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

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 subcuta neous injection, 160 mg/ml – 0.4 ml, manufactured by R-Pharm JSC, Russia) for the treatment of patients with rheuma toid 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.