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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| 23141718 | Meta-analysis of clinical and radiological efficacy of biologics in rheumatoid arthritis p | 2013 Jul | Our aim was to compare all eight biologics available for rheumatoid arthritis in two patient populations, methotrexate-naive patients and inadequate responders to methotrexate, based on a comprehensive literature review. The five TNFα antagonists, rituximab, abatacept and tocilizumab used with methotrexate were compared to methotrexate monotherapy using the ACR50 response as the primary clinical endpoint and absence of radiographic progression after 1 year as the primary radiological endpoint. Odds ratios (ORs) were computed, as well as the number needed to treat (NNT) to obtain an ACR50 response for each biologic. We included 22 studies. Overall, combined biologic therapy was significantly more effective than methotrexate alone in both the naive group (OR: 2.11; 95% confidence interval [95%CI], 1.85-2.41) and the unresponsive group (OR: 4.82; 95%CI: 3.83, 6.08). Crude NNTs were as follows: etanercept, five in the naive group and three in the unresponsive group; adalimumab, seven and three; infliximab, seven and five; abatacept, seven and four; rituximab, five and five; and tocilizumab and certolizumab, four in the unresponsive group. None of the differences was statistically significant. In the naive group, combined biologic therapy was associated with a higher rate of absence of radiographic progression after 1 year compared to methotrexate alone (OR: 2.19; 95%CI: 1.55-3.08). All biologics had approximately the same efficacy. Methotrexate-naive patients treated with biologics had significantly less radiographic progression than those with cellular therapy. | |
| 22505702 | Effect of golimumab on patient-reported outcomes in rheumatoid arthritis: results from the | 2012 Jun | OBJECTIVE: To evaluate the effect of golimumab on physical function, general health, and fatigue in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. METHODS: In the multicenter, randomized, placebo-controlled GO-FORWARD study, 444 adults with active RA despite MTX received subcutaneous placebo + MTX (crossover to golimumab 50 mg at Week 24), golimumab 100 mg + placebo, golimumab 50 mg + MTX, or golimumab 100 mg + MTX every 4 weeks. Physical function and general health were assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI) and Physical and Mental Component Summary (PCS, MCS) scores of the Medical Outcomes Study Short Form-36 questionnaire (SF-36), respectively, through Week 52. Fatigue was measured through Week 24 using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire. RESULTS: Mean improvements from baseline in HAQ-DI, SF-36 PCS, and FACIT-Fatigue scores (Weeks 14 and 24) were significantly greater for golimumab 50 mg + MTX and 100 mg + MTX versus placebo + MTX. Significantly greater proportions of patients treated with golimumab + MTX achieved clinically meaningful improvements from baseline to Weeks 14 and 24 in HAQ-DI, PCS, and FACIT-Fatigue scores. Mean improvements in SF-36 PCS (Week 14), MCS (Week 24), and FACIT-Fatigue (Weeks 14 and 24) scores were significantly greater for golimumab 100 mg + placebo versus placebo + MTX. Mean improvements from baseline in HAQ-DI, SF-36 PCS, and MCS scores through Week 24 were sustained through Week 52. CONCLUSION: Patients with active RA despite MTX had significant improvement in physical function, general health, and fatigue following golimumab + MTX therapy; improvements in physical function and general health were maintained through Week 52. (Clinical Trials Registration NCT00264550). | |
| 22045836 | Health-related quality of life outcomes of adalimumab for patients with early rheumatoid a | 2012 Jan | OBJECTIVE: Rheumatoid arthritis (RA) is associated with significant impairments in health-related quality of life (HRQOL). We evaluated patient-reported outcomes including HRQOL outcomes following adalimumab plus methotrexate (MTX) therapy in patients with early RA. METHODS: PREMIER was a phase III, multicenter, randomized, double-blind, active-comparator clinical trial in early RA. Patients aged ≥ 18 years were randomly assigned to receive adalimumab 40 mg every other week (eow) plus weekly MTX, weekly MTX, or adalimumab 40 mg eow for 104 weeks. American College of Rheumatology (ACR) criteria were used to evaluate clinical efficacy and response. Outcomes were assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI), Short-Form 36 Health Survey (SF-36), Short-Form 6 Dimension (SF-6D), visual analog scale (VAS) assessments of global disease activity (patient's global assessment; PtGA) and pain, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Health Utility Index Mark 3 (HUI-3). RESULTS: Of 799 patients enrolled, 268 received adalimumab plus MTX, 257 received MTX monotherapy, and 274 received adalimumab monotherapy. Patients treated with adalimumab plus MTX demonstrated significant baseline to Week 104 improvements in HAQ-DI (p < 0.0001), SF-36 Physical Component Summary (p < 0.0001), 4 SF-36 domains [physical function (p < 0.0001), bodily pain (p <0.0001), vitality (p = 0.0139), role limitations-physical (p = 0.0005)], SF-6D (p = 0.0152), VAS-PtGA (p < 0.0001), VAS-pain (p < 0.0001), FACIT-F (p < 0.0001), and HUI-3 (p = 0.0034) scores versus patients treated with MTX monotherapy. Both SF-6D and HUI-3 were found to be sensitive preference-based measures for assessing the effects of treatment on multidimensional function. No clinically meaningful differences between adalimumab and MTX monotherapy groups were observed for most measures. For each measure, there was significant association between HRQOL improvement and ACR clinical response. CONCLUSION: Adalimumab plus MTX significantly improved physical functioning and HRQOL in patients with early RA over 2 years of treatment. (ClinicalTrials.gov identifier NCT00195663). | |
| 22364135 | The effect of anti-B-cell therapy on the development of atherosclerosis in patients with r | 2012 | Accelerated development of atherosclerosis (AT) in rheumatoid arthritis (RA) stems from common immune-inflammatory mechanisms underlying the diseases. While the key role of activation of the T-cell immune system component is considered to be proved, the role of B-lymphocytes has been investigated insufficiently. Earlier experimental models demonstrated the "atheroprotective" role of B-cells. At the same time, AT development is associated with activation of the B-cell immune system component and manifested by hyperproduction of antibodies to oxidized low density lipoproteins (oxLDL), heat shock proteins, etc. Wide applications of anti-B-cell therapy stimulate active research on effects of B-lymphocytes and their depletion on AT development in RA patients that have a high risk of cardiovascular events (CVE). Experimental models demonstrated that depletion of B2 cells instead of B1 cells under anti-CD20 treatment resulted in a slower development and progression of AT. Research on cardiovascular effects of chimeric antiCD20 monoclonal antibody (rituximab, RTX) in RA is definitely of high interest. Use of RTX in a combination with methotrexate does not increase the risk of serious side effects, including CVE, compared with the sole use of methotrexate. Currently, only few pilot research reports on favorable effects of RTX on the lipid profile and endothelial function in RA patients have been published. According to other authors, the frequency of CVE in RA patients receiving RTX therapy was somewhat higher than that in patients not treated with RTX. In rare cases such side effects as hypotension and arrhythmia were reported under RTX infusion. In addition, investigation of the combined use of statins and RTX is important, since some data are available on a reduced efficacy of RTX when administered with statins. Therefore, further research is required to clarify the role of the B-cell immune system component in AT development and the impact of anti-B cell therapy on the pathogenetic mechanisms of AT and CVE in RA patients. | |
| 23263550 | Tc-99 m diethylenetriamine-pentaacetic acid (DTPA): is it reliable for assessment of metho | 2013 Dec | Methotrexate (MTX) is commonly employed as the initial DMARD used for the treatment of rheumatoid arthritis (RA). We aimed to contribute to the safety profile of MTX by assessing its cumulative effect on renal filtration. A total of 52 RA adult female patients with normal baseline serum creatinine and GFR at the initial diagnosis of the disease were included. Group 1 (G1) included 30 patients (mean age 40.4 ± 4.4 years) on MTX and NSAIDS, while 22 RA patients (mean age 38.5 ± 8.2 years) who received NSAIDs only served as control group (G2). Renal function was assessed by GFR measurement using technetium diethylenetriamine-pentaacetic acid (Tc-99 m DTPA) at a point of the study time corresponding to disease duration. Twenty-one out of thirty (70 %) in G1 showed reduced GFR compared to 6/22 (27.3 %) in G2 (P = 0.007), with 3.3 ± 0.5 % annual reduction in GFR. Reduced GFR in G1 showed significant negative correlation with age (r = -0.396, P = 0.005), MTX cumulative dose (r = -0.263, P = 0.049), MTX-intake duration (r = -0.293, P = 0.031) and NSAIDs-intake duration (r = -0.344, P = 0.014). Low-dose MTX has a slow cumulative effect on renal filtration manifested by GFR reduction overtime that could be monitored by Tc-99 m DTPA. | |
| 22915624 | Impact of intravenous abatacept on synovitis, osteitis and structural damage in patients w | 2013 Aug | OBJECTIVES: This randomised, double-blind, placebo-controlled phase IIIb study evaluated the impact of abatacept on MRI pathology as a primary outcome in methotrexate (MTX)-refractory patients with rheumatoid arthritis. METHODS: Patients received intravenous abatacept (∼10 mg/kg) or placebo, on background MTX, for 4 months, followed by an 8-month open-label extension (OLE; all patients received abatacept plus MTX). Patients had 1.5T MRI with intravenous contrast at baseline, Months 4 and 12; wrist synovitis (three locations assessed), and wrist and hand (15 and eight locations assessed, respectively) osteitis and erosion were scored using OMERACT-RAMRIS. RESULTS: 26/27 abatacept- and 23/23 placebo-randomised patients completed Month 4 and entered the OLE; 26 and 21 completed Month 12. The primary endpoint was not achieved; mean change (SD) from baseline in synovitis was -0.44 (1.47) for abatacept versus 0.52 (1.38) for placebo (p=0.103) at Month 4. For mean change in synovitis adjusted for baseline score (sensitivity analysis), the difference between groups was -0.69, p=0.078. Adjusted mean changes (SE) in osteitis and erosion were -1.94 (0.86) and 0.45 (0.43) for abatacept, and 1.54 (0.90) and 0.95 (0.45) for placebo. Further MRI improvements were observed up to Month 12 for abatacept and from Months 4 to 12 for placebo-treated patients switched to abatacept at Month 4. Clinical efficacy was shown with abatacept and sustained to Month 12. CONCLUSIONS: Despite small patient numbers, MRI detected structural and synovial benefit, sustained to Month 12 in abatacept+MTX-treated patients, and improvements in structural and inflammatory outcomes for placebo+MTX-treated patients following addition of abatacept. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT00420199. | |
| 21998122 | The effect of biological agents on work participation in rheumatoid arthritis patients: a | 2012 Feb | This study reviewed the effect of biological agents on participation in paid work among patients with rheumatoid arthritis (RA). A systematic literature search was performed to identify published articles reporting the effect of biological agents on employment status, sick leave and/or presenteeism. The quality of included articles was assessed according to the guidelines as proposed by the Dutch Cochrane Centre. Narrative summaries were used to present the data separately for randomised controlled trials (RCTs) as well as controlled and uncontrolled cohort studies. 19 studies (six uncontrolled cohorts, seven controlled cohorts and six RCTs) were included, in which 11 259 patients were treated with biological agents. Employment status improved in four out of 13 studies, absence from work in all 10 studies and presenteeism in seven out of nine studies that reported this outcome. For absenteeism and presenteeism the statistical significance of change or difference was not always provided and results within studies were sometimes conflicting when using different time frames or alternative outcomes. The large heterogeneity in terms of population, design, analyses and most important in outcome measures limits interpretation of the data. RCTs as well as cohort studies showed positive results of biological agents on both absenteeism and presenteeism compared with other disease-modifying antirheumatic drugs (DMARD), continuing the failing DMARD, the general population or the situation before the start of biological agents. The effect on employment status was more conflicting, but 50% of studies that addressed patients with early methotrexate-naive RA showed a positive result on employment status. | |
| 22736476 | Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity. | 2012 Dec | OBJECTIVE: Quantitative assessment of disease activity in rheumatoid arthritis (RA) is important for patient management, and additional objective information may aid rheumatologists in clinical decision making. We validated a recently developed multibiomarker disease activity (MBDA) test relative to clinical disease activity in diverse RA cohorts. METHODS: Serum samples were obtained from the Index for Rheumatoid Arthritis Measurement, Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study, and Leiden Early Arthritis Clinic cohorts. Levels of 12 biomarkers were measured and combined according to a prespecified algorithm to generate the composite MBDA score. The relationship of the MBDA score to clinical disease activity was characterized separately in seropositive and seronegative patients using Pearson's correlations and the area under the receiver operating characteristic curve (AUROC) to discriminate between patients with low and moderate/high disease activity. Associations between changes in MBDA score and clinical responses 6-12 weeks after initiation of anti-tumor necrosis factor or methotrexate treatment were evaluated by the AUROC. RESULTS: The MBDA score was significantly associated with the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) in both seropositive (AUROC 0.77, P < 0.001) and seronegative (AUROC 0.70, P < 0.001) patients. In subgroups based on age, sex, body mass index, and treatment, the MBDA score was associated with the DAS28-CRP (P < 0.05) in all seropositive and most seronegative subgroups. Changes in the MBDA score at 6-12 weeks could discriminate both American College of Rheumatology criteria for 50% improvement responses (P = 0.03) and DAS28-CRP improvement (P = 0.002). Changes in the MBDA score at 2 weeks were also associated with subsequent DAS28-CRP response (P = 0.02). CONCLUSION: Our findings establish the criterion and discriminant validity of a novel multibiomarker test as an objective measure of RA disease activity to aid in the management of RA in patients with this condition. | |
| 21427581 | Update 2011: leflunomide in rheumatoid arthritis - strengths and weaknesses. | 2011 May | PURPOSE OF REVIEW: Leflunomide is often used as a first choice disease-modifying antirheumatic drug after methotrexate. New data are available for efficacy and safety in both, monotherapy and combination with biologicals. RECENT FINDINGS: New data on efficacy demonstrate comparable effect sizes for leflunomide and methotrexate in the treatment of signs and symptoms in combination with tumour necrosis factor-blocking agents and rituximab. Equipotency has also been demonstrated by a recent radiographic outcome study on methotrexate and leflunomide monotherapy. Pharmacogenetic studies indicate an impact of polymorphisms on the variability in serum levels of the compound with potential relevance to effectiveness and tolerability in individual patients. Genetic factors are also likely to contribute to the significantly increased risk for leflunomide-induced pulmonary disease reported in Asia. Because pre-existing interstitial lung disease as well as methotrexate-induced pneumonitis have been identified as risk factors for leflunomide-induced pulmonary disease, the use of leflunomide as an alternative to methotrexate is limited under these conditions. SUMMARY: Effectiveness of leflunomide renders it a potent treatment option in rheumatoid arthritis. The known tolerability issues resulting in a less favourable adherence to therapy constitutes a weakness. However, documented data from large registries indicate that leflunomide is safe as far as the contraindications and recommendations for monitoring are regarded. | |
| 21109516 | Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular even | 2011 Apr | OBJECTIVE: To examine the association of cardiovascular events with tumour necrosis factor (TNF) α antagonist use compared with non-biological disease-modifying antirheumatic drug (DMARD) utilisation in patients with rheumatoid arthritis (RA). METHODS: The study population included 10 156 patients enrolled in the Consortium of Rheumatology Researchers of North America RA registry. Three study cohorts were defined based on three mutually exclusive drug use categories, including TNF antagonists, methotrexate and other non-biological DMARDs. HR were calculated adjusting for cardiovascular risk factors, RA disease characteristics and prednisone use. The primary study outcome was a composite of non-fatal myocardial infarction (MI), transient ischaemic attack (TIA) or stroke and cardiovascular-related death. RESULTS: There were 88 cardiovascular events, including 26 MI, 45 TIA/strokes and 17 cardiovascular-related deaths. After adjusting for age, gender, cardiovascular risk factors and RA disease characteristics, patients using a TNF antagonist experienced a reduced risk of the primary composite cardiovascular endpoint (HR 0.39, 95% CI 0.19 to 0.82) compared with users of non-biological DMARDs. Methotrexate was not associated with a reduced risk (HR 0.94, 95% CI 0.49 to 1.80). Prednisone use was associated with a dose-dependent increased risk (p=0.04). The risk reduction associated with TNF antagonists was also observed for non-fatal cardiovascular events (HR 0.35, 95% CI 0.16 to 0.74). CONCLUSION: TNF antagonist use was associated with a reduced risk of cardiovascular events in patients with RA. | |
| 21285116 | The influence of systemic glucocorticoid therapy upon the risk of non-serious infection in | 2011 Jun | BACKGROUND: Glucocorticoid therapy is strongly associated with an elevated risk of serious infections in patients with rheumatoid arthritis (RA). The association between glucocorticoids and common non-serious infections (NSI) is not well studied. METHODS: A cohort of 16 207 patients with RA aged over 65 years was assembled using administrative data from Quebec. Glucocorticoid and disease-modifying antirheumatic drug (DMARD) therapy were identified from drug dispensing records. NSI cases were defined as first occurrence of a community physician billing code for infection or community-dispensed anti-infectives. A nested case-control analysis was performed considering drugs dispensed within 45 days of the index date, adjusting for age, sex, markers of disease severity, DMARD and comorbidity. RESULTS: For 13 634 subjects, a NSI occurred during 28 695 person-years of follow-up, generating an incidence rate of 47.5/100 person-years. The crude rate of NSI in glucocorticoid-exposed and unexposed person time was 52.4 and 38.8/100 person-years, respectively. Glucocorticoid therapy was associated with an adjusted RR of 1.20 (95% CI 1.15 to 1.25). A dose response was seen, the adjusted RR increasing from 1.10 (<5 mg prednisolone/day) to 1.85 for doses greater than 20 mg/day. All glucocorticoid risk estimates (including <5 mg/day) were higher than that seen for methotrexate (adjusted RR 1.00; 0.95 to 1.04). CONCLUSION: Glucocorticoid therapy is associated with an increased risk of NSI. The magnitude of risk increases with dose, and is higher than that seen with methotrexate, although residual confounding may exist. While the RR is low at 1.20, the absolute risk is high with one additional infection seen for every 13 patients treated with glucocorticoids for 1 year. | |
| 21962388 | Rheumatoid meningitis occurring during adalimumab and methotrexate treatment. | 2012 Jan | Rheumatoid arthritis is well known for multiple extra-articular manifestations. Here, we present a case of chronic rheumatoid meningitis occurring during treatment with methotrexate and the tumour necrosis factor (TNF) alpha antibody adalimumab. Nine and seven months, respectively, into the course of these two treatments, a 59-year-old Caucasian lady with mild, early, seropositive rheumatoid arthritis developed headaches and psychomotor retardation followed by seizures. The diagnosis was confirmed by a brain biopsy showing a necrotizing granulomatous meningitis. Withdrawal of both drugs and high dose corticosteroids led to marked improvement. The addition of the anti-CD20 antibody rituximab allowed discontinuation of the corticosteroids. This is the fifth published case describing the occurrence of rheumatoid meningitis during treatment with TNF blockers. TNF blockers and methotrexate thus do not appear to prevent this complication, and may even contribute to its development. | |
| 22838954 | Clinical pharmacogenetic model to predict response of MTX monotherapy in patients with est | 2012 Jul | BACKGROUND: The performance of a clinical pharmacogenetic model to predict nonresponse of methotrexate (MTX) monotherapy in patients with established rheumatoid arthritis (RA) and failure of disease-modifying antirheumatic drugs (DMARDs) was studied. METHODS: For 75 RA patients receiving MTX monotherapy for 6 months, DNA and clinical data were available. Risk scores for nonresponse at 6 months (disease activity score >2.4), were calculated using the pharmacogenetic prediction model utilizing four clinical factors and four polymorphisms in the genes MTHFD1, AMPD1, ITPA and ATIC. RESULTS: At 6 months, there were 25 responders and 50 nonresponders. Using the clinical pharmacogenetic prediction model, 75% (56 out of 75) were categorized into predicted responders (risk score ≤ 3.5) and predicted nonresponders (risk score ≥ 6). At 6 months, the negative predictive value was 81% (21 out of 26) and the positive predictive value was 47% (14 out of 30). CONCLUSION: The pharmacogenetic model predicts nonresponse to MTX monotherapy, but performs better in DMARD naive recent-onset RA patients than in patients with preceding DMARD failure. | |
| 22776409 | Associations between vitamin D, disease activity, and clinical response to therapy in rheu | 2012 Sep | OBJECTIVES: Vitamin D deficiency is a potential risk factor for autoimmunity. Prior studies of the association between vitamin D levels and rheumatoid arthritis (RA) disease activity have yielded conflicting results. METHODS: Serum 25(OH)vitamin D levels were measured at baseline in 499 participants with active RA, ages 18-85 years, enrolled in a randomised clinical trial of golimumab (Go-Before Trial). Subjects were methotrexate and biologic therapy naïve. Multivariable linear regression was used to assess associations between vitamin D levels and disease activity scores (DAS28), van der Heijde-Sharp (vdHS) erosion scores, and serum inflammatory markers. Generalised estimating equations were used to evaluate the associations between vitamin D status and the response to therapy over 52 weeks, using the DAS28 and ACR response. RESULTS: Forty-eight percent of participants were vitamin D deficient, defined as serum 25(OH)vitamin D <20 ng/mL. Deficiency was not associated with greater DAS28 (β-0.021 [95% CI -0.22, 0.18]), adjusted for age, race, sex, BMI, disease duration and glomerular filtration rate. Vitamin D deficiency was not associated with baseline vdHS scores or inflammatory markers in adjusted or unadjusted models. There was no association between baseline vitamin D deficiency and change in DAS28 (β = -0.024 [-0.30, 0.25]), proportion meeting ACR response (OR 0.82 [0.56, 1.20]), or radiographic progression at 52 weeks (OR 0.91 [0.59-1.40]). CONCLUSIONS: Vitamin D levels were not associated with RA disease activity, inflammatory markers, or vdHS scores at baseline. Furthermore, there was no association between baseline vitamin D level and response to therapy or radiographic progression. | |
| 22462423 | Randomized comparison of etanercept with usual therapy in an Asian population with active | 2012 Apr | AIM: Rheumatoid arthritis (RA) is an important rheumatologic disease in Asia-Pacific countries, as in other parts of the world. However, limited information is available regarding RA therapy in this region. The Asia-Pacific Study in Patients to be Treated With Etanercept or an Alternative Listed DMARD (APPEAL) compared efficacy and safety of etanercept (ETN) + methotrexate (MTX) versus usual disease-modifying anti-rheumatic drugs (DMARDs) + MTX (reflecting regional practice) in subjects with moderate to severe RA from multiple Asia-Pacific countries. METHOD: In this open-label, active-comparator, parallel-design, multicenter study, subjects (n = 300) in the Asia-Pacific region were randomized to ETN + MTX (n = 197) or DMARD + MTX (n = 103). The primary efficacy endpoint was the American College of Rheumatology (ACR) response (ACR-N) area under the curve (AUC) over 16 weeks. RESULTS: Baseline characteristics were similar between groups. At Week 16, ACR-N AUC indicated a significantly greater response with ETN + MTX compared with DMARD + MTX (mean difference -145.3; P < 0.001). Significantly greater proportions of subjects achieved ACR 20, 50 and 70 responses with ETN + MTX versus DMARD + MTX at Week 16 (P < 0.05). Low Disease Activity Score based on a 28-joint count (DAS28 < 3.2) was also achieved by significantly more subjects in the ETN + MTX group versus the DMARD + MTX group (P < 0.001). Greater improvements were shown for DAS28, pain visual analogue scale, health assessment questionnaire, and physician and patient global assessments (P < 0.05) for ETN + MTX versus DMARD + MTX. No new safety signals were found. CONCLUSION: In this Asia-Pacific population of subjects with moderate to severe RA, ETN + MTX showed superior efficacy versus usual DMARD + MTX regimens, with similar safety profiles. | |
| 21586440 | Validation of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: slight | 2011 Aug | BACKGROUND: Recently, an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) collaboration developed new classification criteria for rheumatoid arthritis (RA). OBJECTIVE: To evaluate the diagnostic and discriminative ability of these new criteria compared with the 1987 ACR criteria and the Visser decision rule. METHODS: 455 patients with early arthritis were studied. The diagnostic performance of the criteria was evaluated using methotrexate treatment within 1 year, expert opinion RA and erosive disease as 'gold standards'. Erosive disease was defined as a 0-3 year change in radiographic score of ≥5. RESULTS: The discriminative ability of the three criteria sets (2010 ACR/EULAR, 1987 ACR criteria and Visser algorithm) was similar with areas under the curve of 0.71-0.78 ('gold standard' methotrexate), 0.74-0.80 (gold standard expert opinion RA) and 0.63-0.67 (gold standard erosive disease after 3 years). The sensitivity of the 2010 ACR/EULAR criteria was highest with 0.85 (gold standard methotrexate). 86% of patients with RA and 51% of 'non-RA' patients according to the new criteria used methotrexate. CONCLUSION: The 2010 ACR/EULAR criteria were slightly more sensitive, but otherwise performed similarly to the older criteria. A high percentage of 'non-RA' patients used methotrexate, the gold standard for RA. The ability of the new criteria to identify patients with erosive disease was low, possibly owing to the effect of intensive treatment. | |
| 21515600 | Very early rheumatoid arthritis is the major predictor of major outcomes: clinical ACR rem | 2011 Jul | OBJECTIVES: To identify predictors of clinical remission as well as of no x-ray progression in a cohort of early rheumatoid arthritis (ERA) treated with a tight-control protocol. METHODS: A total of 121 consecutive patients with ERA were treated to reach European League Against Rheumatism (EULAR) and/or American College of Rheumatology (ACR) clinical remission with methotrexate (MTX) for 3 months, then with a combination with anti-tumour necrosis factor if the patient did not achieve a 44-joint Disease Activity Score (DAS44) ≤2.4. At baseline and after 12 months all the patients had hand and foot joint radiographs. Very early rheumatoid arthritis (VERA) was defined as a disease with symptoms of less than 12 weeks. RESULTS: In all, 46.3% of the patients reached DAS remission and 24.8% achieved ACR remission. More than 60% of patients reached remission with MTX. Male sex and an erythrocyte sedimentation rate <35 mm/h at onset arose as significant predictors of EULAR remission, while VERA disease was the only predictor of ACR remission. At baseline, 28.1% of the patients were erosive. Multivariate analysis demonstrated that the only independent predictor of erosiveness was 'not having VERA disease'. After 12 months, VERA was the only factor predicting a lack of new erosions. CONCLUSIONS: VERA represents the best therapeutic opportunity in clinical practice to achieve a complete remission and to stop the erosive course of rheumatoid arthritis. | |
| 22581564 | Use of abatacept in rheumatoid arthritis. | 2012 | Abatacept (CTLA-Ig), a modulator of T-lymphocyte activation, has been approved by the Swiss health regulatory agency Swissmedic for the treatment of active rheumatoid arthritis (RA). This article summarises the key trial findings for this biologic agent in RA in different situations such as early erosive rheumatoid arthritis (RA), biologic-naïve RA, RA before and after the use of methotrexate or TNF-inhibitors and includes safety information from these trials. Based on these data, recommendations for clinical practice in Switzerland are made by a panel of experts. | |
| 22026055 | [Ocular involvement and its' manifestations in rheumatoid arthritis patients]. | 2011 Sep | PURPOSE: To study the type, occurrence and nature of ocular involvement amongst patients with rheumatoid arthritis (RA), and to identify demographic, clinical and/or laboratory variables associated with eye involvement in RA. RESEARCH TYPE: Cross sectional research, retrospective METHODS: The research was conducted among 61 patients diagnosed with rheumatoid arthritis. The subjects were recruited for the research during their periodic visits to the Soroka Hospital Rheumatology Clinic. Comprehensive rheumatologic tests were administered and general health was examined with a prepared questionnaire. Additionally, the subjects' personal files were examined with data collected from general serum rheumatologic tests and details regarding medications administered. The patients were given a comprehensive eye examination, including a visual acuity examination, test for anterior and posterior fragments, a slit lamp examination after pupil dilation, for epithelial cell filaments, tests for dry eye symptoms, including a Schirmer's test, a tear breakup time test, and a corneal examination for epithelial cells and the existence of superficial punctate keratopathy. The subjects were also questioned regarding their dry eye syndrome and a specular microscopy test was performed. The assembled data was processed and analyzed with the aim of finding correlations between the subjective and objective sensations of dry eye symptoms and the activity of rheumatoid arthritis disease, blood tests, medications taken, and the patient's general state of health. RESULTS: The majority of the research subjects (90.2%) were women. Their average age was 51.9 +/- 13.21 years; 31.1% of the subjects complained of eye dryness and, during the eye examination, 85% were found to be suffering from dry eye. The study found a correlation between the objective indicators of keratitis sicca and the following parameters: laboratory values for SGOT (p < 0.03), ESR (p < 0.05), Cr (p < 0.05), TG (p < 0.03), LDL (p < 0.02), Hb (p < 0.01), ALP (p < 0.01), in addition to prednisone medication (p < 0.03, df = 2, x2 = 7.02) and methotrexate (p < 0.03, df = 2, x2 = 8.88). No correlation was found with the following parameters: age, disease duration, smoking, disease severity, other background diseases, and additional laboratory findings including RF and ANA measurements, and consuming other anti-rheumatoid arthritis medications. Similarly, no relation was found with the patients' various subjective syndromes. The average results of the specular microscopy test were 2116.15 +/- 416.59 for the right eye and 2125.67 +/- 446.14 for the left eye. CONCLUSIONS: The significance of the specular microscopy test results is that corneal damage found in rheumatoid arthritis patients occurs only to the external layer and does not affect the endothelial layer. The study indicates that keratitis sicca is prevalent among rheumatoid arthritis patients and must be taken into account regardless of the degree that the disease has progressed, because the severity of the dryness is not dependent on disease progression. Additionally, a discrepancy exists between the patients' subjective sensation of their eye condition and the objective findings of the study. | |
| 21776448 | [A short history of anti-rheumatic therapy - VI. Rheumatoid arthritis drugs]. | 2011 | The treatment of rheumatoid arthritis traditionally includes symptomatic drugs, showing a prompt action on pain and inflammation, but without any influence on disease progression, and other drugs that could modify the disease course and occasionally induce clinical remission (DMARDs or disease modifying anti-rheumatic drugs). This review describes the historical steps that led to the use of the main DMARDs in rheumatoid arthritis, such as gold salts, sulphasalazine, chloroquine and hydroxychloroquine, D-penicillamine, and other immunoactive drugs, including methotrexate, azathioprine, cyclosporin and leflunomide. The historical evolution of use of these drugs is then discussed, including the strategy of progressive ("therapeutic pyramid") or of more aggressive treatment, through the simultaneous use of two or more DMARDs ("combination therapy"). |