Vol 94, No 5 (2022)

Despite great advances in the diagnosis and treatment of immunoinflammatory rheumatic diseases, which have led to a significant improvement in the prognosis in many patients, the fundamental medical problems of this pathology – the restoration of the quality of life and the reduction of mortality to the population level – are far from being resolved. This served as a stimulus for the study of new approaches to the pharmacotherapy of IVRD, one of which is associated with the use of low molecular weight chemically synthesized drugs that inhibit intracellular "signaling" molecules – Janus kinase. Modern advances regarding the use of Janus kinase inhibitors in the treatment of immunoinflammatory rheumatic diseases and COVID -19 are considered.

Aim. To evaluate the possible association of CYP2C8 gene polymorphisms with the clinical efficacy and safety of ketorolac in relation to postoperative pain.

Materials and methods. The study included 107 patients after video laparoscopic cholecystectomy, who received ketorolac (30 mg 2.0 w/m 3 r/d) as postoperative pain relief. All patients were genotyped for CYP2C8. The pain syndrome was assessed using the visual analog scale, the McGill pain questionnaire. The profile of adverse reactions was assessed by the dynamics of red blood counts, as a possible trigger for the development of gastrointestinal bleeding according to the method of global assessment of triggers (Global Trigger Tool – GTT).

Results. According to visual analog scale data: in carriers of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs11572080) after 12, 24, 36, 48 hours the intensity of pain syndrome is lower than in carriers of the wild type (p<0.05). According to the McGill pain questionnaire, there were no statistically significant differences in pain intensity between the two groups.

Conclusion. In carriers of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs11572080), the effectiveness of anesthesia with ketorolac is higher than in carriers of the wild type. Carriage of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs10509681) does not affect the risk of developing adverse reactions after ketorolac anesthesia.

Background. Psoriatic arthritis (PsA) is a complex immune-mediated disease in which a third of patients with psoriasis (PsO) have a inflammatory lesion of both the musculoskeletal system (peripheral joints and axial structures) and extra-articular manifestations (dactylitis, enthesitis, nail PsO, uveitis and inflammatory bowel disease).

Aim. To assess the burden of PsA progression in real practice according to the Russian register of PsA patients.

Materials and methods. Seven hundred thirty seven – M/F=350 (47.5%)/387 (52.5%) – patients with PsA from the Russian register of PsA patients were included. Mean age 47.4±12.7 yrs., duration of PsO 200.6±158.9 mo., PsA – 79.6±81.9 mo. All patients were divided into 2 groups by PsA duration: 1st gr ≤36 mo – 288 (39.1%) and 2nd gr >36 mo – 449 (60.9%). All patients underwent standard clinical examination of PsA activity. Tender (68) and swelling (66) joint count (TJC, SJC), DAPSA, LEI, tenderness of the plantar fascia, PsO BSA (%), PASI, HAQ-DI, PsAID-12, BMI (kg/m²), ESR (mm/h), CRP (mg/l) and comorbidities by ICD-10 were evaluated. Parametric and non-parametric methods of statistical analysis were used. All p<0.05 were considered to indicate statistical significance.

Results. In patients with PsA duration >36 mo we found significant prevalence of erosions by X-Ray, axial PsA, BMI>30 kg/m², HAQ-DI>1, PsAID-12>4, arterial hypertension, metabolic syndrome and overall comorbidity (p<0.05). There were no significant differences between groups in PsO severity by BSA>3%, PASI>1, LEI>1, TJC, SJC, dactylitis, ESR>30 mm/h, CRP>10 mg/l, DAPSA, diabetes mellitus, hyperlipidemia, coronary heart disease and liver damage (p>0.05).

Сonclusion. Long-standing stage PsA is associated with erosions, axial PsA, worst health related quality of life, functional disability and increased cardio-metabolic disorders and overall comorbidity. Our results support the idea to start bDMARDs at early stage of PsA, it can improve better outcomes.

Background. Currently, observations are accumulating indicating the negative effect of therapy with a number of biologic disease-modifying anti-rheumatic drugs (bDMARDs) drugs on the course of COVID-19. These facts determine the relevance of studying the factors of severe course and unfavorable outcome in immuno-inflammatory rheumatic diseases (IIRD) patients treated with bDMARDs in order to develop tactics for managing this category of patients in a pandemic.

Aim. To evaluate the influence of clinical and demographic factors on the risk of development, severity of the course and clinical outcomes of a new coronavirus infection in patients suffering from IIRD and receiving therapy with genetically engineered biological drugs.

Materials and methods. A retrospective analysis of the database of the register of patients with IIRD receiving bDMARDs in the Novosibirsk region was performed, which included 318 patients, 94 of whom had indications of having suffered viral infection/pneumonia for the period from 01.04.2020 to 31.12.2020.

Results. According to the data obtained, at the time of the analysis, 94 people out of 318 patients with IIRD had a new coronavirus infection. Most (53%) of the patients had a mild infection. At the same time, the nosological form, the use of anti-rheumatic drugs and glucocorticoids did not increase the risks of severe coronavirus infection. When using bDMARDs, only anti-B-cell therapy (rituximab) associated with statistically significant increase in the risk of severe/extremely severe COVID-19. The mortality rate according to the analysis of the register was 6,38%.

Conclusion. Patients with IIRD have a high risk of severe coronavirus infection, while the severity of the disease is associated with the type of therapy performed.

Aim. To assess the dynamics of activity of ankylosing spondylitis (AS) during the year after childbirth, to identify predictors of high activity.

Materials and methods. 75 pregnant with confirmed AS (modified New York criteria, 1984) were included for prospective observation. Of these, 44 women were followed up for 1 year after delivery. The average age of the patients was 32.5±5.8 years, the duration of the disease was 149.0±96.3 months. Lactation was established in 40 women and the duration was 10 [4; 12] months.

Results. The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) at 1, 6 and 12 months after giving birth was 2.4 [1.4; 4.2], 2.6 [1.4; 4.4] and 2.7 [1.5; 4.1], respectively (p>0.05). ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score – C-reactive protein) was 2.0 [1.2; 2.7], 1.9 [1.4; 2.5] and 1.7 [1.3; 2.3], respectively (p>0.05). There were no differences between the values of BASDAI, ASDAS-CRP between women with and without lactation. Predictors of high AS activity (BASDAI≥4) 1 month after delivery were: BASDAI≥4 in the 1st (odds ratio – OR 8.1; 95% confidence interval – CI 1,8–37,0) and 2nd trimesters of pregnancy (OR 5.1, 95% CI 1.2–20.6); NRS back pain >4 in the 2nd trimester (OR 4.3, 95% CI 1.1–17.2); cancellation of biological disease-modifying antirheumatic drugs therapy in the 1st trimester of pregnancy (OR 21.0, 95% CI 1.0–440.9). Predictors of high AS activity in 6 months after delivery were: BASDAI≥4 in the 1st (OR 6.5, 95% CI 1.5–28.7), in the 2nd (OR 6.7, 95% CI 1.6–27.8) and in the 3rd trimesters of pregnancy (OR 8.7, 95% CI 1.9–38.6); high activity in 1 month after delivery (OR 4.0, 95% CI 1.0–15.9).

Conclusion. AS activity remains stable for 1 year after delivery. High AS activity during pregnancy was a risk factor for high activity within 6 months after delivery.

Aim. To compare the features of the course of the disease and the therapy in rheumatoid arthritis (RA) patients who meet the criteria of difficult-to-treat RA (D2T).

Materials and methods. The study included 505 RA patients (ACR/EULAR 2010). Rheumatologist experts discussed all patients, since the treatment of RA ware perceived as problematic and/or insufficient. All patients had at least one of the following signs: the activity of the disease is no lower than moderate; the inability to reduce the dose of glucocorticoids to low; rapid radiological progression; RA symptoms causing a decrease in quality of life. The D2T group included 35 patients with true inefficiency or intolerance of two or more of bDMARDs/tsDMARDs of different mechanism of action. The control group (K) included patients with RA who already had experience of taking at least one class of bDMARDs/tsDMARDs (n=291).

Results. On average, every 15 patients (7%) with RA met the EULAR criteria for D2T. The median age of patients in the D2T group was 45 years, which is less than in K (Me 54 [43; 62] years; p=0.046). The duration of RA in both groups was comparable. The severity of articular destruction in D2T was higher than in K (stage IV in 40% and 23%, respectively). Positivity for the RF and ACPA in D2T was less common than in K (60% and 85.9%; 60% and 76.6%, respectively). The presence of systemic manifestations of RA was more typical for K than for D2T (28.6% and 63%, p=0.0001). In the group of D2T patients, the number of previously taken DMARDs was higher than in K (p=0.002). Methotrexate was more often prescribed as the first DMARDs in both groups (in 62.9 and 65.7%, respectively). Initiation of bDMARDs/tsDMARDs therapy in D2T was more often performed by TNF-a inhibitors (OR 2.8; p=0.003) and co-stimulation blocker – abatacept (OR 4.6; p=0.004), and in control – by B-cell inhibitor rituximab (OR 6.9; p<0.0001).

Conclusion. The results of this study suggest that in Russia, as well as abroad, the principle of RA treatment “treat to target” has not yet become widespread, and the development of adequate therapy takes too much time.

Background. The use of virus-neutralizing monoclonal antibodies is an effective method of etiotropic therapy for SARS-CoV-2 in patients of high-risk groups of severe COVID-19. Regdanvimab is a single-component monoclonal antibodies immunoglobulin G1, whose mechanism of action is aimed at binding SARS-CoV-2 virus at the RBD site of the spike protein S1 domain. In the Russian Federation, regdanvimab is approved for emergency administration in COVID-19 for adult patients not requiring respiratory therapy who are at high risk of developing a severe course of the disease.

Aim. To evaluate the efficacy and safety of therapy with regdanvimab in patients with mild/moderate COVID-19 in a short-term hospital unit.

Materials and methods. Virus-neutralizing therapy with regdanvimab was performed at the short-term hospital unit of the Moscow City Clinic. An open retrospective observational single-center study included 92 adult patients with mild/moderate coronavirus infection. All patients had comorbid chronic diseases and belonged to the high-risk group for the development of a severe COVID-19. Inclusion criteria: age 18 to 75 years; presence of a verified diagnosis of COVID-19 of mild/moderate COVID-19, polymerase chain reaction (PCR) confirmed; one or more chronic diseases; first 7 days from the onset of the first symptoms of COVID-19 (including day 7). Exclusion criteria: need for oxygen support. Clinical efficacy was assessed according to the World Health Organization Сlinical Progression Scale and supplemented with laboratory markers at baseline and in dynamics, as well as with monitoring of virus elimination by PCR.

Statistics. Calculations were performed using the statistical computing environment R 4.1.3 (R Foundation for Statistical Computing, Austria). For quantitative indices the median (1; 3 quartiles) was indicated. For binomial signs we calculated 95% confidence intervals according to Wilson's method. Time interval analysis was performed according to the Kaplan–Meier method. The significance level was determined at p<0.05.

Results. A significant decrease in the severity of clinical manifestations according to the World Health Organization Clinical Progression Scale was noted by patients by day 4 after regdanvimab administration. All 92 patients in the cohort were discharged from the hospital l on average on day 5 after regdanvimab administration and on day 9 of the disease. On day 4 after drug administration 82% of patients was being PCR negative. No adverse events related to the administration of regdanvimab were reported during the study.

Conclusion. In real clinical practice, the efficacy and safety of regdanvimab in patients at high risk of severe COVID-19 was confirmed once again, with a positive clinical result observed in a mixed cohort by the causative agent omicron and delta strain.

Sexual dimorphism of chronic diseases is a phenomenon determined by differences in the hormonal status of men and women. In this regard, estrogens, which have a complex effect on the body, are of great interest. In particular, estrogens play an important role in the natural control of pain and inflammation. A decrease in estrogen levels associated with menopause or iatrogenic effects (hysterectomy, use of aromotase inhibitors), as well as mutations of genes responsible for the synthesis of structural components of membrane estrogen receptors (ESR1 and ESR2), can significantly reduce the positive effects of these hormones. Deficiency of estrogen can become one of the reasons for the development of serious pathological changes – in particular, the formation of chronic pain associated with the pathology of the musculoskeletal system.

This article describes the various forms of inflammatory lesions of the aorta and large arteries, including chronic periaortitis, as well as the diagnostic methods are considered. Large vessel vasculitis represent the most common entities, however, there is also an association with other rheumatological or inflammatory diseases, drug-induced or paraneoplastic entities. Instrumental imaging modalities play an important role in the diagnosis.

Systemic vasculitis is a manifold group of systemic autoimmune diseases characterized by the inflammation of the blood vessels. The first clinical cases of systemic vasculitis were described in the Middle Ages, and most of the currently recognised nosological forms were reported in the first half of the 20th century. The first attempt to create a united classification of vasculitis was performed by P. Zeek in 1952. In the following decades accumulation of the data on the etiology and pathogenesis of different vasculitis guided researchers from different countries in their attempts to improve classification. The main principles of classification were the size of the affected blood vessels, disease etiology and pathogenesis. In 1990 American College of Rheumatology (ACR) published classification criteria for seven forms of the systemic vasculitis, that gave a significant contribution to the conduction of large-scale studies in this field. However, the first international nomenclature of vasculitis was developed only in 1994 during the Consensus Conference in Chapel Hill. Revised and augmented version of this nomenclature was created in 2012 and is still valid. An important step in the development of the classification of vasculitis was a joint project of ACR and EULAR aimed to develop new diagnostic and classification criteria for vasculitis (DCVAS). The first result of this project are the new classification criteria for granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis published in 2022. In general, the evolution of the classification of vasculitis occurs under the influence of the progress in the understanding of their etiology and pathogenesis.