Therapy In Rheumatoid Arthritis Patients Research Articles

Serum GM-CSF level is a predictor of treatment response to tocilizumab in rheumatoid arthritis patients: a prospective observational cohort study

BackgroundThe aim of this prospective observational cohort study was to unveil the predictors of treatment response to tocilizumab (TCZ) therapy in rheumatoid arthritis (RA) patients, in terms of clinical characteristics and serum proinflammatory cytokines, especially to explore the predictive value of granulocyte macrophage-colony stimulating factor (GM-CSF).MethodsActive adult RA patients with inadequate response to MTX intending to receive TCZ therapy were recruited prospectively in the study. A total of 174 severe RA patients were included for the identification of the associations between treatment response and the following characteristic features: demographics, medications, disease activity, serum proinflammatory cytokines and so on.ResultsDisease duration (OR = 0.996), tender joint count (TJC)/68 (OR = 0.943), neutrophil ratio (W4/baseline) (OR = 0.224), the high level of GM-CSF > 5 ng/ml (OR = 0.414) at baseline were the independent adverse predictors of good response assessed by clinical disease activity index (CDAI) at week 24 (W24) for TCZ therapy in RA patients. Moreover, DAS28-ESR (OR = 2.951, P = 0.002) and the high level of GM-CSF > 10 ng/ml at baseline (OR = 5.419, P = 0.002) were independent predictors of poor response, but not the high level of GM-CSF > 5 ng/ml (OR = 2.713, P = 0.054). The patients in the high GM-CSF group had significantly higher DAS28-ESR and serum levels of cytokines (IL-17A, IL-1β, IL-6, TNF-α) at baseline, as well as significantly higher rate of non-good response (62.8% vs. 39.4%, P = 0.010) and poor response (27.9% vs. 9.1%, P = 0.004) than the low GM-CSF group at W24. In addition, poor responders had significantly higher levels of GM-CSF with concomitant increase in the serum levels of IL-17A and IL-1β at baseline than those in moderate and good response groups, while serum levels of IL-6 and TNF-α at baseline were not significantly different in three response groups.ConclusionThe high levels of GM-CSF (> 5 ng/ml and > 10 ng/ml) at baseline were the independent predictors of non-good response and poor response to TCZ at W24 respectively. The high level of GM-CSF at baseline is a marker of high disease activity and a predictor of poor response to TCZ in severe RA patients, which may facilitate the development of individualized treatment strategies for refractory RA.

Deciphering the molecular landscape of rheumatoid arthritis offers new insights into the stratified treatment for the condition.

For Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments. We utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs. Subtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. The findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.

Genetic variability of three common NK and γδ T cell receptor genes (FCγ3R, NCR3, and DNAM-1) and their role in Polish patients with rheumatoid arthritis and ankylosing spondylitis.

Various lymphocyte subpopulations, including NK cells as well as γδ T cells, have been considered an important element in the pathogenesis of autoimmune, inflammatory, rheumatic diseases, such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). The aim of this study was to assess the potential role of polymorphic variations in the genes coding for three NK and γδ T cell receptors: NCR3, FCγR3A, and DNAM-1 (rs1052248, rs396991, and rs763361, respectively) in the disease susceptibility and the efficacy of treatment with TNF inhibitors. The study included 461 patients with RA, 168 patients with AS, and 235 voluntary blood donors as controls. The NCR3 rs1052248 AA homozygosity prevailed in RA in patients lacking rheumatoid factor (p = 0.044) as well as in those who manifested the disease at a younger age (p = 0.005) and had higher CRP levels after 12weeks of anti-TNF therapy (p = 0.021). The FCγR3A rs396991 polymorphism was associated with pain visual analogue scale (VAS) values before the initiation of anti-TNF treatment. Lower VAS values were observed in the GG homozygous RA patients (p = 0.024) and in AS patients with the TT genotype (p = 0.012). Moreover, AS heterozygous patients with the TG genotype presented higher CRP levels in the 12th week of anti-TNF treatment (p = 0.021). The findings suggest that the NCR3 rs1052248 AA homozygosity may have an adverse effect on RA, while the T allele potentially plays a protective role in the development of AS. Moreover, the rs1052248 T allele and TT genotype appear to have a favorable impact on the response to anti-TNF therapy in RA patients.

Combination treatment with interferon-γ may be a potential strategy to improve the efficacy of cytotherapy for rheumatoid arthritis: A network meta-analysis

Background: Mesenchymal stem cells (MSCs) are considered a promising therapeutic strategy for rheumatoid arthritis (RA), but the current clinical results are varied. This study is to analyze the therapeutic effect of cell-based strategies on RA. Materials and Methods: The searches were performed with public databases from inception to June 17, 2021. Randomized controlled trials researching cell-based therapies in RA patients were included. Results: Eight studies, including 480 patients, were included in the analysis. The results showed that compared to the control, MSC treatment significantly reduced the disease activity score (DAS) at the second standardized mean difference (SMD): −0.70; 95% confidence interval (CI): −1.25, −0.15; P = 0.01) and 3rd month (SMD: −1.47; 95% CI: −2.77, −0.18; P < 0.01) and significantly reduced the rheumatoid factor (RF) level at the first (SMD: −0.38; 95% CI: −0.72, −0.05; P = 0.03) and 6th months (SMD: −0.81; 95% CI: −1.32, −0.31; P < 0.01). In the network meta-analysis, MSCs combined with interferon-γ (MSC_IFN) had a significant effect on increasing the American college of rheumatology criteria (ACR) 20, ACR50, and DAS <3.2 populations, had a significant effect on reducing the DAS, and decreased the RF level for a long period. Conclusion: MSCs could relieve the DAS of RA patients in the short term and reduce the level of RF. MSC_IFN showed a more obvious effect, which could significantly improve the results of ACR20, ACR50, and DAS <3.2 and reduce the DAS and RF levels.

Aminotransferases activity on additional therapy in rheumatoid arthritis patients with liver disease.

<b>Aim</b><b>.</b> Investigate the effect of additional therapy of atorvastatin, essential phospholipids and their combination on activity of aminotransferases in RA patients with NAFLD.<br /> <b>Materials and Methods.</b> We investigated 126 RA patients and 30 in control. 77 RA patients with NAFLD were divided into three groups. I: 25 RA patients received 10 mg of atorvastatin per day. II: 26 RA patients received essential phospholipids 1800 mg per day. III: 26 RA patients received essential phospholipids 1800 mg per day and atorvastatin 10 mg per day for 6 months.<br /> <b>The results.</b> In the I group, a transient increase in ALT and AST activity was observed to 35.11±3.501 U/l and 30.51±2.19 U/l, respectively, and a spontaneous decrease in elevated transaminases was recorded after 6 months of atorvastatin use. In the II group, a decrease in ALT by 25.6% was observed compared to the indicators before treatment, and they remained unchanged even after 6 months. After 3 months of complex use of atorvastatin and essential phospholipids, ALT activity decreased by 33.8% and AST decreased by 8.2%, which was not observed in RA patients with NAFLD of groups I and II.<br /> <b>Conclusions.</b> Use essential phospholipids 600 mg three times a day and atorvastatin 10 mg per day for 6 months in addition to antirheumatic therapy in RA patients with NAFLD allows to avoid a transient increase in aminotransferases, reduce the severity of hepatotoxic reactions, and avoid stopping or canceling antirheumatic therapy.

Dynamics of modified cardiovascular risk factors in patients with rheumatoid arthritis on the background of 5-year therapy with an interleukin 6 receptor inhibitor

The effect of an inhibitor of interleukin (IL) 6 receptors on the state of the cardiovascular system in patients with rheumatoid arthritis (RA) remains poorly understood, especially with its long-term use.The aim – to study the effect of therapy with the IL-6 receptor inhibitor tocilizumab (TCZ) on the dynamics of modifiable risk factors (RF), total cardiovascular risk (CVR), structural changes in the carotid arteries (CA) and the incidence of cardiovascular complications (CVC) in patients with rheumatoid arthritis during the 260-week follow-up period.Material and methods. The study included 37 patients with active RA (32 women and 5 men) with ineffectiveness and/or intolerance to disease modifying anti-rheumatic drugs (DMARDs); median age was 56 [48; 68] years, disease duration was 92 [49; 158] months; DAS28 (Disease Activity Score 28) – 6.2 [5.5; 6.7] points; all patients were seropositive for rheumatoid factor (RF), 86% – for antibodies to cyclic citrullinated peptide (ACCP). Patients received TCZ therapy 8 mg/kg intravenously every 4 weeks; after 192 [176; 210] weeks, 60% of patients switched to subcutaneous administration of the drug at a dose of 162 mg once a week. In 51% of patients with RA, TCZ monotherapy was performed, in 49% – combination therapy of TCZ with DMARDs. Statins were received by 17 (46%) patients, including 7 patients before and 10 after inclusion in the study. All patients underwent an assessment of traditional risk factors, the total cardiovascular risk was calculated using the mSCORE scale, atherosclerotic vascular lesions were assessed by the detection of atherosclerotic plaques (ASP) of CA. The observation period was 260.4 [251.5; 283.4] weeks.Results. After 260 weeks of TCZ therapy, RA remission was observed in 32 (86%) patients, low activity – in 5 (14%) patients. During the observation period, the frequency of modified RF and the total CVR did not change significantly, an increase in body mass index (BMI) by 11% was recorded, the number of patients with hypercholesterolemia and a reduced level of HDL cholesterol (C) decreased. In patients without statin therapy, there were no significant changes in the blood lipid spectrum. In the group of patients receiving statins, there was an increase in HDL-C by 43%, a decrease in cholesterol levels by 15%, atherogenic index (AI) by 56% (p<0.01 in all cases) and associations between the dynamics of ∆cholesterol and ∆CRP (r=0.35; p=0.04), ∆LDL-C and ∆CRP (r=0.41; p=0.03). Significant structural changes in CA in RA patients by the end of 260 weeks of TCZ therapy were not identified. Initially, intima-media thickness (IMT) CA positively moderately correlated with age (r=0.7; p<0.01), BMI (r=0.37; p<0.01), systolic blood pressure (SBP) (r=0.62; p<0.01) and weakly with lipid spectrum parameters – cholesterol (r=0.29; p<0.01), LDL-C (r=0.36; p<0.01). No new associations of IMT CA by the end of the observation, as well as the relationship of the IMT CA value with the indicators of RA activity and the ongoing therapy, were identified. By the end of the study, the distribution of patients by mSCORE value and CVR level did not change significantly. The incidence of CVC was 0,54 per 100 patient-years over a 260-week period of TCZ use. Conclusion. Against the background of long-term TCZ therapy in RA patients, there was no increase in CVR and significant structural changes in CA. It is necessary to dynamically monitor the blood lipid profile and CVR in RA patients receiving TCZ therapy. Statin therapy can successfully control dyslipidemia in RA patients who receive long-term TCZ.

Effect of acupuncture on ischaemic stroke in patients with rheumatoid arthritis: a nationwide propensity score-matched study

ObjectiveTo demonstrate that acupuncture is beneficial for decreasing the risk of ischaemic stroke in patients with rheumatoid arthritis (RA).DesignA propensity score-matched cohort study.SettingA nationwide population-based study.ParticipantsPatients with RA diagnosed between...

CD39 expression on immune cells predicts methotrexate response in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting mostly small joints, such as hand and foot joints symmetrically with irreversible joint destruction. In this study, the relationship between CD39 expression and the treatment response of RA patients was examined to investigate its potential as a biomarker that demonstrates treatment response. This study included 77 RA patients and 40 healthy controls (HC). The RA patients were divided into 2 groups based on their response to RA treatment, those with a good response to methotrexate (MTX) monotherapy and those with an inadequate response based on the American College of Rheumatology and the European League Against Rheumatism response criteria. Various immunological parameters and Disease Activity Score in 28 Joints (DAS28) were examined between the groups using the Student's t-test. The monocytic myeloid-derived suppressor cell (M-MDSC) percentage was higher in the RA patient group versus the HC group. The CD39 expression in the T lymphocytes were higher in patients that responded well to the MTX compared to those showing inadequate response. Additionally, s negative correlation was found between the DAS28 and CD39 in the T cells. The results showed that the improvement in treatment response to the therapy in RA patients could be because of the enhancement in the CD39/adenosine (ADO) pathway. Therefore, therapies targeting the CD39/ADO pathway in T cells may improve RA treatments.

Efficacy of montelukast as an adjuvant therapy in rheumatoid arthritis patients: A randomized controlled study

ObjectiveThis study aimed to evaluate the efficacy of montelukast in conjunction with non-biologic disease modifying anti-rheumatic drugs (nDMARDs) in rheumatoid arthritis (RA) patients. MethodsThis study was a single-center randomized double-blinded placebo-controlled study. Adult RA patients were included if they had moderate to severe disease activity and were receiving monotherapy or combination of nDMARDs. Eligible patients were randomized, in 1:1 ratio, to receive either 10 mg montelukast or placebo, once daily for 16 weeks. The primary endpoint was the change in the 28-joints disease activity score (DAS28) 16 weeks after treatment. The patients’ quality of life (QoL) was assessed by the Arabic version of the Health Assessment Questionnaire-Disability Index. Moreover, serum levels of vascular adhesion molecule-1 (VCAM-1) were measured. ResultsA total of 87 patients completed the study; 44 in the montelukast arm and 43 in the control arm. After 16 weeks of treatment, disease activity decreased significantly in the montelukast arm with mean change in DAS28 (95% CIs) of −1.5 (−1.7, −1.2) while the control arm showed no improvement (0.2 (0.0, 0.4), p < 0.01). The QoL of the patients improved significantly from baseline in the montelukast arm (p < 0.01) but not in the control arm (p = 0.08). The median (IQR) serum levels of VCAM-1 were significantly lower in the montelukast arm (22.8 (15.0–32.7)) than in the control arm (28.9 (15.4–42.8), p = 0.004). ConclusionThe co-administration of montelukast with nDMARDs in RA patients enhanced the anti-rheumatic effect which was reflected clinically by decreased disease activity.

Management of patients with rheumatoid arthritis in real clinical practice: Switching from interleukin 6 receptor inhibitors to interleukin 6 inhibitor (olokizumab)

Aim. Switching to another biologic with the same mode of action provides greater opportunity for long-term management of patients with rheumatoid arthritis (RA). In clinical practice, especially in the context of the COVID-19 pandemic, such switching occurred for non-medical reasons as well. However, there is no information about switching from interleukin 6 (IL-6) receptor (R) inhibitor to direct IL-6 inhibitor. Objective – to assess the efficacy and safety of therapy in RA patients, after switching from IL-6R inhibitors (tocilizumab (TOC), sarilumab (SAR)) to olokizumab (OKZ) for reasons not related to the loss of their efficacy or adverse events. Material and methods. In this retrospective cohort study efficacy parameters and routine biochemical data were analyzed using descriptive statistics – mean values with standard deviation for continuous parameters and absolute and relative frequency for binary variables. Adverse events (AE) were reported according to patient’s files. The statistical significance and changes of the analyzed variables by visits were determined using paired t-test. Fisher’s exact test or chi-square test was used to compare the proportion of patients with improvement/no change and of patients with worsening. All tests were 2-sided, and p&lt;0.050 was considered statistically significant. As this was an observational study, the statistical criteria have not been pre-specified. Results. We analyzed results obtained during 5 visits (2 visits before switching, switching visit and 2 visits after switching) in 110 RA patients who switched to OKZ 64 mg every 4 weeks subcutaneously (SC). Most patients (79.1%) were women, and 70% of patients were both positive by rheumatoid factor and antibodies to cyclic citrullinated peptide. Mean RA duration was 11 [6; 16] years, previous treatment duration was 44 [27; 62] months and mean interval before switching to OKZ was 35 [31; 68] days. This relatively long interval led to an increase in DAS28-ESR (Disease Activity Score 28 with determination of erythrocyte sedimentation rate) from 2.4 [1.9; 3.0] to 2.6 [2.1; 3.5] and DAS28-CRP (DAS28 with determination of C-reactive protein level) from 2.8 [2.0; 3.3] to 2.9 [2.2; 4.0] (the trends were similar in patients who received combined therapy and monotherapy). After switching, all of RA symptoms and indexes have been improved compared with the switching visit (some of them were significantly better even compared with stable therapy period e. g. DAS28-CRP was 2.4 [2.0; 3.1] in the overall group and 2.4 [2.1; 2.7] in the monotherapy group). AEs were registered in only 7 (6.4%) patients, of which 1 (0.9%) case (an exacerbation of herpes infection) was considered as serious. The most frequent AEs were arthralgia and mild transient leukopenia (2 patients each). There were no deaths. Conclusion. OKZ effectively maintained remission/low activity of RA after switching in both regimens: as add-on to disease modifying anti-rheumatic drugs and as monotherapy, and did not cause any additional safety concerns. The optimal results were reported when intervals before switching to OKZ were closer to those indicated in the instructions for IL-6R inhibitors.

Role of denosumab in bone erosions in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation and synovitis which evolve into joint destruction and deformity. Bone abnormalities are represented by marginal bone erosions and iuxta-articular and generalized osteoporosis. Overactivation of osteoclasts along with dysregulation of osteoblasts are the key events. Bone resorption is mediated by the receptor activator of nuclear factor (NF)-κB (RANK) ligand (RANK-L), responsible for the differentiation, proliferation, and activation of osteoclasts. RANK-L binds its receptor RANK, localized on the surface of preosteoclasts and mature osteoclasts promoting osteoclastogenesis. High levels of RANK-L were demonstrated in active RA patients. Denosumab, a fully human monoclonal antibody, binds RANK-L and suppresses the RANK-RANK-L signaling pathway leading to the inhibition of osteoclastogenesis. A retrospective analysis of published studies such as clinical trials evidenced the efficacy of denosumab in preventing bone erosion progression in RA patients. Key messages Key questions to answer in future include the following: Could denosumab be associated with other biologic therapies in RA patients? Could denosumab block the progression of bone damage in RA? Could denosumab be used for the prevention of bone erosion in RA?

Prothrombotic state in rheumatoid arthritis

Aim. To study the indices of standard coagulogram and thrombodynamics test in native plasma and in the test with phospholipids in relation to the activity of rheumatoid arthritis (RA) and the ongoing therapy.Material and methods. We examined 28 patients with rheumatoid arthritis and eight age- and sex-matched healthy controls: 11 patients with high rheumatoid arthritis activity (DAS28&gt;5.2) (Group 1), nine patients with low and moderate rheumatoid arthritis activity (DAS28&lt;5.2) (Group 2) and eight rheumatoid arthritis patients receiving anticoagulants (Group 3). Results. Elevated fibrinogen was more common in the RA patient groups: 5/11(45%) in group 1, 3/9(33%) in group 2 and 3/8(38%) in group 3. In the control group, fibrinogen was normal, p&gt;&lt;0.05. Increased SFMC was found in all patients in all three groups (100%) and only in 2 of the controls (25%), with p&gt;&lt;0.05. Mean clot density was significantly higher in RA groups than in controls: 26811, 25437 and 24740 versus 20631 c.u. in groups 1, 2, 3 and control, respectively, p&gt;&lt;0,01. In patients with anticoagulants, lag time (1.4 minutes) was longer than without anticoagulants (1.1-1.2 minutes), with p&gt;&lt;0.05 in all cases. Spontaneous clots were detected only in patients: 3 in groups 1 and 1 each in groups 2 and 3. Hypocoagulation was detected only in group 3 in 1/8(12%) patients, and thrombotic readiness status was detected in groups 1 and 2: in 2/11(18%) and 1/9(11%) patients, respectively. The frequency of normal- and hypercoagulation did not differ between the patient and control groups. Conclusion. According to the thrombodynamics test, hypercoagulability is present in RA patients. Thrombodynamics test can be used to identify the risk of thrombosis and to individualize therapy in RA patients. Keywords: prothrombotic state, hypercoagulation, rheumatoid arthritis, thrombodynamics&gt;˂ 5.2) (Group 2) and eight rheumatoid arthritis patients receiving anticoagulants (Group 3).Results. Elevated fibrinogen was more common in the RA patient groups: 5/11(45%) in group 1, 3/9(33%) in group 2 and 3/8(38%) in group 3. In the control group, fibrinogen was normal, p˂ 0.05. Increased SFMC was found in all patients in all three groups (100%) and only in 2 of the controls (25%), with p˂ 0.05. Mean clot density was significantly higher in RA groups than in controls: 26811, 25437 and 24740 versus 20631 c.u. in groups 1, 2, 3 and control, respectively, p˂ 0,01. In patients with anticoagulants, lag time (1.4 minutes) was longer than without anticoagulants (1.1-1.2 minutes), with p˂ 0.05 in all cases. Spontaneous clots were detected only in patients: 3 in groups 1 and 1 each in groups 2 and 3. Hypocoagulation was detected only in group 3 in 1/8(12%) patients, and thrombotic readiness status was detected in groups 1 and 2: in 2/11(18%) and 1/9(11%) patients, respectively. The frequency of normal- and hypercoagulation did not differ between the patient and control groups.Conclusion. According to the thrombodynamics test, hypercoagulability is present in RA patients. Thrombodynamics test can be used to identify the risk of thrombosis and to individualize therapy in RA patients.

The Cost-Effectiveness of and Adherence to Disease-Modifying Antirheumatic Drug (DMARD) Therapy in Rheumatoid Arthritis Patients in a Tertiary Care Teaching Hospital in Uttarakhand, India.

Objective This study was conducted with the aim ofevaluating the cost-effectiveness of and adherence to treatment in patients on disease-modifying antirheumatic drug (DMARD) therapy for rheumatoid arthritis (RA) in a tertiary care teaching hospital in Uttarakhand, India. Methodology This prospective observational study was conducted on 150 rheumatoid arthritis patients presenting to the Rheumatology Outpatient Department (OPD) receiving DMARD therapy (approval number AIIMS/IEC/18/160). The patients were followed up for an average of 10.7 weeks and received drugs in four regimens with methotrexate (MTX) (Regimen 1) having the least contribution with a mean of 46.05 Rs, methotrexate + hydroxychloroquine(MTX + HCQ) (Regimen 2) with 174.15 Rs, methotrexate + hydroxychloroquine + leflunomide (MTX + HCQ + Lef) (Regimen 3) with Rs 371.70, and methotrexate + hydroxychloroquine + leflunomide + biological DMARD adalimumab(MTX + HCQ + Lef + bDMARD adalimumab) (Regimen 4) with 17,349.4 Rs.The cost of drug therapy was assessed by calculating the cost of therapy per month for each patient, and adherence was assessed using the Morisky-Green-Levine Scale (MGLS) at the follow-up visit. Results The overall mean cost of DMARD treatment was 205.81 Rs. The overall DMARD therapy cost-effectiveness was Rs 878.14 for a unit change of Disease Activity Score (DAS28). The most cost-effective treatment came out to be Regimen 1 with the least cost of 290.9Rs for a unit change of DAS28, and the least cost-effective was Regimen 4 with 65,661.8 Rs for a unit change of DAS28. At follow-up, among all subjects of the study, 49 (32.7%) subjects showed high adherence, 71 (47.3%) subjects showed medium adherence, and 30 (20%) subjects showed low adherence. Accordingly, the maximum number of participants fell in the category of medium adherence, i.e., 71 (47.4%). Conclusion Our study concluded that the cost burden varied according to the number of DMARDs being given to the patient. The double-drug therapy of methotrexate + hydroxychloroquine had a maximum "high adherence." On a whole, the majority of patients had "medium adherence" to therapy.

Usage of Biological Therapy in Rheumatoid Arthritis Patients with Chronic Renal Failure: A Retrospective Study from a Single Center

Kronik böbrek hastalığı (KBH) olan romatoid artrit (RA) hastalarında, potansiyel toksisiteleri nedeniyle hastalığı modifiye edici antiromatizmal ilaçların (DMARD) çoğunu ve steroid olmayan antiinflamatuar ilaçları (NSAİİ) kullanmak uygun değildir. Biyolojik DMARD'lar RA hastaları için oldukça etkili bir tedavi seçeneği olsa da böbrek fonksiyonları üzerindeki etkisi ve güvenilirliği tam olarak belirlenememiştir. KBH’si olan RA’lı hastalarda biyolojik tedavilerin kullanımına ilişkin veriler kısıtlıdır. 2011-2018 yılları arasında RA tanısı ile takip ettiğimiz, biyolojik ajan kullanan ve düzenli vizitleri bulunan 700 hasta arasından tahmini glomerüler filtrasyon hızı (eGFR) üç aydan uzun süredir

Genetic Biomarkers as Predictors of Response to Tocilizumab in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

Rheumatoid arthritis (RA) is a lifelong, debilitating disease which incredibly impacts a patient’s quality of life if not treated to the optimal target. The clinical response of tocilizumab, an interleukin-6 (IL-6) inhibitor, is associated with several gene polymorphisms, particularly targeting the IL-6 pathway. This systematic review and meta-analysis seeks to investigate genetic biomarkers that predict the treatment outcome of tocilizumab therapy in RA patients. After evaluating the quality of retrieved records, five studies were chosen to carry out a quantitative synthesis involving 591 participants. We analysed genetic markers of IL-6R single nucleotide polymorphism (SNP)s rs12083537, rs2228145 and rs4329505, FCGR3A, CD69, GALNT18 and FCGR2A. A plausible finding based on meta-analysis revealed that RA patients with homozygous AA genotype for rs12083537 polymorphism of the IL-6R gene demonstrate a better response to TCZ treatment as opposed to homozygous and heterozygous patients with the G allele. Nonetheless, limitations in evaluating the available studies by meta-analysis include a lack of studies with dissimilarities in study design and outcome definitions, small sample sizes with low statistical power and heterogeneity of cohorts, a restricted the number of tested SNPs and small effects for the selected variants. Inconsistent finding remains as a great challenge to forge ahead towards personalised medicine for RA management.

Erratum to: Integrating molecular interactions and gene expression to identify biomarkers to predict response to tumor necrosis factor inhibitor therapies in rheumatoid arthritis patients.

Erratum to: Integrating molecular interactions and gene expression to identify biomarkers to predict response to tumor necrosis factor inhibitor therapies in rheumatoid arthritis patients.

MiRNAs as Biomarkers and Possible Therapeutic Strategies in Rheumatoid Arthritis.

Within the past years, more and more attention has been devoted to the epigenetic dysregulation that provides an additional window for understanding the possible mechanisms involved in the pathogenesis of autoimmune rheumatic diseases. Rheumatoid arthritis (RA) is a heterogeneous disease where a specific immunologic and genetic/epigenetic background is responsible for disease manifestations and course. In this field, microRNAs (miRNA; miR) are being identified as key regulators of immune cell development and function. The identification of disease-associated miRNAs will introduce us to the post-genomic era, providing the real probability of manipulating the genetic impact of autoimmune diseases. Thereby, different miRNAs may be good candidates for biomarkers in disease diagnosis, prognosis, treatment and other clinical applications. Here, we outline not only the role of miRNAs in immune and inflammatory responses in RA, but also present miRNAs as diagnostic/prognostic biomarkers. Research into miRNAs is still in its infancy; however, investigation into these novel biomarkers could progress the use of personalized medicine in RA treatment. Finally, we discussed the possibility of miRNA-based therapy in RA patients, which holds promise, given major advances in the therapy of patients with inflammatory arthritis.

Can biomarkers predict successful tapering of conventional disease-modifying therapy in rheumatoid arthritis patients in stable remission?

Specific guidelines for managing RA patients in clinical remission for ≥6 months on cs-DMARDs are lacking. Tapering of treatment is encouraged, however, without validated biomarkers for success. We aimed to assess the rate of sustained remission after 12 months in patients who either (i) followed structured cs-DMARD tapering or (ii) continued therapy, focusing on the added value of biomarkers as predictors of outcome. RA patients fulfilling 3v-DAS28CRP<2.6 for ≥6 months on stable cs-DMARD therapy were included. Patients were offered structured tapering, with 117 accepting tapering and 83 continuing therapy. Clinical, ultrasound, immunological (T-cell subsets) and patient-reported outcome (PRO) data were collected. The primary endpoint was the proportion of patients in sustained remission without relapse after 12 months. Regression analyses were used to identify predictors of sustained remission. Of those who tapered, 64% remained in clinical remission after 12 months compared with 80% (p=0.018) of patients on stable treatment. In the tapering group, higher levels of CRP, TJC, % inflammation-related T-cell (IRC) and PROs were associated with flare (all p<0.05), with a trend for total PD (p=0.066). A model predicting sustained remission retained RAQoL, total PD and IRC (85% accuracy, AUROC=0.893, p<0.0001). In the non-tapering group, higher CRP, ESR, SJC and shorter disease duration (all p<0.05) were associated with flare, with no parameter able to predict sustained remission. In the tapering group, the combination of clinical, PRO, US and T-cell parameters demonstrated added value for predicting sustained remission compared with clinical parameters alone. These data may inform best tapering practice.

Response and Side Effects from Rheumatoid Arthritis Therapy at Dr. Soetomo General Hospital Surabaya 2017

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease which mainly attacks synovial membrane and causes systemic manifestation. During treatment, controlling disease activity is needed to prevent further complication. On the other hand, medications used in the treatment of RA may bring various side effects. It is important to evaluate side effects from the given therapy.Methods: This study aimed to evaluate response and side effects of therapy in RA patients. The samples were collected from 59 RA patients at Rheumatology Division of Outpatient Clinic in Department of Internal Medicine Dr. Soetomo General Hospital Surabaya in 2017. This study method was descriptive observational with cross sectional design using medical records.Results: Pain was reduced in 83.1% patients, Erythrocyte Sedimentation Rate (ESR) increased in 61.4% patients, and C-Reactive Protein (CRP) decreased in 50% patients. Based on the statistic analysis, ESR decreased significantly (p = 0.012) while CRP decreased not significantly (p = 0.415). The side effects were observed from clinical and laboratory data. Based on clinical symptoms, there were alopecia in 1.7% patient, dyspepsia in 78% patients, infection in 27.1% patients, and other symptoms including itchy skin, neuropathy, hyperuricemia, hyperkalemia and Acute Kidney Injury (AKI). Meanwhile, abnormalities in laboratory data include increased aspartate transaminase (AST) in 3.8% patients, increased alanine transaminase (ALT) in 26.1% patients, increased Blood Urea Nitrogen (BUN) in 7.9% patients, increased creatinine serum in 7.9% patients, decreased hemoglobin in 15.5% patients, and decreased leukocytes in 3.4% patients.Conclusion: Most patients had a good therapeutic response based on decreased pain, while ESR had a significant decrease and CRP did not have significant decrease. Side effects discovered in patients were various

Effects of nonsurgical periodontal therapy in patients with rheumatoid arthritis: a prospective before and after study.

Background: periodontal therapy has been suggested to have systemic effects. However, studies of periodontal therapy in rheumatoid arthritis patients have produced controversial results.Aim: To compare the effects of nonsurgical periodontal therapy on biochemical markers of rheumatoid arthritis and periodontal parameters in patients with and without rheumatoid arthritis.Methods: a prospective before-and-after study was conducted that included 21 participants without and 29 participants with rheumatoid arthritis. Periodontal parameters, Porphyromonas gingivalis detection, C-reactive protein, rheumatoid factor and anti-citrullinated protein antibodies were measured at baseline and three months after nonsurgical periodontal therapy and the changes were statistically assessed.Results: In general, both groups presented statistically significant improvement in periodontal parameters (p<0.05). There was an increase in the counts of P. gingivalis in both groups at three months. In addition, there was a reduction in levels of anti-citrullinated protein antibodies and rheumatoid factor in participants with rheumatoid arthritis. In contrast, C-reactive protein levels increased in both groups but were higher in the rheumatoid arthritis group. Periodontal parameters in rheumatoid arthritis participants under disease-modifying antirheumatic drugs presented a slightly higher improvement (p <0.05).Conclusions: Nonsurgical periodontal therapy has similar improvements in periodontal parameters in patients with and without rheumatoid arthritis. In addition, nonsurgical periodontal therapy may benefit serum levels of anti-citrullinated protein antibodies and rheumatoid factors in patients with rheumatoid arthritis. NCT04658615.