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ID PMID Title PublicationDate abstract
15482266 Telopeptides as markers of bone turnover in rheumatoid arthritis and osteoarthritis. 2004 Sep AIMS: The aim of the present study was to determine if urinary excretion of type I collagen N-terminal telopeptides (UrNTx) and deoxypyridinoline (UrDPD) and serum levels of type I collagen C-terminal telopeptides (SeCTx) differed in patients with rheumatoid arthritis (RA) compared with populations matched for age and gender with and without osteoarthritis (OA). The correlation of markers of bone turnover with disease activity in patients with RA or radiographic severity in patients with OA was also examined. METHODS: Patients with RA aged >50 years (men) and >60 years (women) were identified from computer databases at two tertiary referral centres for rheumatology. Strict exclusion criteria were applied to avoid the effects of factors known to influence markers of bone turnover. Patients with RA and OA were matched for age and sex with a control population free of known arthritic disease and a population with OA. Bone markers were assayed in serum and urine. Urine markers were measured on three consecutive days and mean values used to minimize day-to-day variability of these analytes. RESULTS: The level of UrNTx was elevated in patients with RA compared with normal controls and patients with OA. UrNTx and UrDPD correlated with markers of disease activity in patients with RA (erythrocyte -sedimentation rate and C-reactive protein), but not with -clinical signs of inflammation (swollen and tender joint counts). Patients with OA failed to show any correlation between markers of bone turnover and radiographic severity. CONCLUSIONS: These data support a role for the use of UrNTx and UrDPD in further studies of the patho-physiology of RA and in longitudinal studies designed to modify the course of clinical disease.
12518535 [Functional ability and parameters of disease activity in rheumatoid arthritis]. 2002 After the pain, the loss of functional ability is the most important sign of severity of the disease for patient who suffer from rheumatoid arthritis (RA). Our research is based on the correlation between functional disability with other parameters which determine the course of a disease, its activity and the level of its progression. The sample consists of 40 patients with RA, with mean age 56.67 + 10.1 and mean disease duration 11.1 + 7.69. We examined functional ability of the patient with Health Assessment Questionnaire-HAQ (0-3), pain with Visual Analogue Scale-VAS (0-100), duration of disease, acute phase reactant, morning stiffness, joint counts (28), Ritchie articulare index, radiographic changes and range of motion. Radiographic changes are measured with Short Erosion Scale--SES (Score 0-60), and range of motion with Numerical model of range of motion (1-5). A stronger correlation of HAQ was found with most of the disease activity parameters, but not with acute phaze reactant and the duration of disease. Strong correlation of HAQ exists with the number of tender joints (p < 0.001), number of swelling joints (p < 0.05), with VAS (p < 0.001), Ritchic articulare index (p < 0.001), morning stiffness (p < 0.01), range of motion (p < 0.001) and radiographic progression (p < 0.01). The received correlations say that duration of disease and lab, results do not have an influence on functional ability, but the increase of pain, radiographic progression of the disease and the reduction of range of motion influence aggravation of functional status. Drugs which lead to decrease of pain and radiographic progression, as well as physical therapy which increases range of motion will stop functional disability.
14522089 Functional categorization of HLA-DRB1 alleles in rheumatoid arthritis: the protective effe 2003 Oct Because of past recombination event, human leukocyte antigen (HLA) alleles that are not closely related in overall sequence may come to resemble each other in areas coding for peptide binding regions (PBR) of HLA molecules. Peptide binding is likely to be important for the role of HLA molecules in autoimmune disease. As a result, it has been suggested that a strategy of searching for HLA disease associations that groups alleles in functional categories based on PBR motifs may be more successful than conventional strategies based on studying different alleles. Using such functional categorization, we examined the possibility of discriminating subcategories of HLA-DRB1 alleles associated with rheumatoid arthritis (RA) in a Southern French population. HLA-DRB1 genotyping was performed by polymerase chain reaction with sequence-specific oligonucleotide hybridization or sequence-specific primers. HLA-DRB1 alleles were classified according to a functional categorization that defined seven similar subregion structures or restrictive supertype patterns (RSPs) within pocket 4 of HLA-DR peptide binding groove as the molecular basis for grouping these alleles. HLA-DRB1* RSPs "A," "De," "Q," "Dr," "E," " R," and "a" association with susceptibility or resistance to disease was then studied in 200 RA patients versus 200 controls. DRB1* RSP "A" containing the shared epitope alleles (DRB1*0101, *0102, *0401, *0404, *0405, *0408, *1001, *1402; odds ratio [OR] = 4.35; pc < 0.001) had a predisposing effect, with double-dose effect as expected, OR 6.68 (pc < 0.001). Among the six remaining RSPs, two had significantly protective effect: DRB1* RSP "De" (DRB1*0103, *0402, *1102, *1103, *1301, *1302, *1304; OR = 0.33; p(c) < 0.001), and DRB1* RSP "Q" (DRB1*0701; OR = 0.40; pc < 0.001). One had non-significantly protective effect: DRB1* RSP "Dr" (DRB1*08, *1101, *1104, *1106, *12, *1303, *16; OR = 0.68; p < 0.05, pc = not significant [NS]). Three had neutral effect: HLA-DRB1* RSPs "E" (DRB1*0403, *0407, *0901, *1401; OR = 0.71; p = NS), " R" (DRB1*0301, *0302; OR = 0.76; p = NS), and "a" (DRB1*1501, *1502; OR = 0.94; p = NS). The functional categorization allowed us to discriminate among the HLA-DRB1 alleles those that confer a predisposing effect, a neutral effect, and a protective effect in RA.
15142259 Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis. 2004 Antibodies directed to citrullinated proteins (e.g. anti-CCP [cyclic citrullinated peptide] antibodies) are highly specific for rheumatoid arthritis (RA). These antibodies are produced at the site of inflammation in RA, and therefore citrullinated antigens are also expected to be present in the inflamed synovium. We discuss literature showing that the presence of citrullinated proteins in the synovium is not specific for RA. The RA-specific antibodies are therefore most likely the result of an abnormal immune response that specifically occurs in RA patients. It was recently shown that presence of anti-CCP antibodies precedes the onset of clinical symptoms of RA by years. It thus appears that it may take years for initial events that cause the generation of anti-CCP antibodies to develop into full-blown disease.
16734121 Clinical usefulness of basic fibroblast growth factor and E-selectin in patients with rheu 2004 Angiogenesis plays an important role in the pathogenesis of rheumatoid arthritis (RA). This study assesses basic fibroblast growth factor (bFGF) as an angiogenic factor and soluble E-selectin (sE-sel) as an angiogenic mediator in RA patients and correlates their levels in serum and synovial fluid (SF) with disease activity, functional status and joint derangement. Thirty RA patients and 15 osteoarthritis (OA) patients were clinically, radiologically and laboratory investigated. bFGF, sE-sel, interleukin -1 beta (IL-1beta) and IL-6 in serum of patients and 15 healthy subjects and in SF tapped from knee joints of 9 RA and 9 OA patients were measured by ELISA. Both serum bFGF and sE-sel were significantly elevated in RA compared to OA patients and controls. These levels correlated positively with functional class stages of the disease. SF levels of bFGF and sE-sel showed significant increase in RA than OA patients. Both levels showed positive correlation with each other and with disease functional stages. A positive correlation was also found between SF bFGF with grades of joint derangement assessed radiologically. No significant correlations were observed between bFGF or sE-sel and clinical parameters of disease activity or other biochemical markers. In conclusion, serum and SF b-FGF and sE-sel may be considered as makers of functional status of RA patients. SF bFGF seems to reflect progressive joint derangement.
15730740 [Human cartilage glycoprotein 39 mRNA expression in peripheral blood and synovium mononucl 2004 Dec OBJECTIVE: To investigate the expression of human cartilage glycoprotein 39 (HC gp-39) in peripheral blood mononuclear cells (PBMC) and synovium of rheumatoid arthritis (RA) patients. METHODS: Levels of HC gp-39 mRNA were detected by reverse transcription-polymerase chain reaction in PBMC of 31 patients with RA, 6 with osteoarthritis (OA), 10 with spondylarthropathy (SpA), 5 with systemic lupus erythematosus (SLE), and of 10 healthy controls. Levels of HC gp-39 mRNA were also detected in synovium of 7 patients with RA and 5 with OA. The expression of HC gp-39 was semi-quatificated by HC gp-39/tubulin ratio. RESULTS: HC gp-39 mRNA expression in PBMC was increased in RA patients (the HC gp-39/tubulin ratio was 0.8690 +/- 0.5240), compared with OA (P = 0.024), SpA (P = 0.049), SLE (P = 0.043) and with healthy control subjects (P = 0.033). There were no statistically significant differences among OA, SpA, SLE and healthy controls. The level of HC gp-39 mRNA expression in RA synovium was also significantly higher than the level found in OA (P = 0.04). CONCLUSIONS: HC gp-39 mRNA was obviously overrepresented in RA patients PBMC and synovium. These data support a possible pathogenic role of HC gp-39, as a candidate autoantigen, in the autoimmune response of RA.
15330726 Cost-effectiveness of TNF-alpha-blocking agents in the treatment of rheumatoid arthritis. 2004 Sep The current literature covering cost-effectiveness and cost-utility analyses of biological treatments in patients with rheumatoid arthritis (RA) are reviewed in order to discuss options and limitations for future application of these highly priced drugs in routine clinical practice. The cost-effectiveness and cost-utility ratios of the studies analysed are converted into the corresponding Euros of the publication year. Etanercept treatment achieved a cost-effectiveness ratio of 44,300 Euros (2002)/ACR 20 (20% response according to American College of Rheumatology criteria) and 43,100 Euros (2002)/ACR 70WR (ACR 70 weighted response) compared with sulfasalazine and methotrexate, respectively, in methotrexate-naive RA. In methotrexate-resistant RA, the combination of etanercept and methotrexate is compared to a combination therapy of methotrexate, sulfasalazine and hydroxychloroquine revealing costs of 46,100 Euros (2000)/ACR 20, and 37,700 Euros/ACR 70WR. The cost-utility ratios for infliximab treatment range from 16,000 Euros to almost 166,000/QALY (quality adjusted life-year) gained, the studies investigating etanercept treatment show a ratio of approximately 25,000 Euros and 120,000/QALY gained. No substantial differences of cost-utilities of infliximab and etanercept were found. The administration of these drugs as third-line therapy is regarded cost-effective compared to other well-accepted therapies with comparable cost-utility ratios of < 50,000 Euros/QALY gained. Still, data on economic outcomes of RA trials are sparse and further cost-effectiveness and cost-utility evaluations are needed.
12055776 The impact of disability and disease duration on social support of women with rheumatoid a 2002 Jun The objective was to investigate the impact of physical disability and disease duration on the amount of social support received by female patients with rheumatoid arthritis. Two hundred sixty-four patients were assessed in a cross-sectional study. Disease duration had a negative relationship to daily emotional support; the length of disease duration was related to less emotional support. A combination of long disease duration and high disability was related to a low degree of problem-oriented emotional support. High physical disability was associated with less social companionship. Patients with high disability and few friends and patients with high disability and few neighbours reported less social companionship than patients with high disability and four or more friends or three or more neighbours. The combination high disability and few friends were associated with less problem-oriented instrumental support. Number of friends, age, and personality type all contributed to the variance in social support.
15032315 N-acetyltransferase 2 genotype-related efficacy of sulfasalazine in patients with rheumato 2004 Feb PURPOSE: For the individual optimization of drug therapy with sulfasalazine (SASP), we studied the influence of the N-acetyltransferase 2 (NAT2) genotype on the pharmacokinetics, efficacy, and incidence of adverse reactions of SASP in patients. METHODS: Ninety-six rheumatoid arthritis (RA) patients were treated or had been treated with 0.5 and/or 1.0 g/day of SASP. The wild-type allele (NAT2*4) and three variant alleles (NAT2*5B, *6A, and *7B) of NAT2 were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Plasma concentrations of SASP and its two metabolites, sulfapyridine (SP) and N-acetylsulfapyridine (AcSP), were estimated by HPLC. Therapeutic efficacy and incidence of adverse reactions were also monitored as recommended by the American College of Rheumatology. RESULTS: Patients were classified into three groups by NAT2 genotyping: Rapid Type (homozygote for NAT2*4), Intermediate Type (heterozygote for NAT2*4 and variant alleles), and Slow Type (homozygote for variant alleles). There was no clear difference in the genotype frequencies between RA patients and healthy subjects. NAT2 genotypes significantly affected both the plasma concentration ratios of SP to AcSP (SP/AcSP) and the efficacy of SASP (p < 0.05). Adverse reactions to SASP were found in 26 (27.1%) out of 96 patients, and there was no difference among the three genotype groups. CONCLUSIONS: NAT2 gene polymorphism is related to the plasma SP/AcSP ratio and the efficacy of SASP.
14630402 Association of MICA polymorphism with rheumatoid arthritis patients in Koreans. 2003 Dec To investigate whether genetic variations of MICA are associated with susceptibility to rheumatoid arthritis (RA), the (GCT)n microsatellite polymorphism of the transmembrane domain was analyzed in 144 Korean patients with RA and in 297 unrelated healthy controls. The allele frequency of MICA*A9 significantly decreased in RA patients compared with controls (9.0% vs. 15.3%, odds ratio [OR] = 0.55, p = 0.0098, p(c) = 0.049), whereas the frequency of the MICA*A4 and MICA*A5.1 alleles tended to increase in RA patients (21.2% vs. 14.8%, OR = 1.55, p = 0.018, p(c) > 0.05; 20.5% vs. 15.0%, OR = 1.46, p = 0.0403, p(c) > 0.05). By subgroup analysis, the MICA*A4 allele significantly increased in seropositive RA patients versus controls (23.0% vs. 14.8%, OR = 1.69, p = 0.0082, p(c) = 0.041). HLA-DRB1*0405 was strongly associated with RA (p(c) = 0.0000008), and strong linkage disequilibrium was observed between HLA-DRB1*0405 and MICA*A4 alleles in controls (p(c) = 0.000004) as well as in RA patients (p(c) = 0.0012). In Korean patients, HLA-DRB1*0405 was primarily associated with RA and the weak association of RA with MICA*A4 was secondary to that with HLA-DRB1*0405. Additionally, MICA*A9 might have a weak protective effect on the susceptibility to RA in Koreans.
12904092 Safety and efficacy of disease-modifying antirheumatic agents in rheumatoid arthritis and 2003 Jul The definition of disease-modifying antirheumatic drugs (DMARDs) has changed dramatically over the last decade. Current expectations of efficacy now include amelioration of signs and symptoms of disease activity as well as slowing, if not complete cessation, of disease progression as evidenced by Xray progression and significant improvement of patient function. Rheumatologists assess the safety profile of these agents more critically in an attempt to increase the risk:benefit profile. Traditional agents, such as methotrexate (MTX), sulfasalazine and leflunomide have provided patients with substantial relief of symptoms and some decrease of X-ray progression but have been hampered by the frequent occurrence of significant adverse events (AEs) and inability to maintain benefit for a prolonged period of time. With the increased understanding of the basic mechanism of the disease process, there has been the introduction of four biological disease-modifying agents introduced into clinical practice which have substantially increased the risk:benefit ratio for patients with various rheumatic diseases.
15170918 Effects of high dose methylprednisolone pulse therapy on bone mass and biochemical markers 2004 Jun OBJECTIVE: To study the effects of one year of high dose 6-methylprednisolone pulse therapy (MPPT) on bone mass, seric bone alkaline phosphatase (sBAP), and urinary deoxypyridinoline (uDpyr) in patients with active rheumatoid arthritis (RA), and to compare results with those of patients with active RA treated with oral methylprednisolone (OMP). METHODS: Thirty-one women with active RA were given 1000 mg of MP IV for 3 alternate days, with a mean interval of administration of 76 days (+/- 8.3 SD) for one year (MPPT group). Bone mineral density (BMD) (total body, lumbar spine, and femur neck), plasma levels of sBAP, and urinary concentrations of uDpyr were assessed at the beginning of the treatment and every 3 months until the end of the study. Moreover, erythrocyte sedimentation rate (ESR), Thompson joint score, and early morning stiffness were assessed at study entry and every month. The control group, 31 women with active RA treated with oral MP, was followed in the same way (OMP group). RESULTS: In the MPPT group there was no significant reduction of BMD at any site compared to significant reductions in lumbar BMD at 6 and 12 months and total body BMD and femur neck BMD at 12 months in the OMP group. Also in the OMP group, a significant reduction in the mean sBAP was observed. The mean uDpyr levels were not significantly reduced in either group. CONCLUSION: Our results show that MPPT, compared to continuous therapy with oral corticosteroids, preserves bone mass without modifying the biochemical markers of bone metabolism.
15082476 T cells, fibroblast-like synoviocytes, and granzyme B+ cytotoxic cells are associated with 2004 May OBJECTIVE: To determine immunohistological markers in synovial tissue of patients with early rheumatoid arthritis (RA) which are associated with unfavourable disease outcome. METHODS: Synovial tissue was obtained from 36 patients with RA within 1 year after the initial symptoms and before starting disease modifying antirheumatic drug treatment. Clinical, laboratory, and radiological assessments (Larsen score) were performed at the time of the biopsy and at the end of follow up (mean 58 months, range 38-72). Immunohistological analysis was performed to detect T cells, B cells, plasma cells, fibroblast-like synoviocytes (FLS), macrophages, and granzyme B+ cytotoxic cells. The sections were evaluated by digital image analysis. RESULTS: Patients were divided into two groups based upon the radiological progression per year of follow up: group I with mild progression (n = 20; Larsen <2 points/year); group II with more severe progression (n = 16; Larsen > or =2 points/year). Regression analysis with a univariate model showed that the numbers of granzyme B+ cytotoxic cells (relative risk (RR) = 12, p = 0.003), T cells (RR = 11, p = 0.013), and FLS (RR = 10, p = 0.020) discriminated between groups I and II. A multivariate model demonstrated that the numbers of T cells (RR = 1.2, p = 0.015) and FLS (RR = 1.4, p = 0.013) were independent discriminators between groups I and II. CONCLUSION: The numbers of granzyme B+ cytotoxic cells, T cells, and FLS in synovial tissue of patients with RA are related to the severity of joint damage. The data suggest a pathogenetic role for these cells in the process of joint damage.
12476896 [The relation between plasma leptin concentration and body fat mass in patients with rheum 2002 Aug The prospective, cross-sectional study was undertaken to evaluate the relation between the fat mass and serum leptin level in patients with rheumatoid arthritis (RA). Low body mass and anorexia are commonly found in patients with RA. Inflammatory cytokines may significantly influence the secretion of anorectic hormone--leptin--that was confirmed in both experimental and clinical studies. Fifty-two non-diabetic and non-obese patients (38 females, 14 males) were studied. Mean age was 56 +/- 11 years and mean body mass index (BMI) 24.6 +/- 4.1 kg/m2. The disease activity score (DAS) was 3.9 +/- 1.4; range 1.4-7.4, and disease duration 8.1 +/- 6.7 years. Serum leptin was measured by ELISA and body composition by double X-ray densitometry. Mean serum leptin concentration was 2.8 +/- 1.4 ng/ml in patients with RA was lower than in the control group (4.2 +/- 2.0). In a simple regression analysis leptin did not correlate with BMI (R Spearman = 0.01), C-reactive protein (R = 0.08), total fat mass (R = 0.08), trunk fat (R = 0.05), limbs fat (R = 0.09) and DAS (R = -0.17). This relation was also not influenced by gender or type of immunosuppressive therapy. In a multiple regression model none of the independent variables explained the significant portion of variance of serum leptin. It is concluded that the physiologic relation of serum leptin to body fat stores is not present in patients with RA.
12698600 The effect of social network intervention for women with rheumatoid arthritis. 2003 Spring A partially-controlled intervention study was performed. Female patients with rheumatoid arthritis (RA) were allocated to three groups: the network intervention group (n = 104), the attention control group (n = 85), and the no-treatment control group (n = 75). The network intervention consisted of an assessment session and a network meeting. Patients were assessed at baseline and approximately 10 and 18 months after the intervention. The network intervention group reported an increase in network size. Daily emotional support increased for the intervention patients compared with patients in the attention control group. The degree of social dysfunction was reduced for patients in the intervention group compared to patients in the no-treatment control group. Furthermore, for single patients, the intervention significantly increased the social network size and improved both social functioning, and perceived overall health, compared to both control groups. The results suggest that the social needs of single patients should be given special attention in clinical settings.
11961174 Drug survival, efficacy and toxicity of monotherapy with a fully human anti-tumour necrosi 2002 Apr OBJECTIVES: To compare the 48-week drug survival, efficacy and toxicity of monotherapy with a fully human anti-tumour necrosis factor-alpha (TNF-alpha) monoclonal antibody (moAb) and methotrexate (MTX) in patients with active long-standing rheumatoid arthritis (RA). Secondary aims were to identify potential predictors for clinical response. METHODS: Patients with RA, enrolled in phase I trials with a human anti-TNF-alpha moAb and followed for at least 48 weeks at our centre, were compared with patients receiving MTX monotherapy without folate supplementation. The first 6 weeks of anti-TNF therapy were placebo-controlled and followed by an open-label study. Patients treated with MTX participated in a 48-week, double-blind, phase III study of MTX alone vs MTX with folate supplementation, which was co-ordinated by our department. The studies with anti-TNF-alpha and MTX were performed in the same period and had very similar inclusion, exclusion, response and stop criteria. RESULTS: Sixty-one patients treated with anti-TNF-alpha moAb were compared with 137 receiving MTX monotherapy. At baseline, patients in the anti-TNF-alpha group had a longer disease duration (median 108 vs 50 months, P=0.0001) and a more protracted history of second-line anti-rheumatic drugs than those treated with MTX (median 4 vs 1, P=0.0001). The 48-week dropout rate was lower among patients treated with anti-TNF (23 vs 45% in the MTX group, P<0.005). Proportional hazard analysis showed a significantly lower dropout risk among anti-TNF-treated patients [relative risk (95% confidence interval): 0.28 (0.12-0.6) uncorrected and 0.17 (0.06-0.45) corrected for confounders). The 48-week area under the curve for the disease activity score (DAS) was smaller in the anti-TNF-alpha group than in the MTX group (P=0.005). The percentage of responders was higher in the anti-TNF-alpha group over the whole study period. The median percentage of visits in which a patient fulfilled the European League Against Rheumatism (EULAR) response criteria was 83% in the anti-TNF-alpha group vs 40% in the MTX group (P=0.0001). Clinical and demographic characteristics were, in general, poor predictors for response to therapy at week 48. The clinical response after the first anti-TNF-alpha dose tended to increase the chance of prolonged efficacy of this approach [relative risk (95% confidence interval): 2 (0.75-6.0)]. The previous number of second-line drugs was the only predictive variable for response to MTX to which it was inversely related [relative risk (95% confidence interval): -0.71 (-0.57 to -0.88)]. CONCLUSIONS: In patients with active, long-standing RA, blocking TNF-alpha is more effective and better tolerated than MTX monotherapy. An early response increases the chance of a sustained effect of anti-TNF-alpha. In contrast to MTX, the response to anti-TNF-alpha is not affected by previous disease-modifying anti-rheumatic drug history.
14614165 Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion 2003 Nov 13 BACKGROUND: Effective new therapies are needed for rheumatoid arthritis. Current therapies target the products of activated macrophages; however, T cells also have an important role in rheumatoid arthritis. A fusion protein--cytotoxic T-lymphocyte-associated antigen 4-IgG1 (CTLA4Ig)--is the first in a new class of drugs known as costimulation blockers being evaluated for the treatment of rheumatoid arthritis. CTLA4Ig binds to CD80 and CD86 on antigen-presenting cells, blocking the engagement of CD28 on T cells and preventing T-cell activation. A preliminary study showed that CTLA4Ig may be effective for the treatment of rheumatoid arthritis. METHODS: We randomly assigned patients with active rheumatoid arthritis despite methotrexate therapy to receive 2 mg of CTLA4Ig per kilogram of body weight (105 patients), 10 mg of CTLA4Ig per kilogram (115 patients), or placebo (119 patients) for six months. All patients also received methotrexate therapy during the study. The clinical response was assessed at six months with use of the criteria of the American College of Rheumatology (ACR), which define the response according to its extent: 20 percent (ACR 20), 50 percent (ACR 50), or 70 percent (ACR 70). Additional end points included measures of the health-related quality of life. RESULTS: Patients treated with 10 mg of CTLA4Ig per kilogram were more likely to have an ACR 20 than were patients who received placebo (60 percent vs. 35 percent, P<0.001). Significantly higher rates of ACR 50 and ACR 70 responses were seen in both CTLA4Ig groups than in the placebo group. The group given 10 mg of CTLA4Ig per kilogram had clinically meaningful and statistically significant improvements in all eight subscales of the Medical Outcomes 36-Item Short-Form General Health Survey. CTLA4Ig was well tolerated, with an overall safety profile similar to that of placebo. CONCLUSIONS: In patients with active rheumatoid arthritis who were receiving methotrexate, treatment with CTLA4Ig significantly improved the signs and symptoms of rheumatoid arthritis and the health-related quality of life. CTLA4Ig is a promising new therapy for rheumatoid arthritis.
15535829 Expression analysis of three isoforms of hyaluronan synthase and hyaluronidase in the syno 2004 Hyaluronan is a major molecule in joint fluid and plays a crucial role in joint motion and the maintenance of joint homeostasis. The concentration and average molecular weight of hyaluronan in the joint fluids are reduced in osteoarthritis and rheumatoid arthritis. To elucidate the underlying mechanism, we analyzed the message expression of three isoforms of hyaluronan synthase and hyaluronidase from knee synovium, using real-time reverse transcriptase polymerase chain reaction. Synovia were obtained from 17 patients with osteoarthritis, 14 patients with rheumatoid arthritis, and 20 healthy control donors. The message expression of hyaluronan synthase-1 and -2 in the synovium of both types of arthritis was significantly less than in the control synovium, whereas that of hyaluronidase-2 in the synovium of both arthritides was significantly greater than in the control synovium. The decreased expression of the messages for hyaluronan synthase-1 and -2 and/or the increased expression of the message for hyaluronidase-2 may be reflected in the reduced concentration and decreased average molecular weight of hyaluronan in the joint fluids of patients with osteoarthritis and rheumatoid arthritis.
15286392 The mouse model of collagen-induced arthritis. 2004 Collagen-induced arthritis (CIA) is an experimental autoimmune disease that can be elicited in susceptible strains of rodents (rat and mouse) and nonhuman primates by immunization with type II collagen (CII), the major constituent protein of articular cartilage. Following immunization, these animals develop an autoimmune polyarthritis that shares several clinical and histological features with rheumatoid arthritis. Susceptibility to CIA in rodents is linked to the class II molecules of the major histocompatibility complex (MHC), and the immune response to CII is characterized by both the stimulation of collagen-specific T cells and the production of high titers of antibody specific for both the immunogen (heterologous CII) and the autoantigen (mouse CII). Histologically, murine CIA is characterized by an intense synovitis that corresponds precisely with the clinical onset of arthritis. Because of the pathological similarities between CIA and rheumatoid arthritis, the CIA model has been the subject of extensive investigation. Here, we describe the specifics for establishing the murine model of CIA, including specific requirements for the handling and preparation of the CII antigen, procedures for immunization, selection of susceptible mouse strains for study, and procedures for the evaluation and quantitation of the autoimmune arthritis.
14730599 Impact of initial aggressive drug treatment with a combination of disease-modifying antirh 2004 Jan OBJECTIVE: To compare the efficacy of therapy with a combination of disease-modifying antirheumatic drugs (DMARDs) versus therapy with a single DMARD in the prevention of work disability in patients with early rheumatoid arthritis (RA). METHODS: In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195 patients with recent-onset RA were randomly assigned to receive either combination therapy with DMARDs (sulfasalazine, methotrexate, hydroxychloroquine) plus prednisolone or single therapy with a DMARD with or without prednisolone. After 2 years, the drug treatment strategy was no longer restricted. At baseline, 162 patients (80 in the combination-treatment group and 82 in the single-treatment group) were still working or at least available for work. After 5 years of followup, data on all sick leave and retirement were obtained from social insurance registers or case records. The main outcome for each patient was the cumulative duration of all sick leaves and RA-related disability pensions, divided by the observation period during which the patient was not retired because of another disease or because of age. RESULTS: The cumulative duration of work disability per patient-observation year was significantly lower in those randomized to combination therapy than in those randomized to single therapy: median 12.4 days (interquartile range [IQR] 0-54) versus 32.2 days (IQR 6-293) (P = 0.008, sex- and age-adjusted P = 0.009). This was mainly due to the difference in sick leaves (i.e., work disability periods