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ID PMID Title PublicationDate abstract
17678828 The Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) to 2007 Aug Rheumatoid arthritis (RA) disease activity plays a central role in causing disability both directly and via indirect effects mediated through joint damage, a major sequel of persistent active disease. Evaluation of RA disease activity is therefore important to predict the outcome and effectiveness of therapeutic interventions during follow-up. However, disease activity assessment is among the greatest challenges in the care of patients with RA. We regard measurement of activity as an essential element of following the fate of joint diseases like RA. This evaluation can be facilitated by the use of reduced joint counts and simple indices, such as the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI). These scores are validated outcomes for RA and allow the assessment of: actual disease activity, response to therapy, and achievement of particular states such as remission. The simplicity of these scores enables patients to understand the level of their disease activity, as assessed by the rheumatologist, and to correlate increments and decrements of disease activity directly with all aspects of the disease.
16439441 Racial or ethnic differences in allele frequencies of single-nucleotide polymorphisms in t 2006 Sep BACKGROUND: The anti-folate drug methotrexate (MTX) is commonly used to treat rheumatoid arthritis. OBJECTIVE: To determine the allele frequencies of five common coding single-nucleotide polymorphisms (SNPs) in the methylenetetrahydrofolate reductase (MTHFR) gene in African-Americans and Caucasians with rheumatoid arthritis and controls to assess whether there are differences in allele frequencies among these ethnic or racial groups and whether these SNPs differentially affect the efficacy or toxicity of MTX. METHODS: Allele frequencies in the 677, 1298 and 3 additional SNPs in the MTHFR coding region in 223 (193 Caucasians and 30 African-Americans) patients with rheumatoid arthritis who previously participated in one of two prospective clinical trials were characterised, and genotypes were correlated with the efficacy and toxicity of MTX. Another 308 subjects with rheumatoid arthritis who participated in observational studies, one group predominantly Caucasian and the other African-American, as well as 103 normal controls (53 African-Americans and 50 Caucasians) were used to characterise allele frequencies of these SNPs and their associated haplotypes. RESULTS: Significantly different allele frequencies were seen in three of the five SNPs and haplotype frequencies between Caucasians and African-Americans. Allele frequencies were similar between patients with rheumatoid arthritis and controls of the same racial or ethnic group. Frequencies of the rs4846051C, 677T and 1298C alleles were 0.33, 0.11 and 0.13, respectively, among African-Americans with rheumatoid arthritis. Among Caucasians with rheumatoid arthritis, these allele frequencies were 0.08 (p<0.001 compared with African-Americans with rheumatoid arthritis), 0.30 (p = 0.002) and 0.34 (p<0.001), respectively. There was no association between SNP alleles or haplotypes and response to MTX as measured by the mean change in the 28-joint Disease Activity Score from baseline values. In Caucasians, the 1298 A (major) allele was associated with a significant increase in MTX-related adverse events characteristic of a recessive genetic effect (odds ratio 15.86, 95% confidence interval 1.51 to 167.01; p = 0.021), confirming previous reports. There was an association between scores of MTX toxicity and the rs4846051 C allele, and haplotypes containing this allele, in African-Americans, but not in Caucasians. CONCLUSIONS: : These results, although preliminary, highlight racial or ethnic differences in frequencies of common MTHFR SNPs. The MTHFR 1298 A and the rs4846051 C alleles were associated with MTX-related adverse events in Caucasians and African-Americans, respectively, but these findings should be replicated in larger studies. The rs4846051 SNP, which is far more common in African-Americans than in Caucasians, can also be proved to be a useful ancestry informative marker in future studies on genetic admixture.
16997147 New therapeutics that treat rheumatoid arthritis by blocking T-cell activation. 2006 Oct Despite the recent introduction of several new biological products, there remains a significant unmet medical need in rheumatoid arthritis. A focus on the aberrant activation of autoimmune T cells, which is integral to pathogenesis, is a promising approach involved in several of these new therapies. In choosing a molecular target for the modification of T-cell function, it is argued in this article, that within co-stimulatory pathways, CD80 could have a more compelling rationale than CD86. Data are presented showing that CD80-mediated T-cell activation can be inhibited using a small-molecule antagonist, which offers the potential to prevent the inflammatory process leading to joint destruction.
16881357 [Activity of genetically programmed cell death of lymphocytes in rheumatoid arthritis]. 2006 AIM: To study activity of genetically programmed cell death (PCD) of lymphocytes in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Lymphocytes from 30 RA patients including 14 patients with RA history up to 2 years, and 12 healthy donors were studied for activity of caspase 4, 6, 8 usingfluorescence and caspase substrates 30, 60, 120, 150 and 180 min after start of the reaction and number of 1-2-thread serration of DNA with fluorescence of two DNA-tropic stains--EtBr and 4,6-DAPY Correlation was also studied between lymphocyte activity and RA activity, x-ray stage, duration, level of TNF-alpha. The trend in PCD activity of lymphocytes in immunosuppressive therapy was analysed. RESULTS: The activity of lymphocytic caspases in RA patients was low compared to healthy donors. A negative correlation was found between RA activity and activity of caspase 8 and 6. In RA therapy with methotrexate, sulphasalasine, glucocorticosteroids the activity of caspases and number of 1-thread serrations of DNA were subnormal. CONCLUSION: RA is associated with lymphocyte PCD disorders which may be involved in RA pathogenesis, in formation of clones of potentially autoaggressive lymphocytes, in particular. This process is not normalized by current methods of RA treatment causing unsatisfactory outcomes of RA therapy.
17404480 [Early prediction of joint destruction in rheumatoid arthritis]. 2007 Apr It is proposed by hypothesis that early intervention in rheumatoid arthritis might result in remission or cure. It was undertaken to classify rheumatoid arthritis (RA) in early stage from undifferentiated arthritis (UA) and predict the progression of joint destruction at the first visit using by serological markers and magnetic resonance imaging (MRI) . Logistic regression analysis using the statistical analysis system software demonstrated that the presence of anti-cyclic citrullinated peptide (CCP) antibody and/or immunoglobulin M-rheumatoid factor (IgM-RF) , symmetric synovitis and bone marrow edema and/or bone erosion at entry could discriminate patients with RA from UA or other than RA. A total score of two or more of the three objective measures allowed the prediction for RA with 83% sensitivity and 85% specificity, respectively. The presence of bone marrow edema and/or bone erosion determined by MRI is a forerunner of bone erosion on plain radiography. Both presences of anti-CCP antibody and/or IgM-RF and bone marrow edema determined by MRI may predict the early-stage of RA and the progression of articular destruction. From the above findings, it was recommended that early intervention of anti-rheumatic drugs and/or TNF blocker should be started the UA patients with both autoantibody (anti-CCP antibody and/or IgM-RF) and bone marrow edema determined by MRI.
17722713 Leukocytapheresis (LCAP) for the treatment of rheumatoid arthritis on a maintenance hemodi 2007 Aug A 57-year-old-woman, who was treated with regular maintenance hemodialysis (HD), newly contracted rheumatoid arthritis (RA). Oral predonisolone was effective for alleviating her arthralgia but the RA activity became steroid-dependent. For treatment of poorly controlled synovitis leukocytapheresis (LCAP) showed excellent efficacy in the treatment of her joint pain. No serious adverse effects were observed. Serological markers such as CRP, serum amyloid A, matrix metalloproteinase 3 and peripheral blood lymphocyte count fluctuated with her clinical symptoms. We recommend LCAP as candidate therapy for steroid-dependent patients with RA who are on maintenance HD.
17075187 [Anti-interleukin-6 receptor antibody therapy--from bedside to bench]. 2006 Oct Recent progress in immunology, utilizing molecular biology techniques, has elucidated the molecular mechanism of immune system. In the treatment of autoimmune diseases, molecular targeting therapies utilizing biologics such as monoclonal antibodies are now available. However, exact causes of the most autoimmune diseases are not known and there remain many issues which should be resolved. Interleukin-6 (IL-6) is a cytokine which regulates immune response and inflammation. Deregulated overproduction of IL-6 is involved in the immune-inflammatory diseases such as Castleman's disease and rheumatoid arthritis. A humanized anti-IL-6 receptor antibody tocilizumab has been proven to be therapeutically effective for the diseases. Simultaneously, we have learned new biological activities from the translational research. In this review, a study from bedside to bench is to be discussed.
16510817 Arthroscopic and open synovectomy of the elbow in rheumatoid arthritis. 2006 Mar BACKGROUND: Synovectomy has been advocated for early treatment of the rheumatoid elbow. It has not been determined whether arthroscopic or open synovectomy is better and whether a preoperative arc of flexion of >90 degrees is an important prognostic factor. METHODS: Arthroscopic or open synovectomy was performed in fifty-eight elbows in fifty-three patients with rheumatoid arthritis and radiographic changes in the joint of Larsen grade 2 or less. Clinical symptoms, recurrent synovitis, postoperative complications, and radiographic changes were assessed ten to eighteen years (average, thirteen years) postoperatively. RESULTS: Eleven (48%) of twenty-three elbows in which arthroscopic synovectomy had been performed and sixteen (70%) of twenty-three elbows in which open synovectomy had been performed were mildly or not painful at the latest follow-up evaluation. However, no significant difference was detected between the overall clinical results of arthroscopic synovectomy and those of open synovectomy. In elbows with a preoperative arc of flexion of <90 degrees , the clinical results of the two procedures were comparable. In elbows with a preoperative arc of flexion of <90 degrees , arthroscopic synovectomy provided significantly (p < 0.05) better function than open surgery after mid-term follow-up, and motion and function continued to be better in those patients at the most recent follow-up evaluation. Recurrent synovitis was observed in six elbows that had arthroscopic synovectomy and in three that had open synovectomy, and the Larsen grade increased in both groups. Three elbows with a preoperative arc of flexion of <90 degrees underwent a total elbow arthroplasty to treat ankylosis after open synovectomy. Surgical complications were uncommon and not severe. CONCLUSIONS: Arthroscopic synovectomy of the elbow is a reliable procedure. One of the most favorable indications for either arthroscopic or open synovectomy is a preoperative arc of elbow flexion of >/=90 degrees in patients with early rheumatoid arthritis.
18801688 HLA polymorphism and early rheumatoid arthritis in the Moroccan population. 2008 Oct OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune multifactorial disease which has a great socio-economic impact in Morocco. The association of HLA genes with RA was studied in various ethnic groups but not in the Moroccan population. Our study focused on evaluating the distribution of class I and class II HLA genes among Moroccan patients presenting early signs of RA. METHODS: Forty nine patients diagnosed with early RA were compared to a group of healthy controls matched by age, sex, and ethnic origin. Among the patient group, 34 were seropositive (presence of the rheumatoid factor). HLA typing of the patients and the controls was performed using microlymphocytotoxicity for class I (A and B) and PCR-SSP for class II (DR and DQ). RESULTS: We found a significant increase of the frequency of the HLA-A24 antigen (p=0.03), the DRB1*04 (p=0.004) and DQB1*03 (p=0.03) alleles and a significant decrease of the DRB1*07 allele (p=0.03) in seropositive patients. The analysis of the frequency of the DRB1*01, DRB1*10, and DRB1*14 alleles did not show any difference between the RA patients and the controls. The frequency of DR4-DQ2 and DR4-DQ4 haplotypes was increased in the patients compared to the controls while that of DR7-DQ2 and DR13-DQ6 was decreased. CONCLUSIONS: Our study suggests that DRB1*04 predisposes to RA while DRB1*07 seems protective for the Moroccan patients population. In addition we show the influence of some haplotypes DR-DQ in the susceptibility and protection against the disease.
17444591 Beneficial action of statins in patients with rheumatoid arthritis in a large observationa 2007 May OBJECTIVE: To analyze the possible beneficial effects of statins on the disease activity of patients with rheumatoid arthritis (RA) using a database from a large observational cohort study. METHODS: We studied a total of 7512 patients enrolled in a single-institute based prospective observational cohort of RA patients (IORRA); their information was collected biannually. In this study, cross-sectional data of 4152 patients (female 83.3%, average age 58.4 yrs) in October 2003 were analyzed (Mann-Whitney U-test). RESULTS: Among 4152 patients with RA, 279 (6.7%) were taking statins; patients taking statins had lower C-reactive protein (0.85 vs 1.24 mg/dl, respectively) and lower swollen joint counts (1.80 vs 2.55), but more frequently used corticosteroids (2.88 vs 2.40 mg/day) compared to patients not taking statins. Serum cholesterol level was closely related to the use of corticosteroids. Thus, an adjustment with the dose of corticosteroid was conducted; even taking account of the effects of steroids, RA disease activity indicated by patient's assessment for pain, physician's assessment, and swollen joint counts was significantly lower in patients with statins compared to those without. CONCLUSION: This study indicates that statins have beneficial effects in reducing RA disease activity in the daily practice of rheumatology.
17237906 Impact of TNF inhibition on insulin resistance and lipids levels in patients with rheumato 2007 Sep Patients with rheumatoid arthritis (RA) have increased cardiovascular mortality. TNF-alpha is a critical mediator of inflammation and metabolic response in patients with RA. Increased insulin resistance and dyslipidemia were known risk factors in patients with active RA, however, the regulation of these metabolic parameters by TNF-alpha is poorly understood. Neutralization of TNF-alpha with infliximab offers a unique opportunity to study TNF-alpha-mediated regulation of these metabolic parameters in RA. The aim of the study was to assess the in vivo TNF-alpha-mediated regulation of insulin resistance and lipids levels in RA. Nineteen patients with active RA treated with infliximab were prospectively followed for 14 weeks. Plasma lipids levels and insulin resistance were measured at baseline, 6 and 14 weeks after infliximab treatment. At week 14, the disease activity (DAS-28 score) improved significantly (p < 0.000), with a significant reduction in both C-reactive protein (p = 0.007) and erythrocyte sedimentation rate (p = 0.006) levels. The body weight did not change during the study period. After infliximab treatment, insulin resistance improved as reflected by the significant reduction in the Homeostasis Model Assessment Index. Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and apolipoprotein B (apoB) levels all increased significantly from baseline. Nonetheless, the atherogenic index, LDL-cholesterol/HDL-cholesterol ratio, and the LDL/apoB ratio remained unchanged. Infliximab improves insulin sensitivity and alters lipid profile in patients with active RA.
17611973 Immunopathologic aspects of rheumatoid arthritis: who is the conductor and who plays the i 2007 Jul The inflammatory process of rheumatoid arthritis (RA) resembles a symphony orchestra playing a piece of music--not a song that anyone wants to hear, but a song nevertheless. Each cellular player has a distinct role, and all must coordinate in order to play their discordant "music" successfully. Rheumatoid synovitis consists of resident cells and invading immune cells that together arrange the inflammatory process in RA. There are 3 major types of synovitis that RA can comprise: germinal center synovitis, aggregate synovitis, and diffuse synovitis. Germinal centers are highly organized complex structures that are functionally competent. Aggregates are B cells and T cells arranged in defined follicles, yet they lack germinal center reactions. Diffuse synovitis is the least organized but can still cause significant damage. For each of these types of synovitis, the cellular players and their molecular instruments vary significantly. Differences in lymphoid microorganizations draw attention to the process of lymphoid organogenesis as a fundamental pathway of rheumatoid synovitis, a process that lends stability and sustainability to dysfunctional immune responses. This article will address how tissue-resident and invading cells, in particular T cells, B cells, dendritic cells, and synoviocytes, are brought together in different "symphonic" arrangements and how this process of lymphoid organization affects disease outcome and therapeutic options in RA.
18055474 Utility of animal models for identification of potential therapeutics for rheumatoid arthr 2008 Nov Animal models of rheumatoid arthritis (RA) are widely used for testing potential new therapies for RA. However, the question of which animal model is most predictive of therapeutic efficacy in human RA commonly arises in data evaluation. A retrospective review of the animal models used to evaluate approved, pending RA therapies, and compounds that were discontinued during phase II or III clinical trials found that the three most commonly used models were adjuvant-induced arthritis (AIA) in rats and collagen-induced arthritis (CIA) in rats and mice. Limited data were found for more recently developed genetically modified animal models. Examination of the efficacy of various compounds in these animal models revealed that a compound's therapeutic efficacy, rather than prophylactic efficacy, in AIA and CIA models was more predictive of clinical efficacy in human RA than data from either model alone.
18791055 Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR 2008 Oct OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardised operating procedures, which use a three-step approach: (1) expert-based definition of relevant research questions (November 2006); (2) systematic literature search (November 2006 to May 2007); and (3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature the expert panel recommended that each trial should report the following items: (1) disease activity response and disease activity states; (2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; (3) baseline disease activity levels (in general); (4) the percentage of patients achieving a low disease activity state and remission; (5) time to onset of the primary outcome; (6) sustainability of the primary outcome; (7) fatigue. CONCLUSIONS: These recommendations endorsed by EULAR and ACR will help harmonise the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.
17237117 Cigarette smoking and radiographic progression in rheumatoid arthritis. 2007 Aug BACKGROUND: Smoking is a well-established environmental risk factor for the development of rheumatoid arthritis (RA). However, it remains unclear whether smoking influences RA disease progression and whether smokers have more radiographic damage progression than non-smokers over time. OBJECTIVE: To compare the rates of radiographic damage progression in current smokers and non-smokers in a large prospective RA cohort. METHODS: The SCQM-RA is a population-based registry monitoring disease activity, radiographic damage and symptoms at regular intervals. All patients in the SCQM-RA database with sequential plain radiographs were included. Joint erosions were assessed in 38 hand and foot joints with a validated scoring method. The rate of erosion progression was analysed using multivariate longitudinal regression models and adjusted for potential confounders. RESULTS: 2004 RA patients with a mean of 3.6 sequential radiographs and 3.1 years of follow-up were included. The 545 (27%) current smokers smoked on average 16 cigarettes per day and had a mean past smoking exposure of 20.6 pack-years. Radiographic joint damage progressed at a similar rate in current smokers and non-smokers (p = 0.26). However, smoking intensity was associated with a significant inverse dose-response; heavy smokers (>1 pack-day) progressed significantly less than non-smokers or moderate smokers (p<0.001). CONCLUSION: Radiographic joint damage progressed at an equivalent rate in smokers and non-smokers. Furthermore, a significant trend was observed for reduced radiographic progression and generally more favourable functional scores among heavy smokers, suggesting that cigarette smoke does not accelerate RA disease progression.
18693126 Association of transforming growth factor beta1 gene polymorphism with rheumatoid arthriti 2009 Jan OBJECTIVE: Cytokine genes play important roles in the pathogenesis of rheumatoid arthritis (RA). In RA, the plasma and synovial fluid levels of transforming growth factor beta1 (TGFbeta1) have been shown to be raised. The aim of this study was to investigate the relationship between the TGFbeta1 T869C polymorphism and RA in a Turkish population. METHODS: One hundred and thirty-one patients with a clinical diagnosis of RA and 133 healthy controls were enrolled in this study. Analyses of TGFbeta1 T869C gene were made by the polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: There was no significant difference in genotypic frequency of TGFbeta1 T869C polymorphism between the patients with RA (TT:TC:CC=42.7%:41.2%:16%) and controls (TT:TC:CC=36.1%:48.1%:15.8%) (p=0.48). The age at first occurrence of clinical symptoms of RA did not differ significantly in relation to TGFbeta1 T869C genotypes (p=0.07). Furthermore, there was no significant association between TGFbeta1 T869C genotypes and the presence or absence of radiographic erosions in the patient group (p=0.67). But presence of T allele was associated with 1.92-fold increased risk for RF positivity (p=0.02, OR=1.92, 95% CI=1.08-3.40). CONCLUSION: The allele frequencies for TGFbeta1 T869C polymorphism in RA patients were similar to those in the control group. However, the T allele carriers had 1.92-fold increased risk for RF positivity. Further studies on larger numbers of cases and on the other polymorphic regions of this gene are needed before definite conclusions can be drawn about the role of TGFbeta1 in the etiology of RA.
17704521 Prevalence and associations of hypertension and its control in patients with rheumatoid ar 2007 Sep OBJECTIVES: Rheumatoid arthritis (RA) associates with excessive cardiovascular morbidity and mortality. Hypertension (HT) contributes significantly to the development of cardiovascular disease (CVD). Little is known about the factors that influence blood pressure (BP) in patients with RA. In this study, we assessed the prevalence of HT in a secondary care cohort of RA patients, and aimed to identify factors associated with its presence and inadequate control. METHODS: A total of 400 consecutive RA patients were studied. HT was defined as systolic BP >/=140 mmHg and/or diastolic BP >/=90 mmHg or current use of antihypertensive drugs. The association of HT with several demographic and RA-related factors, comorbidities and drugs was evaluated using logistic regression. RESULTS: HT was present in 282 (70.5%) patients. Of those, 171 (60.6%) received anti-hypertensive therapy, but 111 (39.4%) remained undiagnosed. Of those treated, only 37/171 (21.8%) were optimally controlled. Multivariable logistic regression revealed age (OR = 1.054, CI: 1.02 to 1.07, P = 0.001), body mass index [BMI (OR = 1.06, CI: 1.003-1.121, P = 0.038)] and prednisolone use (OR = 2.39, CI: 1.02-5.6, P = 0.045) to be independently associated with the presence of HT. BMI (OR = 1.11, CI: 1.02-1.21, P = 0.002) and the presence of CVD (OR = 4.01, CI: 1.27-12.69, P = 0.018) associated with uncontrolled HT. CONCLUSIONS: HT is highly prevalent in RA, under-diagnosed particularly in the young, and under-treated particularly in old RA patients with CVD. RA patients receiving steroids should be specifically targeted for screening and treatment; those with any cardiovascular comorbidity may require particularly aggressive monitoring and treatment strategies.
17294867 [Prognostic value of some serological markers of rheumatoid arthritis in assessment of x-r 2006 AIM: To specify significance of some serological markers for diagnosis and x-ray prognosis of rheumatoid arthritis (RA). MATERIAL AND METHODS: A total of 115 RA patients with the disease history not longer than 4 years were examined for serum antibodies to cyclic citrullated peptide (ACCP), rheumatoid factor (RF), antikeratine antibodies (AKA) using enzyme immunoassay and indirect immunofluorescence. RESULTS: ACCP, AKA, IgA-RF, IgM-RF were detected in 79.15%, 47.8%, 64.3%, 89.6% patients, respectively. ACCP was found to be directly correlated with negative x-ray changes in hand and foot joints. ACCP specificity reached 97%, the highest specificity (up to 100%) being in determination of RF and ACCP. CONCLUSION: ACCP is an independent factor increasing significance of x-ray indices and thus allowing prognosis of x-ray outcome of RA.
18001488 Cells of the synovium in rheumatoid arthritis. Chondrocytes. 2007 Rheumatoid arthritis (RA) is one of the inflammatory joint diseases in a heterogeneous group of disorders that share features of destruction of the extracellular matrices of articular cartilage and bone. The underlying disturbance in immune regulation that is responsible for the localized joint pathology results in the release of inflammatory mediators in the synovial fluid and synovium that directly and indirectly influence cartilage homeostasis. Analysis of the breakdown products of the matrix components of joint cartilage in body fluids and quantitative imaging techniques have been used to assess the effects of the inflammatory joint disease on the local remodeling of joint structures. The role of the chondrocyte itself in cartilage destruction in the human rheumatoid joint has been difficult to address but has been inferred from studies in vitro and in animal models. This review covers current knowledge about the specific cellular and biochemical mechanisms that account for the disruption of the integrity of the cartilage matrix in RA.
18821687 An explanation for the apparent dissociation between clinical remission and continued stru 2008 Oct OBJECTIVE: Achieving remission is the aim of treatment in rheumatoid arthritis (RA). This should represent minimal arthritis activity and ensure optimal disease outcome. However, we have previously demonstrated a high prevalence of imaging-detected synovial inflammation in RA patients who were in clinical remission. The purpose of this study was to evaluate the long-term significance of subclinical synovitis and its relationship to structural outcome. METHODS: We studied 102 RA patients receiving conventional treatment who had been judged by their consultant rheumatologist to be in remission, as well as 17 normal control subjects. Subjects underwent clinical, laboratory, functional, and quality of life assessments over 12 months. In addition to standard radiography of the hands and feet, imaging of the hands and wrists was performed with musculoskeletal ultrasonography (US) and conventional 1.5 T magnetic resonance imaging (MRI) at baseline and 12 months, using validated acquisition and scoring techniques. RESULTS: Despite their being in clinical remission, 19% of the patients displayed deterioration in radiographic joint damage over the study period. Scores on musculoskeletal US synovial hypertrophy, power Doppler (PD), and MRI synovitis assessments in individual joints at baseline were significantly associated with progressive radiographic damage (P=0.032, P<0.001, and P=0.002, respectively). Furthermore, there was a significant association between the musculoskeletal US PD score at baseline and structural progression over 12 months in totally asymptomatic metacarpophalangeal joints (P=0.004) and 12 times higher odds of deterioration in joints with increased PD signal (odds ratio 12.21, P<0.001). CONCLUSION: Subclinical joint inflammation detected by imaging techniques explains the structural deterioration in RA patients in clinical remission who are receiving conventional therapy. Our findings reinforce the utility of imaging for the accurate evaluation of disease status and the prediction of structural outcome.