DAS28 Values Research Articles

Porphyromonas gingivalis amount in the tongue biofilm is associated with erosive arthritis in systemic lupus erythematosus.

Several data have demonstrated the occurrence of erosive arthritis in Systemic Lupus Erythematosus (SLE) patients. However, a few studies have focused on the pathogenic mechanisms involved in this feature. The implication of oral pathogens has been proved in Rheumatoid Arthritis: in particular, Porphyromonas gingivalis (Pg), by inducing citrullination, could trigger autoimmune response. Here, we evaluated amount of Pg on the tongue in a cohort of SLE patients with arthritis, focusing on the association with the erosive phenotype. SLE patients with arthritis were enrolled. DAS28 was applied to assess activity. Erosive damage was evaluated by ultrasound at level of MCP (metacarpophalangeal) and PIP (proximal interphalangeals) joints. All subjects underwent a tongue cytologic swab in order to quantify the amount of Pg (real-time PCR). The bacterium expression was obtained from the ratio between the patient's DNA amount and that obtained from healthy subjects. 33 patients were enrolled (M/F 3/30; median age 47years, IQR 17; median disease duration 216 months, IQR 180): 12 of them (36.4%) showed erosive damage, significantly associated with ACPA positivity (p = 0.03) and higher values of DAS28 (p = 0.01). A mean ratio of 19.7 ± 31.1 was found for Pg amount. Therefore, we used Pg mean values as threshold, identifying two groups of patients, namely, highPg and lowPg. Erosive damage was significantly more frequent in highPg patients in comparison with lowPg (60.0% vs 26.0%, p = 0.001). Furthermore, highPg patients showed higher prevalence of skin manifestations, serositis, and neurological involvement (p = 0.005, p = 0.03, p = 0.0001, respectively). The possible contribution of oral microbiota in SLE erosive arthritis was here evaluated for the first time, finding a significant association between erosive damage and higher expression of Pg at tongue level.

P184 Are there any ethnic differences in the response to Janus Kinase Inhibitor therapy for the treatment of rheumatoid arthritis?

Abstract Background/Aims Baricitinib is an oral, synthetic Janus Kinase inhibitor. It has become a commonly used drug in the treatment of rheumatoid arthritis (RA), both as combination therapy and monotherapy. Previous studies have compared drug efficacy in different ethnicities, but no studies have compared the efficacy of baricitinib for the treatment of RA in different ethnicities. Given the large South Asian population in Leicestershire, we reviewed our cohort of RA patients on baricitinib to see whether there is any difference in drug response rates between the Asian and Caucasian cohorts. Methods This was a retrospective study. Patients included were those under the care of rheumatology at University Hospitals of Leicester (UHL) with a diagnosis of RA and either receiving baricitinib, or had received it in the past. Data was collected using the UHL IT systems, clinic letters, and pharmacy records. In addition to ethnicity, we reviewed patient age, gender, concurrent DMARDs used, previous biologics used, baseline and post-treatment DAS28, dropout from therapy, baseline biochemical assays (anti-CCP and RF status) and radiographic findings. Independent T-test was used to compare continuous data and the Pearson Chi-Square test was used to compare categorical data. SPSS was used to analyse the results. Results 120 patients were included in the analysis and data was analysed with PFA. There was no statistically significant difference in the mean DAS28 at baseline (Asian 5.17 vs Caucasian 4.65, p value 0.107) and post-treatment (Asian 2.83 vs Caucasian 3.33, p value 0.404) (see table 1). Comparing both ethnicities, there was no statistically significant difference in previous biologics used, the presence or absence of anti-CCP and RF, and radiographic findings of erosions. Limitations of the study include the low proportion of post treatment DAS28 values recorded and absence of data comparing primary or secondary biologic failure. Conclusion This is the first study of its kind and found no significant difference in baricitinib response between the Asian and Caucasian cohorts. Future studies are needed to evaluate this subject further. Such data is important as it can contribute to a body of evidence that may in future help inform clinical decision making. Disclosure A. Jubber: None. W.H.Z. Hussain: None. A. Moorthy: None.

Numerical study on heterogeneous reaction characteristics of a single coal char particle under air- and oxy-fuel combustion: Effects of particle motion

Research and development of low-carbon combustion technology are necessary to satisfy the requirements of carbon neutrality. Oxy-fuel combustion technology is deemed a promising low-carbon technology it requires further investigation due to N2 replacement by CO2. This study aims to investigate the effects of particle motion modes (i.e., translation and rotation) and their speeds on char reaction characteristics under air- and oxy-fuel combustion. The translational and rotational speeds are described by the particle Reynolds numbers Rep and particle swirl Reynolds numbers Rep,w, respectively. The results indicated that the flame peak temperatures were reduced by 5.1% and 20.4%, and the particle temperatures were decreased by 13.1% and 9.2% under air- and oxy-fuel combustion, respectively, with an increase in the Rep values. However, the peak temperatures of the flame and particle were minimally affected by different Rep,w values. Char consumption rates and the reduced effects on the rates due to N2 replacement by CO2 were enhanced when the Rep values increased. The rates remained nearly unchanged, and the reduced effects remained constant at ∼20% with an increase in the Rep,w values. The proportions of each heterogeneous reaction were nearly unaffected by the increase in the Rep and Rep,w values, the proportion of gasification reaction increased with N2 replacement by CO2, and the surface Damköhler numbers (Das) of oxidation and gasification reactions were predicted. The Das,oxi and Das,gas values decreased significantly with an increase in the Rep and Rep,w values from 0 to 150. The Das values affected by rotational motion speeds (Rep,w) were more significant than those affected by translational motion speeds (Rep).

Therapeutic efficacy of Urtica dioica and evening primrose in patients with rheumatoid arthritis: A randomized double-blind, placebo-controlled clinical trial

BackgroundRheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease. The pharmacological therapy of RA is often symptomatic to mitigate pain and immobility with analgesics and drugs with defined side effects and risks. Complementary medicines might decrease the signs of RA and reduce the need for them. In the present study, the anti-rheumatic, anti-inflammatory, and anti-oxidant effects of Urtica dioica and Evening Primrose Oil (EPO), in patients with RA was investigated. MethodsThis randomized, double‐blind, controlled trial involved 90 RA patients, and randomly assigned them into EPO, Urtica dioica, and placebo groups. The potential effect of these herbal medicines on Disease Activity Score (DAS) 28, Visual Analogue Scale (VAS), Total Anti-oxidant Capacity (TAC), IL-17, Rheumatoid Factor (RF), anti-cyclic citrullinated peptide antibodies (Anti-CCP), C Reactive Protein (CRP), and Erythrocyte Sedimentation Rate (ESR) before and after clinical trial were evaluated. ResultsAfter a three-month follow-up, the mean values of DAS28, IL-17, TAC, RF, and CRP in EPO and Urtica dioica groups were significantly different from the placebo group. However, the VAS, Anti-CCP, and ESR at baseline and at the end of the study were not significantly different between the three groups. After the intervention, the within-group DAS28 in the EPO and Urtica dioica groups, and placebo groups reduced significantly compared to the baseline. ConclusionMedicinal plants EPO and Urtica dioica appeared to decrease inflammatory factors, and can improve the symptoms of RA. Thus, EPO and Urtica dioica have great potential as complementary therapy in RA patients.

Association of rheumatoid arthritis and its severity with human leukocytic antigen-DRB1 alleles in Kurdish region in North of Iraq

BackgroundRheumatoid arthritis is a complex multifactorial chronic disease, the importance of human leukocytic antigen (HLA) as a major genetic risk factor for rheumatoid arthritis was studied worldwide. The objective of this study is to identify the association of HLA-DRB1 subtypes with rheumatoid arthritis and its severity in Kurdish region.MethodsA case–control study recruited 65 rheumatoid arthritis patients and 100 healthy individuals as control group all over the Kurdistan region/Iraq. Both patient and control groups are genotyped using polymerase chain reaction with sequence specific primer. Anti-CCP antibodies were measured by ELISA test. Rheumatoid factor, C-reactive protein, and disease activity score 28 which measured by DAS-28 values were calculated. The DAS-28 was used to assess the clinical severity of the patients.ResultsHLA-DRB1-0404 and HLA-DRB1-0405 frequencies showed a strong association with disease susceptibility (P < 0.001). The frequency of HLA-DRB1-0411 and HLA-DRB1-0413 were significantly higher in control group (P < 0.001). The frequency of rheumatoid factor and Anti-CCP were significantly higher among shared epitope-positive patients compared to shared epitope-negative patients (P < 0.001). Regarding the disease activity by DAS-28, rheumatoid arthritis patients didn’t show significant difference between the shared epitope-positive and shared epitope-negative patients.ConclusionsHLA-DR0404 and HLA-DR0405 alleles are related to RA, while HLA-DR1-0411 and HLA-DRB1-0413 protect against RA in the Kurdistan region in the North of Iraq.

Correlation between percentage of fat mass and level of disease activity in rheumatoid arthritis.

Introduction:Controversies exist regarding the relationship between body fat and disease activity in patients with rheumatoid arthritis. The evaluation of the disease is critical for establishing treatment and prognosis. Fat mass could be a predictive factor for poor prognosis in rheumatoid arthritis because of its association with low- and high-grade inflammation.Objective:To evaluate the correlation between fat mass values and disease activity in patients with rheumatoid arthritis.Materials and methods:This was a cross-sectional study. Eighty female patients diagnosed with rheumatoid arthritis (American College of Rheumatology of 1987) were evaluated. For each one, the evaluation determined fat mass using bioelectrical impedance analysis and disease activity using the Disease Activity Score on 28 joints (DAS28).Results:The mean age was 59.11 ± 9.92 years, with an average disease duration of 14.13 ± 10.13 years; 85% of patients showed a high body fat percentage. Pearson’s correlation between DAS28 values and fat mass was r = 0.035 (p = 0.76).Conclusion:The levels of DAS28 showed no correlation with fat mass percentage. Further studies are required to clarify the factors that can modify these levels.

Патогенетические аспекты коморбидной ассоциации хронической сердечной недостаточности и ревматоидного артрита

The purpose — to analyze the frequency of anemia and decreased glomerular filtration rate (GFR) in patients with chronic heart failure (CHF) and rheumatoid arthritis (RA) and to identify the possible associations of these indicators with the systemic inflammation parameters and the CHF course. Material and methods. The main group consisted of 134 patients with CHF and RA, the comparison group — of 122 patients without RA. The functional class (FC) of CHF was identified according to NYHAI-II. The diagnosis of RA was made on the basis of radiological and serological studies. The radiological stage of RA was I-III according to Steinbrocker. The basic anti-inflammatory drug for RA was methotrexate. A comparative analysis of clinical and laboratory parameters was carried out for patients of both groups, as well as a possible association of hemoglobin levels and GFR with RA activity indicators and CHF severity parameters. The processing was carried out using the STATISTICA 10.0 program. The critical level of significance when testing statistical hypotheses was p &lt; 0.05. Results. Statistically significant differences in the frequency of anemia and a decrease in GFR were revealed between the examined groups. In the group of patients with CHF and RA, direct statistically significant associations of hemoglobin and GFR levels with LVL were revealed, as well as statistically significant associations of hemoglobin and GFR levels with NT-proBNP levels and DAS28 values. Conclusion. Statistically significant associations between the studied parameters were observed in patients with CHF and RA against the background of systemic inflammation, which may negatively affect the course of CHF.

Serum irisin level in rheumatoid arthritis patients: Relationship to disease activity, subclinical atherosclerosis, and cardiovascular risk factors

Aim of the workTo assess serum irisin level in rheumatoid arthritis (RA) patients, determine the relationship between irisin levels, disease activity and cardiovascular (CV) risk factors, and to evaluate its performance in predicting subclinical atherosclerosis and disease activity. Patients and methods60 RA patients and 30 controls were recruited for serological enzyme linked immunosorbant assay (ELISA) testing of irisin levels. Disease activity score (DAS28), health assessment questionnaire disability index (HAD-DI) and American college of rheumatology classification of functional status were assessed. Levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), glycated hemoglobin (HbA1c), insulin and lipid profile were measured. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated. Carotid intimal medial thickness (C-IMT) was measured and echocardiography performed. ResultsSerum irisin levels were significantly lower in patients (9.8 ± 10.6 ng/ml) vs. controls (20.5 ± 13.8 ng; p < 0.001). Irisin levels inversely correlated significantly with C-IMT, body mass index (BMI), HOMA-IR, disease activity and disability. Patients with CV involvement showed significantly lower serum irisin level, increased disease activity and disability. Classifying patients based on cut-off values of DAS28 into low, moderate, and high disease activity, a significant difference in irisin levels was found, being lowest among highly active patients. Irisin performed as an excellent independent indicator of subclinical atherosclerosis (p < 0.001) and high disease activity (p < 0.001) in RA patients. ConclusionIn RA, decreased irisin were significantly associated with increased CV risk and performed better than traditional yardsticks in identifying disease activity. It may act as an independent indicator of subclinical atherosclerosis within RA patients.

Changes of DCE-MRI Parameters in Patients with Rheumatoid Arthritis before and after Therapy and Their Value for the Efficacy Evaluation of Patients.

Objective To explore the changes of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in patients with rheumatoid arthritis (RA) before and after therapy and their value for the efficacy evaluation of patients. Methods Totally, 90 patients with RA confirmed in our hospital between January 2018 and January 2020 were enrolled. All of them were examined with a Siemens Magnetom Avanto 1.5T imaging system, and data about the rate of enhancement in early stage (REE) and steep slope maximum (SSmax) were obtained. Then, the disease activity score in 28 joints (DAS-28), REE, and SSmax were analyzed, and the associations of SSmax and REE with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and DAS-28 were investigated. Additionally, the patients were assigned to the acute-stage group and the chronic-stage group according to their time-signal intensity curves after therapy, and the two groups were compared in SSmax, REE, ESR, CRP, and DAS-28. Corresponding receiver operating characteristic (ROC) curves were drawn for the analysis of potential markers for efficacy improvement in patients. Results After therapy, REE, SSmax, ESR, DAS-28, and CRP in the synovium of all patients declined greatly (all P < 0.05), with higher levels observed in the acute-stage group than those in the chronic-stage group (all P < 0.05). SSmax and REE of patients were positively bound up with their ESR, CRP, and DAS-28 (all P < 0.05). Additionally, according to ROC curve-based analysis, both SSmax and REE can be adopted as biological indexes for distinguishing between patients at the acute phase from those at the chronic stage, and joint detection of them can boost the sensitivity of DAS-28. Conclusion The SSmax and REE levels in RA patients after treatment were significantly decreased, and the levels in patients in the chronic phase were lower than those in patients in the acute phase. SSmax and REE are highly expressed in RA patients, and the combined detection can enhance the value of DAS-28 in the assessment of RA, and it is worthy of clinical promotion.

Dynamics of the level of calprotectin in patients with rheumatoid arthritis during rituximab biosimilar (Acellbia “Biocad”) therapy

Objective.To study the relationship between the level of calprotectin (CP) and RA activity, the level of acute phase reactants, proinflammatory cytokines, chemokines and growth factors, to assess its dynamics during rituximab (RTM) biosimilar therapy.Material and methods.20 patients with RA were examined. All patients received 2 intravenous infusions of RTM (Acellbia®) at a dose of 600 mg with an interval of 2 weeks against the background of methotrexate therapy. The level of CP in blood serum was measured by ELISA.Results.Before starting DAS28 (5.6 [4.9–6.8]), SDAI (27.17 [23.08–39.9]) and CDAI (26.6 [22.25–37.0]) corresponded to the high disease activity. A decrease in disease activity was noted after 12 and 24 weeks of therapy: the DAS28 value was 4.28 [3.24–4.75] and 4.14 [3.11–4.66], respectively (p&lt;0.05). Before the start of therapy, patients with RA had a higher CP level compared with healthy donors 9.68 (4.5–21.5) and 2.39 (1.52–4.45) μg/ml, respectively (p&lt;0.05). Against the background of RTM therapy, there was a decrease in the CP level 12 weeks after the first infusion of the drug in the group as a whole by 26.5% from the initial level, among patients with moderate/no effect of therapy – by 32.7% from the initial level.Conclusion.The CP level significantly decreases during therapy and can be used to monitor the effectiveness of therapy. The predictive value of this laboratory parameter requires further study.

AB0263 THE LEVEL OF 7-HYDROXY METHOTREXATE IN BLOOD CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS DIRECTLY CORRELATES WITH THE LEVEL OF POLYGLUTAMATES OF METHOTREXATE

Background:7-hydroxy Methotrexate (7-hydroxy-MTX) is a phase I metabolite of MTX, which is converted by hepatic aldehyde oxidases. It is known that 7-hydroxy MTX can reduce the effectiveness of methotrexate, which is associated with increased excretion of methotrexate due to a decrease in polyglutamation and binding to enzymes [1].Objectives:To analyze the level of 7-hydroxy-MTX in peripheral blood cells in order to study the correlation of the level of this metabolite with the level of polyglutamates of methotrexate (MTXPGs).Methods:The prospective study included 65 patients aged 53±11 years, 50 women, 13 men, diagnosed with RA, according to the ACR/EULAR 2020 criteria, methotrexate (MTX) naiive. The duration of the disease was 7,5[4;24] months. All patients were administrated MTX subcutaneously at a dose of 10-15 mg/m2. The visits were carried out at weeks 0, 4, 12, 24 and 36, at all visits samples were taken for the content of MTXPGs with 1,2,3 and 4 glutamate residues and 7-hydroxy MTX separately in red blood cells mass (RBC) and mononuclear cells (MO). The mononuclear fraction was isolated by layering on verografin-ficoll. All patients received folic acid at a standard dose of 5 mg 24 hours after parenteral MTX administration. Samples were collected no earlier than 36 hours after MTX administration. All patients had normal renal function. Disease activity was assessed using the DAS28 index calculated by C-reactive protein.Results:The average concentration of 7-hydroxy MTX is shown in Table 1.Table 1.Level of 7-hydroxy MTX in erythrocytes and mononuclear cells, nmol/L, Median [25; 75 quartiles]7-hydroxy MTX level in:4 weeks12 weeks24 weeks36 weeksRBC18,5[3,1;61,5]10,2[3,6;50,8]10,3[1,7;36,8]7,2[0,1;25,3]MO0,8[0,1;15,2]4,0[0,1;42,2]3,5[0,1;8,1]0,4[0,1;8,9]The level of 7-hydroxy-MTX directly correlated with the level of MTXPGs 1-4, and summary MTXPG in both RBC and MO. Analysis of pairwise correlations according to Pearson showed that: after 4, 12 and 36 weeks, the level of 7-hydroxy-MTX did not correlate with the value of DAS28. After 24 weeks of therapy, the level of 7-hydroxy-MTX in RBC was inversely correlated with DAS28 of the disease (p=0.043).Conclusion:The preliminary results indicate a positive correlation between the level of 7-hydroxy-MTX and MTXPGs in RBC and MO. In this regard, the concentration of 7-hydroxy-MTX can be used as a prognostic marker for MTX therapy in the absence of opportunities in clinical centers to measure the entire line of MTXPGs in RBC and MO. Since the data obtained are somewhat at odds with the few literary sources, it is necessary to conduct further research on this fact.

Health-related Quality of Life Outcomes of Adalimumab for Patients With Rheumatoid Arthritis in Korea.

Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disorder that impairs patients' overall health-related quality of life (HRQOL) In this study, we evaluated the effect of adalimumab in Korean patients with active RA on HRQOL. Patients included in the study had moderate to severe active RA that did not respond to conventional drugs with a Disease Activity Score of 28 joints >32 and were biologics-naïve All patients received adalimumab 40 mg subcutaneously every other week and were followed for 24 weeks The primary endpoint was the change in baseline Health Assessment Questionnaire Disability Index (HAQ-DI) score at week 24 Secondary endpoints were changes in the EuroQol 5-dimension 3-Level (EQ-5D-3L) baseline score and Short Form 36-Item Health Survey (SF-36) domain scores at weeks 12 and 24 and change in baseline HAQ-DI score at week 12. In total, 91 Korean patients were included Ninety-three percent of patients were in high disease activity with a baseline mean DAS28 value of 61 within all patients The mean change from baseline in HAQ-DI scores were -046 at week 12 and∼067 at week 24 (p<00001) Additionally, EQ-5D-3L score at weeks 12 and 24 had significantly improved (p<00001) compared to baseline SF-36 at weeks 12 and 24 had significantly improved (p<00001, p=00001) compared to baseline. Treatment with adalimumab resulted in significant improvement in HAQ-DI, EQ-5D-3L, and SF-36 scores at 12 and 24 weeks in Korean RA patient.

Marital Stability and Quality of Couple Relationships after Acquired Brain Injury: A Two-Year Follow-Up Clinical Study.

Couple relationships after acquired brain injury (ABI) could be vulnerable to emotional distress. Previous evidence has demonstrated significant marital dissatisfaction in the first period after a traumatic event, while long-term evaluations are lacking. In this study, we evaluated the impact of a series of demographic and clinical factors on marital stability after two years from the injury. Thirty-five patients (29% female) with mild/moderate ABI (57% vascular, 43% traumatic) and their partners were enrolled. The couples completed a series of psychological questionnaires assessing marital adjustment (Dyadic Adjustment Scale, DAS) and family functioning (Family Relationship Index, FRI) at discharge from the intensive rehabilitation unit and after 2 years. Demographics (i.e., educational level, job employment and religion commitment) and clinical variables (i.e., the Barthel index, aetiology and brain lesion localization) were considered as predictive factors. Regression analyses revealed that the DAS and FRI values are differently influenced by demographic and clinical factors in patients and caregivers. Indeed, the highest educational level corresponds to better DAS and FRI values for patients. In the spouses, the variability of the DAS values was explained by aetiology (the spouses of traumatic ABI patients had worse DAS values), whereas the variability in the FRI values was explained by religious commitment (spending much time on religious activities was associated with better FRI values). Our data suggest that some clinical and demographic variables might be important for protecting against marital dissatisfaction after an ABI.

Joint involvement influences quality of life in systemic lupus erythematosus patients.

Joint involvement represents the major determinant in quality of life (QoL)in Systemic Lupus Erhytematosus (SLE) patients. However, QoLhas been generally evaluated by non-specific questionnaires. We evaluated the relationship between SLE musculoskeletal manifestations and QoL, assessed by LupusQoL. Patients with joint involvement (group A) were compared with those without this feature (group B). Disease activity was assessed by SLEDAI-2k in the whole population, while DAS28 and swollen to tender ratio were applied to assess joint activity. LupusQoL was administered to all the patients. Group A included 110 patients [M/F 8/102; median age 49 years (IQR 13), median disease duration 156 months (IQR 216)], group B 58 [M/F 11/47; median age 40 years (IQR 15), median disease duration 84 months (IQR 108)].We found significanlty lower values in all the LupusQoL domains except for one (burden to others) in group A in comparison with group B. A significant correlation between DAS28 values and all the LupusQoL domains in group A was found; only three domains correlated with SLEDAI-2k. SLE-related joint involvement significantly influences disease-specific QoL. DAS28 better correlated with LupusQoL domains in comparison with SLEDAI-2k, confirming the need for specific musculoskeletal activity indices.

Análisis del componente subjetivo del DAS28 en dos poblaciones de América del Sur con artritis reumatoide en tratamiento con agentes biológicos

Introduction: In patients with rheumatoid arthritis (RA), disease activity is often determined through the DAS28 index. Subjective components included in the index can be influenced by non-inflammatory factors, and overestimate disease activity. The DAS28 index and its subjective components have not been extensively studied in South Americans. Objectives: Analyze the subjective components of DAS28 as well as clinical and serological variables related to it in South American patients with rheumatoid arthritis treated with biologics. Methods: Retrospective longitudinal analysis of patients from BIOBADAGUAY registry. The formula for the subjective component of DAS28 was determined. DAS28 and its components were analyzed for both populations at treatment initiation, and 52 week follow up, and associations with clinical and serological variables were evaluated. Results: The Paraguayan patients had lower mean age, number of comorbidities and less smokers. They were also found to have lower DAS28, sDAS28, PGH and TJC. Country of origin, number of comorbidities, BMI, smoking history and methotrexate use were associated to subjective components of DAS28 at treatment initiation. Changes in sDAS28 at week 52 were highly determined by its initial value. No association was found with objective variables (CRP, ESR, number of treatments.) Conclusions: Variables other than inflammatory disease activity can influence sDAS28 and DAS28 of South American patients. Their management must be individualized and not be based solely on DAS28 value.

EFFICACY AND SAFETY OF TOFACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS IN REAL CLINICAL PRACTICE

Objective: to evaluate the clinical efficacy and safety of the targeted synthetic disease-modifying anti-rheumatic drug (DMARD) tofacitinib (TOFA; Yakvinus®) in patients with active psoriatic arthritis (PsA) at 12 and 24 weeks after starting treatment. To define the place of TOFA in the therapy of PsA patients. Subjects and methods. Examinations were made in 41 patients (17 men and 24 women) with active PsA and an insufficient response to previous treatment with synthetic DMARDs and/or biological agents (BA). Before starting therapy, the median disease activity for psoriatic arthritis (DAPSA) and disease activity score (DAS28) were 44.2 [37.8; 55.3] and 5.5 [4.7; 6.1], respectively. TOFA tablets were prescribed at a dose of 5 mg twice daily for 24 weeks with possible dose escalation to 10 mg twice daily after 12 weeks. At the beginning of the investigation, at 12 and 24 weeks, the investigators assessed disease activity and TOFA therapy efficiency of according to DAPSA, DAS28 and minimal disease activity (MDA) criteria: tender joint count ≤1, swollen joint count ≤1, a psoriasis area severity index (PASI) ≤1 or body surface area (BSA) ≤3%, pain intensity ≤15 mm, patient global assessment ≤20 mm, Health Assessment Questionnaire (HAQ) ≤0.5, and enthesitis ≤1. They also determined the number of patients who had achieved remission (DAPSA ≤4, DAS28 score &lt;2.6), low disease activity (DAPSA 5-14, ≤2.6, DAS28 &lt;3.2) or MDA (5 out of the 7 criteria) during TOFA therapy at 24-week follow-up. The safety of therapy was evaluated by analyzing the drug-induced adverse events (AE): the frequency, severity and time of their occurrence were studied. Results and discussion. At 24 weeks after initiation of TOFA therapy, there was a significant decrease of median DAPSA and DAS28 values as compared to baseline, to 11 [4.3; 17.3] and 2.6 [1.7; 3.4] respectively. The median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) also significantly decreased from 6 [4.2; 7] and 3.8 [2.8; 4.4] to 1.4 [0.6; 3.2] and 1.5 [1; 2.1] respectively. The median BSA was significantly reduced from 3 [1; 5] to 0.5 [0.1; 2]. At 24 weeks after initiation of TOFA therapy, DAPSA and DAS28 low disease activity/remission were achieved by 38.5/23.1% and 17.9/53.9% of patients, respectively. Fifteen (38.5%) patients achieved MDA. 38 (92.7%) of the 41 patients completed a full TOFA therapy cycle. Two patients dropped out of the investigation due to ineffective therapy and one due to AE (diarrhea occurring up to 10 times daily, headache, elevated blood pressure, and lacrimation). At 24 weeks, 14 (34.2%) patients reported to have AE. The most common AE noted in 7 (17.1%) patients were infections: acute respiratory viral infection (n=3), fever (n=2), and folliculitis (n=2). In addition, two patients had diarrhea and two had headache. Conclusion. TOFA is an effective drug for the treatment of PsA patients with moderate or high inflammatory activity, has a significant effect on all clinical manifestations of PsA and has a satisfactory safety profile.

ANALYSIS OF THE RESULTS OF TOFACITINIB THERAPY IN REAL CLINICAL PRACTICE ACCORDING TO THE ALL-RUSSIAN ARTHRITIS REGISTRY (OREL)

Objective: to analyze the results of tofacitinib (TOFA) therapy in real clinical practice according to the All-Russian Arthritis Registry (OREL). Subjects and methods. The OREL Registry included 347 patients (286 (82%) women and 61 (18%) men) with rheumatoid arthritis (RA) who initiated TOFA therapy. The male:female ratio was 1:4.7. The patients’ median age at onset of the disease was 42 years; its duration was 8 years. Most of the patients included in the registry had extended- (n=171 (52%)) or late- (n=148 (45%)) stage of RA. Results and discussion. Prior to initiation of TOFA therapy, RA activity according to DAS28 was high and moderate in 91 (64.5%) and 40 (28.4%) patients, respectively; the median DAS28 value was 5.5 [4.6; 6.2]; SDAI – 30.5 [21.4; 42.9], and CDAI – 28.2 [20.0; 37.1]. The use of TOFA was accompanied by significant decrease of disease activity. After 12 weeks, high RA activity was persistent in 32 (22.7%) patients; the number of patients with moderate activity increased to 77 (54.6%), that of those with low activity rose to 15 (10.6%); remission was observed in 17 (12.1%) patients. 216 (62.6%) and 76 (22%) patients received TOFA as first- and second-line therapy, respectively. TOFA was most frequently prescribed when tumor necrosis factor-á inhibitors (19.6%), rituximab (7.8%), tocilizumab (4.3%), and abatacept (5.2%) were insufficiently effective or poorly tolerated. Conclusion. The results of using TOFA in real clinical practice may suggest that the drug has high efficacy in patients with RA. TOFA can be used at a dose of 5 or 10 mg twice daily as both alone and in combination with disease-modifying anti-rheumatic drugs. TOFA showed similar efficacy in patients who had earlier taken biological agents and in those who had not.

Recombinant Soluble TNF‐α Receptor Fusion Protein Therapy Reduces Insulin Resistance in Non‐Diabetic Active Rheumatoid Arthritis Patients

ObjectiveCurrent evidence highlights a link between insulin resistance (IR) and disease activity in rheumatoid arthritis (RA), suggesting that insulin sensitivity can be improved by treating patients with TNF‐α blockers. Although reduced IR has been shown in RA patients who receive monoclonal antibody treatment, the efficacy remains to be elucidated when using recombinant soluble receptor fusion proteins. In particular, etanercept (ETA) is capable of blocking lymphotoxin‐α, a cytokine‐related to IR‐associated disease status.MethodsA prospective study was carried out in nondiabetic active RA patients receiving a 25‐mg subcutaneous ETA injection twice weekly.ResultsThirty patients aged 31 to 73 years (50.9 ± 10.6), naïve to biological and targeted synthetic disease‐modifying antirheumatic drugs with DAS28 scores of 5.17 to 7.49 (6.11 ± 0.66), were classified into high‐IR and low‐IR groups based on their baseline homeostatic model assessment (HOMA)‐IR levels. No differences were found between the two groups in terms of age, sex, weight, body mass index, seropositivity, and medication profiles before the injection. After a 24‐week therapeutic period, there were reduced HOMA‐IR levels in all patients in the high‐IR group (3.390 ± 0.636 to 2.234 ± 0.870, P < 0.001). A greater decrease in DAS28 values was found in patients with reduced IR than those without a reduction (2.54 ± 0.67 versus 1.46 ± 0.46, P = 0.006) in the low‐IR group.ConclusionWe observed an improvement in insulin sensitivity in nondiabetic active RA patients following 24‐week recombinant soluble TNF‐α receptor fusion protein therapy.

The types of left ventricular remodeling in patients with rheumatoid arthritis

Studying the factors leading to a pathological change in the cardiac structure in patients with rheumatoid arthritis (RA) can contribute to improvement in early diagnosis and to prevention of premature mortality from cardiovascular events.Objective. To study the types of left ventricular (LV) remodeling in patients with RA, by taking into account traditional cardiovascular risk factors, and to assess the clinical and immunological features of RA and the impact of drug therapy.Patients and methods. The investigation enrolled 74 RA patients who underwent assessment of echocardiography findings, by determining the type of LV remodeling, traditional cardiovascular risk factors, clinical and immunological features of the disease, as well as the current drug therapy.Results and discussion. Eccentric LV hypertrophy (ELVH) (n=33 (44.59%)) and concentric LV hypertrophy (CLVH) (n=34 (45.95%)) occurred at almost the same frequency among the pathological types of LV remodeling in patients with RA. Higher DAS28 values (p&lt;0.0001) were noted in ELVH than in CLVH. There were also positive correlations of EHLH with ESR and CRP level (r= 0.51, p&lt;0.0001; r=0.48, p=0.0001, respectively). The higher values of systolic blood pressure (p=0.0002), body mass index (p=0.01), patient age (p=0.0001), and the incidence of dyslipidemia (p= 0.008) were established in CVLH than in ELVH. LV diastolic dysfunction (DD) was detected much more frequently in RA patients with CLVH than in those with ELVH (p=0.01). The DD parameters (peak A, E/A) correlated with the degree (r=0.5, p&lt;0.0001; r=-0.5. p&lt;0.0001) and stage of hypertension (r=0.54, p&lt;0.0001; r=-0.48, p=0.0001, respectively), as well as with peak A and traditional risk factors, such as patient age (r=0.52, p&lt;0.0001), and high-density lipoprotein cholesterol levels (r=-0.48, p=0.0001).Conclusion. Most patients with RA had signs of LV hypertrophy; moreover, ELVH was closely linked with disease activity, whereas CLVH was related to the traditional risk factors.

The influence of tocilizumab immunogenicity markers on the effectiveness of treating rheumatoid arthritis

Purpose. The study assesses the impact of tocilizumab immunogenicity markers on clinical response to conducted treatment in patients with rheumatoid arthritis.&#x0D; Materials and methods. A total of 17 patients with the confirmed diagnosis of RA receiving tocilizumab therapy for more than 1 year were enrolled into the study. Blood serum samples were collected once every six months before every drug injection during 2.5 years of treatment. The concentration of antibodies to tocilizumab and level of tocilizumab was determined using the ELISA. Additionally, DAS28 values were measured at the first and the last patient visit during the course of study, whereas levels of C-reactive protein (CRP), white blood cells, platelets, rheumatoid factor, and circulating immune complexes were only measured at the last examination.&#x0D; Results. Positive correlations between the antibodies to tocilizumab and the last point DAS28 values were found, as well as a negative correlation of tocilizumab level and the level of DAS28.&#x0D; Conclusions. The data obtained indicate a significant effect of serum levels of tocilizumab, as well as of the concentration of antibodies to tocilizumab on the effectiveness of RA treatment. A routine study of these biomarkers might be useful for individualizing treatment approaches for RA patients and determining the causes of tocilizumab resistance.