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ID PMID Title PublicationDate abstract
11177774 Gene therapy for rheumatoid arthritis. 2001 Feb Rheumatoid arthritis (RA) is a painful chronic disorder. Conventional therapies are palliative, not curative. Advances in the understanding of the pathophysiology of RA have led to the development of new therapeutic strategies, including gene therapy. Multiple studies in several different animal models provide proof supporting the use of gene therapy in arthritis. A phase I clinical trial has already been performed successfully on nine women with end-stage RA in the United States, and two other trials are in progress. Limited duration of gene expression impedes the development of a clinically useful genetic treatment for arthritis.
9929017 Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheu 1999 Jan 23 BACKGROUND: Phase II trials of leflunomide, an inhibitor of de-novo pyrimidine synthesis, have shown efficacy in rheumatoid arthritis. This double-blind randomised trial compared leflunomide with placebo and sulphasalazine in active rheumatoid arthritis. METHODS: 358 patients were randomly assigned leflunomide (100 mg daily on days 1-3, then 20 mg daily), placebo, or sulphasalazine (0.5 g daily, titrated progressively to 2.0 g daily at week 4). The primary endpoints were tender and swollen joint counts and investigator's and patient's overall assessments. Analyses were by intention to treat. FINDINGS: The mean changes in the leflunomide, placebo, and sulphasalazine groups were -9.7, -4.3, and -8.1 for tender joint count; -7.2, -3.4, and -6.2 for swollen joint count; -1.1, -0.3, and -1.0 for physician's overall assessment; and -1.1, -0.4, and -1.1 for patient's overall assessment. Leflunomide and sulphasalazine were significantly superior to placebo (p=0.0001 for joint counts; p<0.001 for assessments). Radiographic disease progression was significantly slower with leflunomide and sulphasalazine than with placebo (p<0.01). Most common adverse events with leflunomide were diarrhoea (17%), nausea (10%), alopecia (8%), and rash (10%). Transiently abnormal liver function was seen in three leflunomide-group patients and five sulphasalazine-group patients. There were two cases of reversible agranulocytosis in the sulphasalazine group. INTERPRETATION: Leflunomide was more effective than placebo in treatment of rheumatoid arthritis and showed similar efficacy to sulphasalazine. Leflunomide was well tolerated. This drug may be a useful option as a disease-modifying antirheumatic drug.
11261841 Analysis of agalacto-IgG in rheumatoid arthritis using surface plasmon resonance. 2000 May It is well established that IgG from rheumatoid arthritis (RA) patients are less galactosylated than IgG from normal individuals. Determination of agalacto-IgG may therefore aid in diagnosis and treatment of RA. The decrease in galactosylation of IgG leads to an increase in terminal N-acetylglucosamine residues, which can be detected using a specific lectin from Psathyrella velutina. In the present study IgG from RA and control serum was purified using affinity chromatography. The samples were then, after reduction, analyzed on a BIOCORE 2000 system with immobilized Psathyrella velutina lectin. Using this technique it was possible to discriminate between IgG from RA patients and IgG from control individuals with respect to its content of IgG with terminal N-acetylglucosamine. The affinity biosensor technique makes it possible to detect binding without labeling or using secondary antibodies.
9598880 Serum homocysteine and methylmalonic acid in patients with rheumatoid arthritis and cobala 1998 May OBJECTIVE: To analyze the significance of cobalaminopenia (< 200 pmol/l) in patients with severe rheumatoid arthritis (RA). METHODS: We studied 42 patients with RA and cobalaminopenia (incidence 4%). Most patients had severe and longstanding disease. Concentrations of homocysteine, methylmalonic acid (MMA), gastrin, and pepsinogen 1 were analyzed in sera that had been stored frozen. A capillary gas chromatographic mass spectrometric technique was used to determine homocysteine and MMA. RESULTS: As a group, patients had significantly higher levels of serum homocysteine and serum MMA than laboratory reference probands (p < 0.0001 and p < 0.005, respectively). Individually, 20 of 39 patients had elevated serum levels of homocysteine (> 15 micromol/l). In 12 of 39 patients serum levels of MMA were elevated (> 0.37 micromol/l). Twenty of 42 patients had biochemical signs of disturbed gastric function. CONCLUSION: Our findings were compatible with the hypothesis that cobalaminopenia is one of several biochemical signs of gastrointestinal dysfunction in patients with severe RA. It is suggested that the hyperhomocysteinemia associated with vitamin B12 deficiency, folate deficiency, vitamin B6 deficiency, and impaired renal function may have a role in promoting high cardiovascular morbidity in patients with RA.
11198736 Progressive heart block in active rheumatoid arthritis. 2000 Oct A 68-year-old woman presented with active rheumatoid arthritis (RA) and severe extra-articular manifestations. During the course of her treatment, her electrocardiogram (ECG) transformed from normal sinus rhythm to left bundle branch block and finally to complete heart block (CHB). Investigations ruled out an ischaemic event. A permanent pacemaker was inserted due to the symptoms of heart failure and she made an uneventful recovery. CHB in RA is probably a marker of severity of the disease.
10375846 Inhibitors of tumor necrosis factor: new treatment options for rheumatoid arthritis. 1999 Jun Infliximab and etanercept, both approved by the FDA in 1998, are examples of a new class of disease-modifying antirheumatic drugs that interfere with the action of tumor necrosis factor alpha, one of the key cytokines that promote inflammation. Infliximab is approved for Crohn disease and etanercept for rheumatoid arthritis. Both show promise in treating rheumatoid arthritis, although the long-term risks and benefits of these drugs are not yet known.
11021172 [Clinical features of patients with osteoarthritic knees followed by development of rheuma 2000 Aug We investigated clinical features of patients with osteoarthritic knees followed by development of rheumatoid arthritis (RA) after several year's interval. The subjects were 16 knees of 8 patients with osteoarthritis (OA) including one man and 7 women. The mean age at development of OA knee was 62.8 years (range; 45-73). The mean age at later development of RA was 66.0 years (range; 52-79). The mean follow-up period was 96.4 months (range; 28-191). We evaluated clinical features using the 1987 revised Criteria of the American College of Rheumatology (ACR), laboratory dates including RF, CRP, ESR, the number of joints with RA, and femorotibial angle (FTA). The mean number of features of patients which was fulfilled with the ACR criteria was 3.3 +/- 1.6 at the onset of RA. Only four patients were seropositive through the total follow-up period. The serum level of RF, CRP, and ESR were reduced at the follow-up period. The mean number of the joints involved in RA was 11.0 +/- 5.1 (range; 4-22) and wrist and shoulder joints were involved more frequently than other joints except knees. High tibial osteotomy (HTO) was performed on 5 knees of 3 patients and the mean degree of FTA was 168.8 +/- 1.9 degrees just after surgery. However, 36 months after development of RA, joint destruction and valgus deformity occurred on 3 knees and the mean degree of FTA of 5 knees was ended up to 159.6 +/- 11.3 degrees. Our experiences suggested that RF, CRP, ESR and lesions of other joints should be carefully evaluated in the OA patients with seropositivity or knee hydrarthrosis and that histological analysis for synovium should be assessed by the biopsy at time of HTO or arthroscopic surgery to improve accuracy of diagnosis.
10914843 Progression of radiographic joint erosion during low dose corticosteroid treatment of rheu 2000 Jul OBJECTIVE: The reported prevention of joint damage during treatment with prednisolone 7.5 mg daily in patients with early rheumatoid arthritis (RA)3 may have important implications for management of RA. We evaluated this observation in another patient population. METHODS: Radiographic progression rates in paired hand radiographs were analyzed in 824 patients with RA who participated in a 3 year prospective, randomized clinical trial comparing the nonsteroidal antiinflammatory drugs (NSAID) etodolac (150 or 500 mg bid) and ibuprofen (600 mg qid). Disease modifying antirheumatic drugs (DMARD) were not permitted. Prednisone < or=5 mg daily was continued by 197 patients (mean dose 4.37 mg daily) who had started prednisone therapy at least 6 mo before study entry, but new prednisone starts were not allowed. Standardized hand/wrist radiographs were done yearly and at dropout; joint erosion and narrowing scores of 3 readers were averaged and progression rates were compared. RESULTS: Mean duration of RA was 3.6 years (range 1-7); patients' ages were 21-78 years; 71% were women. Among the 824 patients, those taking prednisone were more likely to have had previous DMARD, and at study entry had higher radiographic scores for joint erosion and joint space narrowing and slightly higher swollen joint counts, C-reactive protein values, and rheumatoid factor titers than those not taking prednisone. However, for the subgroup of 252 patients with RA duration of 12-24 months, prestudy radiographic scores were not different in those taking or not taking prednisone. The mean (+/-SD) monthly rate of increase in erosion scores was 0.228 +/-0.37 for the prednisone patients and 0.206+/-0.35 for patients not taking prednisone (p = 0.994 by ANCOVA). The subgroup with 12 to 24 months' disease duration at entry also showed no significant effect of prednisone treatment on erosion progression. CONCLUSION: Clinically indicated low dose prednisone did not prevent progressive radiographic damage in 197 NSAID treated patients whose physicians had initiated < or =5 mg daily before study entry. The risk/benefit ratio of chronic low dose prednisone in early RA remains uncertain.
9109425 A function for the QKRAA amino acid motif: mediating binding of DnaJ to DnaK. Implications 1997 Apr 15 The amino acid motif QKRAA, when expressed on HLA-DRB1, carries susceptibility to develop rheumatoid arthritis. This motif is the basis of strong B and T cell epitopes. Furthermore, it is highly overrepresented in protein databases, suggesting that it carries a function of its own. To identify this function, we used QKRAA peptide affinity columns to screen total protein extracts from Escherichia coli. We found that DnaK, the E. coli 70-kD heat shock protein, binds QKRAA. Of interest, DnaK has a natural ligand, DnaJ, that contains a QKRAA motif. We found that QKRAA-containing peptides inhibit the binding of DnaK to DnaJ. Furthermore, rabbit antibody to the QKRAA motif can inhibit binding of DnaJ to DnaK. These data suggest that QKRAA mediates the binding of E. coli chaperone DnaJ to its partner chaperone DnaK.
10575273 HLA-DMA alleles are possible new markers of rheumatoid arthritis: study of a Corsican grou 1999 The HLA-DMA gene, along with the HLA-DMB gene, encodes the not classical class II molecule. This molecule catalyzes the class-II-associated invariant-chain peptide (CLIP)-antigen peptide exchange in classical class II molecule peptide-binding groove. As such, the DM heterodimer is an antigen presentation regulator and may be linked to immune system deficiencies such as those observed in autoimmune diseases. The study of DMA gene polymorphism seems be a reasonable approach to provide an answer to this question. Thanks to PCR-derived methods, the relationship between DMA gene polymorphism and rheumatoid arthritis (RA) was demonstrated in the present study. The DMA*0101 allele was observed to confer a significant predisposition to RA while the DMA*0102 allele significantly protected from this disease. Polymorphism experiments with the HLA-DRB1 gene revealed that this relationship between DMA polymorphism and RA is not a consequence of a linkage disequilibrium with the HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore prove to be very useful in the early diagnosis of RA.
11704286 HLA-DRB1*04 alleles in psoriatic arthritis: comparison with rheumatoid arthritis and healt 2001 Nov Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis usually seronegative for rheumatoid factor. An increased frequency of HLA-DR4 has been noted in PsA, particularly among patients with a rheumatoid arthritis like (RA) arthritis. The aim of the current investigation was to compare HLA-DRB1*04 alleles in patients with PsA, patients with RA, and healthy controls. Sample size calculations based on the frequency of HLA-DR4 suggested that 90 individuals in each patient group would be sufficient to address our question. Therefore, 90 HLA-DRB1*04 positive patients from each patient group underwent high resolution molecular typing and were included in this study. Although HLA-DRB1*0401 was the most frequent allele in all groups, its frequency among the PsA patients was lower than that of RA patients and controls. HLA-DRB1*0402 was higher among patients with PsA. Patients with RA were more likely to have more than one shared epitope allele than either PsA or the healthy control group. HLA-DQB1 alleles did not contribute further information. We suggest that the differences in the class II HLA epitope(s) may also be related to interaction specificity with another molecule functioning in the immune response to a putative arthritogenic antigen and result in differences in disease expression.
11276802 Use of the ACCES model to predict the health economic impact of celecoxib in patients with 2000 Dec A Norwegian customization of the Arthritis Cost Consequence Evaluation System (ACCES) pharmacoeconomic model was used to predict the economic and health impact of the introduction of celecoxib in Norway. The model predicts that use of celecoxib can be expected to result in a reduction in gastrointestinal events with concomitant annual net savings of at least Norwegian krone (NOK) 580 per osteoarthritis (OA) patient and NOK 514 per rheumatoid arthritis (RA) patient. In a cost-effectiveness analysis, celecoxib demonstrated economic dominance (i.e. improved health at reduced cost) compared with the currently available alternatives. In sensitivity analyses, the results of this model have been shown to be relatively robust, with celecoxib demonstrating economic dominance or favourable cost-effectiveness ratios in all analyses. Based on these data, it can be concluded that the introduction of celecoxib into the Norwegian non-steroidal anti-inflammatory drug market, and its use as a first-line agent, will provide societal benefits by improving health care at reduced cost in patients with OA and RA.
9833252 Granulocyte and monocyte apheresis suppresses symptoms of rheumatoid arthritis: a pilot st 1998 To investigate if granulocyte and monocyte apheresis mitigates the symptoms of rheumatoid arthritis (RA), and influences production of panmyelocytes (CD15+ CD16- cells) at the bone marrow level, 27 RA patients who had elevated granulocyte counts were recruited. The granulocyte and monocyte apheresis column (G-1 column) is an extracorporeal type device packed with 220 g cellulose acetate beads to which granulocytes and monocytes specifically adhere. Patients received apheresis of 1 hr duration twice per week, 8 times over a period of 4 weeks. To prepare CD15+CD16- cells, iliac bone marrow aspirate was obtained at baseline and at 2 weeks after completion of the apheresis course. Ex-vivo proliferation of bone marrow low density cells and production of IgM-RF were also investigated. Following granulocyte and monocyte apheresis, there was a suppressed tendency in the number of CD15+CD16- cells in patients with high bone marrow CD15+CD16- cell counts at baseline. Clinical assessments 2 weeks after the completion of apheresis therapy showed improvements in swollen joint count (P < 0.001), tender joint count (P < 0.001) and duration of morning stiffness (P < 0.005). The results suggest that granulocytes and monocytes/macrophages have a pathological role in RA and apheresis treatment to reduce or suppress these cells should benefit patients with RA.
11106576 The CD44v7/8 epitope as a target to restrain proliferation of fibroblast-like synoviocytes 2000 Dec CD44 is a receptor for the glycosaminoglycan hyaluronan. It exists in a large range of isoforms because of variability in the pattern of glycosylation (both N- and O-linked) and of multiple splice variants. Human fibroblast-like synoviocytes derived from patients with rheumatoid arthritis express certain CD44 splice variants and we have investigated the functional implications of their expression. We found that the rate of proliferation of fibroblast-like synoviocytes expressing the CD44v7/8 epitope (average doubling time 55 hours) exceeds those obtained from the same synovial specimen but lacking this particular epitope (69 hours). Antibodies against CD44v7/8, but not against other exons, inhibit cell proliferation with concomitant induction of the cell cycle inhibitors GADD45, GADD153 and the cyclin-dependent protein-kinase inhibitors p21Waf/Cip. These data show that expression of CD44v7/8 contributes to the transformed phenotype of fibroblast-like synoviocytes. More importantly, they reveal the presence of a target that might be amenable to pharmacological intervention in the treatment of rheumatoid arthritis.
11592381 Treatment of murine collagen-induced arthritis by ex vivo extracellular superoxide dismuta 2001 Sep OBJECTIVE; Superoxide dismutase (SOD) is a potent antiinflammatory enzyme that has received growing attention for its therapeutic potential. This study was undertaken to examine the efficacy of extracellular SOD (EC-SOD) gene therapy in murine collagen-induced arthritis. METHODS: Embryonic DBA/1 mouse fibroblasts were infected with a recombinant retrovirus expressing human EC-SOD. DBA/1 mice that had been treated with type II collagen were administered subcutaneous injections of 2 x 10(7) EC-SOD-expressing fibroblasts on day 29, when symptoms of arthritis were already present. The severity of arthritis in individual mice was evaluated in a double-blind manner; each paw was assigned a separate clinical score, and hind paw thickness was measured with a caliper. Mice were killed on day 50 for histologic examination of the joints. RESULTS: High serum concentrations of EC-SOD were maintained for at least 7 days. Mice treated with the transgene exhibited significant suppression of clinical symptoms such as disabling joint swelling, deformity, and hind paw thickness, compared with the untreated group (mean +/- SD maximum clinical score in the untreated and the transgene-treated groups 2.71 +/- 1.08 and 1.35 +/- 1.22, respectively; P < 0.01, and hind paw thickness 3.04 +/- 0.18 mm and 2.56 +/- 0.12 mm, respectively; P < 0.05). Histologic abnormalities, including destruction of cartilage and bone, infiltration of mononuclear cells, and proliferation of synovial cells, were also markedly improved in the EC-SOD-treated mice compared with the control group (histopathologic score 7.50 +/- 1.13 and 4.13 +/- 1.88 in the untreated and transgene-treated groups, respectively; P < 0.05). CONCLUSION: These results indicate that EC-SOD gene transfer may be an effective form of therapy for rheumatoid arthritis.
12212193 [Spectrophotometric determination of copper in the hair of the patients with rheumatoid ar 2000 Apr 28 A new color reaction of copper (II) with solochrome cyanine R was studied by spectrophotometry. The results were that in the pH6 of HAc-NaAc buffer solution solochrome cyanine R reacted with copper (II) to form a violet complex; the maximum absorption of the complex was at 565 nm and its apparent molar absorption coefficient was 8.25 x 10(5) L.mol-1.cm-1. Beer's Law was obeyed in the range of 0-0.48 microgram.ml-1. This method was used to determine copper levels in the hair samples of 5 normal persons and 5 rheumatoid arthritis patients. The results showed that the hair copper level of arthritis patients was significantly higher than that of normal persons (P < 0.01).
9259428 Resource utilization and cost of care for rheumatoid arthritis and osteoarthritis in a man 1997 Aug OBJECTIVE: To describe the frequency and costs of medical services for patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in a managed care setting. METHODS: Individual utilization records of medical and pharmacy services for OA and RA patients were obtained from a group-model health maintenance organization (HMO). Estimates were made for costs of drugs and medical services for arthritis from July 1, 1993 to June 30, 1994 using Medicare reimbursement schedules and average wholesale drug prices. Calculated rates for each population were expressed as counts of events or as dollars per person-year. RESULTS: The average individual cost rate of arthritis-related care for 365 RA patients was $2,162 per year, and the total cost of RA care to the HMO was $703,053. Prescription medications accounted for 62% ($436,440) of the total cost of RA care, while ambulatory care accounted for 21% ($150,938), and hospital visits accounted for 16% ($115,674). With regard to 10,101 OA patients, the average individual cost rate was $543 per year, and total cost to the HMO was $4,728,425. Hospital care accounted for 46% ($2,170,890) of the total cost of OA care, medications accounted for 32% ($1,509,637), and ambulatory care accounted for 22% ($1,047,898). CONCLUSION: RA care, in the setting of this study, was characterized by intensive treatment, especially frequent use of medications that were delivered to most patients. Although the cost of RA care per patient was high, cost to the managed care provider was relatively low, owing to the rarity of RA. OA care tended to be infrequent, and the largest component of cost was hospital care for a small proportion of patients (5%). Owing to the greater prevalence of OA, care of OA was nearly 7 times more costly to the managed care provider than was care of RA.
11001380 Efficacy and safety of leflunomide in active rheumatoid arthritis. 2000 Jun Leflunomide, the newest disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA), inhibits de novo pyrimidine biosynthesis. In two placebo-controlled trials, leflunomide was superior to placebo and comparable to sulphasalazine and methotrexate for improving the signs and symptoms of RA, significantly improved functional ability compared with placebo, sulphasalazine and methotrexate, and was superior to methotrexate and comparable to sulphasalazine in slowing radiographically assessed disease progression. In a multinational trial vs methotrexate, leflunomide showed an American College of Rheumatology (ACR) response rate similar to that in placebo-controlled trials. The ACR response rate with methotrexate was significantly greater. Differences between these trials included methotrexate dosing regimens, folate usage and disease duration. Common adverse events with leflunomide included gastrointestinal symptoms, allergic reactions, alopecia and elevated liver enzyme levels. No long-term safety issues were reported with leflunomide at 2 yr. Efficacy of leflunomide was maintained at 2 yr. Leflunomide is a safe and efficacious addition to the roster of anti-rheumatic drugs.
9754015 [An autopsy case of rheumatoid arthritis accompanied with acute exacerbation of interstiti 1998 Jun An autopsy case of rheumatoid arthritis (RA) with acute exacerbation of interstitial pneumonia is reported. A 57-year-old woman with longstanding RA was admitted to our hospital because of progressive dyspnea. On chest roentogenogram, diffuse interstitial shadow was confirmed in both lungs. Chest computed tomography (CT) showed diffuse lesion of elevated density of CT level in both lung. She was diagnosed as an acute exacerbation of interstitial pneumonia, and treated by methylpredonisolone pulse therapy (1,000 mg/day). Although cyclosporin A (2 mg/kg/day) was combined to steroid therapy, she was died of progressive respiratory failure. The histological findings of the lung showed extensive fibrosis with alveolar damage associated with hyaline membranes, edema and hemorrhage in alveolar space.
9021033 Proximal dissection of a popliteal giant synovial cyst: a case report. 1997 Jan Giant synovial cysts in patients with rheumatoid arthritis are well-recognized soft-tissue masses adjacent to the knee. Cases involving the elbow, hip, and other synovial joints have been reported as well. Regardless of location, these expanding, space-occupying lesions usually present with nonspecific symptoms of swelling and pain. Less commonly, the original presentation may be related to the secondary effects of the cyst on nearby anatomic structures. We present a case of a giant synovial cyst originating posteriorly in the knee, which, rather than dissecting distally into the calf, dissected proximally into the posterior soft tissue of the thigh in a patient with long-standing rheumatoid arthritis.