Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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17095373 | Volar dislocation of the extensor carpi ulnaris tendon on magnetic resonance imaging is as | 2006 Nov | PURPOSE: Extensor tendon rupture in rheumatoid wrists is a common problem and causes immediate dysfunction of the digits. The best treatment for tendon rupture may be prophylactic management, although the factors associated with tendon rupture must first be identified. The purpose of this study was to evaluate structures around rheumatoid wrists using magnetic resonance imaging with forearm rotation and to identify factors associated with extensor tendon rupture as indications for prophylactic surgery. METHODS: The subjects were 34 patients (40 wrists) with active rheumatoid arthritis. The extensor digitorum communis (EDC) tendons were ruptured in 15 wrists. Magnetic resonance imaging of the wrists was performed in maximally pronated and supinated positions of the forearm. Axial images of the distal radioulnar joints (DRUJs) were selected to evaluate DRUJ synovitis, dorsal tenosynovitis, volar dislocation of the extensor carpi ulnaris (ECU) tendon, sigmoid notch angle, and the radioulnar ratio (RUR) (ie, the degree of DRUJ subluxation). RESULTS: No significant correlations were found between EDC tendon rupture and DRUJ synovitis, dorsal tenosynovitis, or RUR in pronation. Extensor digitorum communis tendon rupture correlated significantly with volar ECU tendon dislocation, sigmoid notch angle, and RUR in supination. Radioulnar ratio correlated significantly with volar ECU tendon dislocation only in supination and not in pronation. Thus, DRUJ subluxation was advanced even in the supinated wrist with volar ECU tendon dislocation. As a factor associated with EDC tendon rupture, volar ECU tendon dislocation had 87% sensitivity and 76% specificity. CONCLUSIONS: Volar ECU tendon dislocation is associated with increased RUR in supination and EDC tendon rupture. Volar ECU tendon dislocation can thus be considered a factor associated with EDC tendon rupture, and its presence may indicate the need for prophylactic surgical intervention in a subset of rheumatoid arthritis patients. | |
16767553 | Disability and patient's appraisal of general health contribute to depressed mood in rheum | 2006 | The aim of this study was to evaluate the factors responsible for depressed mood in rheumatoid arthritis (RA). Clinical and laboratory measures were collected from 4558 RA patients enrolled in a large clinical cohort study for RA conducted at the Institute of Rheumatology, Tokyo Women's Medical University (IORRA study). A two-question depressed screening included in the U.S. Preventive Services Task Force recommendation were utilized to identify "depressed patients." A total of 1875 (41.1%) were identified as "depressed patients" who presented with symptoms suggestive of depression. Patient's Visual Analog Scale (VAS) for general health (43.3 mm vs 24.6 mm, P < 0.0001) and pain (40.9 mm vs 23.8 mm, P < 0.0001) and the disability index scores measured by the Health Association Questionnaire (HAQ) (0.986 vs 0.574, P < 0.0001) were significantly higher in depressed patients than in nondepressed patients. The presence of three or more comorbidities (odds ratio [OR] 2.157, P < 0.0001), infection (OR 1.754, P < 0.0001), and joint surgery (OR 1.878, P < 0.0001) were significantly correlated with depressed mood in RA. The results of the Generalized Linear Model analysis showed that HAQ disability index (P < 0.0001) and patient's VAS for general health (P < 0.0001) were also strongly and significantly associated to the response variable "probability of depressed patients." Patient appraisal of poor general health and greater disability were associated with depressed mood in RA. | |
17121487 | Advantages and limitations of quantitative measures to assess rheumatoid arthritis: joint | 2006 | Medical care is advanced by quantitative measures, all of which have advantages and limitations. No single "gold standard" measure, analogous to blood pressure, is available for diagnosis, prognosis, and management of rheumatoid arthritis (RA). Four types of measures have been used, including joint counts, radiographs, laboratory tests, and patient questionnaires. Joint counts are the most specific measure for RA but are poorly reproducible and not performed in most standard care. Radiographs provide an objective record of joint damage, but are scored quantitatively only in clinical research and have little prognostic value for long-term outcomes such as work disability and mortality. Laboratory tests are helpful when positive but frequently are "false negative"--for example, rheumatoid factor (RF), erythrocyte sedimentation rate, or C-reactive protein are normal in 30% to 45% of patients. "False positive" results are also seen; most people with RF or antinuclear antibody do not have a disease. Patient questionnaires are useful to assess and monitor patient status and provide the most significant predictive measures for long-term work disability and mortality. A multidimensional health assessment questionnaire is useful in all rheumatic diseases, with scoring templates and medical history information to save time for the rheumatologist and patient in standard care. | |
17075090 | Total elbow replacement with the Souter-Strathclyde prosthesis in rheumatoid arthritis. Lo | 2006 Nov | We assessed the long-term results of 58 Souter-Strathclyde total elbow replacements in 49 patients with rheumatoid arthritis. The mean length of follow-up was 9.5 years (0.7 to 16.7). The mean pre-operative Mayo Elbow Performance Score was 30 (15 to 80) and at final follow-up was 82 (60 to 95). A total of 13 elbows (22.4%) were revised, ten (17.2%) for aseptic loosening, one (1.7%) for instability, one (1.7%) for secondary loosening after fracture, and one elbow (1.7%) was removed because of deep infection. The Kaplan-Meier survival rate was 70% and 53% at ten and 16 years, respectively. Failure of the ulnar component was found to be the main problem in relation to the loosening. Anterior transposition of the ulnar nerve had no influence on ulnar nerve paresthaesiae in these patients. | |
16134727 | Peptidylarginine deiminase 4 (PADI4) identified as a conformation-dependent autoantigen in | 2005 May | OBJECTIVE: Peptidylarginine deiminase (PADI) catalyses the post-translational modification of arginine to citrulline, which is specifically recognized by sera from rheumatoid arthritis (RA) patients. The PADI4 gene has recently been identified as a risk factor for RA. We aimed to determine whether PADI4 constitutes an autoantigen in RA. METHODS: Serum samples were obtained from 42 patients with RA, 19 patients with systemic lupus erythematosus (SLE), 23 patients with other rheumatic diseases, and 40 normal individuals. The presence of antibodies against recombinant human PADI4 (anti-PADI4) was examined using enzyme-linked immunosorbent assay (ELISA) and Western blotting. RESULTS: For ELISA, the prevalence of anti-PADI4 among RA patients (50%) was significantly higher than that of normal individuals (2.5%), SLE (10.5%), and other rheumatic diseases (4.3%), while for Western blot analysis, PADI4 was recognized only by a portion of the ELISA-positive serum samples. CONCLUSIONS: PADI4 is an autoantigen in some RA patients, and its conformational epitope(s) may be important. | |
16956426 | Influence of anti-TNF-alpha infliximab therapy on adhesion molecules associated with ather | 2006 Jul | OBJECTIVE: Chronic systemic inflammation plays a pivotal role in the development of atherosclerosis in rheumatoid arthritis (RA). Soluble (s) adhesion molecules were found significantly increased in RA patients with active disease. Since increased levels of some adhesion molecules were closely linked to the development of endothelial dysfunction and atherosclerosis and administration of anti-TNF-alpha-infliximab resulted in a rapid and dramatic improvement of endothelial function in long-term infliximab treated RA patients, we assessed whether infusion of the chimeric anti-TNF-alpha infliximab might also yield a rapid and favorable effect on serum levels of soluble adhesion molecules in RA patients periodically treated with this drug because of severe disease. METHODS: We recruited patients with RA refractory to conventional therapy seen over a period of 2 months at Hospital Xeral-Calde, Lugo, Spain, who were on periodical treatment with infliximab for at least 14 weeks. Blood samples for determination of sICAM-1, sICAM-3, sVCAM-1, sE-selectin, and sP-selectin levels by ELISA were taken immediately before and after infliximab infusion. RESULTS: Thirty-four RA patients (25 women; mean age: 55.4 years; mean DAS28: 4.27) fulfilled the inclusion criteria. Following infliximab infusion a reduction of the overall mean values of the five adhesion molecules was observed. However, when a Wilcoxon signed-rank test was used, only significant differences for sICAM-3 and sP-selectin were observed. In this regard, sICAM-3 and sP-selectin levels fell in 26 (77%) and 28 (82%) of the 34 patients. CONCLUSION: Our study confirms a rapid and beneficial effect of infliximab infusion on expression of some adhesion molecules in RA patients treated periodically with this anti-TNF-alpha monoclonal antibody because of severe disease. | |
16395745 | Human endogenous retrovirus HERV-K(HML-2) Rec expression and transcriptional activities in | 2006 Jan | OBJECTIVE: Despite abundance in the genome, the possible functions of human endogenous retrovirus (HERV) sequences are not well understood. The involvement of HERV in various disease conditions, such as germ cell tumors or autoimmune diseases like rheumatoid arthritis (RA), has been suggested. We investigated expression of HERV-K(HML-2) env-derived transcripts in normal and RA synovia. METHODS: We analyzed HERV-K(HML-2) expression on the mRNA and protein level by RT-PCR analysis and immunofluorescence labeling of the HERV-K(HML-2) Rec (formerly cORF) protein. We examined synovial cell cultures from normal synovia (n = 9), from patients with RA (n = 26), and osteoarthritis (OA, n = 4), and uncultured synovial tissues (RA, n = 12; normal synovia, n = 1). RESULTS: HERV-K Rec protein was expressed in all normal synovial specimens, and in the majority of RA and OA cases. We demonstrate for the first time expression of HERV-K protein in synovial tissue. RT-PCR and sequence analysis of cloned RT-PCR products confirmed expression of spliced HERV-K(HML-2) env transcripts in normal and in arthritic synovia. In addition to rec mRNA, several alternatively spliced transcripts, including np9, were identified. However, different amounts of the various RT-PCR products indicate different expression levels of HERV-K(HML-2) env-derived transcripts in RA compared to normal synovia, with apparently lower expression levels in arthritic synovia. CONCLUSION: These findings imply a physiological role of HERV-K(HML-2) Rec in synovial tissue. Differences in the expression of HERV-K env-derived transcripts in RA synovia may be caused by disease-specific changes in the general expression pattern. | |
17162380 | Influenza vaccination of patients with systemic lupus erythematosus (SLE) and rheumatoid a | 2006 Jun | The role of influenza vaccination in patients suffering from autoimmune diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), has long been a subject of discussion. The risk of exacerbation of the main disease following vaccination is of particular concern, and needs to be carefully evaluated against the risk of disease flares as a result of infections. Our study included 69 SLE patients and 54 RA patients, all in stable condition. We split the groups into two subgroups each: patients in SLE1 (23 patients) and RA1 (23 patients) received the flu vaccine ("Vaxigrip", Aventis Pasteur) in November 2003. Patients in SLE2 (46 patients) and RA2 (31 patients) were not vaccinated. Throughout the following year, we studied parameters of disease activity and the occurrence of viral respiratory and bacterial infections in our patients. The vaccine was well tolerated in all cases. Vaccinated patients had significantly fewer occurrences of infections. Every viral and bacterial infection resulted in the worsening of the main disease. We believe that influenza vaccine is indicated for SLE and RA patients in stable condition. However, this decision must be made on a patient-by-patient basis. We plan to continue our study with the goal of formulating a better protocol for the clinical practice. | |
15895891 | Altered thiol pattern in plasma of subjects affected by rheumatoid arthritis. | 2005 Mar | OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease which involves the synovial membrane of multiple diarthroidal joints causing damage to cartilage and bones. The damage process seems to be related to an overproduction of oxygen reactive species inducing an oxidative perturbation. Since sulfhydryl groups are primary antioxidant factors, we were interested in investigating the balance of plasma sulfhydryl/disulfides in patients with active RA compared to healthy control subjects. METHODS: Twenty-one patients with RA and 15 age-matched controls were studied. Plasmatic sulfhydryl groups and their disulfide form concentrations were measured by spectrophotometry or HPLC. RESULTS: RA patients showed significantly lower levels of plasma protein sulfhydryls and cysteinyl-glycine compared to healthy controls (p < 0.001). Conversely, cystine and homocystine, and protein-bound cysteine and homocysteine were significantly increased (p < 0.005 in disulfides forms and p < 0.05 in protein mixed disulfides forms). There was a significant correlation between some clinical data (ESR, number of tender/swollen joints) and some of the parameters studied. CONCLUSION: The results of this study indicate a biochemical disturbance of plasma sulfhydryl/disulfides balance in patients with RA compared to controls with an increase in some oxidised forms (disulfides and protein mixed disulfides) and a decrease in free thiols. The increase in total homocysteine, correlated to the higher risk of cardiovascular diseases in RA patients, is associated with higher levels of the oxidised forms, disulfides and protein-thiol mixed disulfides. | |
16947780 | Association of HLA-C3 and smoking with vasculitis in patients with rheumatoid arthritis. | 2006 Sep | OBJECTIVE: To compare HLA-C genotypes and smoking habits in patients with vasculitis or other severe extraarticular manifestations of rheumatoid arthritis (ExRA) with those in RA patients without extraarticular disease. METHODS: Patients were recruited from a large research database of patients with RA at the Mayo Clinic, from 2 Swedish cohorts of prevalent RA cases, and from a regional Swedish early RA cohort. Patients with severe ExRA (n = 159) and control patients with RA but no history of ExRA (non-ExRA controls) (n = 178) were matched for duration of RA and for clinical center. Data on smoking at RA onset, rheumatoid factor (RF) status, and antinuclear antibodies (ANAs) were extracted from the medical records. Polymerase chain reaction-based HLA-C genotyping was performed using a sequence-specific primer kit. RESULTS: The distribution of HLA-C alleles was significantly different between patients with RA-associated vasculitis and non-ExRA controls (P = 0.014). This was mainly due to a positive association of the HLA-C3 allele with vasculitis (allele frequency 0.411 in vasculitis patients versus 0.199 in non-ExRA controls; P < 0.001) and a decreased frequency of HLA-C7 (0.122 and 0.243, respectively; P = 0.018). The association between HLA-C3 and vasculitis was not due to linkage disequilibrium with HLA-DRB1. Smoking (P = 0.001), RF positivity (P < 0.0001), and presence of ANAs (P < 0.0001) were all associated with ExRA. HLA-C3 and smoking were both significant predictors of vasculitis in a multivariate model. CONCLUSION: Vasculitis in RA is associated with HLA-C3. Smoking is an independent predictor of vasculitis and other types of severe ExRA. Our results suggest that these variables are among the genetic and environmental factors that contribute significantly to the pathomechanisms of systemic RA. | |
16755651 | SUMO4 and MAP3K7IP2 single nucleotide polymorphisms and susceptibility to rheumatoid arthr | 2006 Jun | OBJECTIVE: To explore the role of single nuclear polymorphisms (SNP) in 2 candidate genes, SUMO4 and MAP3K7IP2, in susceptibility to rheumatoid arthritis (RA). METHODS: Two cohorts from different Spanish towns totalling 635 patients with RA and 826 controls were studied. Six SNP were genotyped by matrix assisted laser desorption-ionization time-of-flight (MALDI-TOF) with the MassARRAY SNP genotyping system. RESULTS: We found no association with susceptibility to RA for any of the SNP including a previously described functional variant in the SUMO4 gene (163A-->G). RA susceptibility was independent of the haplotypes defined by the 6 SNP and there was also no association with clinical features of RA. Conclusion. SUMO4 and MAP3K7IP2 SNP did not significantly influence predisposition to and features of RA, in contrast to previous genetic and functional evidence that suggested their involvement. | |
15996059 | Diet and risk of rheumatoid arthritis in a prospective cohort. | 2005 Jul | OBJECTIVE: To assess the association between dietary factors and risk of rheumatoid arthritis (RA) in a large prospective cohort. METHODS: Information about dietary intake was obtained from a detailed self-administered food frequency questionnaire completed by 57,053 individuals who participated in a prospective cohort. Linking the cohort to the Danish National Patient Registry we identified patients who developed RA. A rheumatologist scrutinized original medical records for these individuals in order to confirm the diagnosis of RA. Cox proportional hazards regression analyses were performed for dietary and lifestyle factors. RESULTS: The average time of followup in the cohort was 5.3 years (range < 1 mo to 7.7 yrs). Sixty-nine individuals were identified with confirmed incident RA. In multivariate models each increase in intake of 30 g fat fish (> or = 8 g fat/100 g fish) per day was associated with 49% reduction in the risk of RA (p = 0.06), whereas medium fat fish (3-7 g fat/100 g fish) was associated with significantly increased risk of RA. Intake of fruit and coffee was not associated with risk of RA. Furthermore, no associations were found between risk of RA and intake of a range of other dietary factors including long chain fatty acids, olive oil, vitamins A, E, C, D, zinc, selenium, iron, and meat. CONCLUSION: The limited number of patients who developed RA during followup of our large cohort prevented us from concluding that dietary factors are unimportant as risk factors for RA. It appears, however, that if dietary factors are important modifiers of RA risk, they must play a role more than a few years before clinical diagnosis. | |
16920747 | MHC2TA promoter polymorphism (-168*G/A, rs3087456) is not associated with susceptibility t | 2007 Mar | OBJECTIVE: To investigate the association of a single-nucleotide polymorphism (SNP) in the promoter region of MHC2TA gene (-168*G/A, rs3087456), which has previously been described in a Swedish rheumatoid arthritis (RA) cohort, in British Caucasian RA patients. METHODS: We genotyped 733 RA patients and 613 healthy controls for MHC2TA -168*G/A SNP by amplification-refractory mutation system (ARMS). Data were analysed using SPSS version 13.0 software and the chi-square test was applied where appropriate. RESULTS: The MHC2TA -168*G/A SNP was not associated with increased susceptibility to RA in our patients. Stratifying the patients according to the presence or absence of rheumatoid factor (RF) showed the SNP to be more common in RF negative patients, but this did not reach statistical significance. CONCLUSION: We did not confirm the previously reported association of this MHC2TA polymorphism with RA in our UK population despite its ethnic similarities with the Swedish population in which it was first described. | |
16470447 | Ankle arthrodesis by compression screws in rheumatoid arthritis: primary nonunion in 9/35 | 2005 Dec | INTRODUCTION: Today, percutaneous or open arthrodesis of the ankle, using one or several screws for fixation, is a common method for treatment of the rheumatic ankle. However, there is very little information in the literature on the reliability of the method. METHODS: We performed a retrospective radiographic and clinical study on 35 ankles of 35 patients. Function was evaluated using the Mazur and AOFAS scores. For evaluation of activity of the rheumatic disease, we used the HAQ score. RESULTS: 31 ankles had healed--26 at the first attempt and 5 after repeat arthrodesis. There was no difference between 13 cases operated on percutaneously and 22 cases operated on with open technique with respect to radiographic healing. Mean AOFAS total score was 56 of possible 86 points. The AOFAS total score correlated with the severity of the rheumatic disease. 20 patients were satisfied with the result, 12 were somewhat satisfied and 3 patients were dissatisfied although the ankle in 2 of these 3 patients had fused. INTERPRETATION: The use of compression screws for fusion of the rheumatic ankle does not appear to give acceptable results regarding healing and function. | |
17025376 | Adalimumab: a review of its use in adult patients with rheumatoid arthritis. | 2006 | Adalimumab (Humira) is a recombinant, fully human anti-tumor necrosis factor (TNF) monoclonal antibody approved in the US and Europe for the treatment of adult patients with moderate to severe, active rheumatoid arthritis (RA). In combination with methotrexate or standard antirheumatic therapy or as monotherapy, adalimumab effectively reduced signs and symptoms of RA, induced remission, improved physical function and inhibited the progression of structural damage in several randomized, double-blind, placebo-controlled phase III trials. The drug was generally well tolerated, with most adverse events being mild to moderate, and the serious adverse events profile being similar to that generally seen in patients with RA not receiving anti-TNF agents. Adalimumab was at least as cost effective as other anti-TNF agents used in the therapy of RA, and provided significant improvements in patients' health-related quality of life. Overall, adalimumab in combination with methotrexate or standard antirheumatic therapy is valuable as a first-line therapeutic option in patients with early, aggressive RA, and a second-line therapeutic option in patients with long-standing, moderate to severe RA. For the latter indication, adalimumab may also be used as monotherapy. | |
16040164 | [Atherosclerosis and rheumatoid arthritis]. | 2006 Feb | AIMS: To identify studies which have shown that rheumatoid arthritis (RA) is associated with an increase in cardiovascular morbidity and mortality. To identify the different factors that may be involved. To consider what management would decrease the cardiovascular morbidity and mortality of RA. RESULTS: Epidemiological studies have shown that the risk of a cardiovascular event is increased twofold in RA patients irrespective of the traditional cardiovascular risk factors. Non-invasive methods have shown that RA patients have endothelial dysfunction, decreased arterial compliance and increased intima-media thickers, predictive factors for cardiovascular events in comparison to controls after controlling for traditional cardiovascular risk factors. The increased cardiovascular risk is directly mediated by inflammatory syndrome, which also indirectly increases the risk by inducing dyslipidemia and insulin resistance. Treatments also have a hamful effect, whether it be corticosteroid therapy, non-steroidal anti-inflammatory drugs (NSAIDs), or methotrexate (MTX), which leads to hyperhromocysteinemia. CONCLUSION: It should be possible to decrease cardiovascular morbidity and mortality by a strict control of the disease's activity. We should also take measures to combat other cardiovascular risk factors: as low a dose as possible for corticosteroid therapy, limited prescription of NSAIDs, systematic supplementation of MTX with folic acid encouragement of smoking cessation, regular lipid tests and prescription of statins treatment for hyperlipemia in accordance with current recommendations. | |
17172249 | Utility and direct costs: ankylosing spondylitis compared with rheumatoid arthritis. | 2007 Jun | OBJECTIVES: To compare utility and disease-specific direct costs between patients with ankylosing spondylitis (AS) and patients with rheumatoid arthritis (RA) in the Netherlands. METHODS: Patients with AS and those with RA completed questions on disease characteristics, the EuroQol-5D (EQ-5D) to assess utility, and questionnaire resource utilisation. Resource utilisation was assessed prospectively in AS, but retrospectively in RA. True cost estimates (2003) were used to calculate the costs. Differences in disease characteristics between AS and RA were described, and determinants of EQ-5D utility and costs were explored by Cox proportional hazard regressions. RESULTS: 576 patients with RA and 132 with AS completed the questionnaires. EQ-5D utility (0.63 vs 0.7) was lower, and annual direct costs higher in RA (euro5167 vs euro2574). In multivariate Cox proportional hazard regressions, there was no difference in utility between the diagnostic groups, but patients with RA incurred higher direct costs after controlling for age, gender and disease duration. CONCLUSIONS: In patients with RA and patients with AS, who are under the care of a rheumatologist, utility is equally reduced, but healthcare costs are higher in RA after controlling for age, gender and disease duration. These data can be helpful to provide insights into the differences and similarities between the healthcare needs of both patient groups and to identify issues for further research and for policy in healthcare organisations. | |
17444250 | Diagnostic signs and symptoms of psoriatic arthritis. | 2006 Oct | PsA is a distinct pathologic entity with a unique set of diagnostically relevant clinical features. The typical clinical picture of PsA consists of peripheral joint inflammation with an asymmetric pattern of involvement. Furthermore, other clinical signs, such as sacroiliitis, enthesitis, dactylitis, and nail lesions, are also closely associated with the disease. By gaining familiarity with the features of PsA, as well as the ways in which disease presentation may vary, health care professionals will be better equipped to identify this condition, making early treatment, which is an essential step toward optimizing patient outcomes, more readily achievable. | |
16679431 | Expression of the peptide C4b-binding protein beta in the arthritic joint. | 2006 Oct | BACKGROUND: C4b-binding protein (C4BP) is a plasma oligomeric glycoprotein that participates in the regulation of complement and haemostasis. Complement-regulatory activity depends on the C4BPalpha-polypeptide, whereas the C4BPbeta-polypeptide inactivates protein S, interfering with the anti-coagulatory protein C-dependent pathway. OBJECTIVE: To investigate the expression of C4BPbeta in the rheumatoid joint. METHODS: Expression of C4BP was studied in synovial explants from patients with rheumatoid arthritis, osteoarthritis and healthy controls, using immunohistochemistry and in situ hybridisation. C4BP isoforms and free C4BPbeta were studied in synovial effusions from patients with rheumatoid arthritis, osteoarthritis and microcrystalline arthritis (MCA) by immunoblotting; total and free protein S levels were studied by enzyme immunoassay. RESULTS: C4BPbeta was overexpressed in the synovial membranes of patients with rheumatoid arthritis, in close association with the severity of synovitis and the extension of interstitial fibrin deposits. As many as 85% fluids from patients with rheumatoid arthritis contained free C4BPbeta, whereas this unusual polypeptide was present in 50% fluids from patients with MCA and 40% fluids from patients with osteoarthritis. Free protein S at the effusions was pathologically reduced in patients with rheumatoid arthritis and MCA, and remained normal in patients with osteoarthritis. CONCLUSION: C4BPbeta is expressed by the inflamed synovial tissue, where it can participate in processes of tissue remodelling associated with invasive growth. | |
17040110 | Remission, a therapeutic goal in inflammatory arthropathies? Clinical data from adalimumab | 2006 | In recent years, there have been major advances in the management of rheumatoid arthritis (RA), leading to the development of tumour necrosis factor (TNF) antagonists. With these agents, it is possible to arrest joint damage and, by treating early in the disease course, to prevent joint damage. It is also now thought that early treatment can achieve clinical remission in a substantial proportion of patients. With these increased expectations, a change is required in the way clinical improvement and drug efficacy is measured. The existing standard endpoint commonly used in RA clinical trials, the American College of Rheumatology (ACR) 20% response measure, is inadequate for the new goals of therapy that should be based on clinical remission and radiographic assessment.Adalimumab, a fully human anti-TNF monoclonal antibody, has been shown to be effective in achieving remission and preventing radiographic progression of joint damage in patients with RA and other inflammatory arthropathies, including psoriatic arthritis and ankylosing spondylitis. In a placebo-controlled trial in patients with early RA, combination treatment with adalimumab plus methotrexate (MTX) has been shown to be superior to either treatment alone in inducing significant clinical remission while being generally well tolerated. Compared with monotherapy, combination therapy resulted in significantly more patients (49% vs 25%; p < 0.001) remaining in clinical remission after 2 years. Suppression of joint damage assessed by the degree of inhibition of radiographic progression was also significantly higher for patients treated with adalimumab plus MTX (and with adalimumab alone) at 6 months, 1 and 2 years than for those treated with MTX alone. These data support the notion that clinical remission is a realistic therapeutic goal in patients with RA. |