Interleukin 6 receptor inhibitors in the treatment of rheumatoid arthritis during the COVID-19 pandemic, Moscow experience

Objective: to confirm the efficacy and safety of levilimab in patients with rheumatoid arthritis (RA) switched from other interleukin 6 receptor in-hibitors (iIL6R) for non-medical reasons. Patients and methods. A retrospective analysis of data from the register of patients with RA who during the COVID-19 pandemic were switched from foreign iIL6Rs to the Russian drug levilimab. Treatment regimens with levilimab in combination with synthetic disease-modifying antirheumatic drugs (sDMARDs) and/or glucocorticoids (GCs) were used, as well as a monotherapy regimen in case of DMARDs intolerance. Results and discussion. In 150 patients with RA, a successful non-medical switch to levilimab was demonstrated with the preservation and inten-sification of the clinical effect achieved on previous therapy with iIL6R. After switching to levilimab, the DAS28-CRP index decreased by an av-erage of 0.098 at 3 months and by 0.25 at 6 months (p=0.214 for both time points). There was a decrease in the proportion of patients with elevated levels of CRP, as well as with high RA activity. In a number of patients who showed high efficacy of levilimab, it became possible to reduce the dose or number of DMARDs, as well as cease GCs intake. Good tolerability and a favorable safety profile of levilimab were noted, including in relation to the new coronavirus infection that developed during therapy. Conclusion. Therapy with Russian iIL6R levilimab is effective and safe, including in patients switched from other drugs for non-medical reasons, as well as in relation to the novel coronavirus infection that developed during therapy. © 2022, Ima-Press Publishing House. All rights reserved.

[Experience of anticipatory therapy with IL-6 receptor inhibitors and perspectives for its use in the evolution of COVID-19].

The Advisory Board chaired by the chief specialist in infectious diseases of the Ministry of Health of Russian Federation, Professor V.P. Chulanov was held on June 18, 2022 in Saint Petersburg. Aim. The main purpose of the Board was following discussion: the analysis of the real-world data of levilimab as an anticipatory therapy for COVID-19 in hospitalized patients; the review of the experience and perspectives of levilimab as an anticipatory anti-inflammatory option for outpatient patients who meet defined clinical and laboratory criteria. Results. The analyzed data on clinical efficacy and safety formed the basis of recommendations proposed by experts for the use of levilimab in the inpatient and outpatient medical care for COVID-19.

[Efficacy and safety of regdanvimab in patients with mild/moderate COVID-19 and high risk of progression of the disease: a retrospective study in a short-term stay unit].

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 KaplanMeier method. The significance level was determined at p0.05. 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.

[Levilimab and baricitinib prescribing experience in outpatient COVID-19 patients' treatment].

AIM: To study the effect of levilimab or baricitinib in combination with standard therapy (ST) on the incidence of severe viral pneumonia associated with a new coronavirus infection COVID-19. MATERIALS AND METHODS: A multicenter, open-label observational study of the efficacy and safety of levilimab in combination with ST (group 1, n=100), baricitinib in combination with ST (group 2, n=139), or in comparison with ST (group 3, n=200) in outpatients with verified CT-1 pneumonia. RESULTS: According to the results of laboratory tests, patients treated with levilimab in combination with ST had the best dynamics of changes in CRP from reliably the highest level (mg/L) to the lowest in comparison with other groups. In the group of patients with ST, in contrast to the other groups, no dynamics of CRP was observed by day 5 of therapy. In group of hospitalized patients initially receiving levilimab in addition to ST, the rate of transfer to the intensive care unit (2 patients, 9.52%) and length of stay (4 days) was significantly lower compared to the values in patients in both the baricitinib group in combination with ST (7 patients, 15.56%; 5 days [interquartile range 36.5]) and in patients receiving ST alone (7 patients, 15.56%; 5 days [interquartile range 36.5]). Also in hospitalized patients we observed no statistically significant intergroup differences in the incidence of infectious complications and thromboembolic events, which confirms the safety of including levilimab or baricitinib in COVID-19 pathogenetic therapy regimens. Observational results support the hypothesis that the initial inclusion of levilimab or baricitinib in addition to ST is accompanied by a reduced risk of viral pneumonia progression. CONCLUSION: The addition of levilimab or baricitinib to the therapy regimen for coronavirus infection during the outpatient phase has demonstrated a preemptive anti-inflammatory effect and reduced the probability of lung tissue damage progression.

[Criteria for the optimal use of interleukin-6 receptor blockers in patients with COVID-19].

AIM: To determine the criteria for the optimal use of IL-6 receptor blockers in patients with COVID-19 community-acquired pneumonia based on predictors of adverse outcomes. MATERIALS AND METHODS: The single-center, non-randomized prospective study included 190 patients with community-acquired pneumonia caused by coronavirus 2 between the beginning of March and the end of May 2020. Of these, 89 patients received tocilizumab and 101 patients received sarilumab. The study inclusion criterion for the patient was indications for initiating therapy with one of the inhibitors of IL-6 receptors (anti-IL-6R) according to the Interim guidelines (versions 4 and 5). The exclusion criterion was the need to re-prescribe genetically engineered biological therapy (GEBT). The severity of the patient's condition was assessed according to the early warning score (NEWS2), the volume of lung tissue lesions was assessed according to computed tomography (CT). Laboratory monitoring included counting the absolute (abs) number of lymphocytes, serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), D-dimer, lactate dehydrogenase, fibrinogen. Statistical data processing was conducted by nonparametric methods using the IBM SPSS Statistics V-22 software. RESULTS: The phenotype of a patient with a negative outcome prognosis was described: a male patient over 50 years of age with aggravated premorbid background (with cardiovascular diseases, obesity and/or chronic renal disease), lung lesion CT 34, saturation less than 93% upon inhalation of atmospheric air, persisting for 2448 hours after GEBT. According to the blood test, lymphopenia was below 1000 U/L and CRP levels were above 50 mg/L. The laboratory parameters and clinical picture of the patient progressively worsened after 911 days of illness, regardless of the use of Anti-IL-6R. The features of patients monitoring when administering IL-6 receptor blockers have been determined. CONCLUSION: IL-6 receptor blockers should be administered to patients hospitalized with severe COVID-19 before the development of hyperinflammatory reactions. The optimal "therapeutic window" is 78 days of illness.

Baricitinib in the treatment of patients with COVID-19: A review of international data and analysis of clinical results in the Russian Population

The effects of baricitinib, a selective reversible inhibitor of Janus kinase 1 and 2, in the treatment of COVID-19 are associated with different aspects of pathogenesis - inhibition of viral endocytosis, reduction of excessive inflammatory response, and mitigation of vascular and pulmonary damage, which is a strong rationale for using baricitinib to treat patients with COVID-19. In the period from April to May 2020, City Clinical Hospital No. 52 obtained clinical experience of baricitinib clinical use in the therapy of 113 patients with COVID-19:58 (51%) women and 55 (49%) men, whose average age was 57±12.6 years old. Analysis of the results of using baricitinib showed that therapy with baricitinib against the background of standard pathogenetic therapy was found to be effective in 95 (84%) patients and ineffective in 18 (16%). Significant positive changes were shown in comparison with the baseline level of the following indicators: body temperature (from 37.2+0.8°C to 36, ±0.68°C, P=0.000), blood oxygen saturation (from 95.5±3.0% to 96.5±2.2%, P=0.011), C-reactive protein (from 46.1±48.0 mg/L to 33.5±43.7 mg/L, P=0.010), National Early Warning Score (NEWS) (from 1.7±1.3 to 1.1±1.2, p=0.001).From the safety point of view, patients showed a slight decrease in the average value of the number of neutrophils - from (3.1±1.4)xl09 to (3.0±2.0)xl09 and lymphocytes - from (1.8±0,9) x 109 to (1.7±0.9) x 109, as well as minimal multidirectional changes in the mean values of transaminase activity - alanine aminotransferase changed from 33.9±23.6 U/L to 34.9±47.5 U/L, aspartate aminotransferase - from 40.6±49.0 U/L to 38.5±25.5 U/L. In general, the results obtained within the experience of the clinical use of baricitinib in 113 Russian patients with COVID-19 are consistent with the available data from foreign clinical studies and confirm the efficacy and safety of baricitinib. © Team of Authors, 2021.

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

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.

Maintenance oncohematological patients and new coronavirus infection: Experience of the City Clinical Hospital NO 52

Justification. Oncological diseases, along with diabetes, hypertension, cardiovascular and chronic obstructive pulmonary diseases, are associated with severe course and worst prognosis of the new coronavirus infection - COVID-19. Due to the limited number of the international studies and the lack of the domestic publications on the analysis of the course of COVID-19 in patients with oncohematological pathology and the patient management tactics, this work seems extremely topical. Materials and methods. 24.04.2020-31.05.2020, 110 patients with oncohematological pathology associated with new coronavirus infection were observed on the basis of the hematology service of City Clinical Hospital No 52: 59 women and 51 men, mean age 58 (18-90) years. Results. Currently, 24 (22%) patients among 110 are continuing treatment. The outcome of the disease is observed in 86 (78%) patients: 50 (58%) patients were discharged from hospital with complete or partial resolution of pneumonia, 36 (42%) of the 86 patients died. The groups did not differ in gender. The median age was higher in the group of deceased patients (66 vs. 54 years in patients who had a favorable outcome after COVID-19). The somatic status ECOG 3-4 was an independent predictive factor determining the adverse outcome of the disease. The third part of the patients from the group with a fatal cases due to a severe condition in the debut of the disease immediately were hospitalized in the intensive care unit (ICU), 2 (6%) of them had died within the first day. Disposition, according to the nosology showed a significant predominance among patients with an adverse outcome associated with acute leukemia (18% vs 39%). Patients with resistant course of hemoblastosis accounted for 50% of deceased patients. Severe form of the course of COVID-19 infection was twice as frequently (46% vs 84%) among patients with an adverse outcome of the disease, that was associated with both the initial more severe group of patients (33% were hospitalized in the ICU), and less curability of pneumonia against the background of the adverse prognostic factors: the older age group, the predominance of patients with acute leukemia and resistant course of oncohematological diseases. Specific anticancer therapy and COVID-19 therapy were comparable in both groups. Conclusions. Identification of new coronavirus infection against a backdrop of oncohematological disease is associated with a severe course of COVID-19 and high death rate - 42%. According to the preliminary obtained results, the adverse prognostic factors of COVID-19 in patients with oncohematological diseases include: elderly age, the poor somatic status (ECOG 3-4), relapse or progression of hemoblastosis and nosological affiliation to acute leukemia. © 2020 Journal of Modern Oncology. All rights reserved.