Inflammation and coagulation are key basic mechanism of protection against all potentially pathogenic mechanical and biological factors targeting human organism from inner and outer environment. On the other hand, uncontrolled inflammation results in hypercoagulation, inhibition of anticoagulation and alteration of mechanisms responsible for resolution of inflammation, while production of “procoagulant” mediators (thrombin, tissue factor and others), activation of platelets and of vascular endothelial cells maintains inflammation. All factors taken together serve as the basis for a pathological process called thromboinflammation or immunothrombosis. Currently thromboinflammation is considered in the broad sense as a universal pathogenetic mechanism of numerous widespread acute and chronic conditions, including immune-mediated (autoimmune) inflammatory rheumatic diseases, oftentimes complicated by severe irreversible damage to vital organs. Thromboinflammation gained specific attention during СОVID-19 (coronavirus disease 2019) pandemic, caused by SARS-Cov-2 (severe acute respiratory syndrome Coronavirus-2). COVID-19 is considered currently as systemic thromboinflammation syndrome, manifesting via generalized thrombosis of arterial and venous macro- and microvasculature, termed as COVID-19-coagulopathy. The paper discusses common pathogenetic coagulopathy mechanisms in COVID-19 and immune-mediated (autoimmune) inflammatory rheumatic diseases (IMRDs), associated with overproduction of antiphospholipid antibodies, activation of the complement system, and dis-regulated synthesis of proinflammatory cytokines, etc. Delineating the autoimmune subtype of thromboinflammation, identification of genetic (i.e., genes encoding the complement system and others) and molecular-biologic biomarkers associated with higher occurrence of COVID-19-coagulopathy are the most relevant undertakings for the current practice. Gaining insights into mechanisms of thromboinflammation and converting them into potential pharmacotherapies of IMDs would facilitate and accelerate the drafting of effective therapeutic strategies for COVID-19. 

This paper considers the new 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease, discusses essential differences with IgG4-RD comprehensive diagnostic criteria (Umehara H., 2011) and comments their potential use in clinical practice. 

Netakimab (NTK) is a humanized monoclonal antibody targeting interleukin-17A.

Objective. The main objective of BCD-085-5/ASTERA study was to prove superiority of NTK over placebo and assess its’ safety in patients with active AS.

Subjects and methods. BCD-085-5/ASTERA was a double-blind, multicenter, randomized, placebo-controlled, phase III study, which included 228 adult patients with active AS, persisting despite active treatment with NSAIDs. AS was considered active at BASDAI score ≥ 4.0. Patients were blindly randomized (1:1) to receive subcutaneous injections of NTK (120 mg) or placebo at weeks 0, 1, 2 and then every other week up to week 14. Starting from week 16 all patients from NTK group and patients from placebo group not achieving ASAS20 were switched to open label 120 mg NTK s/c once every two weeks. The total duration of treatment with NTK was 3 years.

Results. Higher proportion of patients had ASAS40 response at week 16 (primary endpoint) in NTK arm compared to placebo (40,4 vs 2,6%, р <0,0001, 95% CI [27,4%; 48,1%]). Spinal pain subsided and laboratory inflammation markers decreased within one week after the first NTK injection. NTK safety profile was comparable to that of placebo. The most common for NTK adverse events were neutropenia (7,0%) and ALT increase (6,1%).

Conclusion. Subcutaneous NTK at 120 mg dose demonstrated superior efficacy vs placebo, with fast onset of response and favorable safety profile when used in patients with ankylosing spondylitis. 

Diclofenac Potassium sachets (DPS) is a new faster-absorption and rapid onset of pain relief drug dosage form of Diclofenac with high analgesic potential.

Objective. To assess efficacy and safety of Diclofenac sachets and intramuscular injections in relieving acute pain in patients with rheumatic diseases (RDs).

Materials and methods: The study group included 30 RD patients, 53.3% females and 46.7% males, mean age 41.8 ± 10.7 years, with severe acute pain (≥7 cm VAS pain rating, VAS 0-10 cm). After signing informed consent patients were randomized into DPS 50 mg t.i.d. and Diclofenac 75 mg i/m b.i.d. The first administration of Diclofenac was blind, i.e., patients from both groups were also administered placebo – either placebo injection in Group 1 randomized to sachet or placebo sachet in Group 2. The study lasted for 3 days. Level of analgesia was assessed in 15, 30, 60, 120, 180 minutes after the first administration, then three times a day during two following days and in the morning on day 4. Serum levels of CRP, IL-6 and P substance biomarkers were also monitored.

Results. Pain relief in Group 1 was documented already in 15 min after administration – from 8.1±0.8 to 5.7±1.7 cm VAS (р=0.012), with continuing increase of analgesic effect thereafter. Group 2 demonstrated significant pain relief in 1 hour after Diclofenac administration – from 7.6±0.7 to 4.5±1.9 cm VAS (р=0.04). Based on obtained data analgesic effect was more powerful in Group 1 vs Group 2 in 15 and 30 minutes after drug administration (р=0.019; р=0.037). Starting from the 3rd hour post-administration there was no statistically significant difference in pain intensity between the two groups. Final assessment in the morning on day 4 showed significant pain reduction by 4.5±2.6 cm VAS in Group 1 vs baseline, and by 3.6±1.4 cm VAS in Group 2 (p=0.545). Functional improvement in both groups reached 3.7±1.9 and 3.3±1.3 cm VAS, respectively (p=0.837). The results were rated as “good” and “excellent” by 77.0% in Group 1, and 61.5% – in Group 2 (р=0.302). No correlation between decreasing pain intensity and fluctuating CRP, IL-6, and substance P concentrations was established. Three patients from Group 1 reported new-onset dyspepsia, resulting in discontinuation of treatment in 2 of them. Similarly, 2 discontinuations occurred in 2 patients with new-onset dyspepsia in Group 2, plus one additional withdrawal due to gastric ulcer and elevated blood pressure.

Conclusion. DPS is not inferior to i/m Diclofenac injections in terms of analgesic potential and rapid onset of pain relief. Oral intake is associated with fewer adverse reactions compared to i/m injections. 

Objective. To evaluate B-cell counts in circulation of SS patients prior to initiation and one year after completion of RTM therapy.

Subjects and methods. The study included 71 patients. Median follow up was 13,2±2,0 months (11-18 Mo.). Average cumulative RTM dose during the follow up period was 1,43±0,60 g, with 48 patients receiving < 2 g RTM (Group 1, mean dose 1,1±0,1 g) and 23 patients receiving ≥ 2 g RTM (Group 2, mean dose 2,2±0,6 g). CD19+ lymphocyte counts in peripheral blood were determined using flow cytometry in PSS patients and 20 healthy volunteers matched by sex and age. In SS patients B-cell counts were obtained before initiating RTM, within first month after first administration, then after 6 months and at the end of this study.

Results. Baseline absolute and proportional В-lymphocyte counts in peripheral blood was almost similar in SS patients and healthy subjects. Highest counts were observed in SS patients with <3 years disease duration, showing inverse correlation between baseline absolute (R – 0,36, р=0,003) and proportional (R – 0,48, р=0,001) B cell counts and duration of the disease. Complete B-cell depletion from peripheral circulation was documented one month after RTM administration. It persisted in 79% 6 months later, although initiation of B- cell repopulation was documented in some patients. In one year after RTM initiation В-cell counts were significantly lower than at baseline. Complete or partial depletion was still there in the majority of patients with normal counts achieved only in 10% of SS patients. Inverse correlation was found between absolute B-cell count and cumulative RTM dose (R=-0,237, p=0,048).

Conclusion. Higher RTM doses resulted in more pronounced В-lymphocytes depletion and more evident improvement of lung function. Current state of practice requires further research to identify most optimal regimens in the context of personalized therapy for SS and other immune-mediated inflammatory diseases. 

Objective. To compare clinical features in psoriatic arthritis (PsA) patients with and without axial involvement.
Subjects and methods. 385 PsA patients (172 males and 213 females) from National PsA Register were examined, their diagnosis verified according to CASPAR criteria. Patients’ median age was 45 [35; 54] years, median disease duration – 5,1 [0; 8] years. Pelvis X-ray and HLA-B27 levels in addition to physical examinations were obtained in all patients. Sacroiliitis (SI) was established based on radiographic findings (rSI) including bilateral changes corresponding to at least stage II, or unilateral – corresponding to at least stage III of Kellgren-Lawrence radiographic grading scale. Patients’ radiographs were evaluated by an independent radiologist. Disease activity was assessed using the DAS28 (Disease activity score 28), DAS (Disease activity in psoriatic arthritis) and BASDAI (Bath ankylosing spondylitis disease activity index) scales. 100 mm visual analog scale (VAS) was used for assessment of pain intensity (PI) and the Patient’s Global Assessment of Disease Activity (PtGA). Patients were distributed into two groups: Group 1 included rSI(+) patients, Group 2 – patients without radiologically confirmed SI – rSI (-).
Results. Group 1 included 214 (55,6%) patients with axial involvement, 106 males and 108 females, Group 2 rSI (-) – 171 (44,4%) patients, 66 males and 105 females Proportion of men was significantly higher in RSi(+) group – 49,5% vs 38,6% in rSi(-) group (Odds Ratio, OR – 1,56, 95% CI 1,6-2,4; р = 0,0324). Patient’s median age was 45 [35; 54] and 46 [34; 56] years, respectively (p=0,911). Higher rates of HLA-В27 positivity were found in group rSI(+) patients, than in rSI(-), respectively in 62 out of 126 and in 26 out of 78 patients (OR 1,9, 95% CI 1,1-3,5). Patients from RSI(+) group had more severe erosive peripheral arthritis. Median tender joint counts (TJC) were 9 [14; 18] and 6 [3; 12] (р=0,02), while radiographic feet bone erosions were found in 58 (27,1%) and 29 (17%) patients, respectively (OR 1,8, 95% CI 1,1-3,0). Disease activity was higher in rSI(+) group. Median DAS28 score was 4,3 [3,3; 5,6] and 4,05 [3,03; 4,88] (р=0,02), DAPSA – 28,40 [15,65; 43,65] and 20,0 [12,45; 30,0], (р < 0,01), BASDAI – 1,6 [0; 5,1] and 0 [0; 4,5] (р < 0,01), C-reactive protein (CRP) – 0,9 [0,4; 2,2] mg/dl and 0,8 [0,3; 1,3] mg/dl, respectively (р=0,029). PtGA VAS values were 56,5 [42,3; 70,0] mm and 50,0 [30,0; 60,0] mm (р < 0,01); physicians global assessment (PGA) – 54,0 [40,0; 69,5] mm and 40,0 [25,5; 50,0] mm (р < 0,01); PI VAS values were 50,0 [40,0; 70,0] mm and 50,0 [20,5; 58,8] mm, respectively (р < 0,01). Higher rates of entheses involvement based on the Leeds Enthesitis Index (LEI) and dactylitis were documented in rSI(+) group. Median LEI score was 0 [0; 2] and 0 [0; 1] (p=0,02), while dactylitis was established in 71 (31,2%) and 32 (18,7%) patients, respectively (OR 2,2, 95% CI 1,3-3,5). More severe cutaneous involvement was also found in rSI(+) patients as compared to rSI (-). BSA (Body Surface Area) > 3% involvement was established in 94 (43,9%) and 57 (33,3%) patients, respectively (OR 1,7, 95% CI 1,03-2,4). Axial involvement was associated with more pronounced functional impairment. Median HAQ was 1,0 [0,6; 1,5] and 0 [0-2,2] (р=0,02).
Conclusion. Axial involvement in PsA patients is associated with more severe articular damage, higher enthesitis and dactylitis rates, more severe psoriasis, which should be considered when planning treatment.

Objective. To evaluate the relationship between the manifestations of the immune-inflammatory process with dyslipidemia and morphofunctional parameters of the myocardial state in patients with chronic heart failure (CHF) with a preserved left ventricular ejection fraction (CHF-SFV) against the background of seropositive rheumatoid arthritis (RA).

Subjects and methods. The study involved 57 women with CHF-SFV, formed as a result of coronary heart disease and/or hypertension. All patients had functional class I and II according to NYHA. All patients were divided into comparable groups: the first group included 31 patients with a combination of CHF and seropositive RA of radiological stage I-III, the second group included 26 patients without RA. Patients with RA had a low and moderate degree of activity according to DAS28. The Diagnosis of CHF was verified by ESC (European Society of Cardiology) criteria, the diagnosis of RA – by EULAR/ACR criteria (2010). The therapy was in line with current clinical recommendations. Methotrexate was used as a basic anti-inflammatory drug in patients with RA. The average dosage was 12,9±2,5 mg/week. In the study groups, a comparative analysis of the main laboratory and instrumental indicators used in the diagnosis and monitoring of CHF, as well as the relationship of manifestations of the immunoinflammatory process with dyslipidemia and indicators of diastolic myocardial dysfunction was performed. 

Results. The level of total cholesterol in the CHF group without RA averaged 4,4±0,9 mmol/l and 5,2±2,2 mmol/l in the CHF and RA group (p=0,09); triglycerides – 1,9±0,7 and 1,5±0,9 mmol/l (p=0,3); low-density lipoproteins (LDL – C)-2,6±0,8 and 3,1±1,1 mmol/l (p=0,04); high – density lipoproteins (HDL-C) – HDL) – 1,3±0,2 and 1,3±0,1 mmol/l, respectively (p=0,7). In the group of CHF on the background of RA, a direct relationship between the intake of methotrexate (the average dose was 12,9±2,5 mg/week) and the level of HDL-C: R=0,3; R2=0,1; F=0,9; (p=0,01). In the group of CHF and RA, there was a statistically significant relationship between the ratio of transmittal flow parameters with the level of DAS28 and RF: R=0,5; R2=0,3; F=2,6 (p=0,04).

Conclusion. Against the background of the immuno-inflammatory process caused by RA, a significant increase in the level of LDL was detected, which can negatively affect the course of dyslipidemia in patients with CHF-SFV. There was an increase in the concentration of HDL on the background of treatment with methotrexate in the group of CHF-SFV and RA. A direct correlation of the ratio of parameters of the transmittal flow with the RF and DAS28 levels was found. This relationship may affect the progression of left ventricular diastolic dysfunction in the group of CHF and RA, but prospective studies are needed to clarify its role. 

Objective: To evaluate maternal and neonatal pregnancy outcomes in ankylosing spondylitis (AS) patients.

Subjects and methods. The prospective study included 36 pregnant women with AS (modified New York AS criteria, 1984), all participants were followed. Mean patients’ age was 31.6±4.8 years, age at disease onset – 21.8±10.9 years, duration of the disease – 134,9±89.3 months. Stage II-III sacroiliitis was diagnosed in 88.9% of women, stage IV – in 11.1%. AS activity levels measured by mean BASDAI score in I, II and III trimesters were 2,8±1,7 – 3,2±1,9 – 3,3±2,1, respectively.

Results. 34 pregnancies resulted in live births at median 39 [38; 40] weeks of gestation. Adverse pregnancy outcomes were documented in 2 cases (5.6%): a missed miscarriage at 18 weeks of gestation in a woman with burdened maternal obstetric history and moderate AS activity; and medical abortion at 23d week of gestation because of fetal critical condition owing to persistent high AS activity with severe axial and extra-articular manifestations of the disease. Most common pregnancy complications included threatened early miscarriage (11.1%), threatened premature labor (11.8%), infectious and inflammatory conditions (pyelonephritis in pregnancy, acute respiratory viral infections – 36,1%), iron-deficiency anemia (19,4%), gestational hypothyroidism (11,1%). Preterm birth was documented in 5,9% patients. No association was found between disease activity, therapy, and preterm birth. There were no cases of preeclampsia. 52.9% of the patients had vaginal delivery, and 47.1% had a caesarean section (CS), which was elective in 87.5% of all CS cases. Indications for elective CS included severe hip joints involvement with altered function, and scar on the uterus. Emergency C-section was performed in cases of uterine inertia and preterm discharge of amniotic fluid. Average birthweight of newborns was 3384.4±382.0 g, and length –51.5±2.0 cm, Apgar score was 8.0±0.4/8.9±0.4. Early neonatal complications were documented in 14,3% newborns, Congenital abnormalities were registered in 3 (8.6%) newborns: a slit-like defect of the atrial septum, a defect of the interventricular septum, and unilateral hydronephrosis.

Conclusion. Pregnancy outcomes in AS patients practically do not differ from those in general population, except for higher rates of elective C-sections, being generally favorable given AS activity is adequately controlled and gestation &delivery are thoroughly monitored. AS is not associated with higher rates of severe pregnancy complications and preterm birth. AS seemed to have no negative impact on newborn anthropometric data and health condition in general. No severe neonatal complications occurred. Considering the small sample size, it is impossible to draw definite conclusions about occurrence of various malformations in newborn to mothers with AS at this particular stage of the research. Interdisciplinary consensus is necessary in place to optimize pregnancy and birth management in AS patients 

Modern therapy for rheumatoid arthritis (RA) allows not only to reduce the activity of immune-mediated inflammation and slow down the progression of the disease, but also to quickly eliminate the main symptoms that cause the most concern to patients, such as pain, functional disorders, fatigue. This action has an inhibitor of Janus kinases 1/ 2 – baricitinib, which quickly reduces the activity of inflammation, provides remission in RA, and has a high analgesic effect. The review discusses the role of autoimmune inflammation and the intracellular signaling pathway JAK/STAT (Janus kinase/signal transducers and activators of transcription) in the pathogenesis of chronic pain in RA, the role of baricitinib for effective control of pain intensity and fatigue. 

Non-infectious uveitis is the leading and insufficiently studied cause of irreversible decline in visual functions in patients with immune-mediated inflammatory rheumatic disease (IMIRDs). A multidisciplinary approach to the diagnosis and treatment of uveitis in patients with IMIRDs, involving close collaboration of rheumatologists and ophthalmologists, is the key factor for achieving favorable clinical outcomes. This article sheds light on current clinical, differential diagnostic and therapeutic challenges related to non-infectious uveitis in IMIDs-patients, with specific emphasis on state-of-the art approaches to therapy. 

Neuropsychiatric disorders in juvenile-onset systemic lupus erythematosus (SLE) stay in the focus of attention in recent decades due to significant influence of CNS lesions on SLE course in general, necessity to optimize therapeutic interventions and outline prognosis. This paper considers the prevalence of neurolupus in children and adolescents, specific features of the clinical picture, possible relationships with other SLE manifestations and immunological disorders, aspects of neuropsychiatric disorders pathogenesis and potential influence of growing and developing nervous system on SLE course, resulting in varying neurolupus manifestations and prognosis. 

Immunotherapy with immune checkpoint inhibitors (ICIs) opens up new prospects in treatment of malignancies, although this novel therapy quite often results in development of immune-related adverse events (irAEs), which can limit their clinical use. IrAEs can affect almost any organ system, including the endocrine, respiratory, digestive, nervous, other organs and the skin. Most often irAEs are characterized by moderate degree of severity, but complications are fatal in 2% of patients.The nature of irAEs significantly differs from the adverse reactions associated with use of standard chemotherapeutic agents, which usually cause immunosuppression (due to neutropenia). Of particular interest to clinicians are rheumatic irAEs, which can occur at any time after treatment and tend to persist even after ICIs discontinuation. This review analyzes the prevalence, clinical characteristics, and approaches to treatment of rheumatic irAEs. 

All current challenges and concerns associated with rheumatoid arthritis (RA) in the elderly are analyzed from the point of view of a practicing rheumatologist, including issues of terminology and diagnostics, the need to develop classification criteria for RA presenting at old age. This paper also discusses RA management in the elderly during the coronavirus disease 2019 (COVID-19) pandemic. A multicenter international study, initiated by the League of Eurasian Rheumatologists, can provide necessary insight to develop unified recommendations for RAP. 

Objective. To analyze early surgical outcomes after total hip replacement in systemic lupus erythematosus (SLE) patients.

Subjects and Methods. The study included 42 SLE patients with femoral head osteonecrosis (ON) undergoing 59 total hip replacement (THR) surgeries at the traumatology and orthopedics department of VA Nasonova Research Institute of Rheumatology during 1998-2013 yy. All patients were thoroughly evaluated at baseline and one year after surgery using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), damage index (DI) of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) to assess the degree of irreversible organ damage, Harris hip function scale, and VAS for pain intensity to assess early results of THR procedure.

Results. Significant improvement of pain intensity was documented based on VAS assessments, as well as hip function improvement from 40,0±14,9 (13,8 – 82,7) to 80,8±12 (46,7-96,0) scores based on Harris scale, improvement of SLE activity based on SLEDAI-2K assessment: from 0 -20 scores (median 4[4;8]) at baseline to 0 – 43 scores (median 0[0;4]) at one year, and DI – from 0-12 (median 3[2;5]) to 0 -15 scores one year after THR procedure. Complications including dislocation of femoral component, peroneal nerve paralysis, periprosthetic fracture, venous thrombosis, and delayed wound healing were documented totally in 10,2% of patients. No post-surgery deaths occurred.

Conclusion. The results obtained are indicative of better pain control and improved hip function following THR in SLE patients. 

Despite numerous publications on COVID-19, at present, conceptual thinking of the problem is only at a nascence stage. Treatment of patients with ANCA-associated systemic vasculitis (AAV) during the COVID-19 pandemic is one of the relevant issues. Management of COVID-19 in AAV patients undergoing anti-B cell therapy with rituximab (RTM) requires comprehensive reasoning. This paper presents a case report about COVID-19 in a 59-year-old female with AAV in remission, who was previously treated with RTM. COVID-19 was diagnosed one month after the last RTM administration; there were moderate bilateral pneumonia, fever, and extrapulmonary manifestations, including lesions of the gastrointestinal tract and central nervous system. Clinical outcome of COVID-19 was favorable, with no signs of respiratory failure, and CRP values did not exceed 29 mg/l. We discuss published data on RTM use during COVID-19 pandemic and the effects of B cells and their depletion on the course and outcomes of COVID-19. Our case report and available published data do not allow to consider RTM therapy as a factor associated with severe course of COVID-19 and adverse outcome. Further analysis of COVID-19 in patients with AAV and other rheumatic diseases is important.