimab is a humanized anti-interleukin-17А monoclonal antibody approved for the treatment of psoriatic arthritis, ankylosing spondylitis, moderate to severe psoriasis. Herein, we report the accumulated efficacy data and safety findings of 54-week netakimab treatment during the PATERA study.

The aim of the study was to assess the long-term efficacy and safety of netakimab in patients with active psoriatic arthritis.

Materials and methods. 194 patients with active psoriatic arthritis despite the previous therapy with nonsteroidal anti-inflammatory drugs, conventional or biologic disease-modifying antirheumatic drugs were initially randomized to receive 120 mg netakimab or placebo (1:1) at weeks 0, 1, 2, 4, 6, 8, 10, 14, 18, 22. At week 16 inadequate responders in placebo group were reassigned to netakimab in a blinded manner. From week 24 all patients receive open-label netakimab. The analyzed period includes 54 weeks.

Results. Netakimab demonstrated sustained treatment response. 94.9% of patients in the netakimab group achieved ACR20 at week 54; 89.5% achieved PASI75 response. Axial disease, dactylitis, and enthesitis significantly improved with netakimab. A similar pattern was observed for placebo/netakimab treated patients. Netakimab was well tolerated. The majority of adverse events were mild and moderate. The most frequent treatment-related adverse events were lymphopenia, increased alanine aminotransferase, hypercholesterolemia. Adverse events of grade 3–4 were observed in 2%.

Conclusion. Netakimab demonstrated sustained efficacy in key psoriatic arthritis domains at week 54 with a favorable longterm safety profile.

Aim: to systematize data on the frequency and risk of bone fractures in patients with chronic pancreatitis.

Methods. MEDLINE/PubMed, EMBASE, Cochrane, Google Scholar through October 2020 were searched to identify studies evaluating the prevalence of bone fractures in chronic pancreatitis. For the final analysis, publications with detailed descriptive statistics (total sample size, number of patients with chronic pancreatitis, number of control persons, number of patients with fractures in groups) were selected, allowing the resulting data to be included in the meta-analysis.

Results. The final analysis included 6 studies involving 2 025 918 people (18 844 patients with chronic pancreatitis; 2 007 074 – control subjects). The generalized incidence of fractures in patients with chronic pancreatitis was 14.09% (95% CI: 5.877–25.098). There was significant heterogeneity between the results (p<0.0001; I2=99.58%). Chronic pancreatitis significantly increases the risk of fractures in comparison with control subjects with OR 2.819 (95% CI: 1.855–4.282; I2=97.14%). With the exclusion from the analysis of 2 studies with a wide 95% CI (less than 150 patients with chronic pancreatitis in each), the pooled fracture frequency was 9.25% (95% CI: 1.930–21.221; I2=99.74%).

Conclusion. This meta-analysis demonstrated that CP is a risk factor for fractures. Considering this association, it is advisable to include densitometry in the routine examination algorithms for patients with chronic pancreatitis, as well as to correct osteoporosis in this category of patients in time.

Background. Olokizumab is a new interleukin-6 (IL-6) inhibitor that has demonstrated good efficacy and safety for the treatment of adult patients with moderate to high-grade activity of rheumatoid arthritis in combination with methotrexate with insufficient efficacy of methotrexate monotherapy.

Aim of the study was to evaluate the effectiveness of olokizumab in relation to the patient’s reported outcomes (PROs) based on the results obtained in the CREDO 1 phase III study.

Material and methods. The study included 428 patients with rheumatoid arthritis who were randomized into 3 groups: group 1 – patients who received 64 mg of olokizumab subcutaneously every 2 weeks (q2w) (n=143); group 2 –patients who received 64 mg of olokizumab every 4 weeks (q4w) (n=142); group 3 – patients who had placebo q2w (n=143). PROs included: Health Assessment Questionnaire-Disability Index (HAQ-DI); Patient Global Assessment of Disease Activity (PtGA-VAS); Subject’s Assessment of Pain (VAS); fatigue according to the FACIT-F scale; quality of life according to the EQ-5D questionnaire; physical and mental components of the SF-36 scale. The effectiveness of olokizumab was evaluated by the dynamics of the average PROs values and the proportion of patients who reported improvement compared to the baseline level of ≥ minimum clinically important differences (MCID) for each PROs by weeks 12 and 24 of follow-up.

Results. 396 patients out of 428 included completed the study. When included in the study, patients of different therapeutic groups did not differ in socio-demographic indicators, duration, activity of rheumatoid arthritis, as well as in PROs indicators. Olokizumab therapy, regardless of the dosage regimen of the drug, resulted in a significant improvement in all PROs compared to placebo after 12 weeks, and this improvement sustained until 24 weeks of therapy. The proportion of patients who reached and exceeded MCID at weeks 12 and 24 of follow-up was statistically significantly higher in both olokizumab groups compared to placebo for PtGA, VAS pain, HAQ-DI, FACIT-F. The number of patients who reached or exceeded the MCID on the physical component of the SF-36 scale at week 12 was significantly higher in both olokizumab groups, and at week 24 only in the group 2 compared to the placebo group. The mental component of SF-36 improved in a significantly higher percentage of patients in the group 2 compared to placebo group at weeks 12 and 24, while the group 1 did not significantly differ from placebo group in improving the mental component of SF-36.

Conclusions. Olokizumab therapy in patients with moderate to high-grade activity of rheumatoid arthritis is associated with a significant improvement in all PROs. There was no significant difference between the dosage regimens of olokizumab.

Aim of the study was to clarify the body composition in patients with early rheumatoid arthritis before starting therapy with synthetic basic anti-inflammatory drugs, genetically engineered biological drugs and glucocorticoids using dual-energy X-ray absorptiometry and to assess the effect of inflammation and metabolic syndrome on body composition.

Material and methods. The study included 37 patients (31 women and 6 men) with early rheumatoid arthritis. The control group consisted of 19 healthy donors without rheumatic diseases. Patients with rheumatoid arthritis and the control group were measured by waist size, height and weight, and body mass index was calculated. Body composition was determined by means of dual-energy X-ray absorptiometry using the “Whole Body” program on the HOLOGIC device (USA). The presence of metabolic syndrome was assessed according to the criteria of the International Diabetes Federation (IDF).

Results. Patients with early rheumatoid arthritis had less lean tissue mass, which was negatively correlated with inflammatory markers (ESR and C-reactive protein levels). Overweight and obesity were diagnosed in 24% and 27% of patients with early rheumatoid arthritis, respectively. Patients with rheumatoid arthritis and metabolic syndrome had a higher body weight, body mass index, waist size, and adipose tissue mass than patients without metabolic syndrome. With the help of instrumental methods, it is shown that in rheumatoid arthritis there is a redistribution of fat mass in the body, its predominant accumulation in the trunk area and a parallel decrease in the volume of muscle tissue.

Conclusion. Rheumatoid inflammation and metabolic syndrome affect body composition of patients with early rheumatoid arthritis before the start of antirheumatic therapy.

Objective: to study and analyze the dynamics of prevalence, demographic, social, and clinical manifestations of systemic lupus erythematosus (SLE) in patients living in Kazakhstan.

Materials and methods. Official materials of the Ministry of Health of the Republic of Kazakhstan (2009–2018): statistical compendiums, a consolidated reporting form for medical treatment (N 12). 102 patients (100 women and 2 men) were included in the register of SLE with reliable SLE according to SLICC (ACR, 2012). Assessment of the debut of the disease was carried out according to archival material (medical history, outpatient records) of patients. The activity of the process was evaluated according to SLEDAI-2K, organ damage according to SLICC/ACR (2000).

Results. The total number of patients with SLE over 10 years (2009–2018) more than doubled, the growth rate was 101%. The overwhelming majority of patients with SLE are women (91%). In the study group, Asians (83.33%) predominated by race, of which Kazakhs (76.47%) were young (mean age – 33.85±10.58 years), with a disease duration of 5 (2; 9) years, time from the appearance of the first signs to verification of SLE – 4.5 (3; 12) years. The prevailing acute (49.0%), subacute (33.3%), rather than chronic (18.7%) variants of the course, with high activity according to SLEDAI-2K – 17.64±8.80. The most common clinical manifestations of the disease: skin lesions (98%), joints (79.4%), nervous system (49%), hematological (54.9%) and immunological (100%) disorders. The absence of organ damage (0 points) was detected in 10 (9.8%) cases, low (1 point) – in 21 (20.6%), medium (2–4) – in 61 (59.8%), high (over 4) – in 10 (9.8%) patients.

Conclusion. SLE remains a socially significant disease in Kazakhstan, as evidenced by the dynamics of the increase in incidence (101%) over 10 years (2009–2018). The prevalence of SLE is 24.7 per 100 thousand of the country’s population, lower than in other countries with a predominant Asian population or in comparison with Asian populations. A cohort of patients with SLE was represented by people of the Asian race (83.33%), Kazakhs (76.47%), and young people (33.85±10.58). The analysis revealed a delayed verification of the diagnosis of SLE (on average 4.5 (3; 12) years). Acute variants of the course of the disease with high disease activity according to SLEDAI-2K prevail. Common clinical manifestations of SLE are skin lesions, both acute and chronic (98%), joints (79.4%), damage to the nervous system (49%), hematological (54.9%) and immunological disorders (100%).

The effect of an inhibitor of interleukin-6 (IL-6) receptors on the state of the cardiovascular system in patients with rheumatoid arthritis remains poorly understood.

Objective: to study the effect of therapy with an inhibitor of IL-6 receptors, tocilizumab (TCZ), on the dynamics of modifiable risk factors, total cardiovascular risk, and structural changes in the carotid arteries in patients with rheumatoid arthritis during a 12-month follow-up period.

Material and methods. The study included 40 patients with active rheumatoid arthritis (33 women and 7 men) with ineffectiveness and/or intolerance to basic anti-inflammatory drugs (DMARDs); the median age was 55 (49; 64) years, the duration of the disease – 102 (48; 162) months; DAS28 – 6.2 (5.5; 6.7) points; all patients were seropositive for rheumatoid factor, 80% – for antibodies to cyclic citrullinated peptide. Patients received TCZ 8 mg/kg therapy every 4 weeks: 52% received TCZ monotherapy, 48% received combined TCZ therapy with DMARDs. All patients underwent an assessment of traditional risk factors, the total cardiovascular risk was calculated using the mSCORE, and atherosclerotic vascular damage was assessed by the detection of atherosclerotic plaques.

Results. After 12 months of TCZ therapy, a decrease in disease activity was noted: remission was observed in 25 patients (64%) with rheumatoid arthritis, low disease activity – in 12 (31%); DAS28, HAQ, CRP and ESR concentrations decreased significantly. А high frequency of traditional risk factors was found in rheumatoid arthritis patients: dyslipidemia – 67%, arterial hypertension – 65%, overweight – 55%, burdened heredity for cardiovascular diseases (CVD) – 35%, smoking – 15%. Every third patient had a combination of three or more traditional risk factors. After 12 months of TCZ therapy, the frequency of traditional risk factors did not significantly change, there was an increase in BMI by 2%, an increase in the concentration of HDL-C in serum by 27%, a decrease in the atherogenic index by 28% (p<0.01). Moreover, an increase in the level of HDL-C by the finish was found in patients regardless of statin therapy. Changes in the concentration of other lipids during the observation, including during therapy with statins, were not observed. A negative correlation the dynamics of the levels of ∆HS and ∆CRP (R=−0.37; p<0.05), ∆HS of LDL and ∆CRP (R=−0.42; p<0.01) was found. A very high cardiovascular risk according to the SCORE scale was determined in 78% of patients, moderate – in 2%, and low – in 20% of patients. The distribution of patients by mSCORE value and level of cardiovascular risk were not documented after 12 months of TCZ therapy. No significant structural changes in carotid arteries in rheumatoid arthritis patients were revealed by the end of 12 months of TCZ therapy.

Conclusion. After 12 months of TCZ therapy resulted in decreased rheumatoid arthritis activity, increased the level of HDL-C, atherogenic index, BMI; the frequency of traditional risk factors and the total cardiovascular risk did not change. Despite the very high risk of developing CVD associated with the inflammatory activity of rheumatoid arthritis, the accumulation of traditional risk factors and their combination, subclinical atherosclerotic vascular lesions, no significant structural changes in the carotid arteries were found in rheumatoid arthritis patients on TCZ therapy. Insufficient effectiveness of statin therapy was revealed.

The aim of the study was to study the quality of life of patients with alkaptonuria.

Material and methods. The study included 50 patients with a reliable diagnosis of alkaptonuria aged 18 to 78 years (mean age 58.2±10.8 years). Among them, men predominated (n=31; 62%), in most cases (98%) complaining of pain in the joints and/or spine. For the first time, the articular syndrome debuted at the age of 17 to 39 years (average age of debut – 29.4±4.76 years). The duration of clinical manifestations of the disease before diagnosis ranged from 7 to 47 years (mean 23.35±8.17 years). 74% of patients had a disability group. In the study cohort, the body mass index (BMI) was slightly higher than normal values and averaged 28.18±4.95 kg/m2. The quality of life of patients was assessed using the EuroQol-5D questionnaire (EQ-5D).

Results. The quality of life corresponding to a satisfactory state of health according to EQ-5D was observed in 56% of patients. Their quality-of-life index (LQI) values were more than 0.5. 22% of patients had 0<LQI≤0.5. In some cases, LQI≤0 was detected. In groups with 0<LQI≤0.5 and 0.5<LQI≤1.0, a slight predominance of men was revealed (54.5 and 57.1%, respectively). In the group with LQI<0, these differences were more pronounced, the proportion of men was 81.8% (p<0.01). When comparing the data of this group with the parameters of the most prosperous patients (0.5<LQI≤1.0), statistically significant differences were observed in mobility (p=0.018), personal care (p=0.018), performance of actions in everyday life (p=0.003), pain and discomfort (p=0.003). LQI of patients with alkaptonuria negatively correlated with age (r=–0.38; p<0.01) and the need to use crutches (r=–0.58; p<0.01). Endoprosthetics (at least one large joint) was performed in half (54%) of patients.

Conclusion. In adult patients with alkaptonuria, a significant deterioration in the quality of life was revealed, which is primarily due to damage to the spine and large joints with the need for endoprosthetics in half of the patients. LQI was extremely low, its median was 0.34 [0.02; 0.56] at a norm of 1. Along with traditional tools for assessing joint damage in patients with alkaptonuria, it seems appropriate to use the EQ-5D questionnaire, which reflects various parameters of the quality of life: from the ability to perform actions in everyday life to the severity of pain and depression, which allows screening to receive information about the functional capabilities of patients and develop individual tactics for the provision of medical care, including timely surgical treatment.

Primary hyperparathyroidism (PHPT) is a result of the parathyroid tumors, usually manifesting by elevated serum parathyroid hormone and hypercalcemia. One of the most common complications of PHPT are bone disorders. It mainly occurs as sporadic disease, while the remaining 5–10% is the component of hereditary syndromes, more often – type 1 multiple endocrine neoplasia syndrome (MEN1). MEN1 is caused by the germinal mutation of the oncosuppressor menin gene, founded in all cells of the human body, including the osteogenic cells. Data on the bone state in MEN1 is limited and contradictory. At the same time, some studies indicate that MEN1-related PHPT differs from sporadic form in bone manifestation, which can be presumably associated with the inadequate functioning of mutant menin. The results of experimental works suggest that menin plays an important role in the metabolism and differentiation of bone cells. This article is a literature review on this problem and contains information on the current clinical data on the bone state in patients with MEN1.

The article presents a description of two own observations of the development of acute urate nephropathy in women with asymptomatic hyperuricemia. Clinical data and the results of additional laboratory and instrumental studies are presented; in one of the observations, the morphological picture of intravital biopsy material against the background of prolonged use of diuretics is described. The second case characterizes tophus kidney damage (according to the pathological examination data) without characteristic clinical manifestations of gout in vivo. The authors draw attention to the need to study serum uric acid levels in all cases of acute kidney injury.