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.

ABSTTACT: -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 disease-modifying antirheumatic drugs (DMARDs) and genetically engineered biological drugs (biological DMARDs, or biologics) 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 biologics and to search for alternative therapy programs to maintain control over disease activity. PURPOSE OF THE STUDY: The purpose of the study was 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. On weeks 0, 4, 8, and 12 after the switch, the severity of pain was assessed on the VAS scale, the number of tender and swollen joints (TJC28 and SJC28), the level of acute-phase inflammation markers, the DAS28 (disease activity score), ESR, CRP, CDAI (clinical activity index), and the functional state index HAQ (Health Assessment Questionnaire) were determined, as well as the safety profile of therapy was assessed. RESULTS: Data analysis was performed using median values (Me) were used for data analysis. A significant decrease in TJC28 was detected after 8 and 12 weeks of treatment with olokizumab (Artlegia®) (Me baseline = 10, Me 8 weeks = 4, Me 12 weeks = 4, p < 0.05) and a decrease in TSC28 was detected after 4, 8, and 12 weeks of treatment (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: Me4 weeks = 21, Me4 weeks = 1, p < 0.05, ESR: Mesno = 31, Me4 weeks = 7, p < 0.05). Positive dynamics persisted on 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 week 4 became within the normal range, regardless of the initial values. All activity indices improved from week 4 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; DAS28CRP: 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 week 12 of the study: Me baseline = 1.62, Me 12 weeks = 1.31, p < 0.05. CONCLUSIONS: The study found that switching from rituximab to olokizumab was effective and safe during the COVID-19 pandemic.

Real-World Retention Rate, Effectiveness, and Safety of Netakimab in the Treatment of Patients with Ankylosing Spondylitis: First Year Results of the LIBRA Post-Registration Safety Study.

Netakimab has shown high efficacy in controlled clinical trials in the treatment of AS patients. This article presents results of an observational study of netakimab using in routine clinical practice. OBJECTIVE: : To evaluate retention rates and safety of netakimab in patients with AS in real-world clinical practice. Additionally, the efficacy of netakimab was evaluated at 1-year follow-up. MATERIALS AND METHODS: : Patients were recruited for the study from August 2020 to December 2021 at 23 centers in the Russian Federation. The study included patients who were prescribed netakimab therapy before enrollment, so clinical and medical history data for the first visit were entered retrospectively, and following visits at 12, 24, and 52 weeks of therapy were collected within the study. Drug survival rate was calculated according to Kaplan-Meier analysis. RESULTS: : The study included 137 (93 men and 44 women) patients with AS. The average age of patients was 42.3 (11.9) years, 34.3% of patients had previously received therapy with bDMARD, mainly TNF inhibitors. At the end of the analyzed period (52 weeks of therapy), 90.4% (95% CI, 85.4-95.7) of patients continued treatment with netakimab. The BASDAI and ASDAS-CRP showed statistically significant decreases in scores from baseline at all time points. Netakimab was well tolerated by patients; AEs, related to therapy according to the investigator's opinion, were reported in 7 (5.1%) patients. Two patients stopped taking netakimab due to AEs (terminal ileitis and chronic colitis). CONCLUSIONS: : In real-world clinical practice, netakimab demonstrated high retention rates, a favorable safety profile, and sustained efficacy throughout the first year of therapy.

[Immuno-inflammatory rheumatic diseases and COVID-19: analysis of clinical outcomes according to the data of the register of patients of the Novosibirsk region receiving therapy with genetically engineered biological drugs].

BACKGROUND: Currently, observations are accumulating indicating the negative effect of therapy with a number of biologic disease-modifying anti-rheumatic drugs (bDMARDs) drugs on the course of COVID-19. These facts determine the relevance of studying the factors of severe course and unfavorable outcome in immuno-inflammatory rheumatic diseases (IIRD) patients treated with bDMARDs in order to develop tactics for managing this category of patients in a pandemic. AIM: To evaluate the influence of clinical and demographic factors on the risk of development, severity of the course and clinical outcomes of a new coronavirus infection in patients suffering from IIRD and receiving therapy with genetically engineered biological drugs. MATERIALS AND METHODS: A retrospective analysis of the database of the register of patients with IIRD receiving bDMARDs in the Novosibirsk region was performed, which included 318 patients, 94 of whom had indications of having suffered viral infection/pneumonia for the period from 01.04.2020 to 31.12.2020. RESULTS: According to the data obtained, at the time of the analysis, 94 people out of 318 patients with IIRD had a new coronavirus infection. Most (53%) of the patients had a mild infection. At the same time, the nosological form, the use of anti-rheumatic drugs and glucocorticoids did not increase the risks of severe coronavirus infection. When using bDMARDs, only anti-B-cell therapy (rituximab) associated with statistically significant increase in the risk of severe/extremely severe COVID-19. The mortality rate according to the analysis of the register was 6,38%. CONCLUSION: Patients with IIRD have a high risk of severe coronavirus infection, while the severity of the disease is associated with the type of therapy performed.

Telomere Length of Individual Chromosomes in Patients with Rheumatoid Arthritis.

We analyzed telomere length of individual chromosomes in peripheral blood lymphocytes of healthy individuals and patients with rheumatoid arthritis. Quantitative fluorescent in situ hybridization and subsequent computer analysis of metaphase chromosomes showed that distribution of telomere length on individual chromosomes is different under normal and pathological conditions. Patients with rheumatoid arthritis had significantly shorter chromosome 4p telomeres, which can be essential for pathogenesis of this multifactorial disease. Additionally, disease activity inversely correlated with telomere length on chromosome 10p carrying genes involved in T cell differentiation and proliferation.

Analysis of the levels of tumour necrosis factor (TNF), autoantibodies to TNF, and soluble TNF receptors in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the potential contribution made by autoantibodies against tumour necrosis factor (TNF) to the pathogenesis of rheumatoid arthritis (RA). METHOD: We used affinity chromatography methods and a magnetic separation procedure to purify human autoantibodies specific to TNF. The autoantibodies were used as calibration material to determine the absolute content of autoantibodies to TNF using an enzyme-linked immunosorbent assay (ELISA). TNF content and the levels of soluble TNF receptors types I and II (sTNF-RI and sTNF-RII) were determined using commercial ELISA test kits. RESULTS: We demonstrated significant increases in the levels of TNF, sTNF-RI, and sTNF-RII in the sera of patients with acute RA and in patients with RA who had responded positively to therapy compared with healthy controls. Levels of autoantibodies of the immunoglobulin (Ig)G2, IgG3, and IgG4 subclasses were significantly higher in sera from patients with acute RA than in sera from healthy controls. Level of autoantibodies of the IgG2 subclass were significantly higher in sera from patients with acute RA than in RA patients who had responded positively to therapy. CONCLUSIONS: Acute RA is associated with changes in levels of TNF and soluble receptors for TNF and also in levels of autoantibodies to TNF. Given the magnitude of the changes in levels of different subclasses of autoantibodies to TNF, we propose that these autoantibodies might contribute to the pathogenesis of RA.

[Administration of monoclonal antibodies to B-lymphocytes (rituximab) in rheumatoid arthritis in Russia].

AIM: To assess efficacy and tolerance to anti-B-cell drug rituximab in therapy of rheumatoid arthritis (RA) by the data of RF register of this drug. MATERIAL AND METHODS: Rituximab was studied in 42 patients with high RA activity. 37 patients received rituximab according to a conventional scheme: 2 intravenous 1000 mg infusions with a 2-week interval. The rest patients received 2 intravenous 500 mg infusions. The response was evaluated by DAS28 index. RESULTS: Rituximab administration resulted in almost complete elimination of B-cells from peripheral blood. This produced a significant positive effect manifesting with reduction in the number of inflamed and painful joints. This trend was evident to observation week 8 reaching maximum to week 24. Clinical response correlated with decline of inflammation as shown by ESR and CRP. According to DAS28 index, good and satisfactory results were registered in 8 weeks in 62% patients, in 16 weeks--in 86%, in 24 weeks--in 100%. Rituximab tolerance was good. CONCLUSION: Effective treatment with rituximab for rheumatoid arthritis opened a new perspective in antirheumatic biological therapy and demonstrated an important role of B-cells in the disease development. This drug is recommended for wide use in the treatment of severe rheumatoid arthritis resistant to prior therapy including TNF-alpha blockers.