ABSTRACT
The COVID-19 pandemic has significantly changed the understanding of the safety profile of therapies for immunoinflammatory rheumatic diseases (IRDs). This is primarily due to the negative impact of a number of basic anti-inflammatory drugs (DMARDs) and biological DMARDs on the course and outcomes of a new coronavirus infection. A number of studies have shown that anti-B-cell therapy (rituximab) gave a statistically significant increase in the risk of severe COVID-19 and an increase in mortality. At the same time, the analysis of real clinical practice data dictated the need to establish a number of restrictions on the use of certain classes of biological DMARDs and to search for alternative therapy programs to maintain control over disease activity. Purpose of the study - to evaluate the efficacy and safety of the drug Artlegia (olokizumab), solution for subcutaneous injection, 160 mg/ml - 0.4 ml, manufactured by R-Pharm JSC, Russia) for the treatment of patients with rheumatoid arthritis in real clinical practice after switching with rituximab during the COVID-19 pandemic. Materials and methods. The study included 14 patients with a confirmed diagnosis of rheumatoid arthritis (RA), who were previously on rituximab therapy at a dose of 1000-500 mg twice with an interval of 2 weeks, who received at least one course of therapy with this drug. As RA worsened, patients were switched to olokizumab against the background of standard DMARDs. At 4, 8, 12 weeks after the switch, the severity of pain was assessed on the VAS scale, the number of painful and swollen joints (TJC28 and TSC28), the level of acute phase markers of inflammation, the DAS28 disease activity index calculated using ESR and CRP, and the CDAI (clinical activity index), functional state index HAQ, as well as assessment of the safety profile of therapy. Results. Data analysis was performed using median values (Me) were used for data analysis. A significant decrease of TJC28 was after the injection of olokizumab (Artlegia) in 8 and 12 weeks (Me baseline = 10;Me 8 weeks = 4;Me 12 weeks = 4;p<0.05) and a decrease of TSC28 in 4, 8 and 12 weeks (Me baseline = 9;Me 4 weeks = 3.5;Me 8 weeks = 2.5;Me 12 weeks = 2.0;p<0.05). Laboratory markers of inflammation showed a decrease in CRP and ESR levels after 4 weeks of treatment (CRP: Me baseline = 21, Me 4 weeks = 1 (p<0.05);ESR: Me baseline = 31, Me 4 weeks = 7 (p<0.05)). Positive dynamics persisted at 8 and 12 weeks (CRP: Me 8 weeks = 1, Me 12 weeks = 0;ESR: Me 8 weeks = 4, Me 12 weeks = 5). The level of CRP by the fourth week 4 became within the normal range, regardless of the initial values. All activity indices improved from the fourth week in each evaluation period compared to baseline: DAS28-ESR: Me baseline = 5.52, Me 4 weeks = 3.59, Me 8 weeks = 3.33, Me 12 weeks = 3.22 (p<0.05);DAS28-CRP: Me baseline = 5.39, Me 4 weeks = 3.71, Me 8 weeks = 3.35, Me 12 weeks = 3.45 (p<0.05);CDAI: Me baseline = 28.5, Me 4 weeks = 18.0, Me 8 weeks = 16.5, Me 12 weeks = 16.0 (p<0.05). All patients showed a reduction in pain (VAS scale) by week 8. The functional status of patients, according to the HAQ index, showed a significant decrease only by the 12th week of the study: Me baseline = 1.62, Me 12 weeks = 1.31 (p<0.05). Conclusion. The study found that switching from rituximab to olokizumab was effective and safe during the COVID-19 pandemic.Copyright © 2023 Ima-Press Publishing House. All rights reserved.
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Objective. To review and summarize literature data in studies of safety of the drug products used for the pathogenetic treatment of COVID-19. Materials and methods. As the first stage of monitoring the drug's safety, which are used in the treatment of COVID-19 in Russia, a systematic review of studies of the drug's safety profiles was carried out: Mefloquine, hydroxychloroquine, azithromycin, lopinavir/ritonavir, favipiravir, tocilizumab, olokizumab, baricitinib in the international databases Medline, PubMed, ClinicalTrials.gov and Cochrane Library for the period 2019-2021. Results. The review included 51 articles that met the selection criteria. Based on the results of the review, it can be concluded that the safety profile (frequency, severity and severity) of most drugs repurposed for COVID-19 corresponds to those for the registered indications. At the same time, according to world experience, there is an increase in the number of reports of adverse drug reactions of hydroxychloroquine and azithromycin, which is provoked by the active use of these drugs for combination therapy. Conclusions. According to the literature, a high incidence of adverse events was noted in hydroxychloroquine, chloroquine and azithromycin. Subsequent analysis and comparison of the safety profiles of hydroxychloroquine, chloroquine and azithromycin with data from the national automated information system (AIS) database of Roszdravnadzor is a necessary component of effective and safe pharmacotherapy for COVID-19.Copyright © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
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The aim of the article is to study pharmacokinetic characteristics of intravenous olokizumab in patients with moderate COVID-19 to relieve a hyperinflammation syndrome. Materials and methods. The pharmacokinetic study was conducted as a part of a phase III clinical study (RESET, NCT05187793) on the efficacy and safety of a new olokizumab regimen (intravenous, at the doses of 128 mg or 256 mg) in COVID-19 patients. Plasma concentrations of olokizumab were determined by the enzyme immunoassay. The population analysis was performed using a previously developed pharmacokinetic model based on a linear two compartment. Results. The pharmacokinetic analysis included the data from 8 moderate COVID-19 patients who had been administrated with olokizumab intravenously at the dose of 128 mg. According to the analysis results in this population, there was an increase in the drug clearance, compared with the data obtained in healthy volunteers and the patients with rheumatoid arthritis: 0.435, 0.178 and 0.147 l/day, respectively. The parameters analysis within the framework of a population pharmacokinetic model showed that the main factors for the increased olokizumab clearance are a high body mass index. In addition, the presence of COVID-19 itself is an independent factor in increasing the drug clearance. Conclusion. After the intravenous olokizumab administration, an increase in the drug clearance is observed in moderate COVID-19 patients against the background of the disease course. The main contribution to the increased clearance is made by the characteristics of the population of COVID-19 patients associated with the risk of a severe disease and inflammation. When administered intravenously at the dose of 128 mg, a therapeutically significant olokizumab level was maintained throughout the acute disease phase for 28 days. Copyright © 2022 Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute. All rights reserved.
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Aim – to evaluate the efficacy and safety of olokizumab in hospitalized patients with moderate to severe coronavirus disease COVID-19. Material and methods. A multicenter non-interventional retrospective study of olokizumab treatment in hospitalized patients with COVID-19 was conducted. The initial population in this study included 2926 patients with COVID-19. Patients with moderate or severe disease who were taking corticosteroids as part of standard therapy were selected for this analysis. The final population was 1738 patients. A test group (standard therapy: corticosteroids, antiviral, pathogenetic or symptomatic therapy in combination with olokizumab) and a comparison group (standard therapy only) were formed. Each group included 869 patients. The primary end point was all-cause mortality from the start of anti-inflammatory therapy to the end of follow-up. We also analyzed the incidence of transfer and the length of stay of patients in the intensive care unit, the duration of hospitalization, as well as the change in C-reactive protein level. Results and discussion. It was found that olokizumab significantly reduces the all-cause mortality compared with standard therapy: 54 (6.21%) cases compared with 111 (12.77%) in the control arm, p<0.001, odds ratio (OR) 2.21 [1.57;3.1]. The results of factor analysis confirmed that olokizumab increases the odds of recovery, OR 2.41 (95% CI 1.64–3.54, p<0.001). In addition, patients in olokizumab group showed significantly lower plasma CRP levels compared with control group. Already on the 2nd day after the start of therapy the CRP level was almost 2 times lower in the olokizumab group than in the control group (the median was 13 [5.6;28.55] mg/l and 25 [15.3;79.25] mg/L in the olokizumab and comparison groups, respectively). Conclusion. The results of the study confirm the clinical data on the efficacy of olokizumab as therapy for COVID-19 patients. © 2022 Tomsk Polytechnic University, Publishing House. All rights reserved.
ABSTRACT
Background. Production of pro-inflammatory cytokines includinginter leukin 6(IL-6) is activated in COVID-19. Using olokizumab which inhibits IL-6 production in treatment of COVID-19 is pathogenetically justified. The aim. To study in real clinical practice the efficacy and safety of using the IL-6 inhibitor (olokizumab) intreatmen tofpatients with confirmed COVID-19pneumonia. Materials andmethods. The first group included 41 hospitalized patients with confirmed COVID-19 pneumonia having complex therapy including olokizumab. The control group consisted of 66 patients with confirmed COVID-19 pneumonia who did not have therapy with IL-6 inhibitor. We analyzed clinical (volume of lung involvement, respiratory failure degree, body mass index)andlaboratory data (levels of T-troponin, lactate, procalcitonin, natriuretic peptide, C-reactive protein, fibrinogen, D-dimer, ferritin, erythrocyte sedimentation rate, glomerular filtration rate). Results. The groups didnotdiffer in gender, age, body mass index of patients, volume of lung tissue injury, and duration of hospitalization (p > 0.05). Respiratory failure of 2-3rd degree was more common in patients of the first group (χ2 = 6.3;p = 0.010). The initial levels of C-reactive protein (50.9 [34.2;76.2] and 32.2 [9.9;69.1] mg/L respectively;p = 0.009) and fibrinogen (6.0 [5.3;6.7] and 5.2 [4.3;6.2] g/l respectively;p= 0.005)in patients having therapy including olokizumabwere significantly higher than in the control group. The levels of erythrocyte sedimentation rate, fibrinogen andferritin, D-dimer, detectedupon admission of patients to the hospital, didn'thave statistically significant differences. At discharge, the erythrocyte sedimentation rate in patients receiving olokizumab was statistically significantly lower (9.0 [5.5;14.5] and 13.0 [7.0;27.0] mm/h;p = 0.018). Conclusions. Using olokizumabin the treatment patientwithCOVID-19 pneumonia hasdemonstrateda positive effecton clinical and laboratory parameters (erythrocyte sedimentation rate, fibrinogen level) in patients with pronounced inflammatory changes and respiratory impairment. © 2022 Acta Biomedica Scientifica. All rights reserved.
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SESSION TITLE: Systemic Disease with Diffuse Lung Symptoms Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Rapidly progressive interstitial lung disease (RP-ILD) is a rare and potentially fatal manifestation of dermatomyositis (DM) and has considerable impact in terms of the prognosis. CASE PRESENTATION: A 52-year-old male demonstrated DM-typical rash, fever, mialgias, and mild muscle weakness 3 months after asymptomatic COVID-19 infection. Two weeks later dysphonia and progressive dyspnea appeared. Lung CT scan showed the picture of organizing pneumonia. His COVID-19 PCR test was negative multiple times. Laboratory tests revealed the following numbers: ALT 210 IU/L, AST 748 IU/L, LDH 613 IU/L, CPK 1165 IU/L, ferritin 1145ϻg/l, CRB 11 mg/l. The patient was tested positive for anti-Ro52 antibodies, while anti-synthetase and scleroderma-associated antibodies were not discovered. Anti-melanoma differentiation-associated gene 5 (MDA5) test was not available due to the lack of the necessary test systems in the country. The patient was diagnosed with DM. Combined immunosuppressive therapy was administered, including: oral prednisolone 60 mg per day and 720 mg intravenously, dexamethasone 64-24 mg intravenously per diem, ciclosporin 200 mg и cyclophosphamide 600 mg, and 3 plasmapheresis sessions followed by an intravenous immunoglobulin. As a result of the therapy, muscle weakness disappeared and CPK levels returned to normal limits, however dyspnea progressed and ferritin levels hit 3500ϻg/l. After the following 3 weeks of intensive combined immunosuppressive therapy, the patient demonstrated symptoms of severe respiratory failure (RF). CT scan showed multiple traction bronchiectasis, wide areas of ground glass opacity, pneumomediastinum and subcutaneous emphysema of a neck and supraclavicular regions. Ciclosporin was replaced with tofacitinib with the dose of 10 mg per diem, IL-6 inhibitor (olokizumab 256 mg) was injected intravenously, massive broad-spectrum antibiotic therapy was administered. RF progressed and the patient was put on mechanical ventilation. The patient died of acute RF and sepsis a week later. DISCUSSION: RP-ILD is a common manifestation of severe MDA5+ DM, which is also associated with necrotizing vasculitis and amyopathic/hypomyopathic muscle involvement. In this case acute ILD in a patient with typical DM could also have been provoked by previous COVID-19 infection. CONCLUSIONS: The courses of disease for COVID-19 and MDA5+ DM have several similarities, which means it can be the same for their pathogenesis and clinical manifestations. In spite of early screening and intensive immunosuppressive therapy in such cases, the prognosis of patients with DM and RP-ILD is still poor and is associated with high mortality. Reference #1: Wang G, Wang Q, Wang Y, et al. Presence of Anti-MDA5 Antibody and Its Value for the Clinical Assessment in Patients With COVID-19: A Retrospective Cohort Study. Front Immunol. 2021 Dec 20;12:791348. doi: 10.3389/fimmu.2021.791348. PMID: 34987516;PMCID: PMC8720853. DISCLOSURES: No relevant relationships by Lidia Ananyeva No relevant relationships by Maria Aristova No relevant relationships by Liudmila Garzanova No relevant relationships by Anna Khelkovskaya-Sergeeva No relevant relationships by Dmitry Kulikovsky
ABSTRACT
Most subjects with the COVID-19 experience mild to moderate symptoms, but approximately 10% of cases suffer from severe course of disease. IL-6 inhibitors are actively used to neutralize and prevent the cytokine storm. Olokizumab is a humanized monoclonal antibody belonging to the G4/Kappa immunoglobulin isotype that selectively binds to human IL-6 and effectively neutralizes it. AIM: To evaluate the efficacy and safety of Artlegia (olokizumab) for the treatment of subjects with a disease caused by the SARS-COV-2 virus in a real-world clinical setting. MATERIALS AND METHODS: The analysis included data of 610 subjects aged 55.0812.68 years who received olokizumab at a single dose of 160 mg/mL 0.4 mL subcutaneously as a preemptive anti-inflammatory therapy. The comparison group included 511 subjects aged 55.2311.23 years who received standard therapy without IL-6 inhibitors. Control Endpoints: 1. Positive clinical changes on Day 7. 2. Changes in the CRP levels on Days 1, 2, and 7. 3. Duration of oxygen therapy. 4. Number of days in hospital. 5. Number of adverse events. 6. Disease outcome. RESULTS: If a cytokine storm occurs, immune regulatory events will trigger the development of either a protective immune response or an exacerbated inflammatory response. The use of preemptive anti-inflammatory therapy has both a short-term and, most importantly, a long-term effect on the T and B parts of the immune process. These aspects definitely require further research and observation. CONCLUSION: The use of olokizumab to treat the new COVID-19 coronavirus disease has demonstrated a positive effect on clinical and laboratory parameters. Primarily, it affects the severity of clinical parameters by improving the general condition already on the first day of observation, and decreasing body temperature to normal values. The changes in the C-reactive protein levels show a significant effect of the IL-6 inhibitor on the systemic inflammatory response.