ABSTRACT
Background: Data from multiple rheumatological cohorts have shown that treatment with rituximab (RTM) is associated with higher COVID-19 morbidity and mortality. Information about the course of COVID-19 in patients (pts) with Sjogren's syndrome (SjS) is still lacking. Objectives: To compare clinical course of COVID-19 in pts with SjS treated with anti-CD20 monoclonal antibody (RTM) and treated with synthetic disease-modifying antirheumatic drugs and low doses of glucocorticoids. Methods: Single center observational study. Pts with SjS were screened for SARS-CoV-2 infection anamnesis via telephone interview. Diagnosis of SjS was based on ECR/EULAR 2016 criteria. COVID-19 diagnosis was based on positive PCR test and typical clinical features (CT signs, fever and anosmia). RTM was administered as two infusions of 1000 mg each 2 weeks apart, and then 500 mg every 6 months. Results: 387 pts with SjS were interviewed, 142 of them with confrmed SARS-CoV-2 were included in the study and divided into 2 groups. The frst group (gr) consisted of 86 pts (79 women and 7 men) receiving RTM (gr R), median age was 56 years (33-66,5 years), and median rituximab treatment duration was 36 months (12-42 months). Pts in the control gr (gr C), 56 pts did not receive RTM (55 women and 1 man), their median age was 50 years (35-69 years). Median time from last RTM administration to COVID-19 symptoms onset was 4 months (2-6 months). Ten pts had concomitant RA, 4 pts-SLE, 5 pts-Systemic sclerosis. Fifteen pts had MALT-lymphoma anamnesis. Additionally, 15 pts (10.5%) had pulmonary involvement secondary to rheumatic disease. In total 37 pts had chronic ischemic heart disease and/or severe arterial hypertension, diabetes mellitus type 2. In gr R 31 pts (36%), and in gr C 13 (23%) required hospitalization due to marked shortness of breath and long febrile period (p=0,1). Anti-IL6 treatment or/and Jak inhibitors were prescribed to 17 of 31 pts (54.8%) in gr R and to 5 of 13 (38%) in gr C (p=0,1). The risk of hospitalization was slightly higher in pts with comorbidity (p=0.06) and with a history of lymphoma (p=0.056) and didn't correlate with the following parameters: age, the duration of RTM therapy, lung damage. A high rate of hospitalization correlated with a shorter period between the administration of the RTM and the development of COVID-19 (R=0,387, Spearmaǹs Rank Correlation). Anti-SARS-CoV-2 IgG were measured in 66 pts, 47 (71%) of them were positive. Positive Anti-SARS-CoV-2 IgG were signifcantly more often detected in gr C (84% vs. 57,6%). No correlation was found between the formation of antibodies and the duration of RTM therapy or the time from the last RTM administration. Conclusion: According to our data anti-CD20 therapy doesn't predispose SjS pts to severe course of COVID-19. Lymphoma anamnesis, cardiovascular diseases and diabetes have greater impact on COVID-19 severity. Obviously, anti-CD20 therapy negatively affected the formation of specifc anti-SARS-CoV-2 humoral immunity.
ABSTRACT
Background: The key link in the therapeutic drug monitoring of methotrexate (MTX) is the measurement of the concentrations of its most stable metabolites, as well as products of the early and late stages of MTX conversion (short-chain polyglutamates). Metabolic rate of MTX can depend on the clinical characteristics of patients and concomitant drug therapy. Objectives: To reveal the regularity of the distribution of various metabolites in patients who responded and did not respond to MTX therapy. To compare groups of patients with different responses to MTX according to clinical characteristics. Methods: The study included 79 RA diagnosis according to ACR/EULAR 2010 criteria, 65 (82%) women and 14 (18%) men, aged 53 ± 11 years, naiive to MTX. All patients had normal renal excretory function (GFR more than 60 ml/min). All patients were prescribed MTX of 10-15 mg/m2 of body surface. Achievement of therapy targets was established according to the EULAR therapy response criteria. The determination of MTX monoglutamate in erythrocytes (ER) and mono-nuclear cells (MO), as well as the main metabolites of MTX-polyglutamates with 2,3 and 4 glutamate residues (MTXPG 2-4), as well as 7-hydroxymethotrexate (7-OH-MTX) was measured by the tandem chromatomass spectrometry after 4, 12 and 24 weeks of therapy, the result was expressed in nmol/L. The calculation was performed using the statistical data analysis package Statistica 10 for Windows (StatSoft Inc., USA) using the methods of parametric and nonparametric statistics. Results: By the 24th week of therapy, 34 (43%) (group 1) patients achieved the targets of therapy, 36 (46%) did not achieve (group 2). MTX withdrawn in 5 (6%) patients-due to adverse reactions. 4 (5%) were unable to continue to participate due to SARS-CoV2 pandemic. After 4 weeks of treatment, the concentration of various MTX metabolites did not differ in the groups. After 12 weeks of therapy, signifcant differences were found in the content of 7-OH MTX in the ER: 28.19 [7.28;58.07] and 5.89 [0.79;20.03], respectively (p=0.002);the concentration of the remaining fractions did not differ. Group 1 showed a higher concentration of 7-OH-MTX in MO after 24 weeks of therapy-5.23 [1.39;12.52] and 1.05 [0.07;3.55], respectively (p = 0.006). No differences between the concentrations of other MTX metabolites were found. The groups were matched for age, body mass index, duration of RA, and disease activity at the baseline. In group 2, patients used statins more often (2 (6%) versus 6 (37%), p = 0.01), however, there were no statistically signifcant differences in the concentration of MTX metabolites in the groups of patients taking and not taking statins. Conclusion: The concentration of 7-OH-MTX after 12 and 24 weeks of therapy is statistically higher in the group of patients who responded to therapy. 7-OH-MTX appears to be a more persistent metabolite of MTX, therefore, it is more applicable for therapeutic drug monitoring of MTX. Patients taking statins may be potential nonresponders to MTX therapy.
ABSTRACT
The prescribing of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (iJAK) during the COVID-19 pandemic requires a balanced approach and tight monitoring of the patients. The aim of the study was to study the effect of bDMARDs and iJAK inhibitors on the condition of patients with rheumatoid arthritis (RA), taking the patients reported outcomes, as well as the incidence of COVID-19 in these patients. Materials and methods. A telephone survey was conducted of 254 patients with RA (average age – 49.8±13.7 years;64.4% of patients are positive for rheumatoid factor;women – 83.5%;DAS28 score – 5.4±1.6 points), who in the period from January 2020 to June 2021 were prescribed bDMARDs or iJAK for the first time: 148 (58.3%) – rituximab;57 (22.4%) – tumor necrosis factor α inhibitors;20 (7.9%) – iJAK;17 (6.7%) – interleukin 6 inhibitors;12 (4.7%) – abatacept. Results. At the time of the survey, 204 (80.3%) patients continued taking prescribed medications. The main reason for the interruption of treatment was administrative problems. Synthetic DMARDs (mainly methotrexate and leflunomide) were received by 68.0%, glucocorticoids – 45.3%, nonsteroidal anti-inflammatory drugs – 44.5% of respondents. Among patients treated with bDMARDs or iJAK, 68.1% noted «the state of symptoms acceptable to the patient», the absence of frequent joint pain – 65.3%, the absence of increased fatigue – 14.3%. The incidence of COVID-19 and hospitalization associated with this disease did not differ in individuals who continued and stopped using bDMARDs or iJAK: 41.2% and 44.6%, 13.7% and 14.0%, respectively (p=0.80884). There were no statistically significant differences in the incidence of COVID-19 and hospitalization associated with this disease in patients taking various bDMARDs or iJAK. Conclusion. Despite the COVID-19 pandemic, rituximab remains one of the most popular bDMARDs. About a third of patients receiving bDMARDs or iJAK are not satisfied with their condition. More than 40% of patients who received these drugs suffered COVID-19;14.0% required hospitalization.
ABSTRACT
Background: An accessible and sensitive and sensitive method for determining antibodies to a new coronavirus infection is often the key to timely provision of the necessary medical care to patients with rheumatic diseases Objectives: Compare methods for determining antibodies to SARS-CoV-2 using a rapid test and enzyme-linked immunosorbent assay (ELISA) Methods: Methods for determining antibodies to SARS-CoV-2 using an express test (Chromatographic express test SARS-CoV-2 IgG / IgM (Xiamen Biotime Biotechnology, China)) and by ELISA (Reagent kit for enzyme immunoassay of class G immunoglobulins and class M to SARS-CoV-2 (Vector-Best, Russia)) were compared. 80 patients were included with a diagnosis of rheumatoid arthritis 26 (33%), psoriatic arthritis -9 (11%), osteoarthritis -15 (19%), rheumatic heart disease 1 (1%), SLE 2 (3%), deramtomyositis 3 (4%), systemic sclerosis 5 (6%), systemic connective tissue diseases 4 (5%), including Sjogren's syndrome, spondyloarthritis 15 (19%). 17 (21%) denied a history of COVID-19 symptoms. 63 (79%) noted any signs of COVID-19 3.095 ± 1.45 months before the test (Median 3 [2;4] months). 63 (79%) noted any signs of COVID-19 109 ± 43 days before the test (Median 111 [78;135] months). The ELISA method was considered the standard. Results: When comparing the results of the express test and the determination of IgG antibodies to SARS-CoV-2 in serum, the following was obtained: the sensitivity of the express test is 99%. When comparing the results of the express test and the determination of IgM antibodies to SARS-CoV-2 in serum, it was obtained: among 66 samples with a negative result by the express test method, IgM was detected in 6 cases by ELISA/ So, 7.5% of 80 samples were false negative. In 3 of 14 samples with a positive result by the express test, IgM by ELISA was not detected. So, 3.75% of 80 samples were false-positive. (Table 1). When comparing the results of the IgM express test and ELISA, the following was obtained: the sensitivity of the express test was 33%, the specificity was 85%.Conclusion: When comparing the results of the express test and the determination of IgG antibodies to SARS-CoV-2 in serum, the sensitivity of the express test is 99%. Determination of IgM antibodies to SARS-CoV-2 using a rapid test is less reliable than determination using ELISA.