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ID PMID Title PublicationDate abstract
22321280 [Association between systemic inflammation and autoimmunity parameters and plasma lipid in 2011 Oct OBJECTIVE: The purpose of this study was to observe the association between inflammation status/autoimmune antibodies and plasma lipid in patients with rheumatoid arthritis (RA). METHODS: A total of 402 RA patients were admitted into our hospital during January 2008 to March 2009 and 225 RA patients who met the inclusion criteria were selected to perform a full lipid profile examination including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), anti-keratin antibody (AKA), anti-perinuclear factor autoantibody (APF) and complement (C) were also evaluated. Atherogenic index of plasma (AIP) was calculate by the formula Log (TG/HDL-C). RESULTS: (1) There were 12.9%, 10.2% and 14.2% patients with elevated TC, LDL-C and TC respectively, patients with reduced HDL-C accounted for 43.6%. (2) C(3) was higher in elevated TC group than normal TC group (P < 0.05). ESR and CRP were significantly higher in decreased HDL-C group than in normal HDL-C group (P < 0.05). CRP, C(3) and C(4) were significantly higher in elevated LDL-C group than in normal LDL-C group (P < 0.05). (3) Multiple stepwise regression analysis showed that C(3) was positively correlated with TC (R(2) = 0.067, P < 0.05). Both ESR and CRP were negative correlated with HDL-C (R(2) = 0.202, P < 0.05). CRP and anti-CCP were positively correlated with LDL-C (R(2) = 0.129, P < 0.05). ESR and C(4) were positively correlated with AIP (R(2) = 0.046, P < 0.05). CONCLUSION: This study showed that rheumatoid arthritis is associated with an abnormal lipid profile, especially in patients with increased inflammation markers and autoimmune antibodies. Moreover, ESR and C(4) were predictors of increased AIP in this cohort.
23061423 Crohn's disease diagnosis during adalimumab treatment. 2013 Feb IBD flares or new diagnosis in patients receiving anti-TNF because of other diseases than IBD are rare events but the possibility of a paradoxical reaction must be considered as with psoriasis or uveitis. We present a patient suffering from RA who had a new CD onset after a two-year adalimumab treatment.
21132352 Actively targeted low-dose camptothecin as a safe, long-acting, disease-modifying nanomedi 2011 Apr PURPOSE: Camptothecin (CPT), a potent topoisomerase I inhibitor, was originally discovered as an anticancer agent to induce programmed cell death of cancer cells. Recent evidence suggests that, similar to cancer, alterations in apoptosis and over-proliferation of key effector cells in the arthritic joint result in rheumatoid arthritis (RA) pathogenesis. Initial in vitro studies have suggested that camptothecin inhibits synoviocyte proliferation, matrix metalloproteinases expression in chrondrocytes and angiogenesis. This study is one of the first to test, in vivo, RA as a new indication for CPT. METHODS: To circumvent insolubility, instability and toxicity of CPT, we used biocompatible, biodegradable and targeted sterically stabilized micelles (SSM) as nanocarriers for CPT (CPT-SSM). We also surface-modified CPT-SSM with vasoactive intestinal peptide (VIP) for active targeting. We then determined whether this nanomedicine abrogated collagen-induced arthritis (CIA) in mice. RESULTS: Based on our findings, this is the first study to report that CPT was found to be efficacious against CIA at concentrations significantly lower than usual anti-cancer dose. Furthermore, a single subcutaneous injection of CPT-SSM-VIP (0.1 mg/kg) administered to CIA mice mitigated joint inflammation for at least 32 days thereafter without systemic toxicity. CPT alone needed at least 10-fold higher dose to achieve the same effect, albeit with some vacuolization in liver histology. CONCLUSION: We propose that CPT-SSM-VIP is a promising targeted nanomedicine and should be further developed as a safe, long-acting, disease-modifying pharmaceutical product for RA.
21474637 Effects of a group-based exercise and educational program on physical performance and dise 2011 Jun BACKGROUND: Evidence supports the use of educational and physical training programs for people with rheumatoid arthritis (RA). OBJECTIVE: The purpose of this study was to evaluate the effects of a group-based exercise and educational program on the physical performance and disease self-management of people with RA. DESIGN: This was a randomized controlled trial. SETTING: The study was conducted at a rehabilitation center in the Netherlands. PARTICIPANTS: Thirty-four people diagnosed with RA participated in the study. Participants were randomly assigned to either an intervention group (n=19) or a waiting list control group (n=15). INTERVENTION: The intervention in this study was an 8-week, multidisciplinary, group therapy program for people with RA, consisting of physical exercise designed to increase aerobic capacity and muscle strength (force-generating capacity) together with an educational program to improve health status and self-efficacy for disease-self-management. MEASUREMENTS: The main outcome measures were maximum oxygen uptake (Vo(2)max), muscle strength of the elbow and knee flexors and extensors, health status, and perceived self-efficacy. All data were recorded before intervention in week 1, after intervention in week 9, and at follow-up in week 22. RESULTS: The intervention group showed significant improvement (12.1%) in Vo(2)max at week 9 compared with the control group (-1.7%). Although significant within-group changes were found over time for muscle strength of the upper and lower extremities and health status that favored the intervention group, no between-group changes were found regarding these outcomes. LIMITATIONS: An important limitation was the small number of participants included in our study, which may have resulted in a lack of power. CONCLUSIONS: The present group-based exercise and educational program for people with RA had a beneficial effect on aerobic capacity but not on muscle strength, health status, or self-efficacy.
21658223 The usefulness of magnetic resonance imaging of the hand and wrist in very early rheumatoi 2011 Jun 9 INTRODUCTION: Magnetic resonance imaging (MRI) was used to study the hand and wrist in very early rheumatoid arthritis (RA), and the results were compared with early and established disease. METHODS: Fifty-seven patients fulfilling the new American College of Rheumatology criteria for RA, 26 with very early RA (VERA), 18 with early RA (ERA), and 13 with established RA (ESTRA), (disease duration < 3 months, < 12 months, and > 12 months, respectively) were enrolled in the study. MRI of the dominant hand and wrist was performed by using fat-suppressed T2-weighted and plain and contrast-enhanced T1-weighted sequences. Evaluation of bone marrow edema, synovitis, and bone erosions was performed with the OMERACT RA MRI scoring system. RESULTS: Edema, erosions, and synovitis were present in VERA, and the prevalence was 100%, 96.15%, and 92.3%, respectively. Significant differences in edema and erosions were found between VERA and ESTRA (P < 0.05). No significant difference was found in synovitis. CONCLUSIONS: Edema, erosions, and synovitis are findings of very early RA. MRI, by detecting these lesions, may play an important role in the management of these patients.
22985804 Treat to target strategy in rheumatoid arthritis: real benefits. 2013 Mar Treating rheumatoid arthritis (RA) with a goal or «Treat to target» strategy is a therapeutic proposal taken from cardiovascular and endocrine literature. It proposes that the therapeutic target in RA should be a state of remission, or an alternative goal could be a low disease activity. Rheumatologists should measure and register disease activity in every clinical visit and if the goal has not been reached, therapeutic adjustments should be made. Current evidence from clinical trials and a meta-analysis supports the notion that this strategy has important clinical benefits in patients with early RA when compared with routine care. It is also described that using protocolized treatment offers greater benefits. Recent data from Dutch cohorts is presented showing its successful implementation. A discussion is offered on the need of more studies in established RA.
21930734 In early rheumatoid arthritis, patients with a good initial response to methotrexate have 2012 Feb OBJECTIVE: To investigate the 2-year clinical and radiological outcomes of patients with early rheumatoid arthritis (RA; symptom duration <1 year) who had initially responded well to methotrexate monotherapy. METHODS: In the SWEFOT trial, all 487 patients started methotrexate (target dose 20 mg/week). After 3-4 months, 147 had low disease activity, 28-joint based disease activity score (DAS28) ≤3.2. These patients were not randomly selected but were followed in regular care for 2 years. Clinical outcomes and radiographic progression according to the van der Heijde modified Sharp (SvdH) score were analysed. RESULTS: The majority of the 147 patients continued on methotrexate monotherapy. After 1 and 2 years, DAS28 remission was achieved in 59.6% and 71.8% and mean observed DAS28 values were 2.53 and 2.25, respectively. Despite the favourable clinical course, a proportion of the patients progressed radiographically with a mean (SD) increase in the SvdH score after 2 years of 3.90 (6.84). There was no significant difference in progression between patients in DAS28 remission versus not in remission (p=0.73). At baseline, approximately half the patients had no radiographic damage, while after 2 years the proportion was approximately 20%. CONCLUSION: Most early RA patients who achieve low disease activity after 3-4 months of methotrexate monotherapy continue to have low disease activity during 2 years follow-up, and additional treatment is needed infrequently. Some radiological progression occurs in most patients, and may be marked or severe in some, even despite sustained DAS28 remission. Close monitoring for radiological progression is thus warranted.
21844154 Biologic disease-modifying drug treatment patterns and associated costs for patients with 2011 Oct OBJECTIVE: To assess the influence of biologic treatment patterns on healthcare costs for patients with rheumatoid arthritis (RA) initiating tumor necrosis factor-α (TNF-α) antagonist therapy. METHODS: Patients with 2 RA diagnoses (International Classification of Diseases, 9th ed, 714.xx), and without psoriasis or Crohn's disease, were identified in a US employer-based insurance claims database. A sample of 2545 was constructed based on an index event of initiating TNF-α antagonist therapy and 30 months of continuous enrollment. Baseline characteristics were assessed in the 6-month pre-index period and treatment patterns were determined during the 12-month post-index period. Medical service and prescription drug costs were analyzed for Months 13-24 using multivariate regression analysis to control for baseline characteristics and time-varying confounding associated with treatment and disease severity. RESULTS: In the first year after TNF-α initiation, 89% used a single TNF-α antagonist; only 9% and 2% had switched TNF-α antagonists or received non-TNF biologic disease-modifying antirheumatic drugs, respectively. Descriptive analyses revealed pairwise differences between groups (p < 0.05) in baseline characteristics (comorbidities, RA-related procedure use, and prescription drug use). Controlling for observed baseline characteristics, costs were greater for those treated with multiple vs single TNF-α antagonists: annual RA-related prescription drug costs ($8,340 vs $7,058; p = 0.012), RA-related healthcare costs ($15,048 vs $13,312; p = 0.008), and total healthcare costs ($26,697 vs $21,381; p < 0.001). CONCLUSION: In this sample, the majority of patients with RA were treated with a single TNF-α antagonist over the first year on therapy. For those who switched therapy, Year 2 RA-related and total direct healthcare costs were higher, adjusting for claims-based measures of RA disease severity.
22298074 [Clinical significance of serum cartilage biomarkers in the treatment of rheumatoid arthri 2012 Feb With the current use of biologics in RA, numerous patients can achieve clinical remission, however structural joint damage occurs in substantial numbers of the patients. The present study assessed cartilage damage during 54-week anti-TNF therapy, using serum cartilage markers, and potential advantages of these markers were evaluated. Levels of serum hyaluronan decreased with decreasing levels of CRP in both early and established RA, whereas indicator of type II collagen synthesis/degradation, C2C/CP II decreased only in early RA group. Levels of COMP and keratin sulfate significantly decreased and increased compared to baseline, respectively, by week 54 in established RA. Strikingly, C2C/CP II levels were universally improved in early RA, regardless of CRP levels or EULAR response grade. In contrast, C2C/CP II levels universally worsened in established RA, even though patients achieved good response. As a role of surrogate marker reflecting therapeutic efficacy of biological therapy, C2C/CP II appears particularly useful for determining the degree of ongoing structural joint deterioration, which is dissociated from clinical assessment of disease activity in RA.
21267737 [Hand and wrist surgery]. 2011 Jan Despite improved medical treatment of rheumatoid arthritis, carpal tunnel compression, caput ulnae syndrome and palmar and dorsal tenosynovitis with potential tendon rupture represent urgent surgical indications. While diagnostic and therapeutic synovectomy may guide medical treatment, it should be performed before joint instability and destructive arthritis are established. Swan-neck and Boutonniere deformities as well as ulnar or radial drift of metacarpophalangeal (MCP) joints or the wrist can only be corrected when the involved joints are supple and intact. In the presence of destructive arthritis, partial and total wrist fusion, arthroplasties of the MCP joints and arthrodeses of the distal interphalangeal joints are recommended.
22657383 Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with card 2012 Oct OBJECTIVE: The methionine sulfoxide reductase A (MSRA) gene is related to oxidative stress that has been involved in the susceptibility to rheumatoid arthritis (RA) in genome-wide pathway analysis and replication studies. The aim of the present study was to determine whether the MSRA gene is implicated in susceptibility to cardiovascular (CV) disease in RA patients. METHODS: A total of 1302 patients fulfilling the 1987 American College of Rheumatism classification criteria for RA were genotyped for the MSRA rs10903323 (G/A) polymorphism. Two hundred and thirty-three (17.9%) patients experienced CV events. Human leucocyte antigen (HLA)-DRB1 genotyping was performed using molecular-based methods. Multiple logistic regression models were constructed with adjustments for gender, age at RA diagnosis, follow-up, rheumatoid shared epitope, and traditional CV risk as potential confounders. RESULTS: There were no statistically significant differences in the allele or genotype frequencies for the MSRA rs10903323 polymorphism between RA patients who experienced CV events and those who did not. However, an adjusted logistic regression model disclosed that the minor allele G yielded a marginally significant increased risk of CV events in this series of patients with RA [p = 0.05, odds ratio (OR) 1.68, 95% confidence interval (CI) 1.00-2.85]. When the logistic regression model was adjusted for anti-cyclic citrullinated peptide (anti-CCP) antibody status instead of for shared epitope, an increased risk of having ischaemic heart disease was found in patients carrying the minor allele G (p = 0.04, OR 2.00, 95% CI 1.03-3.88). CONCLUSION: The MSRA rs10903323 gene polymorphism may be implicated in the increased risk to develop CV events, in particular ischaemic heart disease, observed in RA patients.
22916341 Tofacitinib for the treatment of moderate to severe rheumatoid arthritis. 2012 Aug The autoimmune disease rheumatoid arthritis (RA) causes severe disability through chronic and destructive inflammation of the synovial joints. Currently available therapeutic options, including disease-modifying antirheumatic drugs (DMARDs) and biologic agents, often fail to adequately prevent disease progression. Tofacitinib (CP-690550) is an inhibitor of the Janus kinase family; tyrosine kinase receptors expressed in lymphoid cells that are involved in the signaling of cytokines important for the production and function of various immune cells implicated in RA pathogenesis. Tofacitinib has been evaluated in phase II, phase III and long-term extension studies, as both monotherapy and in combination with methotrexate and other DMARDs, and demonstrates statistically significant and clinically meaningful improvements in the signs and symptoms of RA, patient health, physical functioning and quality of life, while having a manageable safety profile. It is currently under evaluation for approval for the treatment of adults with RA by several regulatory agencies around the world.
23101488 Second-hand exposure to tobacco smoke and its effect on disease activity in Swedish rheuma 2013 Jan OBJECTIVES: We studied the prevalence and effect on disease activity of ever having had second-hand exposure to tobacco smoke in Swedish rheumatoid arthritis (RA) patients who had never smoked. METHODS: Between 1992 and 2005, 2,800 patients were included in the BARFOT early-RA study in Sweden. Disease Activity Score 28 joints (DAS28), C-reactive protein (CRP), Health Assessment Questionnaire (HAQ), rheumatoid factor (RF), general health and pain visual analogue scales (VAS), and drug treatment were registered at inclusion and at follow-up at 3, 6, and 12 months and 2 and 5 years. EULAR response criteria were applied at the same follow-up points. In 2010, a self-completion postal questionnaire was sent to 2,102 patients in the BARFOT study enquiring about lifestyle habits such as whether they had ever been exposed to tobacco smoke as a result of someone else smoking. RESULTS: A total of 963/1,421 patients (68%) had had second-hand exposure to tobacco smoke. At 3, 6, and 12 months, at 2 years, and at 5 years of follow-up, there were no differences in EULAR response between patients who had never smoked and who had been exposed or had not been exposed second-hand to tobacco smoke (p=0.91, p=0.88, p=0.84, p=0.61 and p=0.85, respectively). CONCLUSIONS: We did not find any association between second-hand exposure to tobacco smoke and disease activity in RA.
23103818 [Progress in the treatment targeting intracellular signaling in the context of osteoimmuno 2012 Nov The appropriate intracellular signaling pathways are activated via binding of receptors on the cell surface to ligands such as cytokines and cell surface antigens. The tyrosine kinase transduce the first "outside to in" signals to be phosphorylated following receptor binding to its ligand. Among them, members of Janus kinase (Jak) family and Spleen tyrosine kinase (Syk) family are essential for the signaling pathways of various cytokines and are implicated in the pathogenesis of autoimmune inflammatory disease. The development of low molecular weight kinase inhibitors targeting Jak and Syk appears to be successful for the treatment of rheumatoid arthritis, a representative inflammatory disease. These inhibitors also succeed to regulate joint destruction. On the other hand, calcineurin inhibitors such as tacrolimus and vitamin D are also effective for immune regulation as well as bone metabolism through the inhibition of nuclear factors. Taken together, regulation of cellular signals functioning on immunity as well as bone metabolism may have a potential to approach to the treatment of osteo-immune diseases.
22238028 Gene expression patterns in peripheral blood cells associated with radiographic severity i 2013 Jan Gene expression profiling may be used to stratify patients by disease severity to test the hypothesis that variable disease outcome has a genetic component. In order to define unique expression signatures in African American rheumatoid arthritis (RA) patients with severe erosive disease, we undertook a gene expression study using samples of RNA from peripheral blood mononuclear cells (PBMCs). RNA from baseline PBMC samples of 96 African American RA patients with early RA (<2 years disease duration) was hybridized to cDNA probes of the Illumina Human HT-V3 expression array. Expression analyses were performed using the ca. 25,000 cDNA probes, and then expression levels were compared to the total number of erosions in radiographs of the hands and feet at baseline and 36 months. Using a false discovery rate cutoff of Q = 0.30, 1,138 genes at baseline and 680 genes at 36 months significantly correlated with total erosions. No evidence of a signal differentiating disease progression, or change in erosion scores between baseline and 36 months, was found. Further analyses demonstrated that the differential gene expression signature was localized to the patients with the most erosive disease (>10 erosions). Ingenuity Pathway Analysis demonstrated that genes with fold change greater than 1.5 implicated immune pathways such as CTLA signaling in cytotoxic T lymphocytes. These results demonstrate that CLEAR patients with early RA having the most severe erosive disease, as compared to more mild cases (<10 erosions), may be characterized by a set of differentially expressed genes that represent biological pathways with relevance to autoimmune disease.
21161318 β1,4-galactosyltransferase-I in synovial tissue of collagen-induced rat model of rheumato 2011 Sep β1,4-galactosyltransferase-I (β1,4-GalT-I), which is one of the best-studied glycosyltransferases, plays a key role in the synthesis of selectin ligands such as sialyl Lewis (sLe(x)) and sulfated sLe(x). Previous studies showed that inflammatory responses of β1,4-GalT-I-deficient mice were impaired because of the defect in selectin-ligand biosynthesis. However, the expression of β1,4-GalT-I and its biological function in rheumatoid arthritis (RA) remain to be elucidated. The mRNA and protein expression of β1,4-GalT-I increased in synovial tissue of the RA group compared with the Normal group at 10d and 15d after collagen-induced. Double staining indicated β1,4-GalT-I overlapped with macrophage-like synoviocytes (MLSs), fibroblast-like synoviocytes (FLSs), neutrophils and tumor necrosis factor-α (TNF-α). Moreover, β1,4-GalT-I mRNA in FLSs in vitro was affected in a dose- and time-dependent manner in response to TNF-α stimulation. ELISA revealed that expression of TNF-α was attenuated in FLSs in vitro treated with β1,4-GalT-I-Ab. We therefore suggest that β1,4-GalT-I may play an important role in the inflammation process of RA synovial tissue, which would provide the foundation for further researching into the concrete mechanism of β1,4-GalT-I in RA.
22823398 Role of interleukin-6 in stress, sleep, and fatigue. 2012 Jul Chronic low-grade inflammation, in particular increased concentrations of proinflammatory cytokines such as interleukin (IL)-6 in the circulation, is observed with increasing age, but it is also as a consequence of various medical and psychological conditions, as well as life-style choices. Since molecules such as IL-6 have pleiotropic effects, consequences are wide ranging. This short review summarizes the evidence showing how IL-6 elevations in the context of inflammatory disease affect the organism, with a focus on sleep-related symptoms and fatigue; and conversely, how alterations in sleep duration and quality stimulate increased concentrations of IL-6 in the circulation. Research showing that acute as well as chronic psychological stress also increase concentrations of IL-6 supports the notion of a close link between an organism's response to physiological and psychological perturbations. The findings summarized here further underscore the particular importance of IL-6 as a messenger molecule that connects peripheral regulatory processes with the CNS.
23073692 No increased mortality in patients with rheumatoid arthritis treated with biologics: resul 2013 Sep OBJECTIVE: To investigate the influence of biologics on mortality and risk factors for death in rheumatoid arthritis (RA) patients. METHODS: RA patients treated with at least one dose of biologics in daily practice in six large rheumatology institutes ("biologics cohort") were observed until 15 May 2010 or death, whichever occurred first. Mortality of the biologics cohort and the "comparator cohort" (comprising patients among the IORRA cohort who had never been treated with biologics) was compared to that of the Japanese general population. Factors associated with mortality were assessed by a Cox model. RESULTS: Among 2683 patients with 6913.0 patient-years of observation, 38 deaths were identified in the biologics cohort. The probability of death in patients lost to follow-up, calculated using the weighted standardized mortality ratio (SMR), was 1.08 [95 % confidence interval (CI) 0.77-1.47] in the biologics cohort and 1.28 (95 % CI 1.17-1.41) in the comparator cohort. Pulmonary involvement was the main cause of death (47.4 %), and the disease-specific SMR of pneumonia was 4.19 (95 % CI 1.81-8.25). Risk factors for death included male gender [hazard ratio (HR) 2.78 (95 % CI 1.24-6.22)], advanced age (HR 1.07, 95 % CI 1.03-1.11), and corticosteroid dose (HR 1.08, 95 % CI 1.01-1.17). CONCLUSION: Mortality in RA patients exposed to biologics did not exceed that in patients not exposed to biologics, but death from pulmonary manifestations was proportionally increased in RA patients exposed to biologics.
22193221 Objective assessment of abnormal gait in patients with rheumatoid arthritis using a smartp 2012 Dec A disturbance in gait pattern is a serious problem in patients with rheumatoid arthritis (RA). The aim of the present study was to examine the utility of the smartphone gait analysis application in patients with RA. The smartphone gait analysis application was used to assess 39 patients with RA (age 65.9 ± 10.0 years, disease duration 11.9 ± 9.4 years) and age-matched control individuals (mean age, 69.1 ± 5.8 years). For all RA patients, the following data were obtained: disease activity score (DAS) 28, modified health assessment questionnaire (mHAQ), and assessment of walking ability. Patients walked 20 m at their preferred speed, and trunk acceleration was measured using a Smartphone. After signal processing, we calculated the following gait parameters for each measurement terminal: peak frequency (PF), autocorrelation peak (AC), and coefficient of variance (CV) of the acceleration peak intervals. The gait parameters of RA and control groups were compared to examine the comparability of the 2 groups. Criterion-related validity was determined by evaluating the correlation between gait parameters and clinical parameters using Spearman's correlation coefficient. The RA group showed significantly lower scores for the walking speed, AC, and CV than the control group. There were no significant differences in PF. PF (gait cycle) was mildly associated with gait speed (P < 0.05). AC (gait balance) was moderately associated with the DAS, mHAQ, gait ability, and gait speed (P < 0.05). CV (gait variability) was moderately associated with the DAS, gait ability, and gait speed (P < 0.05). This is the first study to examine the use of a smartphone device for gait pattern measurement. The results suggest that some gait parameters recorded using the smartphone represent an acceptable assessment tool for gait in patients with RA.
23242182 Investigation of rheumatoid arthritis genetic susceptibility markers in the early rheumato 2013 Feb OBJECTIVE: The TRAF1 genetic region conferring susceptibility to rheumatoid arthritis (RA) has been reported to associate with radiological damage. We aimed to test RA genetic susceptibility markers for association with a continuous measure of radiological damage over time using longitudinal modeling techniques. METHODS: Sixty-seven RA susceptibility variants were genotyped in 474 patients in the Early Rheumatoid Arthritis Study (ERAS) using Sequenom MassArray technology. Correlation between genetic markers and Larsen score was assessed longitudinally using zero-inflated negative binomial regression to include repeat measurements in the same individual at different timepoints. Genetic markers associated with radiological damage in ERAS were tested using the same modeling techniques on previously published data from the Norfolk Arthritis Register (NOAR). RESULTS: The single marker associated longitudinally with Larsen score in ERAS (p = 0.02) and in NOAR (p = 0.04) was rs2900180 at the TRAF1 locus. Analysis of individual timepoints in ERAS showed that rs2900180 displays its effect primarily on the extent of Larsen score early in the disease course. Combined longitudinal analysis of the 2 cohorts suggests further association of several loci with Larsen score (KIF5A, PTPN22, AFF3, TAGAP) and therefore a significant accumulation of RA severity markers among RA susceptibility markers (p = 0.016). CONCLUSION: The marker rs2900180 is associated with the extent of radiological damage in the ERAS cohort. This represents the second independent study correlating rs2900180 at the TRAF1 locus with radiological severity in RA. Replication in a large dataset is required to establish the role of other RA susceptibility loci in disease severity.