Immune-mediated Inflammatory Rheumatic Diseases Research Articles

Imbalanced machine learning classification models for removal biosimilar drugs and increased activity in patients with rheumatic diseases.

Predict long-term disease worsening and the removal of biosimilar medication in patients with rheumatic diseases. Observational, retrospective descriptive study. Review of a database of patients with immune-mediated inflammatory rheumatic diseases who switched from a biological drug (biosimilar or non-biosimilar) to a biosimilar drug for at least 6 months. We selected the most important variables, from 18 variables, using mutual information tests. As patients with disease worsening are a minority, it is very difficult to make models with conventional machine learning techniques, where the best models would always be trivial. For this reason, we computed different types of imbalanced machine learning models, choosing those with better f1-score and mean ROC AUC. We computed the best-imbalanced machine learning models to predict disease worsening and the removal of the biosimilar, with f1-scores of 0.52 and 0.63, respectively. Both models are decision trees. In the first one, two important factors are switching of biosimilar and age, and in the second, the relevant variables are optimization and the value of the initial PCR. Biosimilar drugs do not always work well for rheumatic diseases. We obtain two imbalanced machine learning models to detect those cases, where the drug should be removed or where the activity of the disease increases from low to high. In our decision trees appear not previously studied variables, such as age, switching, or optimization.

Long COVID in inflammatory rheumatic diseases-what's in a name?

Long COVID in inflammatory rheumatic diseases-what's in a name?

JAK inhibition in the treatment of inflammatory rheumatic diseases.

The most common immune-mediated inflammatory rheumatic diseases, rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis and have reached significant advances in recent years with the introduction of biological therapies against cytokines and immune cells, but also against intracellular enzymes, specifically Janus kinases (JAKs). Intracellular JAK signalling is activated by binding of various cytokines or growth factors to the respective cellular receptors, allowing the activation of STAT (Signal Transducers and Activators of Transcription) transcription factors and ultimately the transcription of genes with important roles during the innate and adaptive immune response. Four Janus kinases have been described: JAK1, JAK2, JAK3 and tyrosine kinase-2 (TYK2). Four JAK inhibitors (tofacitinib, baricitinib, upadacitinib and filgotinib) are currently approved for the treatment of rheumatoid arthritis, and some for the treatment of psoriatic arthritis and axial spondyloarthritis. JAK inhibitors have varying selectivity against individual kinases. Some JAK inhibitors are being tested in other rarer systemic connective tissue diseases. The general advantages of JAK inhibitors are oral administration, rapid onset of action, and efficacy in monotherapy. The safety profile of JAK inhibitors compared with biologic therapy appears to be comparable, with a higher incidence of herpes zoster, and an increased incidence of major cardiovascular disease, thromboembolic complications, and cancer in at-risk patients is discussed. The aim of this paper will be to summarize the latest findings on JAK inhibitors in approved indications for the most common rheumatic diseases.

The impact of immunomodulating treatment on the immunogenicity of COVID-19 vaccines in patients with immune-mediated inflammatory rheumatic diseases compared to healthy controls. A Swedish nationwide study (COVID19-REUMA).

To elucidate antibody responses after the second and third dose of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with biologic/targeted disease modifying anti-rheumatic drugs (b/ts DMARDs). Antibody levels to antigens representing spike full length protein and spike S1 were measured before vaccination, 2-12weeks after the second dose, before and after the third dose using multiplex bead-based serology assay. Positive antibody response was defined as antibody levels over cut off (seropositivity) in seronegative individuals or≥4-fold increase in antibodies in individuals seropositive for both spike proteins. Patients (n=414) receiving b/ts DMARDs (283 had arthritis, 75 systemic vasculitis and 56 other autoimmune diseases) and controls (n=61) from five Swedish regions participated. Treatments groups were: rituximab (n=145); abatacept (n=22); Interleukin 6 receptor inhibitors [IL6i (n=79)]; JAnus Kinase Inhibitors [JAKi (n=58)], Tumour Necrosis Factor inhibitor [TNFi (n=68)] and Interleukin12/23/17 inhibitors [IL12/23/17i (n=42)]. Percentage of patients with positive antibody response after two doses was significantly lower in rituximab (33,8%) and abatacept (40,9%) (p<0,001) but not in IL12/23/17i, TNFi or JAKi groups compared to controls (80,3%). Higher age, rituximab treatment and shorter time between last rituximab course and vaccination predicted impaired antibody response. Antibody levels collected 21-40weeks after second dose decreased significantly (IL6i: p=0,02; other groups: p<0,001) compared to levels at 2-12week but most participants remained seropositive. Proportion of patients with positive antibody response increased after third dose but was still significantly lower in rituximab (p<0,001). Older individuals and patients on maintenance rituximab have an impaired response after two doses of COVID-19 vaccine which improves if the time between last rituximab course and vaccination extends and also after an additional vaccine dose. Rituximab patients should be prioritized for booster vaccine doses. TNFi, JAKi and IL12/23/17i does not diminished humoral response to primary and an additional vaccination.

Experience with Tixagevimab and Cilgavimab (Evusheld) in 86 rheumatic patients undergoing anti-B cell therapy with rituximab

The problem of prevention of coronavirus disease 2019 (COVID-19) in patients with immune-mediated inflammatory rheumatic diseases (IMRD) remains highly relevant. The presence of IRD is associated with a high risk of disease and severe course of COVID-19 during immunosuppressive treatment, primarily anti-B cell therapy with rituximab (RTX), and a low level of post-vaccination response in such patients. A new strategy for the prevention and treatment of COVID-19 are virus-neutralizing monoclonal antibodies to coronavirus; currently, combined long-acting monoclonal antibodies tixagevimab and cilgavimab (Evusheld) are registered for prevention in the world and the Russian Federation. . Tixagevimab and cilgavimab (TC) show neutralizing activity against SARS-CoV-2, including the Omicron strain, primarily its variants BA.4, BA.5, BA.2.75 ("Centaur").Objective – to evaluate the efficacy and safety of TC for pre-exposure prophylaxis of COVID-19 in rheumatic patients receiving RTX, based on a prospective observational study.Materials and methods. The main group included 86 patients with various IMRD receiving RTX: 50 of them had ANCA-associated systemic vasculitis (AAV), 15 – rheumatoid arthritis, 9 – Sjogren’s syndrome (SS), 4 – IgG4-related disease, 3 – systemic lupus erythematosus (SLE), 3 – dermatomyositis (DM), 2 – systemic scleroderma (SSD). Median age was 59 (19–82) years; male : female ratio – 1:1,8. From March 26 to August 30 2022, patients received a single intramuscular injection of TC in a total dose of 300 mg, mainly after RTX (in 52% of cases, in 28% on the next day after RTX). The control group included 42 patients with AAV (median age – 45 (35–71) years; male : female ratio – 1:1), also treated with RTX, who did not receive pre-exposure prophylaxis of TC. The duration of observation was 7 months, until November 1 2022. At this time, 98% of confirmed cases of coronavirus in the Russian Federation were Omicron. A telephone and/or online survey of patient has been conducted to detect cases of COVID-19 and adverse reactions.Results. In the TC group, confirmed coronavirus infection have been detected in 17 (20%) patients (AAV – 10, SS – 3, SSD – 2, SLE – 1, DM – 1), with fever in 7 (8%), only in one case hospitalization was required (lung damage was not detected in computed tomography), in two cases, according to CT mild lung damage (CT 1–2), there were no deaths. Good TC’s tolerability was noted, signs not associated with COVID-19 or progression of IMRD after administration of TC were observed in 8 (9%) patients (GPA – 3 MPA – 1, RA – 2, SLE – 1, IgG4-related disease – 1), adverse reactions definitely associated with the use of TC were not found. The most serious event not associated with coronavirus infection was the progression of polyneuropathy in a patient with RA. In the control group, 3 (7%) patients were diagnosed with COVID-19, one with severe lung injury (CT 3, pulmonary embolism) and death.Conclusions. The data of clinical studies and our own clinical experience evidence the effectiveness of the use of a combination of long-acting monoclonal antibodies TC (Evusheld), registered for indications for pre-exposure prophylaxis and treatment of COVID-19. Patients with IMRD treated with RTX have a favorable safety profile of TC. The introduction of virus-neutralizing monoclonal antibodies, a new drug class for the prevention and treatment of infectious diseases, opens significant prospects for improving the prognosis of patients with IRD.

P062 Immune responses to mRNA vaccines against SARS-CoV2 in patients with immune-mediated inflammatory rheumatic diseases

Abstract Background/Aims Patients with immune-mediated rheumatic diseases (IMRD) are commonly treated with immunosuppressors and are prone to infections. Recently introduced mRNA SARS-Cov2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-We aim to fully characterize B and T cell immune responses elicited by mRNA SARS-Cov2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccinés immunogenicity. Methods Humoral, CD4 and CD8 immune responses were investigated in 147 SARS-Cov2-naïve patients with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-Cov2 mRNA vaccine. Responses were compared with age, gender, and disease-matched IMRD patients not receiving immunosuppressors and with healthy controls Results IMRD patients showed decreased seroconversion rates (63% vs 100%, p = 0.04) and cellular immune responses (59% vs 100%, p = 0.007). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept deeply affected humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed severely impaired humoral responses but cellular responses were often preserved. Antibody titers were reduced with mycophenolate and azathioprine but preserved with leflunomide. Conclusion IMRD patients exhibit impaired SARS-CoV-2 vaccine-immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show the most deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine’s immunogenicity. Disclosure C. Sieiro Santos: None. S. Calleja Antolín: None. C. Moriano Morales: None. C. Álvarez Castro: None. E. Díez Álvarez: None. J. Garcia Ruiz de Morales: None.

Remote self-collection of capillary blood using upper arm devices for autoantibody analysis in patients with immune-mediated inflammatory rheumatic diseases

ObjectivesTo evaluate the feasibility, accuracy, usability and acceptability of two upper arm self-sampling devices for measurement of autoantibodies and C reactive protein (CRP) levels in patients with immune-mediated rheumatic diseases...

OP0172 THE IMPACT OF IMMUNOMODULATING TREATMENT ON THE IMMUNOGENICITY OF COVID-19 VACCINES IN PATIENTS WITH IMMUNE-MEDIATED INFLAMMATORY RHEUMATIC DISEASES COMPARED TO HEALTHY CONTROLS. A SWEDISH NATIONWIDE STUDY (COVID19-REUMA)

BackgroundInitial studies on the immunogenicity of COVID-19 vaccines in patients with immune-mediated inflammatory rheumatic diseases (IRD) reported diminished antibody response in general, and particularly when treated with rituximab or abatacept (1). Additional data are needed, especially for patients with IRD and immunomodulatory treatments.ObjectivesTo elucidate the antibody response after two doses of COVID-19 vaccine in patients with IRD treated with biologic or targeted synthetic disease modifying anti-rheumatic drugs (b/ts DMARDs) as monotherapy or combined with conventional synthetic DMARDS (csDMARDs).MethodsAntibodies against two antigens representing Spike full length protein and Spike S1 and a Nucleocapsid C-terminal fragment (used to confirm previously COVID-19 infection) were measured in serum obtained before and after the second vaccination using a multiplex bead-based serology assay (2). Patients with IRD receiving immunomodulating treatment, followed at a rheumatology department and healthy individuals (controls) were recruited from five Swedish regions. Antibody positivity was classified as the signal passing an antigen specific cutoff based on the mean intensity signal of 12 selected negative pre-pandemic controls plus 6SD for Spike/S1 and 12SD for Nucleocapsid-C. Good vaccine response was defined as having antibodies over cut-off level for both spike antigens. Percentage of responders in each treatment group was compared to controls (Chi2 test). Predictors of antibody response were determined using logistic regression analysis.ResultsIn total, 414 patients (320 RA/JIA/psoriatic arthritis/axial spondylarthritis, 60 systemic vasculitis and 32 other IRD) and 61 controls participated. Patients receiving rituximab (n=145; 65% female; mean age 65years), abatacept (n=21; 77% female; mean age 66 years), IL6 inhibitors (n=77; 74% female; mean age 64years), JAK-inhibitors (n=58; 75% female, mean age 53years), TNF-inhibitors (n=68; 66% female; mean age 44years;), IL17 inhibitors (n=42; 54% female; mean age 44years) and controls (n=61; 74% female, mean age 49years) were studied. Patients receiving IL6 inhibitor (81.0%), abatacept (43.8%) or rituximab (33.8%) had a significantly lower antibody response rate compared to controls (98.4%), further pronounced if combined with csDMARD (p&lt;0.001) (Figure 1). In the adjusted logistic regression analysis, higher age, rituximab, abatacept, concomitant csDMARD but not IL6 inhibitors, concomitant prednisolone, or a vasculitis diagnosis, remained significant predictors of antibody response (Table 1). All vaccines were well tolerated. 14 (3.4%) patients reported an increased activity in their IRD following vaccination.ConclusionIn this nationwide study including IRD patients receiving b/ts DMARDs a decreased immunogenicity of COVID-19 vaccines was observed in patients receiving rituximab, abatacept and to some extent IL-6 inhibitors. Concomitant csDMARD gave further attenuation. Patients on rituximab and abatacept should be prioritized for booster doses of COVID19 vaccine.

COVID-19 vaccine acceptance over time in patients with immune-mediated inflammatory rheumatic diseases

Before the global distribution of COVID-19 vaccines, we observed substantial concerns among non-immunocompromised people about the lack of long-term research or the occurrence of adverse events after vaccination, and concerns among patients with immune-mediated inflammatory rheumatic diseases about interactions with their underlying autoimmune disease or immunosuppressive treatment regimens.1 Our findings have since been replicated,2,3 but there is as yet no data on how patients' thoughts and behaviour have evolved as vaccines were distributed, or data that compare COVID-19 vaccine coverage between patients with rheumatic immune-mediated inflammatory diseases and healthy controls.

Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory rheumatic diseases

BackgroundPatients with immune-mediated rheumatic diseases (IMRDs) are commonly treated with immunosuppressors and prone to infections. Recently introduced mRNA SARS-CoV-2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were...

Psychiatric aspects of spondyloarthritis

Spondyloarthritis refers to immune-mediated inflammatory rheumatic diseases characterized by the most pronounced pain, inflammatory activity and disability of patients of working age. One of the most frequent comorbid to spondy-loarthritis diseases that weigh down the course and outcomes are anxiety-depressive spectrum disorders. Chronic inflammation with hyperproduction of cytokines of the interleukin-23/interleukin-17 axis and violation of intracellular signaling of these cytokines, developing against the background of a violation of the stress and immune response, is a key pathogenetic mechanism that combines spondyloarthritis and anxiety-depressive spectrum disorders, and dictates approaches to their therapy. The article discusses the current understanding of the prevalence of mental disorders among patients with spondyloarthritis and their negative impact on the course and outcomes of the rheumatic disease, the common pathogenesis and provoking factors, the influence of antidepressants on spondyloarthritis outcomes and anti-inflammatory drugs, primarily interleukin-17 inhibitors and tumor necrosis factor alpha inhibitors on the symptoms of anxiety-depressive spectrum disorders.

Autoimuni inflamatorni sindromi izazvani adjuvansima (silikonskim implantima dojki i filerima)

Introduction: Silicone breast implants (SBI) have been used since 1962 in the reconstruction of post-mastectomy cases, in augmentation of the breast, or for cosmetic purposes, while fillers with biopolymer (FB) have been used since the 1990s. Today, they are considered adjuvants of the immune system. Most complications of SBI and FB are local in nature, but some patients experience systemic symptoms, which are defined as adjuvant-induced autoimmune inflammatory syndrome (ASIA). Aim: The aim of this study is to demonstrate the possible association of silicone breast implants and FB with the development of immune-mediated inflammatory rheumatic diseases (IMIRD). Material and methods: The research represents retrospective study which involved 15 female patients with immune-mediated inflammatory rheumatic diseases, 6 of whom were patients with implanted silicone breast implants for cosmetic reasons, and 9 patients with placement of fillers with biopolymer on the lips. Results: The average time from silicone implantation to the onset of the first symptoms was 6.10 ± 5.3 (range 6 months to 24 years). The following immune-mediated inflammatory rheumatic diseases were recorded: 3 patients with systemic sclerosis (SSc), 3 patients with undifferentiated arthritis, 3 patients with seropositive rheumatoid arthritis, 1 patient with systemic lupus erythematosus, 2 patients with undifferentiated SCTD, 2 patients with mixed connective tissue disease, and one patient with unexplained systemic disease. Seven patients had the Raynaud phenomenon. Spontaneous abortions were reported in 2 patients. Conclusion: Earlier reports that silicone breast implants and biopolymer fillers are safe, today are changing with the description of ASIA syndrome.

Comorbid infections in spondyloarthritis: a modern view of the problem

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.

Type II diabetes mellitus risk assessment using FINDRISC questionnaire in systemic lupus erythematosus patients

Objective. To evaluate the prevalence of traditional risk factors in systemic lupus erythematosus (SLE) patients, assess the 10-years risk of developing type 2 diabetes mellitus (DM) in SLE patients and identify those necessitating preventive interventions following altered glucose metabolism using the Finnish Type 2 Diabetes Risk Score (FINDRISK) questionnaire.Materials and methods. The study included 119 SLE patients (107 women, 12 men, with median age 39 [33; 47] years and mean disease duration 6 [1,12] years.The control group included 100 age and sex matched individuals without immune-mediated inflammatory rheumatic diseases and without previous DM history. The 10-years risk of developing type 2 DM in SLE patients and the controls assessed using the Russian adaptation of Finnish Type 2 Diabetes Risk Score questionnaire. Fasting glucose levels in venous blood were measured in all SLE patients. Glucose levels ≥6.1 mmol/L were interpreted as fasting hyperglycemia.Results. The prevalence of traditional type 2 DM risk factors in SLE patients was as follows: abdominal obesity was found in 63.9%, lack of physical activity – in 62.2%, intake of antihypertensive drugs— in 52.9%, BMI ≥25 kg/m2 in 42.0%, unhealthy diets – in 40.3%, family history of DM – in 35.3%, age over 45 years – in 32.8%, history of hyperglycemia episodes – in 15.1%. Abdominal obesity and intake of antihypertensive drugs were more often documented in SLE patients, while all other risk factors were equally represented in SLE and control groups. On average 3 [2; 5] risk factors were found in each SLE patient. Low type 2 DM risk was a more rare phenomenon in SLE patients vs healthy controls (36.1 and 51%, р&lt;0.05). Primary type 2 DM prophylaxis recommended in case of moderate, high and very high risk was more often indicated in SLE vs the healthy controls (29.4 and 17.0%, р=0.03), including those younger than 45 years (18.3 and 6.1% respectively, р=0.05). Fasting hyperglycemia was found in 1.2% patients with low-slightly increased type 2 DM risk and in 16.1% individuals with moderate, high and very high risk (p=0.04).Conclusions. High prevalence of such traditional type 2 DM risk factors as abdominal obesity, lack of physical activity and intake of antihypertensive drugs was demonstrated in SLE patients. Finnish Type 2 Diabetes Risk Score questionnaire identified moderate, high and very high 10-year risk of developing type 2DM in 29.4% SLE patients, necessitating prophylactic interventions in view of altered glucose metabolism.

Coronavirus disease-2019 (COVID-19): value of IL-6 inhibitors

The coronavirus disease 2019 (COVID-19) pandemic has drawn attention to new clinical and fundamental issues in the immunopathology of human diseases. Since in COVID-19 it is the ‘‘hyperimmune’’ response, called cytokine storm syndrome, which forms the basis of the pathogenesis of acute respiratory distress syndrome (ARDS) and multiorgan dysfunction in COVID-19, special attention is drawn to the possibility of “repurposing” (drug repurposing) of some widely used for treatment immune-mediated inflammatory rheumatic diseases (IMIRDs) anti-inflammatory drugs, including glucocorticoids (GC), disease-modified anti-rheumatic drugs (DMARDs), biologic agents and ‘‘targeted’’ DMARDs. In the spectrum of cytokines involved in the pathogenesis of cytokine storm syndrome in IMIRDs and COVID-19, great importance is attached to the pro-inflammatory cytokine, interleukin IL-6. The development and introduction into clinical practice of monoclonal antibodies (mAbs) that inhibit the activity of IL-6 are among the major advances in the treatment of IMIRDs, and in recent years, critical conditions within the framework of the cytokine storm syndrome, including in COVID-19. The review discusses the materials of numerous studies devoted to the problems of the efficacy and safety of mAbs to the IL-6 receptor (tocilizumab) and other mAbs that inhibit the activity of this cytokine in COVID-19. Despite the effectiveness of inhibiting IL-6 in patients with severe COVID-19, many theoretical and clinical problems of immunopathology and pharmacotherapy of this disease require further study.

Coronavirus disease 2019 (COVID-19) and immune-mediated inflammatory rheumatic diseases: at the crossroads of thromboinflammation and autoimmunity

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.

BARICITINIB: NEW PHARMACOTHERAPY OPTIONS FOR RHEUMATOID ARTHRITIS AND OTHER IMMUNE-MEDIATED INFLAMMATORY RHEUMATIC DISEASES

Deciphering the mechanisms of the pathogenesis of immune-mediated inflammatory rheumatic diseases (IMIRDs) in conjunction with designing a wide range of biological agents is one of the major medical advances in the 21st century. A new promising area of pharmacotherapy for IMIRDs is associated with the design of the so-called targeted oral medications that primarily include Janus kinase (JAK) inhibitors. The review presents new data on the efficacy and safety of the new JAK inhibitor baricitinib in treating rheumatoid arthritis and other IMIRDs.

IMMUNOPATHOLOGY AND IMMUNOPHARMACOTHERAPY OF CORONAVIRUS DISEASE 2019 (COVID-19): FOCUS ON INTERLEUKIN 6

The Coronavirus Disease 2019 (COVID-19) pandemic has drawn closer attention than ever before to the problems of the immunopathology of human diseases, many of which have been reflected when studying immune-mediated inflammatory rheumatic diseases (IIRDs). The hyperimmune response called a cytokine storm, the pathogenetic subtypes of which include hemophagocytic lymphohistiocytosis, macrophage activation syndrome, and cytokine release syndrome, is among the most serious complications of IIRDs or treatment for malignant neoplasms and may be a stage of COVID-19 progression. A premium is placed to interleukin-6 (IL-6) in the spectrum of cytokines involved in the pathogenesis of the cytokine storm syndrome. The clinical introduction of monoclonal antibodies (mAbs) that inhibit the activity of this cytokine (tocilizumab, sarilumab, etc.) is one of the major advances in the treatment of IIRDs and critical conditions within the cytokine storm syndrome in COVID-19. The review discusses data on the clinical and prognostic value of IL-6 and the effectiveness of anti-IL-6 receptor and anti-IL-6 mAbs, as well as prospects for personalized therapy of the cytokine storm syndrome in COVID-19.

Revisiting hydroxychloroquine and chloroquine for patients with chronic immunity-mediated inflammatory rheumatic diseases

Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.

COVID-19: the new challenge for rheumatologists

Currently, the infection caused by the new coronavirus COVID-19 is considered by the global community as an emergency of international concern. Rheumatologists are particularly concerned about this problem, since patients with immune-mediated inflammatory rheumatic diseases (IMIRDs) are at higher risk for infectious diseases and receive immunosuppressive treatment. The use of disease-modifying antirheumatic drugs and biological agents increases the incidence of serious infections, but insufficient/no monitoring of IMIRD activity is an even greater risk factor for infectious complications. In addition, the role of vaccination mainly against influenza and pneumococcal infection is substantially increasing in modern conditions, since the risk of death from respiratory tract infections is quite high in patients with IMIRDs, which is very important in the context of the current COVID-19 pandemic.The paper presents an update on the incidence of viral infections in patients with IMIRDs and also discusses whether antirheumatic drugs can be used to treat COVID-19.