Turkish Rheumatoid Arthritis Patients Research Articles

A national, multicenter, secondary data use study evaluating efficacy and retention of first-line biologic treatment with tocilizumab in patients with rheumatoid arthritis in real-life setting: results from TURKBIO registry

Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody that targets the IL-6 receptor. TCZ found to be efficacious and has a good tolerated safety profile in rheumatoid arthritis (RA) patients. The aim of this study was to describe the disease activity and retention rate in Turkish RA patients who were prescribed TCZ as first-line biologic treatment in a real-world setting. Secondary data obtained from adult RA patients’ files was used in a multicenter and retrospective context. Clinical Disease Activity Index (CDAI), Disease Activity Score in 28 joints with ESR (DAS28-ESR), and retention rates of TCZ were evaluated at related time points. 130 patients (87.7% female) with a mean age of 53 years (SD; 15.0) were included in the study. Mean RA duration was 14 years and median duration of follow-up was 18.5 months. Number of patients with ongoing TCZ treatment at 6, 12, and 24 months were 121 (93%), 85 (65%), and 46 (35%), respectively. Remission rates at 6, 12, and 24 months per CDAI (< 2.8) and DAS28-ESR (< 2.6) scores were 61.5, 44.6, 30%, and 54.6, 40.8, 27.7%, respectively. Both CDAI and DAS28-ESR scores significantly improved at 6, 12 and 24 months (p < 0.001 for both). At 24 months, 23 patients (17.6%) discontinued TCZ, of whom majority (17/23) were due to unsatisfactory response. Retention rates of TCZ at 6, 12, and 24 months were 93, 84.3, and 72.2%, respectively. In this real-world study, TCZ as a first-line biologic therapy was found to be efficacious and showing high retention rates. These real-world study results are in line with previous randomized studies.

Efficacy, retention, and safety of tofacitinib in real-life: Hur-bio monocentric experience

Background/aimTo assess the real-life efficacy, retention rate, and safety data of tofacitinib in rheumatoid arthritis (RA) patients.Materials and methodsWe analyzed all patients registered in the HURBİO database who received at least 1 dose of tofacitinib. Patients who received at least one dose were included in retention analysis; patients with at least 1 control visit were included in efficacy and safety analysis. Factors predicting good response at the last follow-up visit were analyzed by logistic regression analysis. Drug retention rates were calculated using the Kaplan–Meier method and predictors of drug retention were determined by Cox proportional hazard model. Adverse events, reasons for switching, and discontinuation were also determined.Results Two hundred and forty-seven (210, 85.0% female) patients were included in the study. The median duration of tofacitinib treatment was 10.2 (20.2) [med, (IQR)] months. Two hundred and four (82.6%) patients were included in safety and efficacy analysis; 45.6% of patients were in low-disease activity (LDA) state (DAS28-CRP ≤ 3.2). Predictors of LDA were being biologic-naïve [aOR 2.53 (1.31–4.88); 95% CI] and RF negativity [aOR 2.14 (1.12–4.07); 95% CI]. At 1 year, the overall tofacitinib retention rate was 63.9% with no relevant predicting factor. Response and retention rates of tofacitinib were similar in patients with and without concomitant csDMARDs. Treatment failure was the most common cause of discontinuation. The most common infectious and laboratory adverse events were herpes zoster infection (3.9 per 100 patient-years) and elevation in ALT (x3UNL: 9.7 per 100 patient-years), respectively.ConclusionTofacitinib is effective as monotherapy or in combination with csDMARDs. It is a well-tolerated treatment option in Turkish RA patients.

The relationship between bristol rheumatoid arthritis fatigue scales and disease activity of patients with rheumatoid arthritis.

Fatigue is a symptom that affects the 40-80% of patients with rheumatoid arthritis (RA) and impairs the quality of life. The aim of this study was to assess multidimensional fatigue scales, the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ) and the Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scale (BRAF-NRS) and to evaluate their relationship with disease activity in Turkish RA patients. The study included 180 patients with RA. The Disease Activity Score (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI) were used to evaluate disease activity. The participants comprised of 142 females and 38 males. The mean ± standard deviations of DAS28, CDAI, and SDAI were 3 ± 1.24, 9.51 ± 7.96, and 10.5 ± 8.38 respectively. All scales except the emotional subscale were correlated with disease activity. The emotional subscale correlated with CDAI and SDAI but not with DAS28. The results of the study indicated that fatigue and disease activity were correlated. Fatigue is a symptom that impairs the quality of life but it can be easily coped with by controlling disease activity. Thus, it should be assessed in a multidimensional perspective.

Comments on: The Knowledge Level of Turkish Rheumatoid Arthritis Patients about Their Diseases

This letter contains a brief comment about the "The Knowledge Level of Turkish Rheumatoid Arthritis Patients about Their Diseases " that presented by Bozbas and Gurer. In this trial authors attracts the attention of the readers on patient education in a chronic disease. Study aimed to assess the level of disease specific knowledge of the patients with Rheumatoid Arthritis. Patients with Rheumatoid arthritis (RA) were evaluated about the awareness level of patients, and the “Patient Knowledge Questionnaire in Rheumatoid Arthritis (PKQ-RA)” was used in this high-quality study. Firstly, studied internal consistency of the Turkish version of PKQ-RA was high with Cronbach’s alpha of 0.71. and according to the results most of the patients (86.7%) reported that they had gained the information about RA from their physicians. Age, education, socioeconomic status, and family history of disease were associated with the Patients’ knowledge levels. But in conclusion authors unnoticed a previous study titled as “The assessment of knowledge level about their disease in patients with rheumatoid arthritis” and published by Karahan et al. In this earlier study authors firstly used the Turkish version of the PKQ-RA to evaluate the level of knowledge about the disease of patients with RA. Also, authors reported the very low level of knowledge. These two papers gain important contribution about the needs of the patient education. Patient education is important step of the treatment in the chronic disease and more clinical studies need especially from developed countries such as Turkey.

Reliability, validity, and cross-cultural adaptation of the Turkish version of the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire.

Up to 98% of rheumatoid arthritis (RA) patients experienced fatigue. It is an important physical and cognitive symptom which has overwhelming, uncontrollable, and unpredictable affects throughout their whole life. RA fatigue composes of complex and multi-dimensional components which are pain, stress, depression, inflammation, and disability. The acknowledgement of fatigue is important, and fatigue should be measured in all RA trials alongside the core set. The aim of this study was to determine reliability and validity of Turkish version of Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire in RA patients. One hundred RA patients were evaluated in the study. Exclusion criteria were determined as patients with cognitive impairment, illiterate patients, unable to understand and speak Turkish, under the age of 18, and over the age of 75. To validate Turkish version of Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ) (BRAF-MDQ-T), all participants answered BRAF-MDQ-T, Multidimensional Assessment of Fatigue (MAF) scale, and Short Form-36 vitality (SF-36 VT). BRAF-MDQ-T was applied again 7days later for test-retest reliability. Validity, internal consistency, and test-retest results were based on a sample of 100 patients. Internal consistency reliability of BRAF-MDQ-T was Cronbach α = 0.95 which was excellent. The correlation between the total scores of the BRAF-MDQ-T scale and the total scores of MAF-T was statistically significant (r = 0.82, p < 0.001). The correlation between the total scores of the BRAF-MDQ-T scale and the subscale scores of SF-36 VT was statistically significant (r = - 0.64, p < 0.001). The BRAF-MDQ-T is a valid and reliable scale for the assessment of fatigue in Turkish rheumatoid arthritis patients.

The functional variants of endothelial nitric oxide synthase gene associated with rheumatoid arthritis in Turkish adults.

This study aimed to investigate whether functional variants of endothelial nitric oxide synthase (eNOS) gene play any role in rheumatoid arthritis (RA) ethiopathogenesis and treatment in the Turkish population. Because, eNOS variants are responsible for alteration of the NO level in plasma, by reducing/increasing the endothelial NO synthesis. In the study, two eNOS gene variants (G894T and intron 4 VNTR A/B) were examined at extracted DNAs from 65 peripheral blood cell of RA patients. For the control, blood samples obtained from 70 healthy persons were studied. Genotyping of molecular variants was performed by PCR-RFLP and/or PCR technique. The data obtained was compared in itself and response to therapy. We found that "TT genotypic frequency" for the G894T variant was significantly associated with RA with an overall risk of 8.3-fold (p 0.029). No association was identified between intron 4 VNTR A/B variant and RA. At the 6months, the mean visual analog scale (VAS), health assessment questionnaire (HAQ), and disease activity score for 28 joints (DAS 28) improvement was not significant among groups. Improvement in DAS was significantly better in anti-TNF treatment than disease-modifying antirheumatic drugs (DMARD) treatment treated subgroup. We report for the first time that variants in the eNOS "TT" genotype might be contributed to the increased risk of RA in the Turkish population. These results imply that functional variants of eNOS gene might have an effect on RA patients and response to anti-TNF treatment. In addition, the results suggest that eNOS variants might be associated and affect host susceptibility and/or response to treatment in Turkish RA patients.

Evaluation of tool-like receptor-2 and 4 and interleukin-6 gene expressions in Turkish rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a progressive inflammatory disease. Although the etiology and pathogenesis of RA are not known well, genetic and environmental factors are proposed to initiate an autoimmune process. We aimed to investigate mRNA expression levels of Toll-like receptor-2 (TLR-2), TLR-4, and interleukin-6 (IL-6) genes in RA disease. This study was conducted with 50 patients who were diagnosed with RA according to the American College of Rheumatology classification criteria for RA and 50 age-matched healthy control individuals who did not have any joint diseases and autoimmune diseases. We collected whole blood from all participants and analyzed expression of TLR-2, TLR-4, and IL-6 genes at mRNA level using real-time qPCR. TLR-2 expression was detected to increase 3.8-fold and IL-6 expression was detected to increase 6.8-fold in RA patients compared to healthy controls. No difference was found between patient and control groups with regard to TLR-4 expression. Overexpression of TLR-2 and IL-6 may be responsible for RA pathogenesis. Inhibition of both TLR and IL signaling pathways may prevent joint inflammation and destruction.

Translation and validation of the Turkish language version of the Rheumatoid Arthritis Disease Activity Index-5.

The purpose of this study was to translate the Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5), which is a tool for measuring disease activity in rheumatoid arthritis (RA) patients, into Turkish language and prove its validity, reliability and sensitivity to changes. Translation from the original German version was performed according to the standardized methods. One hundred and two patients with RA completed in the Turkish RADAI-5 twice within 3days interval. Internal consistency and test-retest reliability was investigated by calculating Cronbach's alpha and intra-class correlation coefficients (ICC), respectively. Validity was assessed by analyzing the correlations between the Turkish RADAI-5 and some measurement tools evaluating the disease activity, functional status and quality of life. To test the scale's responsiveness to the changes, another 23 patients with uncontrolled disease activity and three newly diagnosed RA patients completed the RADAI-5 before and after a biologic agent or methotrexate treatment. There were no floor or ceiling effects. Cronbach's alpha (0.91) and ICC (0.997) values certified the Turkish version's reliability. Strong correlations between the Turkish questionnaire and Disease Activity Score-28 (DAS28), DAS28-CRP, DAS28-three variables, Health Assessment Questionnaire, Rheumatoid Arthritis Quality of Life questionnaire, patient's and doctor's global assessments, tender joint count proved the convergent validity of the scale. Effect size (3.08) demonstrated that the Turkish RADAI-5 is sensitive to the changes. The Turkish RADAI-5 is a feasible, reliable and valid questionnaire and sensitive to changes; thus it can be used to monitor disease activity in Turkish RA patients.

SAT0074 Comparison of the Two Definitions of Disease Activity Score (Das)28 in Turkish Patients with Rheumatoid Arthritis (RA)

BackgroundIn some countries, including Turkey, reimbursement criteria require a DAS28 score of >5.1 for initiating anti-TNF therapy in patients with rheumatoid arthritis. DAS28 score can be calculated based on C-reactive...

AB0172 Assessment of disease activity in rheumatoid arthritis by routine assessment of rheumatoid arthritis disease activity index (radai) and its relation with disease activity score 28 (das28), clinical disease activity index (cdai) and simplified disease acti

BackgroundEvaluation of disease activity is essential in decision of the treatment and monitoring the therapies in rheumatoid arthritis (RA). Rheumatoid Arthritis Disease Activity Index (RADAI) appears as an attractive form...

Case Management in Care of Turkish Rheumatoid Arthritis Patients

This study examined the effectiveness of a case management (CM) intervention in the care of patients with rheumatoid arthritis (RA) as a pilot study in a teaching hospital in Turkey. Two groups were compared with respect to disability, quality of life, cost, and patient satisfaction: RA patients who received CM plus usual nursing care and RA patients who received usual nursing care alone. All patients underwent follow-up interviews at 3 and 6 months after being discharged from the hospital. Disability scores were significantly better in the RA group receiving CM, but there were no significant differences between the two groups with regard to quality of life, patient satisfaction, and total healthcare costs. Using CM in the care of patients with RA may favorably affect disease-related outcomes.

Associations of HLA-DRB1 alleles with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in northern east part of Turkey

The aim of this study was to investigate the associations between human leukocyte antigen (HLA)-DRB1 alleles with genetic susceptibility to rheumatoid arthritis (RA) and production of antibodies against cyclic citrullinated peptide (anti-CCP antibody) and rheumatoid factor (RF) in Turkish RA patients. We studied 291 RA patients and 253 controls. Genotyping was performed by polymerase chain reaction with sequence-specific oligonucleotide probes hybridization method. Serum levels of anti-CCP antibody, IgM-RF and high sensitive C-reactive protein titers were measured by commercial kits using immunological methods. We found that HLA-DRB1*04 and *09 alleles were associated in anti-CCP+ and anti-CCP+ RA patients (P < 0.0001 and P < 0.001, respectively), while DRB1*01 and *04 were determined to be higher in RF+ RA patients (P < 0.001 and P < 0.0001, respectively). Moreover, DRB1*11 and DRB1*13 alleles were determined to be lower in RF and anti-CCP/RF+ RA patients (P < 0.001 for both). HLA-DRB1*04 was identified as a common responsible allele for susceptibility to the disease in anti-CCP, RF and anti-CCP/RF- RA patients (P = 0.0018, P = 0.0004 and P = 0.0023, respectively). HLA-DRB1*13 allele alone was found to be protective against to anti-CCP+ and RF- RA (P = 0.0003 and P = 0.006, respectively). On the contrary, there was no protective allele in anti-CCP/RF- RA as well as anti-CCP- RA patients. This study indicates that associate and protective HLA-DRB1 allele distributions are different in autoantibody (anti-CCP or RF or anti-CCP/RF)+ RA and autoantibody- RA patients, with exceptions of DRB1*04 and DRB1*13.

Rheumatoid arthritis risk associates with DNA repair gene XRCC1 Arg399Gln polymorphism in Turkish patients

Rheumatoid arthritis (RA) is an autoinflammatory disease with a genetic background. The synoviocytes in RA shows cellular transformation with tumor-like features, and RA patients have genomic instability and relaxation of DNA repair mechanisms. The polymorphisms in BER repair pathway genes, XRCC1 and OGG1, may change the response to inflammation via altered DNA repair capacity. In this study, we aimed to investigate the relationship between the risk of RA and XRCC1 Arg194Trp, Arg399Gln, and OGG1 Ser326Cys polymorphisms in a group of Turkish RA patients. XRCC1 Arg194Trp, Arg399Gln, and OGG1 Ser326Cys polymorphisms were investigated by PCR-RFLP method in 100 RA patients and 158 healthy control subjects. The results were statistically analyzed by calculating the odds ratios (OR) and their 95% confidence intervals (95% CI) using the χ(2)-tests. RA patients in this study had significantly higher frequencies of XRCC1 Arg399Gln polymorphism in both homozygote (GG) (35%, OR: 7.78 [95% CI: 3.65-16.59], P < 0.001) and heterozygote (AG) forms (41%, OR: 2.17 [95% CI: 1.19-3.96], P < 0.01) and also increased frequency of 399Gln (G) allele (55%, OR:2.99 [95% CI: 1.67-5.37], P < 0.001). We conclude that XRCC1 Arg194Trp, and OGG1 Ser326Cys polymorphisms are not associated with RA; however, Arg399Gln polymorphism is a significant risk factor of RA, and carriers of 399Gln (G) allele have greater risk of RA.

The investigation of toll-like receptor 3, 9 and 10 gene polymorphisms in Turkish rheumatoid arthritis patients

Toll-like receptors (TLRs) play an important role in the induction and regulation of the innate immune system or adaptive immune responses. Genetic variations within human TLRs have been reported to be associated with a range of immune-related diseases. This study was conducted to investigate the frequencies of TLR3 rs3775290, TLR9 rs187084, and TLR10 rs4129009 polymorphisms and to detect between polymorphisms and autoantibody positive as RF, collagen type II, anti-RNP, and anti-CCP in patient group. We performed a case-control study of 100 rheumatoid arthritis (RA) cases and 100 healthy controls matched on age, sex, and residence. All polymorphisms in TLRs were determined by polymerase chain reaction-based restriction fragment length polymorphism. Serum autoantibody level was measured using quantitative ELISA. SNPs were genotyped in all samples. Our results showed that TT genotype for SNP 1237 T/C increased the RA risk significantly (p<0.05). No statistically significant differences were found in the TLR3 and TLR10 genotypes or allele distribution between RA patients and control individuals. No associations were noted with autoantibody production and TLR3, TLR9, and TLR10 polymorphisms genotypes (p>0.05). Our study suggests that a single nucleotide polymorphism (rs187084) in TLR9 gene may be a susceptibility factor for RA in Turkish population. Further studies are required to explore the role of TLRs gene polymorphisms in the risk of RA, especially in ethnically different populations to confirm our results.

No Association Between Myeloperoxidase Gene G-463A Polymorphism And Rheumatoid Arthritis

Myeloperoxidase (MPO) has been involved in the pathogenesis of several diseases such as rheumatoid arthritis (RA) through excessive production of reactive oxygen species (ROS) as well as through its genetic polymorphism. We examined whether G-463A polymorphism of Myeloperoxidase (MPO) gene was associated with RA. Exactly, 75 patients with RA and 90 healthy control subjects were included in this study. The genotyping was determined by polymerase chain reaction- restriction fragment length polymorphism method. The association between these single nucleotide polymorphism (SNP) and RA was analyzed using chi-square test and de-Finetti program. Genotype distributions and allele frequency of RA patients were not significantly different from healthy controls. In addition, it was also determined that there was no deviation from Hardy-Weinberg Equilibrium in any groups (p&gt;0.05). Whether there was an association between MPO gene G-463A gene polymorphism and RA was investigated for the first time in this study in literature and it was demonstrated that it did not exist in the Turkish RA patients. It was planned to investigate the other polymorphisms of MPO gene in the future.

The Val762Ala polymorphism in the poly(ADP-ribose) polymerase-1 gene is not associated with susceptibility in Turkish rheumatoid arthritis patients

The findings of the studies on poly(ADP-ribose) polymerase-1 (PARP-1) have suggested that the enzyme inactivation provides significant protection against systemic or tissue inflammation in animal models. It has also shown that the single-nucleotide polymorphism (Val762Ala) of the PARP-1 causes about 40% decrease of enzyme activity. The aim of this study was to analyze the association of the PARP-1 Val762Ala polymorphism in Turkish patients with rheumatoid arthritis. A total of 128 RA patients and 165 normal controls from the same geographic region were studied and polymerase chain reaction (PCR)-based restriction analysis was used to identify Val762Ala polymorphism of the PARP-1. Association analyses were performed using chi (2) tests. Our results indicated that the distribution of the PARP-1 genotypes and alleles did not differ significantly among subjects with or without RA (P > 0.05). The results of the study indicate that, for our Turkish sample, the V762A polymorphism of the PARP-1 may not be involved in susceptibility to RA, implying that the polymorphism may not function as a candidate gene marker for screening RA patients.

Tumor necrosis factor-alpha and Interleukin-10 gene promoter polymorphisms in Turkish rheumatoid arthritis patients

Tumor necrosis factor and interleukin 10 have been implicated in the pathogenesis of rheumatoid arthritis (RA). Certain single-nucleotide polymorphisms (SNPs) within the promoter region of the IL-10 and TNF genes have been associated with altered levels of circulating IL10 and TNF. We aimed to explore the association of IL-10 and TNF-alpha polymorphisms in Turkish RA patients. We analyzed the association of TNF-alpha (-308G/A, -238G/A, -376G/A) and IL10 (-1082G/A, -819C/T, -592C/A) polymorphisms in 98 Turkish patients with rheumatoid arthritis and 122 healthy subjects using ARMS-PCR. The correlation of these findings with RF positivity and erosive disease in RA patients was also sought. A significant association was found between having RA and -1082 G allele (p=0.008; OR=1.44, 95% CI 1.11-1.86). There was no association between RA and -819C/T polymorphism. Significant differences were observed in IL10 GCC and ACC haplotypes distribution between RA and control subjects (p=0.006; OR=1.46, 95% CI 1.13-1.89 and p=0.011; OR=1.43, 95% CI 1.09-1.88, respectively). No statistically significant association was found between TNF-alpha 308G/A, -238G/A, -376G/A polymorphisms and RA. No significant association was found between RF positivity and erosive disease and TNF-alpha, IL10 gene polymorphisms. In addition, when combined genotypes were analyzed, no significant difference was found between RA patients and healthy controls. Our findings suggest that IL-10 1082 G/A polymorphism or GCC, ACC haplotypes may be associated with RA in Turkish patients.

Ethnicity may be a reason for lipid changes and high Lp(a) levels in rheumatoid arthritis

There are so many studies that suggest the changes in lipid profiles and lipoprotein (a) [Lp(a)] are associated with early atherosclerosis in rheumatoid arthritis (RA). But there are some opposite studies also. Because of marked ethnicity differences in the distribution of Lp(a), we aimed to investigate the associations of Lp(a) levels and lipid changes in Turkish RA patients. There were 30 women and 20 men, a total of 50 patients with RA (mean age 47.6 +/- 13.2 years), included and 21 healthy women and 14 healthy men (mean age 45.7 +/- 14.5 years) were recruited as a control (C) group. Serum Lp(a), total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels were analysed for each group. Analysis of six different studies was performed. In the RA and C groups, mean serum Lp(a) levels were 39.7 +/- 64.4 and 10.5 +/- 13.4 mg/dl, respectively (P=0.001). Mean TC levels were 189.2 +/- 142.5 and 174.0 +/- 29.3 mg/dl (P=0.294), mean TG levels were 121.4 +/- 65.4 and 106.5 +/- 80.0 mg/dl (P=0.030), mean HDL-C levels were 44.5 +/- 10.0 and 47.7 +/- 4.8 mg/dl (P=0.014) and mean LDL-C levels were 94.3 +/- 35.3 and 102.0 +/- 24.6 mg/dl (P=0.98), respectively. Analysis of the six studies showed Lp(a) level was higher and HDL level was lower in RA patients than in healthy controls. Patients with RA may have altered lipid profiles from one country to another one. Especially in Turkey, higher serum Lp(a), lower HDL-C and higher TG levels may be found in RA patients instead of some findings of other countries showing different results. Ethnicity may be a reason for these findings.