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ID PMID Title PublicationDate abstract
19737478 [Inhibitory effect of triptolide on interleukin-18 and its receptor in rheumatoid arthriti 2009 Jul AIM: To determine the effects of triptolide (TP) on the expression of interleukin-18 (IL-18) and its receptor in phorbol 12-myristate 13-acetate (PMA)-stimulated rheumatoid arthritis synovial fibroblasts (RASF). METHODS: RASF were pretreated with TP (0-100 microg/L) for 2 h before stimulation with PMA (50 microg/L). The bioactivity of IL-18 in the supernatant was detected based on IFN-gamma secretion from IL-18-responding human myelomonocytic KG-1 cells. IL-18 level was analyzed by ELISA. To estimate the protein and mRNA expression of IL-18 and IL-18Ralpha in RASF, Western blot and quantitative RT-PCR were performed. Nuclear factor-kappaB (NF-kappaB) activity in the whole-cell extract of treated RASF was also measured using an ELISA-based method. RESULTS: TP effectively inhibited the bioactivity of IL-18 in PMA-stimulated RASF. The expression of IL-18 and IL-18R at protein and gene levels was reduced by TP. NF-kappaB activity in PMA-stimulated RASF was profoundly suppressed by TP. These effects showed a high correlation with TP concentration (0-100 microg/L). CONCLUSION: TP effectively inhibited the expression of IL-18 and its receptor in PMA-stimulated RASF. These results suggest a mechanism of TP in RA therapy.
19116197 Automatic quantification of joint space narrowing and erosions in rheumatoid arthritis. 2009 Jan Rheumatoid arthritis (RA) is a chronic disease that affects and potentially destroys the joints of the appendicular skeleton. The precise and reproducible quantification of the progression of joint space narrowing and the erosive bone destructions caused by RA is crucial during treatment and in imaging biomarkers in clinical trials. Current manual scoring methods exhibit high interreader variability, even after intensive training, and thus, impede the efficient monitoring of the disease. We propose a fully automatic quantitative assessment of the radiographic changes that result from RA, to increase the accuracy, reproducibility, and speed of image interpretation. Initial joint location estimates are obtained by local linear mappings based on texture features. Bone contours are delineated by active shape models comprised of statistical models of bone shape and local texture. These models are refined by snakes which increase the accuracy and allow for a fitting of pathological deviations from the training population. The method then measures joint space widths and detects erosions on the bone contour. Joint space widths are measured with a coefficient of variation of 2%-7% for repeated measurements and erosion detection exhibits an area under the receiver operating characteristic (ROC) curve of 0.89. Model landmarks serve as a reference system along the contour. These landmarks enable the definition of joint regions and more specific follow-up monitoring. The automatic quantification allows for a remote analysis, relevant for multicenter clinical trials, and reduces the workload of clinical experts since parts of the process can be managed by nonexpert personnel.
21180264 An evaluation of the tuberculin skin test for anti TNF alpha prophylaxis in patients with 2010 AIM: The tuberculin skin test (TST) has recently been proposed as a screening procedure for latent TB prior to anti-tumor necrosis factor (TNF) alpha therapy. Our aim was to evaluate TST levels in patients receiving anti TNF alpha due to ankylosing spondylitis (AS) and rheumatoid arthritis (RA). MATERIALS AND METHODS: 73 AS patients (52 male, 21 female) and 33 RA patients (11 male, 22 female) were enrolled in the study. Patients' clinical and demographic characteristics were recorded. Average age +/- standard deviation was 38.8 +/- 7.2 years for AS and 40.7 +/- 13 for RA. Median number of immunosuppressive agents used was 1 (min-max) (0-2) in AS and 2 (2-3) in RA. To determine the activity of the disease, BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) was measured in AS patients, and DAS 28 (Disease Activity Index) was used in RA patients. TST was performed using the Mantoux method in all patients. RESULTS: Mean BASDAI was 5.1 +/- 0.8 in AS, and DAS 28 score in RA was 5.7 +/- 0.5. Both, AS and RA patients had active disease. TST values were higher in AS than in RA patients. TST values were 11.5 +/- 6.5 mm in AS patients, compared to 7.0 +/- 6.4 mm in RA patients. A positive correlation between disease duration and TST was determined in AS patients. There was also a weak correlation in RA patients between immunosuppressive use and TST (r = 0.37, p = 0.032). No correlation was determined with disease activation in AS or RA patients. CONCLUSION: This is the first study to evaluate the correlation between the use of multiple immunosuppressive agents and TST. We determined that TST is correlated with disease duration in AS and with the use of multiple immunosuppressive agents in RA (Tab. 3, Ref. 21).
19403553 Randomized controlled trial for clinical effects of varying types of insoles combined with 2009 Jun OBJECTIVE: To determine the effects of specialized shoes with insoles in patients with rheumatoid arthritis and the differences in terms of type of insole and anatomical location of foot pathology. DESIGN: Single-blinded randomized controlled trial. SETTING: Outpatients of physical medicine and rehabilitation clinic at university hospital. SUBJECTS: Forty-two patients with rheumatoid foot lesions were randomly assigned to two different orthotic intervention groups. The anatomical locations of the foot lesions were recorded (hindfoot or forefoot). INTERVENTION: Participants were provided with an extra deep forefoot-rockered shoe and either a custom-made semi-rigid insole or a ready-made simple soft insole. They wore the provided footwear for at least 3 hours a day over six months. MAIN OUTCOME MEASURES: Primary outcome measures were foot pain visual analogue scale (VAS) scores and Foot Function Index (FFI). Secondary outcome measures were erythrocyte sedimentation rate and C-reactive protein levels in blood, amounts of medications and active joint counts. These were checked at baseline and post intervention. RESULTS: Eight patients dropped out at follow-up after six months of treatment. At six-month follow-ups, VAS scores and total Foot Function Index scores had decreased significantly in both groups versus baseline but intergroup comparison showed no significant differences in view of type of insoles and anatomical locations of foot pathology. CONCLUSIONS: We were unable to identify differences between the types of insoles in terms of their clinical effects or between anatomical locations of foot lesions in the two groups, but both groups improved. Therapeutic shoes plus soft insoles might be effective enough in terms of foot pain and foot function for specific patients with rheumatoid foot problems regardless of the location of foot pathology.
18793234 Early prosthetic valve failure in a patient with rheumatoid arthritis. 2009 Jan Heart lesions in patients with rheumatoid arthritis (RA) are well documented in literature; however, in the majority of cases these are incidental findings at postmortem. Most patients do not require cardiac surgical intervention unless they develop complications such as significant valvular regurgitation. Patients with RA often require orthopedic operations and therefore a bioprosthetic valve replacement is normally advocated to avoid problems related to anticoagulation. We report a case of a 64-year-old woman with seropositive RA who had undergone bioprosthetic aortic valve replacement three years previously. She re-presented with early prosthetic valve failure due to accelerated degeneration and calcification. This was treated successfully with redo replacement with a mechanical prosthesis. Here, we discuss our experience and debate the various valve choices available that should be considered in patients with rheumatoid disease.
20370905 Influence of HLA DRB1 alleles in the susceptibility of rheumatoid arthritis and the regula 2010 INTRODUCTION: The purpose of this study was to investigate the association between HLA-DRB1 alleles with susceptibility to rheumatoid arthritis (RA) and production of antibodies against citrullinated proteins (ACPA) and rheumatoid factor (RF). METHODS: We studied 408 patients (235 with RA, 173 non-RA) and 269 controls. ACPA, RF and HLA-DR typing were determined. RESULTS: We found an increased frequency of HLA DRB1 alleles with the shared epitope (SE) in ACPA-positive RA. Inversely, HLA DRB1 alleles encoding DERAA sequences were more frequent in controls than in ACPA-positive RA, and a similar trend was found for HLA DR3. However, these results could not be confirmed after stratification for the presence of the SE, probably due to the relatively low number of patients. These data may suggest that the presence of these alleles may confer a protective role for ACPA-positive RA. In RA patients we observed association between SE alleles and ACPA titers in a dose-dependent effect. The presence of HLA DR3 or DERAA-encoding alleles was associated with markedly reduced ACPA levels. No association between RF titers and HLA DR3 or DERAA-encoding alleles was found. CONCLUSIONS: HLA DRB1 alleles with the SE are associated with production of ACPA. DERAA-encoding HLA-DR alleles and HLA DR3 may be protective for ACPA-positive RA.
20574553 The uses and limitations of whole-body magnetic resonance imaging. 2010 Jun BACKGROUND: Whole-body magnetic resonance imaging (WB-MRI) is a modern imaging method, free of ionizing radiation, which provides high-resolution display of individual organ systems and of the anatomy of the entire body. METHODS: Selective literature review RESULTS: Multi-channel WB-MRI scanners enable both the high-resolution imaging of the entire body and focused studies of individual organs, through the use of various sequence techniques and contrast modes. The initial application of combined cardiovascular and oncological imaging protocols for the screening of asymptomatic persons has already revealed many cases of cardiovascular disease and of tumors with serious clinical implications. The diagnostic accuracy of M staging with WB-MRI lies in the range of 93% to 97%. WB-MRI provides good contrast of the bone marrow, and has thus been used for the diagnosis of malignant bone marrow disease as well: in particular, it is especially sensitive for multiple myeloma and plays an important role in prognostication and therapeutic decision-making in this disorder. To date, WB-MRI has not been shown to be superior to other diagnostic techniques with respect to hard endpoints, such as prolongation of survival. It also carries the risk of false positive findings. CONCLUSION: Despite these encouraging results, undirected screening by WB-MRI without an appropriate indication, as is currently being practiced in many institutions, is decidedly inadvisable in view of its predicted diagnostic yield below 2% and the lack of evidence for its cost-effectiveness.
19363452 Factors influencing fracture risk, T score, and management of osteoporosis in patients wit 2009 Jun OBJECTIVES: This study examined a wide array of clinical factors to evaluate their influence on fracture risk and T scores in women with rheumatoid arthritis (RA) and determine if women with RA who are at risk for osteoporosis (OP) are adequately treated with OP medications. METHODS: Data from 8419 female RA patients participating in the Consortium of Rheumatology Researchers of North America registry from March 02, 2006 to August 15, 2006 was evaluated. Covariates included medication subgroups, demographic, and clinical parameters. Lumbar spine and hip T scores and fracture rates were studied in relation to the variables. Use of OP medications in patients with OP risk factors was also evaluated. RESULTS: Postmenopausal status and higher modified health assessment questionnaire score (mHAQ) had a negative effect on lumbar spine score,while marriage, education, and body mass index had a positive effect. A similar trend was found with hip T scores. Increase in overall fracture risk correlated with postmenopausal status, mHAQ, and prednisone use, while tumor necrosis factor monotherapy was associated with decreased overall fracture risk. mHAQ was also associated with nonhip/nonspine fractures. Eighty percent of patients had at least 1 risk factor for OP, but only 32% were on OP medications. Only 54% of patients with 3 risk factors were on OP medication. CONCLUSIONS: In RA, postmenopausal status, mHAQ, and prednisone use were associated with a higher overall fracture risk. Women with RA who were at risk for OP may have been inadequately treated with OP medications.
20169874 [Hand deformity in adult rheumatoid arthritis and juvenile chronic arthritis]. 2009 Sep Adult rheumatoid arthritis (RA) is the most common of rheumatoid diseases, that may cause hand dysfunction in some patients. Its equivalent in children is juvenile chronic arthritis (JCA). The aim of our study was to evaluate differences in hand deformity between children with JCA and adults with RA. The prospective study was performed on two groups of patients: 15 with JCA (average age 13.1 years, range from 9 to 18 years) and 15 with RA (average age 53.6 years, range from 42 to 60 years). Both groups were similar in terms of Seyfried classification system and duration of the disease--7.9 years for children and 8.6 for adults. Clinical assessment was performed according to Swanson and Seyfrieda classification system. Patients with RA had only radial wrist "deviation" and those with JCA had both radial and ulnar wrist deviation. In MCP joints in adult's group fingers were always in ulnar position and in children's group finder position was opposite to wrist position. "Swan neck" deformity of fingers from II to V was found in both groups. "Buttonhole deformity" was more often seen in older group. Pain of wrist and in IP joints was more often found and was more severe in RA group. Hypertrophy of synovium and subluxation of IP and wrist joust were found with similar frequency in both groups. In other joints subluxation was rare. Concluding, radial wrist deviation is typical for RA patients. Children with JCA had both radial and ulnar wrist deviation. In MCP joints deformity is always opposite to wrist deviation.
19333951 Quantitative heritability of anti-citrullinated protein antibody-positive and anti-citrull 2009 Apr OBJECTIVE: The majority of genetic risk factors for rheumatoid arthritis (RA) are associated with anti-citrullinated protein antibody (ACPA)-positive RA, while far fewer genetic risk factors have been identified for ACPA-negative RA. This study was undertaken to quantify the contribution of genetic risk factors in general, and of the predisposing HLA-DRB1 shared epitope (SE) alleles in particular, to the ACPA-positive and ACPA-negative subsets of RA, by computing their heritability and assessing the contribution of the HLA SE alleles. METHODS: One hundred forty-eight RA twin pairs, in which at least 1 twin of each pair had RA, were tested for ACPAs and typed for HLA-DRB1 genotypes. Heritability was assessed in a logistic regression model including a bivariate, normally distributed random effect, representing the contribution of unobserved genetic factors to RA susceptibility, with the correlation of the random effects fixed according to twin zygosity. The contribution of the HLA SE alleles to genetic variance was assessed using a similar model, except that estimates were based on genotype-specific population prevalences. RESULTS: The heritability of RA among the twin pairs was 66% (95% confidence interval [95% CI] 44-75%). For ACPA-positive RA, the heritability was 68% (95% CI 55-79%), and for ACPA-negative RA it was 66% (95% CI 21-82%). Presence of the HLA SE alleles explained 18% (95% CI 16-19%) of the genetic variance of ACPA-positive RA but only 2.4% (95% CI 1.6-10%) of the genetic variance of ACPA-negative RA. CONCLUSION: The heritability of ACPA-positive RA is comparable with that of ACPA-negative RA. These data indicate that genetic predisposition plays an important role in the pathogenesis of ACPA-negative RA, for which most individual genetic risk factors remain to be identified.
20072093 Risk factors for development of subaxial subluxations following atlantoaxial arthrodesis f 2010 Jul 15 STUDY DESIGN: Retrospective radiographic/imaging study. OBJECTIVE: To evaluate preoperative and sequential postoperative radiographs following C1-C2 arthrodesis for atlantoaxial subluxation in patients with rheumatoid arthritis (RA) to determine risk factors for the development of subaxial subluxations (SAS). SUMMARY OF BACKGROUND DATA: The development of SAS has often been observed after C1-C2 arthrodesis. However, there have been no previous reports on the correlation between radiographic parameters and the incidence of postoperative SAS. METHODS: The study group comprised of 58 patients with RA who underwent C1-C2 arthrodesis due to atlantoaxial subluxation. There were 5 men and 53 women with a mean age of 55.8 years. The mean follow-up period was 137 months. Nineteen patients with a postoperative SAS after C1-C2 arthrodesis were classified as the SAS+ group. Other 39 patients without a postoperative SAS were included in the SAS- group. Clinical outcomes and plain radiographs were reviewed retrospectively and compared between the 2 groups. RESULTS: The difference between pre- and postoperative atlantoaxial (AA) angles in the SAS+ group was significantly greater than those in the SAS- group (P = 0.039). The C2-C7 angles changed significantly between pre- and postoperative periods in the SAS+ group (P = 0.039), but not in the SAS- group (P = 0.897). It was suggested that a large AA angle and a small C2-C7 angle observed at the early postoperative period were the risk factors for the development of SAS. We also demonstrated that a high incidence of the C3-C4 SAS resulted from excessive bone fusion at the C2-C3. CONCLUSION: Excessive correction of AA angle is likely to cause loss of cervical lordosis, resulting in the development of postoperative SAS. In addition, extensive bony union at C2-C3 following C1-C2 arthrodesis frequently leads to the development of extensive SAS at the C3-C4.
19368420 Tocilizumab: a review of its use in the management of rheumatoid arthritis. 2009 Tocilizumab (RoActemra or Actemra) is a recombinant humanized monoclonal antibody that acts as an interleukin (IL)-6 receptor antagonist. Intravenous tocilizumab 8 mg/kg (and no less than 4.8 mg), in combination with methotrexate, is approved in the EU for the treatment of moderate to severe active rheumatoid arthritis in adult patients with inadequate response to, or who are intolerant of, prior disease-modifying anti-rheumatic drug (DMARD) or tumour necrosis factor (TNF) antagonist therapy. It may also be administered as monotherapy in patients intolerant of methotrexate or in whom methotrexate therapy is inappropriate. Tocilizumab is also approved in Japan for the treatment of polyarticular-course juvenile idiopathic arthritis, systemic-onset juvenile idiopathic arthritis and Castleman's disease. Intravenous tocilizumab was effective and generally well tolerated when administered either as monotherapy or in combination with conventional DMARDs in several well designed clinical studies in adult patients with moderate to severe rheumatoid arthritis. Tocilizumab-based therapy was consistently more effective than placebo, methotrexate or other DMARDs in reducing disease activity, and some trials also showed significant benefits with tocilizumab in terms of reducing structural joint damage and improving health-related quality of life (HR-QOL). Notably, tocilizumab-based therapy was effective in patients with long-standing disease in whom anti-TNF therapy had previously failed. More data are required to determine the comparative efficacy and safety of tocilizumab versus other biological agents and to establish their relative cost effectiveness. However, the present data suggest that tocilizumab is an important emerging treatment option in adult patients with moderate to severe rheumatoid arthritis.
19727791 Changes in auditory ossicles in rheumatoid arthritis: scanning electron microscopic study. 2010 Mar The aim of this study was to define the existence of surface changes on auditory ossicles caused by rheumatoid arthritis. The study comprised of nine pairs of auditory ossicles (mallei and incudes) from autopsy of patients with rheumatoid arthritis, and five pairs of ossicles from persons without RA, taken during autopsies. The specimens were studied with JEOL JSM 5300 type scanning electron microscope. Surface changes of auditory ossicles were defined, affected areas were calculated, and expressed in percentage of total surface. Changes in auditory ossicles in patients with rheumatoid arthritis are significantly higher than in control ossicles, both on ossicular surface and articulations. Increased lysis of incudes, especially in the region of long propagation, corresponds to vascular damage. Articular degeneration is also present, indicating specific rheumatoid alteration. Both changes are statistically more intense in cases with longer duration of disease. In conclusion, rheumatoid arthritis reduces vascularity of auditory ossicles and causes degeneration of articular surfaces.
19116913 Folate receptor beta as a potential delivery route for novel folate antagonists to macroph 2009 Jan OBJECTIVE: To determine the expression of folate receptor beta (FRbeta) in synovial biopsy tissues and peripheral blood lymphocytes from rheumatoid arthritis (RA) patients and to identify novel folate antagonists that are more selective in the targeting and internalization of FRbeta than methotrexate (MTX). METHODS: Immunohistochemistry and computer-assisted digital imaging analyses were used for the detection of FRbeta protein expression on immunocompetent cells in synovial biopsy samples from RA patients with active disease and in noninflammatory control synovial tissues. FRbeta messenger RNA (mRNA) levels were determined by reverse transcription-polymerase chain reaction analysis. Binding affinities of FRbeta for folate antagonists were assessed by competition experiments for 3H-folic acid binding on FRbeta-transfected cells. Efficacy of FRbeta-mediated internalization of folate antagonists was evaluated by assessment of antiproliferative effects against FRbeta-transfected cells. RESULTS: Immunohistochemical staining of RA synovial tissue showed high expression of FRbeta on macrophages in the intimal lining layer and synovial sublining, whereas no staining was observed in T cell areas or in control synovial tissue. Consistently, FRbeta mRNA levels were highest in synovial tissue extracts and RA monocyte-derived macrophages, but low in peripheral blood T cells and monocytes. Screening of 10 new-generation folate antagonists revealed 4 compounds for which FRbeta had a high binding affinity (20-77-fold higher than for MTX). One of these, the thymidylate synthase inhibitor BCG 945, displayed selective targeting against FRbeta-transfected cells. CONCLUSION: Abundant FRbeta expression on activated macrophages in synovial tissue from RA patients deserves further exploration for selective therapeutic interventions with high-affinity-binding folate antagonists, of which BCG 945 may be a prototypical representative.
19177263 Magnetic resonance imaging in the assessment of metacarpophalangeal joint disease in early 2009 Mar OBJECTIVES: The aim of this study was to determine whether magnetic resonance imaging (MRI)-related entheseal changes including osteitis and extracapsular oedema could be used to differentiate between metacarpophalangeal (MCP) joint involvement in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: Twenty patients (10 each with early RA and PsA) had dynamic contrast-enhanced MRI (DCE-MRI) of swollen MCP joints. Synovitis and tenosynovitis was calculated using quantitative analysis including the degree and kinetics of enhancement of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Periarticular bone erosion and bone oedema were scored using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) proposals. Entheseal-related features including extracapsular soft tissue enhancement or regions of diffuse bone oedema were also evaluated. RESULTS: MRI was not able to differentiate at the group level between both cohorts on the basis of entheseal-related disease but a subgroup of PsA patients had diffuse extracapsular enhancement (30%) or diffuse bone oedema (20%). The RA patient group had a greater degree of MCP synovitis (p<0.0001) and tenosynovitis than PsA patients (p<0.0001). There were no significant differences in either the total number of erosions (p = 0.315) or the presence of periarticular bone oedema (p = 0.105) between the groups. CONCLUSION: Although conventional MRI shows evidence of an enthesitis-associated pathology in the MCP joints in PsA, this is not sufficiently common to be of diagnostic utility.
19927781 Magnetic resonance imaging evaluation of the cervical spine in patients with rheumatoid ar 2009 Jun AIM: To investigate by magnetic resonance (MR) imaging the occurence of cervical spine (CS) involvement in rheumatoid arthritis (RA) patients. METHODS: Thirty consecutive unselected patients, who fulfilled the revised American College of rheumatology criteria for RA, were investigated. All patients had a complete physical and laboratory evaluation. Radiological evaluation included hand and wrist x-rays, as well as CS radiographs in anteroposterior, lateral and lateral in full flexion views. In addition, MR (Spin Echo T2-weighted saggital scans, palin and contrast enhanced T1-weighted sagittal and axial scans) was performed in all patients. Hand x-rays were evaluated according to the Sharp score. Disease activity was assessed by disease activity score for 28 joint indices (DAS-28). RESULTS: There were 25 females and 5 males with a mean age of 46.6 years (23-67) and mean disease duration 9 years (1-22). Twenty three patients (76.6%) had positive IgM rheumatoid factor (RF). Five patients presented clinical findings, mainly cervical pain and stiffness of CS (four with positive and one with negative MR), while radiological findings of CS involvement were found in seven patients (23%). Five patients (16.6%) presented MR findings of CS involvement (anterior atlantoaxial subluxation 100%; vertical subluxation 20%; peridental pannus 80%; dens erosion 40%; brainstem compression 20%). Atlantoaxial subluxation correlated with high DAS-28, high level of swellen joint, high level of C-reactive protein and advanced erosive changes of the wrist and hand (high level of Sharp score) in the univariate analysis. CONCLUSION: We conclude that the frequency of CS involvement in RA patients is high. In pateints with active erosive peripheral disease it is very probable to also have some changes in CS. These may be clinically important and in such cases, MR offer valuable information.
18829616 Impact of adalimumab on work participation in rheumatoid arthritis: comparison of an open- 2009 Jun BACKGROUND AND OBJECTIVES: Rheumatoid arthritis (RA) causes considerable disability and often results in loss of work capacity and productivity. This study evaluated the impact of adalimumab, a tumour necrosis factor antagonist with demonstrated efficacy in RA, on long-term employment. METHODS: Data from an open-label extension study (DE033) of 486 RA patients receiving adalimumab monotherapy who previously did not respond to at least one disease-modifying antirheumatic drug (DMARD) and had baseline work status information were compared with data from 747 RA patients receiving DMARD treatment in a Norway-based longitudinal registry. Primary outcomes included the time patients continued working at least part time and the likelihood of stopping work. Secondary outcomes included American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) responses and disease remission. Outcomes were compared 6, 12 and 24 months after enrolment. RESULTS: During a 24-month period, the 158 patients who received adalimumab and were working at baseline worked 7.32 months longer (95% CI 4.8 to 9.1) than did the 180 patients treated with DMARDs, controlling for differences in baseline characteristics. Regardless of baseline work status, patients receiving adalimumab worked 2.0 months longer (95% CI 1.3 to 2.6) and were significantly less likely to stop working than those receiving DMARDs (HR 0.36 (95% CI -0.30 to 0.42) for all patients and 0.36 (95% CI 0.15 to 0.85) for patients working at baseline, respectively). The patients who received adalimumab were also considerably more likely to achieve ACR responses and disease remission than DMARD-treated patients. Patients who achieved EULAR good response and remission were less likely to stop working, but this relationship was only seen in patients receiving DMARDs. CONCLUSIONS: Patients with RA who received adalimumab experienced considerably longer periods of work and continuous employment, and greater rates of clinical responses, than patients receiving DMARDs. The mechanism by which adalimumab decreases likelihood of stopping work seems to be different from that of DMARD treatment and independent of clinical responses.
19104082 Cytokine-induced human IFN-gamma-secreting effector-memory Th cells in chronic autoimmune 2009 Feb 26 T-helper (Th) cells activated by cytokines in the absence of T-cell receptor ligation are suspected to participate in inflammatory processes by production of interferon-gamma (IFN-gamma). Still, the relevance of such a mechanism has not been addressed in humans. Here we demonstrate that a subset of human effector-memory Th cells expressing functional interleukin-12R (IL-12R), IL-18Ralpha, and CCR5 ex vivo can be induced to secrete IFN-gamma by cytokines signaling via the IL-2R common gamma-chain in combination with IL-12 and IL-18. Cytokine-driven IFN-gamma production depends on JAK3- and p38 mitogen-activated kinase signals and is sensitive to suppression by CD25(++) regulatory T cells. Contrary to IFN-gamma(+) Th cells induced upon antigen-specific stimulation, their cytokine-activated counterparts characteristically lack expression of costimulator 4-1BB (CD137). Strikingly, the majority of Th cells infiltrating inflamed joints of rheumatoid arthritis patients is equipped with receptors prerequisite for cytokine-induced IFN-gamma secretion. Among these cells, we detected a substantial fraction that secretes IFN-gamma directly ex vivo but lacks 4-1BB expression, indicating that cytokine-induced IFN-gamma(+) Th cells operate in autoimmune inflammation. Our data provide a rationale for how human effector-memory Thcells can participate in perpetuating inflammatory processes in autoimmunity even in the absence of T-cell receptor ligation.
19638061 Rheumatoid arthritis patient education: RA patients' experience. 2009 Jul AIM AND OBJECTIVE: The purpose of this paper is to describe the content of patient education as portrayed and evaluated by rheumatoid arthritis (RA) patients. BACKGROUND: Rheumatology nurses have an important role in educating and supporting RA patients. However, there is a lack of knowledge of the RA patients' own perspective of patient education. DESIGN: Survey. METHOD: Data for this study were collected from 173 RA patients from 11 hospitals and 23 health centers using open-ended questions. Fifty-seven percent (57%) of the patients described the content of patient education and eighty-one percent (81%) evaluated it expressing their experience and satisfaction with it. Data were analysed using descriptive and non-parametric statistical tests. RESULTS: Rheumatology nurses mostly gave their RA patients information about how to use the anti-rheumatic drugs prescribed to them (26%). About half (51%) of the patients were satisfied with patient education. However, every fourth patient (24%) was not satisfied, the main reason for the dissatisfaction being that nurses did not focus on the patient's emotional support. The patients of over 57 years of age and those who had suffered from RA for over five years were more satisfied with their education than the others. CONCLUSIONS: It is important that rheumatology nurses, besides passing on medical treatment-related information, concentrate on RA patients' emotional well-being. RELEVANCE TO CLINICAL PRACTICE: The results provide a useful insight into RA patient education. Nurses should avoid merely passing on information in a routine workmanlike way. It is important that they take time to discuss their patients' feelings and worries especially with newly diagnosed patients. RA patient education should balance patients' information needs with their need for emotional support.
20976214 Role of interleukin 17 in arthritis chronicity through survival of synoviocytes via regula 2010 Oct 15 BACKGROUND: The use of TNF inhibitors has been a major progress in the treatment of chronic inflammation. However, not all patients respond. In addition, response will be often lost when treatment is stopped. These clinical aspects indicate that other cytokines might be involved and we focus here on the role of IL-17. In addition, the chronic nature of joint inflammation may contribute to reduced response and enhanced chronicity. Therefore we studied the capacity of IL-17 to regulate synoviolin, an E3 ubiquitin ligase implicated in synovial hyperplasia in human rheumatoid arthritis (RA) FLS and in chronic reactivated streptococcal cell wall (SCW)-induced arthritis. METHODOLOGY/PRINCIPAL FINDINGS: Chronic reactivated SCW-induced arthritis was examined in IL-17R deficient and wild-type mice. Synoviolin expression was analysed by real-time RT-PCR, Western Blot or immunostaining in RA FLS and tissue, and p53 assessed by Western Blot. Apoptosis was detected by annexin V/propidium iodide staining, SS DNA apoptosis ELISA kit or TUNEL staining and proliferation by PCNA staining. IL-17 receptor A (IL-17RA), IL-17 receptor C (IL-17-RC) or synoviolin inhibition were achieved by small interfering RNA (siRNA) or neutralizing antibodies. IL-17 induced sustained synoviolin expression in RA FLS. Sodium nitroprusside (SNP)-induced RA FLS apoptosis was associated with reduced synoviolin expression and was rescued by IL-17 treatment with a corresponding increase in synoviolin expression. IL-17RC or IL-17RA RNA interference increased SNP-induced apoptosis, and decreased IL-17-induced synoviolin. IL-17 rescued RA FLS from apoptosis induced by synoviolin knockdown. IL-17 and TNF had additive effects on synoviolin expression and protection against apoptosis induced by synoviolin knowndown. In IL-17R deficient mice, a decrease in arthritis severity was characterized by increased synovial apoptosis, reduced proliferation and a marked reduction in synoviolin expression. A distinct absence of synoviolin expressing germinal centres in IL-17R deficient mice contrasted with synoviolin positive B cells and Th17 cells in synovial germinal centre-like structures. CONCLUSION/SIGNIFICANCE: IL-17 induction of synoviolin may contribute at least in part to RA chronicity by prolonging the survival of RA FLS and immune cells in germinal centre reactions. These results extend the role of IL-17 to synovial hyperplasia.