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ID PMID Title PublicationDate abstract
12858437 Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humani 2003 Jul OBJECTIVE: To evaluate the safety and pharmacokinetics of multiple infusions of a humanized anti-interleukin-6 (IL-6) receptor antibody, MRA, in patients with rheumatoid arthritis (RA). METHODS: In an open label trial, 15 patients with active RA were intravenously administered 3 doses (2, 4, or 8 mg/kg) of MRA biweekly for 6 weeks, and pharmacokinetics were assessed. Patients continued on MRA treatment for 24 weeks, and were then assessed for safety and efficacy. RESULTS: The treatment was well tolerated at all doses with no severe adverse event. Increased total serum cholesterol was detected as an MRA related reaction in 10/15 (66%) patients. There was no statistically significant difference in the frequency of adverse events among the 3 dose groups. There were no new observations of antinuclear antibody or anti-DNA antibody, and no anti-MRA antibody was detected. The T1/2 increased with repeated doses and as the dose increased. T1/2 after the 3rd dose of 8 mg/kg reached 241.8 +/- 71.4 h. In 12/15 (80%) patients whose serum MRA was detectable during the treatment period, objective inflammatory indicators such as C-reactive protein, erythrocyte sedimentation rate, and serum amyloid A were completely normalized at 6 weeks, although there was no statistically significant difference in efficacy among the 3 dose groups. Nine of 15 patients achieved ACR 20 at 6 weeks. At 24 weeks, 13 patients achieved ACR 20 and 5 achieved ACR 50. CONCLUSION: Repetitive treatment with MRA was safe and normalized acute phase response in patients with RA. Optimal dosing schedule was not defined in this small study, but maintenance of serum MRA concentration seemed important to achieve efficacy.
12468117 Establishing a standard for patient-completed instrument adaptations in Eastern Europe: ex 2003 Jan The widely used generic patient-completed measures of health status were developed in the USA or the UK. Few Eastern European versions of these measures have been produced and these have used questionable translation methodologies. Clinical trials now commonly include patients from Eastern Europe and require the use of patient-completed instruments. The absence of such instruments led to the development of a Hungarian version of the Nottingham Health Profile (NHP). The adaptation process employed (translation, field-testing and psychometric assessment) also served as a test of whether the standardised rigorous methodology used for adapting the NHP could be applied in Eastern Europe. Few problems were found in producing a conceptually equivalent Hungarian NHP that was acceptable to interviewees. Reliability and internal consistency of the Hungarian NHP were comparable to other language versions. The measure also correlated as expected with perceived physical disability, general health, disease severity and rating of day. This successful adaptation confirms the value of the methodology applied. The Hungarian NHP will be invaluable as an outcome measure in both clinical and health economic trials and (in the absence of a generic quality of life instrument) as a comparator instrument for the validation of future Hungarian adaptations of disease-specific quality of life instruments.
12754542 Rheumatoid arthritis. Radiological changes in the cervical spine. 2003 Apr OBJECTIVE: To describe the radiographic cervical spine changes in rheumatoid arthritis patients. METHODS: Forty-nine patients (37 females and 12 males) diagnosed with rheumatoid arthritis at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia, between June 1998 and June 2000, were studied for their radiographic cervical spine changes. Their mean age at disease onset was 41.4 +/- 13.4 years (range of 18-73) and mean duration of the disease was 9.1 +/- 6.28 years (range of 2-34). Their demographic data including rheumatoid factor status was obtained. Standard conventional radiographs of cervical spine were obtained to study the cervical spine changes. RESULTS: Cervical spine radiographic changes were found in 34 patients (27 females and 7 males), 10 had subluxation (7 with atlanto-axial subluxation, 2 with sub-axial subluxation, and one with lateral subluxation). No vertical impaction was seen. Erosion of odontoid process was seen in one patient. All were rheumatoid seropositive. CONCLUSION: Cervical spine changes in patients with rheumatoid arthritis are common, in particular subluxation in the upper cervical spine. Our study showed somewhat lesser prevalence of these changes. These were clinically correlated with disease duration, female sex, and rheumatoid factor, but were not statistically significant.
12375313 Clinical usefulness of genetic information for predicting radiographic damage in rheumatoi 2002 Oct OBJECTIVE: To determine whether knowledge of genetic information aids the prediction of radiographic damage for patients with rheumatoid arthritis (RA) in whom extensive sociodemographic, family history, clinical, and immunologic information is available. METHODS: Subjects included 146 Caucasian women who were participants in a community based longitudinal study of RA. Our primary outcome measure was the severity of erosive disease. Nongenetic covariates included age at RA onset, disease duration, family history of RA, education level, family income, baseline values of function, painful and swollen joint groups and pain rating, and rheumatoid factor positivity. All women were genotyped for the HLA-DRB1 shared epitope (SE) and the tumor necrosis factor a (TNFa) microsatellite. Likelihood ratio tests (LRT) were performed to evaluate the usefulness of genetic information for predicting radiographic damage in RA, after adjusting for nongenetic covariates. Receiver operating characteristic (ROC) curves displaying the sensitivity and specificity of combinations of nongenetic and genetic information were derived, and the areas under the curves (AUC) were compared. RESULTS: Genetic information contributed significantly to the prediction of radiographic damage in RA even after adjusting for all nongenetic covariates (p value for LRT = 0.0019). The odds ratio describing the risk of severe erosive disease among individuals who had inherited both the SE and TNFa allele 11 (TNFa11) was 7.6 compared to individuals who were SE and TNFa11 negative. Analysis of ROC curves confirmed the usefulness of genetic information. CONCLUSION: Genetic information is useful for predicting radiographic damage in RA even for patients in whom extensive sociodemographic, family history, clinical, and immunologic information is available.
12135431 Association of NRAMP1 promoter gene polymorphism with the susceptibility and radiological 2002 Apr The natural resistant-associated macrophage protein 1 (NRAMP1) has been proposed as a candidate gene for the susceptibility to autoimmune diseases. In this study, the possible role of the functional polymorphism located at the promoter region of NRAMP1 gene in the susceptibility and clinical outcome of rheumatoid arthritis (RA) was investigated. A total of 141 Spanish RA patients and 194 controls previously typed for HLA-DRB1* were genotyped for the NRAMP1 polymorphism. No significant differences in the distribution of frequencies among RA patients and controls were observed. Nevertheless, when patients and controls were stratified according to their HLA shared epitope (SE) status, an increase of 2/2 genotype among SE-negative (SE-) patients with respect to SE- controls was observed (23% vs 7%, OR = 3.74, 95% CI 1.31-10.72). In addition, the possible role of this polymorphism in the clinical course of RA was investigated in a subgroup of 82 patients who were prospectively followed during a mean of 9 years. After follow-up, an increase of patients with the homozygous 2/2 genotype was detected among those with severe small joint radiological involvement: 73% of patients 2/2 had a severe form in contrast to 37% of patients with the genotype 2/3 and 30% of patients bearing 3/3 OR = 5.45, 95% CI 1.14-34.24). In conclusion, NRAMP1 gene promoter polymorphism could influence the radiological severity of rheumatoid arthritis and disease susceptibility, particularly in individuals lacking HLA-linked risk factors.
12148597 Chemically modified ribozyme targeting TNF-alpha mRNA regulates TNF-alpha and IL-6 synthes 2002 Jul Rheumatoid arthritis (RA) is chronic polyarthritis in which a variety of inflammatory cytokines play a role. Since tumor necrosis factor-alpha (TNF-alpha) is one of the most important cytokines in the pathogenesis of RA, we evaluated the feasibility of ribozymes as a therapeutic agent to control the inflammatory process of RA synovium. A hammerhead ribozyme against TNF-alpha was chemically modified to increase nuclease resistance and added to RA fibroblastlike cell cultures without using a delivery system. The cellular uptake of fluorescent-labeled ribozyme into synovial cells was found to last at least 48 hr by confocal laser scanning microscopy. The ribozyme targeting TNF-alpha gene inhibited both the expression of TNF-alpha mRNA and the secretion of TNF-alpha and IL-6. The cytotoxic effect by the ribozyme on synovial cells was negligible when determined by an alamar blue assay. Chemically modified ribozymes designed to suppress the TNF-alpha gene may be potential as a therapeutic agent for rheumatoid arthritis.
12180719 Cardiovascular risk factors in Chilean patients with rheumatoid arthritis. 2002 Aug OBJECTIVE: Epidemiologic studies have shown an increased mortality rate in patients with rheumatoid arthritis (RA). The most common cause of death in these patients is cardiovascular disease. We estimated the frequency of and examined risk factors for coronary artery disease in Chilean patients with RA. METHODS: Fifty-four patients with RA were studied: 87% were women, with a mean age (+/- standard deviation) of 51 +/- 13 yrs, 92% were rheumatoid factor positive, and 51% had radiological erosions; 32 age and sex matched healthy controls were studied. Traditional cardiovascular risk factors and RA-specific variables were determined. Lipid profile, lipoprotein(a) [Lp(a)], homocysteine, ultrasensitive C-reactive protein (CRP), anticardiolipin (aCL), anti-beta2-glycoprotein I (anti-beta2-GPI) and antioxidized low density lipoprotein (ox-LDL) antibodies were measured. RESULTS: Median concentration of homocysteine was significantly higher in patients with RA than in controls: 10 (range 5.4-37.4) versus 8.3 (3.6-17.8) micromol/l (p = 0.001). Patients with RA who gave a history of cardiovascular disease had the highest concentrations of homocysteine: 15.1 (13.1-19.7) versus 9.9 (5.4-37.4) micromol/l (p = 0.001). We found no differences between patients and controls in lipid profiles or Lp(a), or for other traditional risk factors. Anti-ox-LDL, IgG aCL, and IgG anti-beta2-GPI antibody levels were similar in both groups. IgM subtypes were higher in patients with RA than in controls, but in low titers. CONCLUSION: Our data suggest that a high homocysteine concentration could be an important risk marker for cardiovascular disease in patients with RA.
14745976 From the cradle to the clinic: VEGF in developmental, physiological, and pathological angi 2003 Nov Formation of new blood vessels, which is fundamental in embryonic development, occurs through a combination of angiogenesis and vasculogenesis. Angiogenesis also plays a vital role postnatally, especially in reparative processes such as wound and fracture healing. Some of these events, especially in fracture healing, recapitulate processes observed in developmental angiogenesis. However, dysregulated angiogenesis is well documented to underlie a number of pathological disorders, including rheumatoid arthritis (RA). The vascular endothelial growth factor (VEGF)/VEGF receptor system is the best characterized regulator of angiogenesis. VEGF is expressed in a range of cells in response to soluble mediators (such as cytokines and growth factors), cell-bound stimuli (such as CD40 ligand), and environmental factors (such as hypoxia). As a consequence, this molecule is vital in the modulation of physiological and pathological angiogenesis. This review will focus in particular on the role played by VEGF in embryogenesis and skeletal growth, in fracture healing (in which increased angiogenesis is likely to be beneficial in promoting union), and in RA (in which excessive angiogenesis is thought to play a significant role in disease pathogenesis). In the not-too-distant future, targeting VEGF may prove to be of benefit in the treatment of diseases associated with excessive or aberrant angiogenesis, such as malignancies and RA.
12519043 Human fetal adrenal transplant: a possible role in relieving intractable pain in advanced 2002 BACKGROUND: The art of transplant surgery has gone a long way in establishing itself as an important discipline in medicine with the support of molecular biology, immunology, biochemistry, etc., as the ultimate treatment for the restoration of function of a failing organ. With the progressive increase in the life expectancy of human beings, there is an increasing discrepancy in the demand and supply of organ grafts. A less efficient alternative could be synthetic or mechanical grafts. Nucleated cell therapy, that is, cellular transplant, is a promising new area of study with its proven efficacy in neuro-degenerative disorders, hematopoietic disorders, diabetes and trauma-induced tissue loss, to name a few. Human fetal cell/tissue with its intrinsic hypo-antigenic advantage (up to 20 weeks of study), could be an interesting area of cellular/tissue transplant. Our research group has earlier reported on the safe use of umbilical cord whole blood and the successful transplant of a human fetal lung, heart, pancreas, liver, thymus, in an artificially prepared vascular subcutaneous axillary fold in which there was no feature of hyper-acute, acute or chronic rejection of the graft in HLA- and sex-randomized adult recipients, without concomitant immunosuppressives or radiation of the host to potentiate the survival of the fetal graft (within 20 weeks of gestation) within the lowest observation period of one month. The present study was aimed at examining the role of developing fetal adrenal transplants for patients with rheumatoid arthritis and severe pain due to involvement of inflammatory and neuropathic components. MATERIALS AND METHOD: Ten cases were enrolled in the present study after thorough informed consent and approval by the ethical committee of the institute. The age of the patients varied from 50 to 76 years and the group was comprised of three males and seven females. The age of the adrenal grafts varied from 16 to 20 weeks and these were collected from mothers admitted for hysterotomy and ligation. These long-standing rheumatoid patients (suffering for five to 15 years), presented with at least four of the seven 1987 revised criteria of the American College of Rheumatology for diagnosis of rheumatoid arthritis. A 2.5 cm long and 2 cm deep tissue space was dissected and prepared in each transplant recipient at the axilla using diathermy and knife after infiltrating the site with one percent lignocaine solution. The tissue collected from the consenting mother undergoing hysterotomy and ligation was inserted into this site, and the site was closed with 00 atraumatic vicryl. All necessary pre- and postoperative surgical precautions were taken to prevent infections. Sequential total count and differential count of leucocytes were undertaken to analyze the impact of the transplant on the host. After one month, a part of the transplanted fetal tissue was recovered for histological staining to examine whether there was any graft versus host reaction. RESULTS AND ANALYSIS: All ten patients tolerated the transplant procedure well. There was no fever, intractable pain or any other specific serious side-effect which could justify the removal of the transplant before one month. There was no discharge from the incision site and the healing of the scar was by and large normal. There was no unusual leucocytosis, lymphocytosis and the retrieved graft tissue did not suggest transplant rejection. However, there was definite pain relief, reduction in swelling and improvement of mobility of varying degree in a majority of the patients which was perceivable from the 15th day onwards. There was also a sense of well being (in 80%) and a gain in weight of three pounds or more (in 70%) among the fetal transplant recipients. DISCUSSION AND CONCLUSION: To understand the underlying mechanism, in case of pregnancy immunotolerance, we are of the opinion that emphasis should be placed on the role of non-specific and non-cytopathic blocking antibodies produced during pregnancy. The hypo-antigenicity of the developing human fetal system may possibly contribute to the production of this blocking antibody during pregnancy, and thus may play a role in the lack of recognition by the host's HLA system. This behaviour of the developing human fetal tissue provides some advantages over adult tissue for fetal cell/tissue transplantation purposes. The relief of pain, inflammation and restoration of mobility may be due to the effect of the transplanted adrenal graft, with the medullary component contributing to endorphin-like substance liberation and the cortical component contributing to glucocorticoid synthesis.
15593224 Association of rheumatoid arthritis treatment response and disease duration with declines 2004 Dec OBJECTIVE: To examine the association of treatment response and disease duration with changes in rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody levels among patients with rheumatoid arthritis (RA). METHODS: The study sample included 66 RA patients who completed double-blind, randomized clinical protocols and for whom baseline and followup serum samples were available. Anti-CCP and RF levels were measured using commercially available assay kits. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to describe the association of response and disease duration with declines in antibody levels. RESULTS: Patients had a mean +/- SD age of 49.9 +/- 12.0 years and were predominantly female (n = 51; 77%). The mean +/- SD duration between the times at which the baseline and followup serum samples were obtained was 13.7 +/- 8.6 months. Among the 64 subjects with positive antibody at baseline, 33 (52%) experienced a > or =25% reduction in the anti-CCP antibody level during the course of treatment, and 35 patients (55%) had a > or =25% reduction in RF. After adjustment for the baseline anti-CCP antibody level, only a shorter disease duration (< or =12 months) was significantly associated with a decline in the level of anti-CCP antibody (OR 3.0, 95% CI 1.0-8.8), and no association with treatment response was observed. Conversely, treatment response was the only significant determinant of a decrease in RF levels (OR 3.6, 95% CI 1.2-10.4). CONCLUSION: Shorter disease duration predicts greater declines in anti-CCP antibody levels with treatment in RA. Although treatment response is a robust determinant of a decrease in RF, it does not appear to be associated with declines in the anti-CCP antibody level.
12491118 [Therapy optimization studies torn between science and funding]. 2002 There is no doubt that clinical studies are valuable cornerstones in the development of rational diagnostics and therapy, for the patients' safety, for quality assurance as well as for the development of a body of evidence in medicine. Well recognized multicentric study groups are active in several medical disciplines in Germany. Public funding resources however are miserable as compared to other countries. For example in hematology and oncology funds are almost exclusively available by private foundations as the Deutsche Krebshilfe only. Additionally physicians and institutions who are actively promoting clinical studies have to pay charges for patients' insurance and for registration of studies by the authorities. Furthermore there are increasing difficulties obtaining reimbursement for patients' care in clinical studies. In this context outdated regulations of the German Sozialgesetzbuch V lawbook play an important role. In summary a pronounced reform deficit paired with bureocratic tendencies has become manifested. The most important demands are in this situation: a reliable and realistic regulatory basis for treatment-related clinical studies has to be created. Studies on treatment strategies with registered drugs have to be free from the obligatory patients' insurance which is required for study with non-registered drugs. It has to be clarified that in these studies some regulations of good clinical practice as obligatory external monitoring and source data verification are not feasible and will not be required. The Sozialgesetzbuch V has to be adapted and the actual ban of clinical studies in private practice has to be ended. Treatment related clinical studies have to be free from charges of ethical committees and regulatory authorities. Thereby the financial overload of clinical studies could be reduced and some motivation for further bureocratic proliferation is removed. Finally a longterm, reliable funding resource has to be created independently from the pharmaceutical industry. A possible model could be a foundation for treatment-related studies which is financed by public funds and by funds from the reimbursement companies.
12712258 Expression of fibronectin splice variants and oncofetal glycosylated fibronectin in the sy 2004 Jan OBJECTIVE: The aim of this study was to define and compare the expression of fibronectin (Fn) isoforms in synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Using monoclonal antibodies specific for total Fn, extra domain (ED)-A Fn, ED-B Fn, and oncofetal glycosylated Fn, we studied the expression of the Fn isoforms in synovium. Furthermore, in situ hybridization for the detection of ED-B Fn mRNA including a double labeling technique for the detection of cell type was applied. RESULTS: Strong expression of total Fn, ED-A Fn, oncofetal glycosylated Fn and, to a lesser extent, ED-B Fn could be demonstrated in the synovial lining layer in both RA and OA. Stromal and vessel expression of Fn isoforms was more prominent in RA tissue. Pannus tissue showed strong labeling with ED-B Fn. CONCLUSION: The expression of alternatively spliced isoforms of Fn is associated with tissue remodeling and, as a partial process of this phenomenon, with neovascularization rather than underlying disease, X-ray status, or parameters of acute inflammation. In the lining layer, Fn expression correlates with hyperplasia associated with cell recruitment but not with proliferative status. Most remarkably, the expression of ED-B Fn in pannus tissue seems to be associated with the invasive phenotype described in RA tissue.
12455817 HLA haplotypes and susceptibility to rheumatoid arthritis. More than class II genes. 2002 Our aim was to examine, using microsatellite (ms) markers, the contribution of the telomeric part of the HLA region to rheumatoid arthritis (RA) predisposition in the Spanish population. We have looked at the distribution of DQB1, DRBI and five ms loci (D6S1014, D6S273, D6STNFa, MIB and C1-2-5) within the HLA region in 147 Spanish RA patients and 202 control subjects. A total of 19 conserved ms configurations were observed, twelve of them in linkage disequilibrium with particular DQB1-DRB1 haplotypes. Interestingly, haplotype c1 (DQB1*0201-DRB1*0301-D6S1014*143-D6S273*139-D6STNFa*99-MIB*350-C1-2-5*196) was significantly associated with RA predisposition. As part of this haplotype, the MIB*350 allele was found to be a risk factor independently of the RA-predisposing haplotypes. The present results along with data from others prove the existence of a second predisposing locus located inside the MHC region, and suggest that might be located within the TNFa-HLA-B region.
15238644 Contrast-enhanced dynamic and static MRI correlates with quantitative 99Tcm-labelled nanoc 2004 Nov OBJECTIVE: The aim of this study was to evaluate the roles of contrast-enhanced dynamic and static magnetic resonance imaging (MRI) and quantitative 99Tcm-labelled nanocolloid (NC) scintigraphy in detecting wrist joint inflammation in early rheumatoid arthritis (RA) patients. METHODS: Twenty-eight early RA patients (median symptom duration 5 months, range 1-12 months) underwent MRI, NC scintigraphy, laboratory and clinical examinations. Static wrist MRI scans were retrospectively scored for synovitis, bone oedema and erosions by two independent readers using the recently published rheumatoid arthritis MRI scoring system (RAMRIS). Twenty NC scans were analysed quantitatively by measuring maximum 99Tcm-NC uptake in three small areas of each wrist. From the same locations on the wrists, dynamic MRI gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) enhancement rates (E-rate) were measured. The average 99Tcm-NC uptake of the whole wrist region was also measured and average E-rates were calculated. Correlations between MRI and NC scintigraphy measurements were calculated. Correlations between imaging methods of the wrist and the global measures of inflammation (laboratory and clinical examinations) were also assessed. RESULTS: Strong correlations emerged between maximal 99Tcm-NC uptake and MRI E-rates, reflecting similar performance of the methods in detecting local synovial inflammation. 99Tcm-NC uptake and MRI E-rate correlated with semiquantitative scoring of synovitis and bone oedema from static MRI scans. The erythrocyte sedimentation rate (ESR) correlated with MRI scores, E-rate and 99Tcm-NC uptake. No correlation between the clinical parameters and the imaging methods was detected. Inter-observer reliability for scoring synovial hypertrophy, bone oedema and bone erosions from static MR images were high (single-measure fixed-effects intra-class correlations 0.87, 0.93 and 0.91 respectively). Intra-observer reliability for E-rate and 99Tcm-NC measurements of 10 randomly picked scans was found to be high, with an intra-class correlation of 0.92; 95% confidence interval (CI) 0.84-0.96 and 0.99; 95% CI 0.98-1.00, respectively. CONCLUSIONS: Objective information about wrist joint inflammation can be obtained with contrast-enhanced dynamic MRI and quantitative 99Tcm-labelled NC scintigraphy. MRI also allows visualization and semiquantitative scoring of bone oedema and erosions of the wrist. Dynamic MRI and NC scintigraphy are safe and easy to perform, and they can be used in a long-term follow-up of rheumatoid patients.
12879272 Glutathione S-transferase M1, T1, and P1 gene polymorphisms and carotid atherosclerosis in 2004 May We assessed the contribution of genetic polymorphisms of glutathione S-transferase M1 ( GSTM1), T1 ( GSTT1), and P1 ( GSTP1, Ile105Val) to carotid atherosclerosis in 40 postmenopausal rheumatoid arthritic (RA) women without histories of smoking. We measured mean intima-media thickness (IMT) and plaque of the common carotid arteries by ultrasonography and evaluated relationships among the known risk factors for atherosclerosis, genetic polymorphisms, RA outcomes, and markers of inflammation. Subjects with the GSTT1-0 genotype had greater IMT ( P<0.05). On univariate analysis, carotid IMT was positively associated with age, systolic BP, antihypertensive drug use, and the GSTT1-0 genotype ( P<0.05). When compared to subjects with a double-positive GSTM1/T1 genotype, IMT in those with concurrent lack of the GSTM1 and GSTT1 genes was significantly increased ( P=0.008). This study suggests that the GSTT1-0 genotype might have an interaction with carotid atherosclerosis related to RA in Korean postmenopausal RA women without histories of smoking.
15140783 Long term evaluation of radiographic disease progression in a subset of patients with rheu 2004 Jun OBJECTIVES: To assess the effect of long term (>2 years) leflunomide treatment on radiographic progression in patients with RA. METHODS: Patients treated with leflunomide for >2 years in one of three phase III trials and subsequent extensions, for whom paired, evaluable radiographs at baseline and study end point were available, were included. Radiographs of hands and feet were assessed according to the modified Sharp/van der Heijde scoring method, for erosion, joint space narrowing, and total score. Changes from baseline were assessed, and a predicted yearly progression rate estimated for each patient. RESULTS: 128 of the original 824 patients were included, with mean disease duration 5.1 years and mean leflunomide treatment duration 4.3 years until the final x ray examination. The mean change from baseline in total score was 8.6 with yearly adjusted rate 1.9, and the median change was 2 with yearly adjusted rate 0.5, compared with 7.9 and 4.9, respectively, before leflunomide treatment. After treatment, the rate improved in 92/128 (72%) patients and deteriorated in 21/128 (16%). In 42 (33%) patients who had a total score >0 at baseline, no radiographic progression occurred after leflunomide treatment. CONCLUSIONS: In a subset of patients who continued treatment long term, leflunomide treatment reduced the rate of radiographic damage.
12810423 Effectiveness of a measurement feedback system on outcome in rheumatoid arthritis: a contr 2003 Jul BACKGROUND: With the help of a measurement feedback system, the treatment strategy for individual patients with rheumatoid arthritis (RA) can be adjusted to achieve optimal control of disease activity. OBJECTIVE: To study whether a measurement feedback system is effective in reducing disease activity in patients with RA. METHODS: Forty eight rheumatologists and 264 patients participated in a controlled clinical trial. A three month control period was followed by a 12 month period, where feedback on disease activity, disability, and damage was provided to the rheumatologist. The primary outcome measure was the rheumatoid arthritis disease activity index (RADAI). RESULTS: The feedback system was used for 142/228 (62%) patients. Disease modifying antirheumatic drug changes occurred in 69/169 (41%) patients. In patients with high disease activity and feedback use (n=70), the RADAI decreased in the feedback period by -0.27 points per 30 days (p<0.05), as compared with the control period. Patients for whom the feedback system was used had a better outcome than non-users. CONCLUSION: Much more training on the use of a feedback system and outcome measures, as well as the inclusion of explicit treatment guidelines will be necessary to increase the clinical use of measurement feedback and, possibly, to reduce disease activity for a larger number of patients with RA.
14719190 Value of antibodies to citrulline-containing peptides for diagnosing early rheumatoid arth 2003 Dec OBJECTIVE: To compare the diagnostic values of antiperinuclear factor (APF), antikeratin antibody (AKA), and anti-cyclic citrullinated peptides (anti-CCP) to discriminate between patients with and without rheumatoid arthritis (RA) and to determine the diagnostic value of anti-CCP used alone or with other tests. METHODS: Two hundred and seventy patients with early arthritis underwent standardized investigations in 1995-1997. The clinical utility of APF, AKA, and anti-CCP in first-visit sera was evaluated using receiver-operating characteristic curves. Combinations of anti-CCP with other laboratory tests were assessed by multiple logistic regression. RESULTS: Anti-CCP, APF, and AKA were not perfectly correlated with one another. Anti-CCP with 53 UI as the cutoff was 47% sensitive and 93% specific, versus 52% and 79%, and 47% and 94%, for APF and AKA, respectively. Multiple logistic regression selected anti-CCP, AKA, IgM-rheumatoid factor (RF) ELISA, and the latex test. CONCLUSION: Rheumatologists can routinely use 2 or 3 tests for diagnosing RA (latex and/or IgM RF ELISA, and either AKA or anti-CCP ELISA) and can add a third or fourth test when the diagnosis remains in doubt.
12746893 Dynamic gadolinium-enhanced magnetic resonance imaging of the wrist in patients with rheum 2003 May OBJECTIVE: To determine the efficacy of dynamic gadolinium-enhanced magnetic resonance imaging (MRI) of the wrist in the evaluation of disease activity in patients with rheumatoid arthritis (RA). METHODS: Thirty-six patients with RA (with different degrees of disease activity) and 5 healthy controls were studied. MRI was performed with a low-field (0.2T), extremity-dedicated machine. After an intravenous bolus injection of gadolinium-diethylenetriamine pentaacetic acid, 20 consecutive fast spin-echo images of 3 slices of the wrist were obtained every 18 seconds. RESULTS: The curves of synovial membrane enhancement identified the following 2 groups: controls and RA patients in remission, and RA patients with active or intermediately active disease. Both the rate of early enhancement (REE) and relative enhancement (RE) were significantly higher in patients with active RA than in those with inactive RA and controls. The REE and RE were significantly correlated with the number of swollen joints (P < 0.00001 and P = 0.003, respectively), the number of tender joints (P < 0.00001 and P = 0.004, respectively), the Ritchie index (P = 0.0002 for both REE and RE), the Disease Activity Score (P = 0.0004 and P = 0.0008, respectively), the Health Assessment Questionnaire (HAQ) (P = 0.0002 and P = 0.0007, respectively), early morning stiffness (P = 0.001 and P = 0.009, respectively), the C-reactive protein level (P = 0.015 and P = 0.03, respectively), the erythrocyte sedimentation rate (P = 0.03, RE only), and alpha2 globulins (P = 0.036 and P = 0.028, respectively). CONCLUSION: Our data support use of dynamic MRI for discriminating active from inactive RA. Enhancement curves are associated not only with laboratory and clinical indicators of inflammation, but also with the HAQ, a relevant predictor of RA functional outcome. This technique can be repeated frequently and is an excellent candidate for the ideal method for the followup of patients with RA.
12188437 DRB1*04 subtype in Thai patients with rheumatoid arthritis. 2002 Jun Rheumatoid arthritis (RA) in a Thai population is significantly associated with HLA-DR4. The frequency of DR4 was 43 per cent in RA patients and 20 per cent in the healthy controls (p = 0.00008, OR = 3.06, 95% CI = 1.71, 5.52). To analyze which DR4 alleles were associated with the disease, the authors subtyped 52 DR4-positive RA patients compared to 28 DR4-positive healthy controls by amplification with DR4-specific primers followed by direct sequencing. Six DR4 alleles (DRB1*0401, *0403, *0404, *0405, *0406, and *0410) were found in the RA patient group while 5 alleles (DRB1*0401, *0403, *0405, *0406, and *0407) were found in the control group. Both groups were predominated by DRB11*0405, but there was a significant increase in the frequency of DRB1*0405 in DR4+ RA patients compared to DR4+ healthy controls (84.6% vs 46.4%, p = 0.0008, OR = 6.35, 95% CI = 1.96, 21.08). DR4 which shared epitope alleles (DRB1*0401, *0404, *0405) were observed in 47 (90.3%) DR4+ patients and 15 (53.5%) DR4+ controls (p = 0.0005, OR = 8.15, 95% CI = 2.29, 33.2). In addition, the authors found that DRB1*0403 was significantly decreased in DR4+ RA patients compared to controls (p = 0.0065, OR = 0.07, 95% CI = 0, 0.67).