Cohort Of Rheumatoid Arthritis Patients Research Articles

Seven Year Outcomes of the Silicone Arthroplasty in Rheumatoid Arthritis (SARA) Study: Level 2 Evidence

Grant received from: National Institute of Arthritis and Musculoskeletal and Skin Diseases - 2R01 AR047328-06 - An Outcome Study of Rheumatoid Hand Arthroplasty There is no financial information to disclose. Rheumatoid arthritis (RA) often causes debilitating deformities of the hand. Silicone metacarpophalangeal joint arthroplasty (SMPA) has been used for over 50 years to correct hand deformities, but high level evidence for effectiveness is lacking. The SARA study is an NIH-funded, multicenter study following a large cohort of RA patients with severe hand deformities. The purpose of this paper is to compare outcomes for a surgical and a non-surgical cohort of rheumatoid arthritis patients after 7 years of follow-up. RA patients with a defined level of deformity were enrolled from 1 of 3 study sites. Patients were not randomized owing to strong patient preference and chose whether to undergo SMPA or not. Patients were assessed at 6 months and then yearly for up to 7 years. Outcomes included the Michigan Hand Outcomes Questionnaire (MHQ), Arthritis Impact Measurement Scales (AIMS2), and functional measures (grip/pinch strength, Jebson-Taylor test, and ulnar drift, extensor lag and arc of motion measurements at the metacarpophalangeal (MCP) joints. A total of 73 SMPA and 97 non-SMPA subjects were enrolled at baseline. Because of withdrawals, deaths, and loss to follow-up, 25 SMPA and 52 non-SMPA patients had data at 7 years follow-up. Although nonsurgical subjects had better mean MHQ scores at baseline, the surgical subjects had improved scores over time. After adjusting for baseline differences, surgical patients had significantly better outcomes for overall MHQ score and the function, aesthetics and satisfaction domains. Additionally, SMPA subjects had significantly better measures for ulnar drift, extensor lag and MCP joint arc of motion at 7 years after adjusting for baseline covariates. No significant improvements in grip or pinch strength were observed in either group. •The benefits of SMPA reported at earlier assessments were maintained at the 7 year postoperative follow-up.•Non-surgical subjects remained stable in hand function over time.•SMPA subjects reported substantial improvements in ulnar drift and extensor lag, their ability to perform activities of daily living, and decreased pain.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Pitfalls in the assessment of smoking status detected in a cohort of South African RA patients.

This study was conceived in an attempt to explain the unexpectedly high frequency of elevated levels of serum cotinine measured retrospectively in a cohort of predominantly black South African females with rheumatoid arthritis (RA), findings that were inconsistent with the smoking histories derived from health questionnaires. The discrepant findings suggested either a greater tendency towards underreporting of smoking status in the study cohort, or possible confounding effects of the use of smokeless tobacco products. In addition to the cohort of RA patients (n=138, of whom 115 (83%) were female), blood samples were also taken from a second cohort consisting of 29 declared smokers, 18 (62%) of whom where females, 29 smokeless tobacco (SLT) users (all female), and 22 non-users of any tobacco products, 18 (82%) of whom were females. Serum cotinine levels were determined using an ELISA procedure. Cotinine levels of >10.0ng/ml were detected in serum specimens from 43 (31%), RA patients of whom 35 (81%) were female, with a median value of 50.1ng/ml and interquartile range (iqr) of 68.6. Only 18 of the 35 females indicated that they smoked. The groups of declared smokers and SLT users had equivalent median serum cotinine levels of 88.0ng/ml (iqr=10.8ng/ml) and 87.0ng/ml (iqr=15.6ng/ml), respectively, while cotinine was undetectable in specimens from non-tobacco product users (<0.2ng/ml). Users of SLT products in South Africa are predominantly female and have serum cotinine levels which are comparable with those of current smokers, raising concerns about the validity of measurement of cotinine as the sole objective marker of smoking status in populations with high usage of SLTs. This situation can be rectified by ensuring that usage of SLT products is accurately recorded in health questionnaires, while inclusion of measurement of one or more additional, objective biomarkers of smoking in combination with cotinine may enable reliable distinction between smoking and usage of SLTs which, given the associated risks, is a strategy of particular relevance in RA.

Replication of Associations of Genetic Loci Outside the HLA Region With Susceptibility to Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis.

ObjectiveGenetic polymorphisms within the HLA region explain only a modest proportion of anti–cyclic citrullinated peptide (anti‐CCP)–negative rheumatoid arthritis (RA) heritability. However, few non‐HLA markers have been identified so far. This study was undertaken to replicate the associations of anti‐CCP–negative RA with non‐HLA genetic polymorphisms demonstrated in a previous study.Methods The Rheumatoid Arthritis Consortium International densely genotyped 186 autoimmune‐related regions in 3,339 anti‐CCP–negative RA patients and 15,870 controls across 6 different populations using the Illumina ImmunoChip array. We performed a case–control replication study of the anti‐CCP–negative markers with the strongest associations in that discovery study, in an independent cohort of anti‐CCP–negative UK RA patients. Individuals from the arcOGEN Consortium and Wellcome Trust Case Control Consortium were used as controls. Genotyping in cases was performed using Sequenom MassArray technology. Genome‐wide data from controls were imputed using the 1000 Genomes Phase I integrated variant call set release version 3 as a reference panel. Results After genotyping and imputation quality control procedures, data were available for 15 non‐HLA single‐nucleotide polymorphisms in 1,024 cases and 6,348 controls. We confirmed the known markers ANKRD55 (meta‐analysis odds ratio [OR] 0.80; P = 2.8 × 10−13) and BLK (OR 1.13; P = 7.0 × 10−6) and identified new and specific markers of anti‐CCP–negative RA (prolactin [PRL] [OR 1.13; P = 2.1 × 10−6] and NFIA [OR 0.85; P = 2.5 × 10−6]). Neither of these loci is associated with other common, complex autoimmune diseases. Conclusion Anti‐CCP–negative RA and anti‐CCP–positive RA are genetically different disease subsets that only partially share susceptibility factors. Genetic polymorphisms located near the PRL and NFIA genes represent examples of genetic susceptibility factors specific for anti‐CCP–negative RA.

Integrative genomic deconvolution of rheumatoid arthritis GWAS loci into gene and cell type associations.

BackgroundAlthough genome-wide association studies (GWAS) have identified over 100 genetic loci associated with rheumatoid arthritis (RA), our ability to translate these results into disease understanding and novel therapeutics is limited. Most RA GWAS loci reside outside of protein-coding regions and likely affect distal transcriptional enhancers. Furthermore, GWAS do not identify the cell types where the associated causal gene functions. Thus, mapping the transcriptional regulatory roles of GWAS hits and the relevant cell types will lead to better understanding of RA pathogenesis.ResultsWe combine the whole-genome sequences and blood transcription profiles of 377 RA patients and identify over 6000 unique genes with expression quantitative trait loci (eQTLs). We demonstrate the quality of the identified eQTLs through comparison to non-RA individuals. We integrate the eQTLs with immune cell epigenome maps, RA GWAS risk loci, and adjustment for linkage disequilibrium to propose target genes of immune cell enhancers that overlap RA risk loci. We examine 20 immune cell epigenomes and perform a focused analysis on primary monocytes, B cells, and T cells.ConclusionsWe highlight cell-specific gene associations with relevance to RA pathogenesis including the identification of FCGR2B in B cells as possessing both intragenic and enhancer regulatory GWAS hits. We show that our RA patient cohort derived eQTL network is more informative for studying RA than that from a healthy cohort. While not experimentally validated here, the reported eQTLs and cell type-specific RA risk associations can prioritize future experiments with the goal of elucidating the regulatory mechanisms behind genetic risk associations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-0948-6) contains supplementary material, which is available to authorized users.

High-resolution (18)F-FDG PET/CT for assessing disease activity in rheumatoid and psoriatic arthritis: findings of a prospective pilot study.

Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) commonly affect the small joints of the wrist and hand. We evaluated the performance of a new, high-resolution extremity positron emission tomography (PET)/CT scanner for characterizing and quantifying pathologies associated with the two arthritides in the wrist and hand joints. Patients with RA or PsA underwent fluorine-18 fludeoxyglucose ((18)F-FDG) PET/CT wrist and hand imaging, respectively, on the high-resolution scanner. Calibrated CT images and co-registered PET images were reconstructed. PET/CT was derived for the radiocarpal and pisiform-triquetral compartments, joints with erosive changes, sites of synovitis or tenosynovitis and the nail bed and were correlated with clinical and MRI findings. Significantly elevated (18)F-FDG uptake was measured for the radiocarpal and pisiform-triquetral compartments and at sites of bone erosion, synovitis, pannus and oedema, compared with unaffected joints (p < 0.05) in patients with RA, consistent with their clinical findings. In patients with PsA, significantly elevated (18)F-FDG uptake was measured for joints with synovitis compared with unaffected joints (p < 0.05), with patterns of (18)F-FDG uptake along the tendons, at the enthesis and in the nail bed, consistent with tenosynovitis, enthesitis and nail dystrophy, respectively. High-resolution (18)F-FDG PET/CT imaging of the wrist and hand is feasible in an RA or PsA patient cohort and is capable of providing quantifiable measures of disease activity (synovitis, enthesitis, oedema and bone destruction). High-resolution PET/CT imaging shows promise as a tool for understanding the pathogenesis of the arthritic process and for non-invasive, objective assessment of RA or PsA severity and therapy selection.

028 The Incidence and Predictors of Flare in a Cohort of Rheumatoid Arthritis Patients

028 The Incidence and Predictors of Flare in a Cohort of Rheumatoid Arthritis Patients

FCGR3A-V158F polymorphism is a disease-specific pharmacogenetic marker for the treatment of psoriasis with Fc-containing TNFα inhibitors.

Psoriasis is a multifactorial skin disease affecting ~2% of world's population, causing a dramatic decrease in patients' quality of life and a significant increase in health-care expenses. Biological agents such as the anti-TNFα ones had an enormous impact in patients' therapy; however, a significant proportion of them do not respond well, an outcome attributed mainly to genetic factors. Recently, in a large European cohort of rheumatoid arthritis patients we have shown association with variation in the receptors that correspond to the Fc portion of the biological agents. As both diseases share common immunological fingerprints, we examined the hypothesis that they share common pharmacogenetic markers. Analysis of FCGR2A-H131R and FCGR3A-V158F polymorphisms in 100 psoriasis patients showed association only with respect to FCGR3A-V158F and response to etanercept (P=0.018). Interestingly, no association was found between FCGR2A-H131R and response to anti-TNFα therapy (P=0.882). This study suggests a role for FCGR3A-V158F polymorphism unique for psoriasis.

The interleukin-20 receptor axis in early rheumatoid arthritis: novel links between disease-associated autoantibodies and radiographic progression.

BackgroundRheumatoid arthritis (RA) is often characterized by the presence of rheumatoid factor, anti-citrullinated protein antibodies, and bone erosions. Current therapies can compromise immunity, leading to risk of infection. The interleukin-20 receptor (IL-20R) axis comprising IL-19, IL-20, and IL-24 and their shared receptors activates tissue homeostasis processes but not the immune system. Consequently, modulation of the IL-20R axis may not lead to immunosuppression, making it an interesting drug target. We evaluated the role of the IL-20R axis in RA and associations between plasma cytokine levels and clinical disease.MethodsPlasma IL-19, IL-20, and IL-24 levels were measured in early RA patients during a treat-to-target strategy by enzyme-linked immunosorbent assays. The IL-20R1 and IL-22R1 levels in paired peripheral blood mononuclear cells and synovial fluid mononuclear cells from a different cohort of RA patients were evaluated by flow cytometry and confocal microscopy. Monocytes/macrophages were stimulated with heat-aggregated human immunoglobulin immune complexes and immune complexes containing citrullinated fibrinogen, and osteoclasts were incubated with IL-19, IL-20, and IL-24.ResultsThe plasma concentrations of IL-20 and IL-24 (but not IL-19) were increased in early RA patients compared with healthy controls (both P < 0.002) and decreased after 6 months of treatment (both P < 0.0001). The expression of IL-22R1 (but not IL-20R1) was increased on monocytes from RA synovial fluid compared with monocytes from both RA and healthy control peripheral blood. The plasma concentrations of IL-20 and IL-24 were increased in rheumatoid factor and anti-citrullinated protein antibody positive compared with negative early RA patients (all P < 0.0001). Immune complexes stimulated the production of the IL-20R cytokines by monocytes/macrophages. Increased baseline plasma concentrations of IL-20 and IL-24 were associated with Sharp-van der Heijde score progression after 24 months (Spearman’s rho = 0.19 and 0.26, both P < 0.05) in the early RA patients. The IL-22R1 was expressed by osteoclast precursors and in multinucleated osteoclasts. IL-20 and IL-24 increased the secretion of monocyte chemoattractant protein 1 by these cells.ConclusionsThis study suggests that IL-20 and IL-24 link RA-associated autoantibodies with radiographic progression via the IL-22R1. Modulation of this axis holds promise as feasible anti-erosive treatment modalities in seropositive RA.

Correlations between immunogenicity, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab.

The aim of this study was to evaluate the real-life immunogenicity of anti-drug antibodies, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab (TCZ). We evaluated 126 TCZ-treated patients with rheumatoid arthritis (16 males and 110 females; mean age 59±12 years, range 26–83; mean disease duration 11±5 years) with inadequate 12-week response to any synthetic and biological disease-modifying anti-rheumatic drugs, in a retrospective analysis. One-hundred and seven patients were treated with methotrexate mean dose 12.6±1.3 mg/week in combination with TCZ, 13 received TCZ monotherapy, and six received leflunomide 20 mg/day plus TCZ; all patients were treated with prednisone mean dose 6.4±1.2 mg/day. They had a 28-joint Disease Activity Score (DAS28) of >3.2, an erythrocyte sedimentation rate (ESR) of >30 mm/hour, and CRP levels of >1.0 mg/dL. We evaluated at baseline and after 6 months of treatment: DAS28; rheumatoid factor (RF) IgM, IgA, and IgG; anti-citrullinated peptide antibody; ESR; CRP; TNF-α; and IL-6. TCZ and anti-TCZ antibodies were detected using LISA-TRACKER Duo TCZ. TCZ levels of <10 µg/mL were considered low and >10 µg/mL high. After 6 months of treatment only one patient was positive for anti-TCZ antibodies. There were correlations between DAS28, ESR, and CRP and IL-6 levels in all patients. Comparison of the 84 patients with TCZ levels of <10 µg/mL and the 42 with TCZ levels of >10 µg/mL showed the following differences: DAS28: 3.09±1.32 vs 2.78±1.32, P=0.0005; ESR: 27±14.8 vs 14±12 mm/hour, P=0.0001; CRP: 1.47±1.05 vs 0.65±0.80 mg/dL, P=0.0086; TNF-α: 10.2±1.2 vs 9.9±1.1 pg/mL, P=0.999; IL-6: 3.65±4.75 vs 3.62±4.41 pg/mL, P=0.97; anti-citrullinated peptide antibody: 85.2±93.7 vs 86.7±90.3 IU/mL, P=0.94; RF IgM: 72.4±62.7 vs 68.3±61.6 IU/mL, P=0.754; RF IgA: 41.7±36.4 vs 47.8±42.1 U/mL, P=0.449; and RF IgG: 46.4±46.1 vs 59.3±58.2 U/mL, P=0.212. These findings show that the occurrence of anti-drug antibodies against TCZ is very rare and that there are statistically significant correlations between TCZ levels of >10 µg/mL and ESR, CRP levels, and DAS28.

Methotrexate is not associated with increased liver cirrhosis in a population-based cohort of rheumatoid arthritis patients with chronic hepatitis B.

A few studies showed that long-term methotrexate (MTX) use exacerbates liver fibrosis and even leads to liver cirrhosis in rheumatoid arthritis (RA) patients. We therefore conducted a population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic hepatitis B (CHB)-related cirrhosis among RA patients. We analyzed data from the National Health Insurance Research Database in Taiwan and identified 631 incident cases of RA among CHB patients (358 MTX users and 273 MTX non-users) from January 1, 1998 to December 31, 2007. After a median follow-up of more than 6 years since the diagnosis of CHB, a total of 41 (6.5%) patients developed liver cirrhosis. We did not find an increased risk of liver cirrhosis among CHB patients with long-term MTX use for RA. Furthermore, there was no occurrence of liver cirrhosis among 56 MTX users with a cumulative dose ≧3 grams after 97 months’ treatment. In conclusion, our data showed that long-term MTX use is not associated with an increased risk for liver cirrhosis among RA patients with CHB. However, interpretation of the results should be cautious due to potential bias in the cohort.

Study of chronic periodontitis in rheumatoid arthritis patients and its relation to serum anticitrulinated peptide antibody levels

Background Recently discovered evidence suggests that periodontitis might have a direct role in initiating and sustaining the immunoinflammatory responses in rheumatoid arthritis (RA), besides the risk factors that are common to both conditions. Aim The aim of this study was to determine the prevalence of chronic periodontitis in a cohort of Egyptian RA patients and their first-degree relatives and siblings compared with a control group and its relation to serum anticitrulinated peptide antibody (ACPA) levels. Patients and methods This study was carried out on three groups: group I included 100 patients with RA who fulfilled the 2010 ACR/EULAR classification criteria for RA and had less than 5 years’ disease duration. They were recruited from the Rheumatology Unit and Rheumatology Outpatient Clinic at Alexandria Main University Hospital. Group II included 50 first-degree relatives and siblings of RA patients who were free of clinical joint disease, and group III included 50 age-matched and sex-matched healthy subjects referred for general dental treatment at the Dental Clinic of Alexandria Main University Hospital. RA disease activity was assessed by applying Disease Activity Score 28, and the functional state of the patients was assessed by applying the Health Assessment Questionnaire. All subjects underwent a dental examination, including Probing Pocket Depth (PPD), Clinical Attachment Loss (CAL), Plaque Index (PI), and modified Gingival Index. The ACPA levels in serum were evaluated in group I, group II, and group III participants with periodontitis. Results Group I patients had significantly more periodontitis than group II (P Conclusion Our study shows an association between RA and chronic periodontitis. Individuals with RA are more likely to experience periodontitis.

Smoking Functions as a Negative Regulator of IGF1 and Impairs Adipokine Network in Patients with Rheumatoid Arthritis.

Objectives. Smoking is pathogenic for rheumatoid arthritis (RA) being tightly connected to the genetic and serological risk factors for this disease. This study aims to understand connections between cigarette smoking and serum levels of IGF1 and adipokines in RA. Methods. Serum levels of IGF1 and adipokines leptin, adiponectin, resistin, and visfatin were measured in two independent cohorts of RA patients from Gothenburg (n = 350) and Leiden (n = 193). An association of these parameters with smoking was tested in a direct comparison and proved by bivariate correlation analysis. The obtained associations were further tested in multivariate regression models where the confounders (age, gender, disease duration, and BMI) were controlled. Results. The smokers had significantly lower serum levels of IGF1, adiponectin, and leptin compared to never smokers. In regression analysis, smoking and low leptin, but not adiponectin, were associated and predicted low IGF1. Additionally, high disease activity and high BMI increased the probability of low leptin. Conclusions. The study indicates cigarette smoking as an important cause of a relative IGF1 and leptin deficiency in RA patients. This novel association between smoking and hypoleptinemia may be of importance for long-term prognosis of RA and for prediction of comorbidities.

Adherence to Anti-Tumor Necrosis Factor Therapy Administered Subcutaneously and Associated Factors in Patients With Rheumatoid Arthritis.

Adherence to biologic therapy is relatively poorly studied in rheumatoid arthritis (RA) because many of the studies have investigated the drug persistence, which represents only a surrogate of adherence. The aims of this study were to determine the extent of adherence in RA patients with subcutaneously administered anti-tumor necrosis factor methotrexate agents and to identify the risk factors for nonadherence. A cohort of RA patients who started a subcutaneous anti-tumor necrosis factor treatment were enrolled. After 12 months of treatment, all patients completed the 4-item Morisky Medication Adherence Scale questionnaire. Associations between beliefs and nonadherence and the influence of demographic, clinical, and radiographic features were assessed using logistic regression model. A total of 209 (80.4%) of the 260 patients were included in the analyses. Forty-three of 209 patients were considered nonadherent to their medication (20.6%) according to the 4-item Morisky Medication Adherence Scale. More than half (53.1%) of patients showed at least 1 form of nonadherent behavior.The logistic model showed that low disease activity (P = 0.003), higher patient-physician discordance ratings (P = 0.012), older age (P = 0.041), and a high number of comorbid conditions (P = 0.011) were significantly associated with increased likelihood of nonadherence. The overall nonadherence with subcutaneous biologic therapy is relatively high among RA patients and should be taken into account when a patient's response to treatment is unsatisfactory.

Abstract 10336: Left Ventricular Deformation at 2-year Follow-up in Treatment-naive Rheumatoid Arthritis Patients is Associated With High Inflammation Parameters: A Open Cohort Study

Introduction: Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease (CVD). The role of autoimmunity and especially citrullination in the pathogenesis of the increased risk of CVD and the time-course of left ventricular (LV) dysfunction are unknown. Hypothesis: To assess LV function by speckle-tracking echocardiography and the amount of coronary calcium by coronary computer tomography (CCT) in relation to anti-cyclic citrullinated peptide antibody (anti-CCP) status during a 2-year follow-up period in a open cohort of treatment-naive RA patients. Methods: Thirty-nine treatment-naive early RA patients (21 women) were included at time of diagnosis and followed for 2 years. Disease activity, IgM rheumatoid factor (IgM-RF) and anti-CCP was assessed at time of diagnosis and at 2-year follow-up. We assessed both the LV deformation by speckle-tracking echocardiography whereby we measured global longitudinal systolic strain (GLS) and coronary calcium score (Agatston′s score) by coronary computer tomography (CCT) at time of diagnosis and at 2-year follow-up. Results: We found GLS similar at baseline and after 2-year follow-up (GLSBASELINE: -16.56±3.1% vs. GLS2-YEAR: -16.27±2.8%; p=0.66). However, in patients with anti-CCP ≥340 at baseline and patients who persistently had an anti-CCP ≥340 at 2-year follow-up (n=10), we observed a significant decrease in deformation compared to patients who did not (n=29); (2.9±3.2% vs. -0.6±2.7%; p=0.002). Furthermore, we observed a significant association between the changes in GLS over 2 years (GLSDELTA: 0.27±3.21%) and anti-CCP (r=0.63; p&lt;0.0001), which remained significantly associated (p&lt;0.0001) after correction for relevant confounders. No significant progression in coronary calcium score was observed in the observation period. Conclusions: LV deformation is reduced in treatment-naive RA patients with persistently elevated anti-CCP and deformation abnormalities is associated with the degree of anti-CCP positivity in a 2-year follow-up period. Our observations make deformation analysis by speckle-tracking echocardiography a strong tool to detect early development of myocardial dysfunction in treatment naive RA.

Loci associated with N-glycosylation of human IgG are not associated with rheumatoid arthritis: a Mendelian randomisation study

ObjectivesA recent study identified 16 genetic variants associated with N-glycosylation of human IgG. Several of the genomic regions where these single nucleotide polymorphisms (SNPs) reside have also been associated with...

Early medication use in new-onset rheumatoid arthritis may delay joint replacement: results of a large population-based study.

IntroductionUse of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) may prevent joint damage and potentially reduce joint replacement surgeries. We assessed the association between RA drug use and joint replacement in Quebec, Canada.MethodsA cohort of new-onset RA patients was identified from Quebec’s physician billing and hospitalization databases from 2002–2011. The outcome was defined using procedure codes submitted by orthopedic surgeons. Medication use was obtained from pharmacy databases. We used alternative Cox regression models with time-dependent variables measuring the cumulative effects of past use during different time windows (one model focussing on the first year after cohort entry) for methotrexate (MTX), and other DMARDs. Models were adjusted for baseline sociodemographics, co-morbidity and prior health service use, time-dependent cumulative use of other drugs (anti-tumor necrosis factor [anti-TNF] agents, other biologics, cyclooxygenase-2 inhibitors [COXIBs], nonselective nonsteroidal antiinflammatory drugs [NSAIDs], and systemic steroids), and markers of disease severity.ResultsDuring follow-up, 608 joint replacements occurred among 11,333 patients (median follow-up: 4.6 years). The best-fitting model relied on the cumulative early use (within the first year after cohort entry) of MTX and of other DMARDs, with an interaction between MTX and other DMARDs. In this model, greater exposure within the first year, to either MTX (adjusted hazard ratio, HR = 0.95 per 1 month, 95 % confidence interval, 95 % CI 0.93-0.97) or other DMARDs (HR = 0.97, 95 % CI 0.95-0.99) was associated with longer time to joint replacement.ConclusionsOur results suggest that longer exposure to either methotrexate (MTX) or other DMARDs within the first year after RA diagnosis is associated with longer time to joint replacement surgery.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0713-3) contains supplementary material, which is available to authorized users.

E55. Smoking Prevalence in an Established Cohort of Rheumatoid Arthritis Patients in a Large UK Teaching Hospital

E55. Smoking Prevalence in an Established Cohort of Rheumatoid Arthritis Patients in a Large UK Teaching Hospital

The impact of C677T and A1298C MTHFR polymorphisms on methotrexate therapeutic response in East Bohemian region rheumatoid arthritis patients.

Some single-nucleotide polymorphisms (SNPs) might be predictive of methotrexate (MTX) therapeutic outcome in rheumatoid arthritis (RA). The aim of this study was to determine whether SNPs in the methylenetetrahydrofolate reductase (MTHFR) gene are predictive of MTX response. Comparison was made using EULAR response criteria and according to the change of DAS28 (∆DAS28) after a 6-month MTX treatment in RA patient cohort. The two SNPs C677T (rs1801133) and A1298C (rs1801131) have been genotyped. A total of 120 patients were enrolled in the study, and all of them fulfilled the American College of Rheumatology 1987 RA criteria and are currently or previously taking MTX oral treatment, either as a monotherapy (n=65) or in a combination with other disease-modifying antirheumatic drugs (n=55). Genotyping was performed using qPCR allelic discrimination. We did not found any association of C677T and A1298C genotypes with MTX treatment inefficacy in dominant model (OR 1.23, 95% CI 0.57-2.65, P=0.697; and OR 0.98, 95% CI 0.47-2.14, P=1.0, respectively), or in recessive and codominant models. However, when ∆DAS28 after a 6-month therapy was used as a measure of treatment efficacy, the 677CT and 1298AC genotypes were found to be significantly associated with less favorable response to MTX (P=0.025 and P=0.043, respectively). In addition, even lower ∆DAS28 was determined for double-mutated 677CT-1298AC heterozygotes. It means that a synergistic effect of 677CT and 1298AC genotypes was observed. Nevertheless, the DAS28 baseline was lower here comparing to other genotypes. Unexpectedly, quite the opposite trend-i.e., better response to MTX-was found in genotypes 677CC-1298CC and 677TT-1298AA. It is an intriguing finding, because these double-mutated homozygotes are known for their low MTHFR-specific activity. Global significance was P=0.013, η (2)=0.160-i.e., large-size effect. Thus, our data show greater ability of 677CC-1298CC and 677TT-1298AA genotypes to respond to MTX treatment.

Prevalence, incidence and characteristics of the metabolic syndrome (MetS) in a cohort of Mexican Mestizo early rheumatoid arthritis patients treated with conventional disease modifying anti-rheumatic drugs: the complex relationship between MetS and disease activity.

IntroductionA higher prevalence of metabolic syndrome (MetS) has been described in rheumatoid arthritis (RA), along with an association with disease activity. Objectives were to describe prevalence of MetS at RA diagnosis in a cohort of Mexican Mestizo early RA patients, and to define a causal association between MetS and disease activity.MethodsThe study population was a prospective cohort. At baseline and at fixed 6-months-intervals, patients had medical evaluations, fasting serum glucose, triglycerides, high-density lipoprotein cholesterol and acute reactant-phase determinations. MetS was defined according to international criteria and body mass index (BMI) ≥30 kg/m2 was used as a surrogate of the waist circumference. The study was approved by the internal review board. Appropriated statistics and Cox regression analysis were used. All statistical tests were two-sided and evaluated at the 0.05 significance level.ResultsUp to March 2014, data from 160 patients were analyzed. At baseline, they were more frequently middle-aged females and had moderate to high disease activity. Prevalence of MetS varied from 11.3% to 17.5% in patients and was lower to that from matched controls (versus 26.3% to 30%, P ≤0.01).Up to last follow-up, 39 patients (34.5%) developed incidental MetS. In the Cox regression analysis, cumulative disease activity score (DAS) 28 (odds ratio (OR): 1.81, 95% confidence interval (CI): 1.346 to 2.433, P = 0.000) and baseline BMI (OR: 1.13, 96% CI: 1.035 to 1.236, P = 0.007) were the only predictors for incidental MetS.RA patients with incidental MetS accumulated more disease activity and had less frequent remission than their counterparts. Logistic regression analysis showed that incidental MetS (OR: 0.2, 95% CI: 0.01 to 0.99, P = 0.052) and baseline DAS28 (OR: 0.4, 95% CI: 0.2 to 0.9, P = 0.02) were the only predictors for achieving or maintaining sustained (≥6 months) remission.ConclusionsMetS prevalence in a cohort of early RA patients was lower than that from matched controls. Cumulative disease activity and higher BMI were risk factors for incidental Mets; higher baseline disease activity and incidental MetS prevented sustained remission. In addition to disease activity, MetS needs to be controlled to impact disease outcomes.

Temporal Dissociation between Disease Activity Reduction and Improvements in Fatigue and Physical Function After Infliximab in Rheumatoid Arthritis

Objective: To evaluate the temporal responses to infliximab in fatigue and other selected parameters of physical function, inflammation, disease activity, and QOL in a cohort of rheumatoid arthritis patients. Methods: A prospective study was conducted. At baseline (PRE), after two (POST 2) and six (POST 6) months of treatment with infliximab (3 mg/Kg), fatigue, muscle function and strength, quality of life, disease activity, and markers of inflammation were assessed in 25 consecutive patients. Results: Infliximab treatment resulted in a significant reduction in fatigue at POST 2 and POST 6 when evaluated by both Chalder and the Global Fatigue VAS scale. Similarly, improvements in physical function at POST 2 and POST 6 as assessed by both the timed-stands test and SF-36 physical functioning domain was also observed. Conversely, disease activity, as assessed by DAS-28, remained unchanged at POST 2 and improved only at POST 6. The reduction in clinical markers of inflammation (i.e. CRP and ERS) did not reach significance at POST 2 or at POST 6, except for a trend in CRP after 6 months of treatment. Muscle strength remained unchanged throughout the trial. Additionally, no significant correlations were found between delta changes of either disease activity or inflammation parameters and physical function and fatigue parameters. Conclusion: These findings clearly reveal a temporal dissociation between the improvements in fatigue, physical function, and quality of life and the reduction in disease activity in response to infliximab in rheumatoid arthritis patients. The predictive value of these early response factors merits further investigations.