In patients with immune-mеdiated (autoimmune) rheumatic diseases (IMIRD), there are a number of factors (advanced age, uncontrolled inflammation, initially irreversible damage to internal organs, comorbid pathology, genetic and other factors) that can potentially lead to an increase in “sensitivity” to SARS-CoV -2 (severe acute respiratory syndrome coronavirus-2) and concomitant viral and bacterial infections, an increase in the risk of a severe course of COVID-19 (coronavirus disease 2019), a decrease in the effectiveness of therapy for both IMIRDs and COVID-19. An important area of pharmacotherapy for IMIRDs and other autoimmune diseases is associated with the use of anti-B-cell drugs, primarily rituximab (RTX), which is a chimeric (mouse/human) monoclonal antibody (mAb) to the CD20 antigen of B cells. At present, in Russia, the RTM biosimilar, acellbia (BIOCAD), is widely used, which is not inferior to RTX in terms of efficiency and safety. The problems of anti-B-cell therapy during the COVID-19 pandemic in relation to the risk of infection, severe course and insufficient effectiveness of vaccination against SARSCoV- 2 are considered. According to the recommendations of the Association of Rheumatologists of Russia, a more rigorous assessment of indications for induction and maintenance therapy of RTX therapy and harmonization of the timing of drug administration and vaccination is required.

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Деплеция в-клеток при иммуновоспалительных ревматических заболеваниях и коронавирусная болезнь 2019 (covid-19)

The problem of coronavirus disease 2019 (Coronavirus diseases, COVID-19) two years later still remains relevant both socially and medically. As one of the methods of combating the current COVID-19 pandemic, most experts rely on the widespread use of vaccination. However, the use of vaccines against SARS-CoV-2 in patients with rheumatic diseases (RD) raises a number of issues related to the effectiveness, immunogenicity, and safety of immunization, including leveling the risks of exacerbation of the underlying disease or the development of new autoimmune phenomena. For this reason it is very important to analyze data on the above-mentioned aspects in real time, especially given that patients of the rheumatology circle were excluded from the clinical development programs of vaccines against SARS-CoV-2. This review presents the results of last year’s research on the safety of vaccination against COVID-19 in patients with RS. A brief description of the main anticovedic vaccines is given. Post-vaccination adverse events were quite frequent after the first, second or both doses of vaccines in patients with RS, which is consistent with the data obtained in the general population. In general, the frequency of exacerbation of RD after vaccination against COVID-19 seems to be quite low (5–7%) and has no significant associations with a specific vaccine or anti-rheumatic therapy. At the same time, unambiguous interpretation of these data is difficult for at least three reasons: a) in many studies, only the symptoms developing after the first dose of the vaccine were taken into account; b) the time-limited post-vaccination follow-up period; c) significant discrepancies in the interpretation of exacerbations of the disease. Within the framework of the problem under consideration, there are still a lot of questions, the answers to which should be obtained in large prospective controlled studies.

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Vaccination against SARS-CoV-2 in rheumatic diseases: Safety issues

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

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Janus kinase inhibitors in immunoinflammatory diseases: 10 years of clinical practice in rheumatology

In the third year of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2, COVID-19) pandemic doctors are encountering a new pathology – post-COVID-19 syndrome (PCS, long covid). Musculoskeletal manifestations are among the most common and may present as myalgia, arthralgia, or arthritis. Currently, there is no generally accepted definition of the disease, its duration, classification, or diagnostic criteria, and no single view on the “content” of musculoskeletal manifestations of PCS. We have enough descriptions of the debut of rheumatoid arthritis (RA) after SARS-CoV-2. That is a question: it is a coincidence, or COVID-19 may be a trigger factor of RA? We thought that SARS-CoV-2 infection may be a trigger factor for new rheumatic musculoskeletal diseases, including rheumatoid arthritis or COVID-19 can unmask previously undetected RA. The occurrence of arthritis may be a sign of PCS with transient character. So arthritis in the post covid period may induce problems in differential diagnosis of rheumatic diseases. 

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Rheumatoid arthritis and post-COVID-19 syndrome

Objective: to assess the safety of COVID-19 vaccines in patients with immunoinflammatory rheumatic diseases (IRD) in real clinical practice.Patients and methods. A cross-sectional study of patients with IRD, who were admitted to V.A. Nasonova Research Institute of Rheumatology for inpatient or outpatient treatment. All patients received at least 1 dose of vaccine against COVID-19 (main group). The control group consisted of vaccinated persons without IRD. All participants were interviewed by the researcher by filling out a unified questionnaire, additional information was obtained from medical records.Results and discussion. The study included 204 patients with IRD (151 of them were vaccinated with Sputnik V, 31 with Sputnik Light, 19 with СoviVac, 3 with EpiVacCorona; 173 patients received the second component of vaccine) and 131 subjects without IRD (101 of them were vaccinated with Sputnik V, 17 – CoviVak, 5 – Sputnik Light, 2 – EpiVacCorona, 6 – Pfizer/BioNTech; 124 patients received the second component of the vaccine). The number of patients with IRD who had both local and systemic reactions after administration of the first component of the vaccine was significantly less than in the control group (19.6 and 38.9%, respectively; p<0.001). Similar differences were noted after the administration of the second component (15.6 and 27.4%, respectively; p=0.013). Adverse events (AEs) such as pain at the injection site without restriction of movement, weakness, fever, arthralgia/myalgia and chills were significantly more common in the control group after the administration of the first component of the vaccine. After complete immunization, AEs were absent in 35.8% of patients with IRD and in 21% of controls (p=0.006). Exacerbations of IRD and new autoimmune phenomena were not registered in any case.Conclusion. According to preliminary data, vaccination against COVID-19 in patients with IRD appears to be quite safe. Further studies are needed to investigate the safety, immunogenicity, and clinical efficacy of COVID-19 immunization in rheumatic patients.

Safety of COVID-19 vaccines in patients with immunoinflammatory rheumatic diseases (preliminary data)

In mid-2021, the SARS-CoV-2 (Severe Acute Respiratory coronavirus 2) infection, which caused the coronavirus disease (COVID-19) pandemic, affected more than 157 million people in all regions of the world and led to more than 3.2 million deaths. It is assumed that elderly age, uncontrolled inflammation, anti-inflammatory therapy, comorbid pathology, genetic and other factors can potentially lead to an increase in “sensitivity” to viral and bacterial infections, including SARS-CoV-2. The new version of the recommendations of the Association of Rheumatologists of Russia formulates the main provisions concerning the tactics of managing patients with Immune-mediated Rheumatic Diseases during the ongoing COVID-19 pandemic.

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Coronavirus disease 2019 (COVID-19) and immune-mediated rheumatic diseases. Recommendations of the association of rheumatologists of Russia

Upadacitinib (UPA), a JAK inhibitor, is a new therapeutic option that allows patients with insufficient response to therapy with basic anti-inflammatory drugs (DMARDs) or genetically engineered biological drugs (GEBDs) to achieve the goals of therapy for rheumatoid arthritis (RA). Despite the availability of convincing data from international randomized clinical trials, there is insufficient information about the efficacy and safety profile of UPA, the quality of life of patients receiving the drug in real clinical practice. Aim of the study – to assess the efficacy and tolerability of the UPA drug at a dose of 15 mg/day in patients with rheumatoid arthritis with moderate and high disease activity and to assess their quality of life in real clinical practice. Materials and methods . The study included 41 patients with RA with insufficient effect of previous therapy with DMARDs or GEBDs, persisting moderate or high disease activity, who were initiated with UPA therapy in 7 rheumatological centers of the Russian Federation. To assess the activity of the disease, standard indices were used: DAS28- ESR, DAS28-CRP, SDAI, CDAI. Functional ability was assessed according to the HAQ questionnaire, quality of life – according to the EQ-5D questionnaire, the activity of the disease according to the patient’s opinion – according to the RAPID-3 index. The HADS scale was used to identify the states of depression, anxiety and emotional disorder. Results . During the first week of taking the drug, there was a marked decrease in pain from 60 to 30 mm on a visual analogue scale, which lasted until the third month of therapy. There was a statistically significant decrease in morning stiffness, the number of painful and swollen joints, health assessments by the doctor and patient, erythrocyte sedimentation rate and C-reactive protein (p≤0.001). A decrease in disease activity was also noted according to the dynamics of the activity indices DAS28, SDAI, CDAI (p<0.001). The goals of therapy (remission or low disease activity) by the 3rd month of therapy according to the combined indices of activity DAS28-ESR and DAS28-CRP reached 44.8 and 63.4% of patients, respectively, according to the SDAI index – 56.7%, according to the CDAI index – 25.9%. A pronounced improvement in joint function (70% improvement according to the criteria of the American College of Rheumatology) was noted by 33.3% of patients, population indicators of functional state (HAQ≤0.5) had 15.8% of patients. The difference in the HAQ index by the 3rd month of therapy compared to the indicator before treatment was –0.60 points. The quality of life, assessed by patients using the EQ-5D questionnaire, improved in 98.5% of patients, with a 70% improvement noted in more than a third of them (41.7%). The drug was well tolerated, no adverse reactions were registered by the 3rd month of therapy, all patients continued treatment. Conclusions . The first results of the use of UPA in RA patients with insufficient efficacy of previous therapy with DMARDs or GEBDs in real clinical practice indicate its efficacy and safety, an improvement in the functional state and quality of life of patients by the 12th week of the study.

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The first experience of using upadacitinib in the treatment of rheumatoid arthritis in real clinical practice (results of the multicenter project “RACURS”)

A. M. Lila

Papers

Coronavirus disease 2019 (COVID-19) and immune-mediated rheumatic diseases. Recommendations of the association of rheumatologists of Russia

The first experience of using upadacitinib in the treatment of rheumatoid arthritis in real clinical practice (results of the multicenter project “RACURS”)