RESULTS OF A 12-WEEK OPEN-LABEL, NON-INTERVENTIONAL STUDY OF THE EFFICACY AND SAFETY OF OLOKIZUMAB THERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS AFTER SWITCHING FROM ANTI-B-CELL THERAPY DURING THE SARS-COV-2 PANDEMIC.

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.

Safety profile assessment of drug products used for the pathogenetic treatment of COVID-19.

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.