Репозиторий Университета

© 2018 Ima-Press Publishing House. All rights reserved. Objective: to investigate the effect of various biological agents (BAs), including combined treatment with rituximab (RTM) and belimumab (BLM), on the activity of systemic lupus erythematosus (SLE) and to evaluate their efficacy and impact on some parameters of humoral immunity. Subjects and methods. BAs were prescribed to 54 patients with a reliable diagnosis of SLE with high and medium activity according to SLEDAI-2K; 40 of them received RTM, 7 – BLM; 7 – combined therapy with RTM and BLM. Clinical and laboratory examinations were made in all the patients at the time of their inclusion and then every 3 months during a year. The results were assessed using SLEDAI-2K, BILAG index, Lupus Erythematosus National Assessment (SELENA)-SLEDAI Flare index (SFI) (a moderate, severe exacerbation), and SLE Responder Index (SRI). Results and discussion. At 3, 6, and 12 months after start of therapy, the use of BAs in all the patients resulted in a disease activity reduction. It was statistically significant (p < 0.00001) in the RTM group; and no statistical analysis was carried out in the BLM and RTM+BLM groups due to the small numbers of patients. At the same time, there was a progressive decrease in the levels of anti-double-stranded DNA (ds-DNA) antibodies (Abs) and an increase in the concentration of the complement fractions C3 and C4 in the RTM and RTM+BLM groups (p < 0.05) at one-year follow-up. After 12 months of therapy with BAs, there was a decrease in IgG (p < 0.02) and IgM (p < 0.03) levels; but overall it remained within the reference ranges. Prior to therapy, irreversible organ damages were recorded in 23 (42.6%) of the 54 patients. The increased damage index at 12 month was observed only in patients receiving RTM, which is probably due to the use of higher-dose glucocorticoids. Conclusion. All three methods of therapy with BAs in SLE patients demonstrated good efficiency shown as a significant decrease in clinical and laboratory activity measures that were assessed by SLEDAI-2K and the levels of anti-ds-DNA and complement components C3 and C4. The decrease in immunoglobulin levels did not go beyond the reference values. Therapy with BLM and RTM+BLM allowed for managing patients with the low and average doses of oral glucocorticoids, which contributed to the reduction of not only the activity, but also risk of irreversible organ damages.

© 2018 Ima-Press Publishing House. Mental disorders (MDS) of the anxiety-depressive spectrum (ADS) and cognitive impairment (CI) substantially deteriorate the course and efficiency of therapy for rheumatoid arthritis (RA). There have been practically no studies on the impact of psychopharmacotherapy (PPT) for MDS on the efficacy of standard disease-modifying antirheumatic drugs (DMARDs) and biological agents (BAs). Objective: to investigate the impact of adequate PPT for MDS of ADS on the efficacy of DMARDs and BAs in patients with RA. Subjects and methods. The investigation included 128 patients (13% men and 87% women) with documented RA in accordance with the 1987 American College of Rheumatology (ACR) criteria. The patients' mean age was 47.4}0.9 years; the median duration of RA was 96 [48; 228] months. DAS28 averaged 5.34}0.17. 75.1% of the patients received DMARDs. The diagnosis of MDS was based on the ICD-10 codes, by applying a semi-structured interview and the Hospital Anxiety and Depression Scale. Changes in the pattern and severity of ADS were evaluated using the Hamilton Anxiety Scale and the Montgomery-Asberg Depression Rating Scale. Clinical and psychological procedures were used to diagnose CI. At baseline, ADS was detected in 123 (96.1%) patients: major depression in 41 (32.1%), minor depression in 53 (41.4%), and anxiety disorders in 29 (22.6%). CI was diagnosed in 88 (68.7%). PPT was offered to all the patients with MDS; 52 agreed to treatment and 71 refused. The following therapeutic groups were identified according to the performed therapy: 1) DMARDs (n = 39); 2) DMARDs + PPT (n = 43); 3) DMARDs + BAs (n = 32); 4) DMARDs + BAs + PPT (n = 9). The dynamics of MDS and the outcomes of RA were estimated in 112 (91.0%) and in 83 (67.5%) of the 123 patients at one-and five-year follow-ups, respectively. The efficiency of RA therapy was evaluated from the changes in DAS28 and SDAI. Results and discussion. One year later, the patients who had received the complete cycle of PPT and took DMARDs achieved a satisfactory effect twice more frequently (58.1 and 32.3%, respectively; relative risk (RR) = 0.53; 95% confidence interval (CI), 0.2-1.39; p = 0.024) and did not respond to therapy 3 times less often (21.0 and 58.1%, respectively; RR = 2.41; 95% CI, 0.87-6.71; p = 0.001) according to the EULAR criteria than those who had refused PPT. The patients with MDS who received DMARDs + PPT during one year were unresponsive to therapy significantly less frequently than those who received DMARDs and BAs without PPT (21 and 44.8%, respectively; RR = 0.6; 95% CI, 0.21-1.7; p = 0.029). After 5 years of follow-up, the probability of no response to RA therapy in MD patients who received only DMARDs was 3.6 times higher than in those who had PPT (66.7% and 10.4%, respectively; RR = 3.58; 95% CI 0.82-15.5; p < 0.001). The patients adequately treated with DMARDs and BAs for MDS according to the DAS28 showed 1.3-fold more frequently good and satisfactory results (100 and 76.2%, respectively; p = 0.14) than those who refused PPT, but these differences were not statistically significant because the DMARD+BA+PPT group was small. Five-year follow-up indicated that DAS28 remission was more common in the patients receiving DMARDs and PPT than in those who had DMARDs and no PPT (34.5 and 8.3%, respectively; RR = 1.79; 95% CI, 0.34-9.24; p = 0.024). DAS28 remission was somewhat more frequently observed among the patients receiving DMARDs, BAs, and PPT than among those taking DMARDs and BAs (33.3 19.0%, respectively; RR = 1.64; 95% CI, 0.28-9.57; p = 0.34), but these differences were insignificant. Remissions according to the 2011 ACR/EULAR criteria were achieved by only the patients having DMARDs and PPT (6.9% and 13.8% after 1 and 5 years, respectively). Conclusion. Adequate treatment of MDS in RA patients results in a significant increase in the efficiency of antirheumatic therapy.

© 2018 Ima-Press Publishing House. All right reserved. The response rate to therapy for rheumatoid arthritis (RA) rarely exceeds 60%. Mental disorders (MDs) of the anxiety-depressive spectrum (ADS) and cognitive impairment (CI) substantially affect the evaluation of the efficiency of RA therapy. Adequate psychopharmacotherapy is one of the possible approaches to optimizing the treatment of RA. The factors influencing the efficiency of RA therapy with standard disease-modifying antirheumatic drugs (DMARDs) and biological agents (BAs) in combination with adequate psychopharmacotherapy have not been previously identified. Objective: to determine the predictors of response to therapy in patients with RA receiving DMARDs and BAs with or without adequate psychopharmacotherapy for ADS disorders. Subjects and methods. The investigation included 128 patients (13% men and 87% women) with a reliable diagnosis of RA. At baseline, 75.1% of patients received DMARDs; 7.8% - BAs. ADS disorders were detected in 123 (96.1%) patients. Psychopharmacotherapy was offered to all the patients with MDs; 52 patients agreed to treatment and 71 refused. The following therapeutic groups were identified according to the performed therapy: 1) DMARDs (n = 39); 2) DMARDs + psychopharmacotherapy (n = 43); 3) DMARDs + BAs (n = 32); 4) DMARDs + BAs + psychopharmacotherapy (n = 9). The changes of MDs symptoms and the outcomes of RA were assessed in 83 (67.5%) patients at five-year follow-up. The efficiency of RA therapy was evaluated with DAS28 (EULAR criteria). Predictors of response to therapy were determined using linear regression modeling. Results and discussion. At 5 years, 22 (26.5%) and 37 (44.6%) patients were recorded to show good and moderate responses to therapy, respectively; 24 (28.9%) patients were non-respondents. The linear regression model included 14 factors (p<0.001). The high values of DAS28 (β=0.258) at the inclusion; belonging to therapeutic groups 2 (β=0.267), 3 (β=0.235), and 4 (β=0.210), the absence of diabetes mellitus (β=-0.230), and experience in using glucocorticoids (β=-0.230) were associated with a high likelihood of response to therapy; high body mass index (β=-0.200) and long RA duration (β=-0,181), a high level of rheumatoid factor (β=-0.176), a history of myocardial infarction (β=-0.153), schizotypic disorder (β=-0.132), and extra-articular manifestations of RA (β=-0.106), and older age (β=-0.102) were related to a low probability of response. The area under the ROC curve for the model was 0.99 (p<0.001). Conclusion. BA therapy and psychopharmacotherapy, along with younger age, shorter duration and high activity of RA, a low level of rheumatoid factor, lower body mass index, the absence of diabetes mellitus, myocardial infarction, and extra-articular manifestations of RA in the history, schizotypic disorder, and experience in using glucocorticoids are associated with a greater likelihood of a good and moderate treatment response.