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ID PMID Title PublicationDate abstract
17565662 Lack of association between the chemokine receptor 5 polymorphism CCR5delta32 in rheumatoi 2007 Jun 12 BACKGROUND: The chemokine receptor CCR5 has been detected at elevated levels on synovial T cells, and a 32 bp deletion in the CCR5 gene leads to a non-functional receptor. A negative association between the CCR5Delta32 and rheumatoid arthritis (RA) has been reported, although with conflicting results. In juvenile idiopathic arthritis (JIA), an association with CCR5 was recently reported. The purpose of this study was to investigate if the CCR5Delta32 polymorphism is associated with RA or JIA in Norwegian cohorts. METHODS: 853 RA patients, 524 JIA patients and 658 controls were genotyped for the CCR5Delta32 polymorphism. RESULTS: The CCR5Delta32 allele frequency was 11.5% in the controls vs. 10.4% in RA patients (OR = 0.90; P = 0.36) and 9.7% in JIA patients (OR = 0.85; P = 0.20). No decreased homozygosity was observed for CCR5Delta32, as previously suggested. CONCLUSION: Our data do not support an association between the CCR5Delta32 allele and Norwegian RA or JIA patients. Combining our results with those from a recently published meta-analysis still provide evidence for a role for CCR5Delta32 in RA, albeit substantially weaker than the effect first reported.
18811030 Do we need to replace the patella in knee arthroplasty for rheumatoid disease? 2008 Aug We have examined the anterior knee function in two patient groups who had undergone primary knee arthroplasty without patellar resurfacing to identify differences for osteoarthrosis compared with rheumatoid disease. We identified two consecutive series of patients who had undergone knee replacement surgery for either osteoarthritis or rheumatoid disease between 1992 and 1994 under the care of a single surgeon using the same implant and surgical technique. There were 90 patients in each group. All were examined and asked to complete a questionnaire so as to determine Hospital for Special Surgery (HSS) score, Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) score, Bartlett patellar score and a Visual Analogue score (VAS) for any persistent anterior knee pain at rest. We failed to identify any significant differences in terms of anterior knee function between these two groups of patients. The re-operation rate was similar for both groups. It would appear that primary knee replacement for rheumatoid disease is met with a similarly good outcome for anterior knee function despite absence of patellar resurfacing. We would question the contention that patellar resurfacing is necessary for patients undergoing knee replacement for rheumatoid disease.
17951673 Genotyping of synovial fibroblasts: cDNA array in combination with RAP-PCR in arthritis. 2007 Evaluation of differentially regulated genes is essential for the development of novel therapeutic approaches in multifactorial diseases such as rheumatoid arthritis (RA). RA synovial fibroblasts (RASF) are key players in inflammation and cartilage destruction. Therefore, RASF are important cellular targets for the analysis of gene expression profiles. Such analyses may include a comparison of SF from nontreated RA patients with those from treated RA patients, and may also be used to evaluate which genes and intra-cellular processes can be modulated through genetic modification, gene transfer, and drug treatment for the identification of the pathways driving the destructive behavior of these cells. This chapter reports the combination of RNA arbitrarily primed polymerase chain reaction (RAP-PCR) and cDNA array with defined genes for a highly sensitive analysis of gene expression profiles in RASF using small amounts of total RNA. RNA can be extracted from cultured SF, isolated, and analyzed using RAP-PCR with different arbitrary primers for first-and second-strand synthesis to generate a radioactive labeled probe which can be used for cDNA array hybridization. Visualization and evaluation of gene expression can be performed by phosphorimaging in combination with an array-specific software analyzing system followed by statistic evaluation of the generated data. In summary, the combination of RAP-PCR combined with cDNA arrays is a sensitive method to identify differentially expressed genes in RASF with high specificity, especially for low abundant mRNAs.
18590109 [Characteristics of a cytokine profile of T-lymphocytes of peripheral blood and synovial f 2008 AIM: To assess cytokine-producing activity of T-lymphocytes of peripheral blood and synovial fluid in rheumatoid arthritis (RA). MATERIAL AND METHODS: The study group consisted of 58 RA female patients aged 28-53 years (mean age 42.1 +/- 2.9 years) with at least 5-year history of RA (mean 10.7 +/- 4.9 years). The control group consisted of 37 healthy women matched by age. Spontaneous production of IL-2, IL-4, IFNgamma (IFNgamma) and TNFalpha (TNFalpha) by CD3(+) and CD3(-) lymphocytes was estimated after 4 hours of incubation in 37 degrees C with phorbol-12-myristate-13-acetate (PMA, 50 ng/ml, Sigma, France), ionomycin (1 mcg/ml, Sigma, France) and brefeldin A (10 mcg/ml, Sigma, France). RESULTS: In RA there is a decrease in a relative and absolute count of peripheral blood T-lymphocytes which occurs spontaneously and due to nonspecific stimulation of synthetizing IL-4, TNFalpha and IFNgamma. IFNgamma-producing lymphocytes (CD3(+) IFNg(+)/CD3(+) IL-4(+) = 4.45 +/- 1.56) prevail in the synovial fluid in RA, but count of lymphocyte IFNgamma , IL-2 and TNFalpha(+) in the synovial fluid is lower than in peripheral blood. CONCLUSION: One of the causes of low count of TNFalpha, IFNgamma and IL-4 producing T-lymphocytes in peripheral blood is migration of relevant TC-subpopulations to the affected joints. Migration of TC1-lymphocytes into the synovial fluid does not result in their prevailing count in the synovial fluid vs peripheral blood.
18388521 Immunization of patients with rheumatoid arthritis with antitumor necrosis factor alpha th 2008 May PURPOSE OF REVIEW: The aim of this study is to highlight the recent findings on the use of methotrexate and/or TNFalpha-blockers in adult patients with rheumatoid arthritis and their effects on the immune response to various vaccines. RECENT FINDINGS: Regarding influenza vaccination, methotrexate monotherapy is not associated with a decreased response, whereas the use of etanercept and infliximab in combination with methotrexate may cause lower titers and lower response rates. Concerning pneumococcal vaccination, methotrexate seems to impair responsiveness. The concomitant use of adalimumab and methotrexate is also associated with decreased response, whereas the concomitant use of etanercept or infliximab seems not to have an effect on response rates. As immunological pathways seem to play a major role, T-cell-dependent pneumococcal vaccines are designed to achieve higher response rates and protective titers. SUMMARY: Patients with rheumatic disorders are more likely to develop preventable infectious diseases, which underlines the importance of adequate immunoprotective titers. Several studies have shown that the combination of methotrexate and certain TNFalpha-blockers are affecting the responsiveness to vaccines. Further findings indicate that the response also depends on what type of vaccine is used.
16539817 Modification of neutrophil function by plasma of rheumatoid arthritis patients treated wit 2006 Jan OBJECTIVE: To examine whether the release of superoxide anions from neutrophils of healthy donors was affected when incubated with plasma from infliximab-treated rheumatoid arthritis (RA) patients. METHODS: Fifteen consecutive seropositive RA patients were treated with 3mg/kg infliximab on weeks 0, 2, 6, and 14. Disease activity was assessed by DAS28 score and by IL-6 level. Neutrophils from healthy donors were incubated with plasma drawn before each infliximab treatment. PMA-stimulated superoxide release was measured by the ferricytochrome C reduction method. RESULTS: 53% of the patients had a favorable clinical response. IL-6 levels showed a significant decline at week two, with a gradual increase thereafter. Treatment with infliximab did not change the superoxide production. However, when the group was divided retrospectively to responders (DeltaDAS28 > -1.2) and non-responders (DeltaDAS28 < -1.2), two different patterns were seen, although the pre-treatment levels were similar: Among the responders IL-6 remained low at its 2 weeks level till week 14, while in the non responders IL-6 increased 3 times (P < 0.03) from week 2 to 14. The responders showed mild, but continuous, reduction of superoxide release, while in the non-responders it increased significantly from week 2 on. CONCLUSION: The reduction in IL-6 in RA sera following anti-TNFalpha therapy has little influence on the capacity of these sera to stimulate healthy neutrophils to produce superoxide, suggesting the existence of non-TNFalpha non-IL-6 dependent neutrophil-stimulating mediators in RA sera. The increasing level of IL-6 among the non-responders after initial dramatic decline might represent an escape phenomenon, possibly caused by alternative mediator(s). Clinically, this IL-6 "escape" might be used as a tool for early identification of responders from non-responders.
17328047 Serum macrophage inhibitory cytokine 1 in rheumatoid arthritis: a potential marker of eros 2007 Mar OBJECTIVE: The transforming growth factor beta superfamily member macrophage inhibitory cytokine 1 (MIC-1) is expressed upon macrophage activation, regulated by the p53 pathway, and linked to clinical events in atherosclerosis and cancer. Since rheumatoid arthritis (RA) shares similar etiopathologic mechanisms with the above diseases, we sought to determine the clinical utility of determining MIC-1 serum levels and MIC-1 genotype in the management of RA. METHODS: Ninety-one RA patients were recruited. Serum was collected from 83 of these patients and synovial biopsy samples were collected from the remaining 8 patients. Of the 83 patients from whom serum was collected, 61 were treated on an outpatient basis (defined as having nonsevere disease), and 22 patients went on to undergo hemopoietic stem cell transplantation (HSCT) (defined as having severe disease). RESULTS: Serum levels of MIC-1 were higher in RA patients and reflected disease severity independently of classic disease markers. MIC-1 was detected in rheumatoid synovial specimens, and allelic variation of MIC-1 was associated with earlier erosive disease and severe treatment-resistant chronic RA. Additionally, algorithms including serum and/or allelic variation in MIC-1 predicted response to HSCT, the presence of severe disease, and joint erosions. CONCLUSION: Determination of serum levels of MIC-1 and MIC-1 genotype may be clinically useful in the management of RA as well as in selection of patients for HSCT, since they predict disease course and response to therapy. The data indicate a potential role for MIC-1 in RA pathogenesis. These results warrant larger prospective studies to fully delineate and confirm a role for MIC-1 genotyping and serum estimation in patient selection for HSCT and in the management of RA.
17768173 Factorial randomised controlled trial of glucocorticoids and combination disease modifying 2008 May OBJECTIVE: Treating early active rheumatoid arthritis (RA) with disease modifying antirheumatic drug (DMARD) monotherapy achieves incomplete outcomes and intensive treatment seems preferable. As the relative benefits of combining two DMARDs, one DMARD with glucocorticoids and two DMARDs with glucocorticoids are uncertain we defined them in a factorial trial. METHODS: A 2-year randomised double-blind factorial trial in patients with RA within 2 years of diagnosis treated with methotrexate studied the benefits of added ciclosporin, 9 months intensive prednisolone or both (triple therapy). The primary outcome was the number of patients with new erosions. Secondary outcomes included Larsen's x-ray scores, disability, quality of life and adverse events. FINDINGS: 1391 patients were screened and 467 randomised. Over 2 years 132 (28%) changed therapy and 88 (19%) were lost to follow-up. The number of patients with new erosions was reduced by nearly half by adding ciclosporin or prednisolone (p = 0.01 and 0.03); both treatments reduced increases in Larsen's x-ray scores by over 2 units (p = 0.008 and 0.003). A further reduction in erosive damage was seen with combined use of both treatments. Their effects on erosive damage appeared independent. Triple therapy reduced disability and improved quality of life compared with methotrexate; ciclosporin and prednisolone acted synergistically. More patients withdrew because of adverse events with triple therapy, without an increase in serious adverse effects. CONCLUSIONS: This study confirms the existence of a "window of opportunity" in early RA, when intensive combination therapy produces sustained benefits on damage and disability. Although methotrexate-prednisolone combinations reduce erosive damage, the synergistic effect of two DMARDs is needed to improve quality of life.
17989918 A pilot study of acupuncture as adjunctive treatment of rheumatoid arthritis. 2008 May We evaluated the efficacy of acupuncture as a useful adjuvant treatment in the management of rheumatoid arthritis (RA). A pilot, randomized, double-blind, and controlled clinical trial was conducted. Forty RA patients with active disease despite stable therapy for at least the preceding 1 month were randomized to receive a standard protocol of acupuncture (AC) or superficial acupuncture at non-acupuncture points (controlAC) for 9 weeks. The primary outcome was achievement of 20% improvement according to the American College of Rheumatology (ACR) 20 criteria after five and ten treatment sessions and after 1 month of follow-up. Secondary measures included Disease Assessment Scale (DAS), tender and swollen joint count, morning stiffness, Health Assessment Questionnaire (HAQ), visual analogue scale (VAS) of pain, physician global assessment of activity disease, physician and patient global assessment of treatment, and inflammatory markers (erythrocyte sedimentation rate and C-reactive protein). There was not significant difference between the groups regarding the number of patients that reached ACR20 at the end of the treatment (p=0.479). However, after 1 month of follow-up, there was a trend in favor of the AC group, with p=0.068. Compared with the controlAC, the AC group also demonstrated significant improvement in the patient and physician global assessment of treatment and physician global assessment of disease activity, but there was no difference on other clinical and laboratorial measures. On the other hand, only the AC patients had within group improvement on the variables DAS, HAQ, morning stiffness, patient and physician global assessment of treatment, and physician global assessment of disease activity in comparison to baseline visit. Despite the improvement of some studied variables, there was no significant difference in the proportion of patients that reached ACR20 between the AC and controlAC groups. This negative result can be related to the small sample size, selection of patients, type of acupuncture protocol applied, and difficulties in establishing an innocuous and trustworthy placebo group to studies involving acupuncture.
17729297 Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a lar 2007 Sep OBJECTIVE: Induction of malignancy is a major concern when rheumatoid arthritis (RA) is treated with biologic therapy. A meta-analysis of RA biologic clinical trials found a general increased risk of malignancy, but this risk was not found in a large observational study. We undertook this study to assess the risk of malignancy among biologic-treated patients in a large US observational database. METHODS: We studied incident cases of cancer among 13,001 patients during approximately 49,000 patient-years of observation in the years 1998-2005. Cancer rates were compared with population rates using the US National Cancer Institute SEER (Surveillance, Epidemiology, and End-Results) database. Assessment of the risk of biologic therapy utilized conditional logistic regression to calculate odds ratios (ORs) as estimates of the relative risk, further adjusted for 6 confounders: age, sex, education level, smoking history, RA severity, and prednisone use. RESULTS: Biologic exposure was 49%. There were 623 incident cases of nonmelanotic skin cancer and 537 other cancers. The standardized incidence ratios and 95% confidence intervals (95% CIs) compared with SEER data were as follows: all cancers 1.0 (1.0-1.1), breast 0.8 (0.6-0.9), colon 0.5 (0.4-0.6), lung 1.2 (1.0-1.4), lymphoma 1.7 (1.3-2.2). Biologics were associated with an increased risk of nonmelanotic skin cancer (OR 1.5, 95% CI 1.2-1.8) and melanoma (OR 2.3, 95% CI 0.9-5.4). No other malignancy was associated with biologic use; the OR (overall risk) of any cancer was 1.0 (95% CI 0.8-1.2). CONCLUSION: Biologic therapy is associated with increased risk for skin cancers, but not for solid tumors or lymphoproliferative malignancies. These associations were consistent across different biologic therapies.
17181916 Ultrasound imaging for the rheumatologist V. Ultrasonography of the ankle and foot. 2006 Sep Ultrasonography (US) is a useful tool for imaging, which can be used for the assessment of joints and periarticular structures in all rheumatological disorders. In patients with pain and/or swelling of the ankle and foot, US provides information about the presence of joint effusion, synovitis, tenosynovitis, tendinosis, and tendons tears, helping in the differential diagnosis between joint or tendon/enthesis involvement. Moreover, US allows clinicians to monitor and guide needle positioning to inject pharmaceutical substances more safely and effectively even in hard-to-reach sites. US represents an accurate, safe and low-cost technique that can be used for the examination of the ankle and foot in rheumatic disorders.
17153844 Cigarette smoking and autoimmune disease: what can we learn from epidemiology? 2006 Cigarette smoking has been causally linked to the development of multiple autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, Graves' hyperthyroidism, and primary biliary cirrhosis, among others. We review the known biologic effects of cigarette smoke, in particular its actions on the immune system, and the epidemiologic evidence associating smoking with increased risk of each of these autoimmune diseases. Interactions between cigarette smoking and genetic and immunologic factors, such as the human leukocyte antigen (HLA)-shared epitope, rheumatoid factor, anti-cyclic citrullinated peptide antibodies, and anti-double stranded DNA antibodies, may point to mechanisms in disease pathogenesis.
16339293 Pharmacoeconomic study of patients with chronic inflammatory joint disease before and duri 2006 Jul OBJECTIVE: To evaluate medical and work disability costs for patients with chronic inflammatory joint disease during one year before and one year after institution of infliximab treatment in routine clinical practice. METHODS: Starting from 1999, clinical and laboratory variables for patients treated with biological agents for inflammatory rheumatic diseases were systematically recorded at Helsinki University Central Hospital. From this database clinical information was collected on 96 patients in whom infliximab was started during the period 1999 to 2001. Economic analyses were based on costs incurred because of outpatient and inpatient visits, orthopaedic operations, drugs used, and days on sickness or rehabilitation allowance. Medical and work disability costs were calculated separately for the one year period before (period I) and the one year period after institution of infliximab (period II). RESULTS: Of the study group of 96 patients (arthritis duration 16 years (range 3 to 43)), 74 completed one year of infliximab treatment. Their clinical and laboratory variables improved significantly. The mean increase in medical costs during period II was euro12 015 (95% confidence interval, 6496 to 18,076). A minimal decrease in work disability costs occurred-mean decrease euro130 (-1268 to 1072). CONCLUSIONS: One year treatment with infliximab in patients with longstanding aggressive arthritis showed a good clinical effect but raised medical costs significantly. Work disability costs failed to show a substantial decrease. Starting infliximab in the earlier stages of chronic arthritis could in the long term prevent work disability and thus decrease the total cost to society.
16915399 Kinematic adaptation of locomotor pattern in rheumatoid arthritis patients with forefoot i 2007 Jan Rheumatoid arthritis (RA) is a leading cause of disability, which affects primarily the forefoot. Moreover, the forefoot is the final ground body interface for transmitting forces produced by the plantar flexors in order to move the body forward. Therefore, a dysfunction in patients with arthritis might induce important changes in gait, such as modifications in the coordination between legs to correct a reduced range of motion (ROM) and to produce smooth stride motions. First, we wanted to investigate the modifications of gait parameters in order to get a deeper understanding of the locomotor adaptation after a distal joint impairment. Second, we wanted to extract the mechanisms used to compensate for these impairments. In order to carry out this study, RA patients with forefoot impairment and healthy subjects were asked to walk along a straight line at two different velocities and were recorded by a motion analysis system. Patients were able to produce an efficient pattern despite a reduction of the ROM of the forefoot. At normal speed, the substantial modification of the locomotor pattern was linked to the adaptation of the lower-limb segment coordination and to the loss of ROM. Compensative mechanisms are the results of an efficient adaptation that offset the effect of the lesions. In contrast, at high speed, all of the kinematic modifications observed at natural speed vanished. It seems that pain and its associated sensory signals help to update the motor command and compel patients to adjust the descending command to the altered representation of distal mobility. Finally, the mechanical consequences of these changes are of particular interest since different levels of force exerted at the hip, knee and ankle might result in a supplementary structural alteration of these joints.
17324971 Beta-endorphin, Met-enkephalin and corresponding opioid receptors within synovium of patie 2007 Jul OBJECTIVE: Intra-articularly applied opioid agonists or antagonists modulate pain after knee surgery and in chronic arthritis. Therefore, the expression of beta-endorphin (END), Met-enkephalin (ENK), and mu and delta opioid receptors (ORs) within synovium of patients with joint trauma (JT), osteoarthritis (OA) and rheumatoid arthritis (RA) were examined. METHODS: Synovial samples were subjected to double immunohistochemical analysis of opioid peptides with immune cell markers, and of ORs with the neuronal markers calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH). RESULTS: END and ENK were expressed by macrophage-like (CD68(+)) and fibroblast-like (CD68(-)) cells within synovial lining layers of all disorders. In the sublining layers, END and ENK were mostly expressed by granulocytes in patients with JT, and by macrophages/monocytes, lymphocytes and plasma cells in those with OA and RA. Overall, END- and ENK-immunoreactive (IR) cells were more abundant in patients with RA than in those with OA and JT. ORs were found on nerve fibres and immune cells in all patients. OR-IR nerve fibres were significantly more abundant in patients with RA than in those with OA and JT. muORs and deltaORs were coexpressed with CGRP but not with TH. CONCLUSIONS: Parallel to the severity of inflammation, END and ENK in immune cells and their receptors on sensory nerve terminals are more abundant in patients with RA than in those with JT and OA. These findings are consistent with the notion that, with prolonged and enhanced inflammation, the immune and peripheral nervous systems upregulate sensory nerves expressing ORs and their ligands to counterbalance pain and inflammation.
17393416 Up-regulation of stromal cell-derived factor 1 (CXCL12) production in rheumatoid synovial 2007 Apr OBJECTIVE: Stromal cell-derived factor 1 (SDF-1) is a potent chemoattractant for memory T cells in inflamed rheumatoid arthritis (RA) synovium. This study was undertaken to investigate the effect of interleukin-17 (IL-17) and CD40-CD40L interaction on SDF-1 production in RA fibroblast-like synoviocytes (FLS). METHODS: Synovial fluid (SF) and serum levels of SDF-1 in RA patients were measured by enzyme-linked immunosorbent assay (ELISA). The SDF-1 produced by cultured RA FLS was evaluated by real-time polymerase chain reaction and ELISA after FLS were treated with IL-17 and inhibitors of intracellular signal molecules. The SDF-1 level was also determined after FLS were cocultured with T cells in the presence and absence of IL-17. RESULTS: Concentrations of SDF-1 in the sera and SF were higher in RA patients than in osteoarthritis patients, although the increase in the serum levels did not reach statistical significance. The production of SDF-1 in RA FLS was enhanced by IL-17 stimulation. This effect of IL-17 was blocked by inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase), NF-kappaB, and activator protein 1 (AP-1). When FLS were cocultured with T cells, SDF-1 production was up-regulated, especially in the presence of IL-17, but FLS were inhibited by neutralizing anti-IL-17 and anti-CD40L antibodies. Addition of RA SF to cultured RA FLS significantly up-regulated SDF-1 messenger RNA expression, which was hampered by pretreatment with anti-IL-17 antibody. CONCLUSION: SDF-1 is overproduced in RA FLS, and IL-17 could up-regulate the expression of SDF-1 in RA FLS via pathways mediated by PI 3-kinase, NF-kappaB, and AP-1. Our findings suggest that inhibition of the interaction between IL-17 from T cells and SDF-1 in FLS may provide a new therapeutic approach in RA.
17969901 [Clinical observation on effect of total glucosides of paeony combined with methotrexate o 2007 Sep OBJECTIVE: To observe the effect of total glucosides of paeony (TGP) combined with methotrex-ate (MTX) on rheumatoid arthritis (RA). METHODS: Two hundred and sixty patients were assigned to two groups, the treated group (180 cases) was orally administered with MTX plus TGP, and the control group (80 cases) with MTX plus sulfasalazine (SSZ). The therapeutic course for both groups was 24 weeks. The clinical effect and the indexes for RA were observed after treatment. RESULTS: The total effective rate at the 4th, 8th, 12th, 24th week of the treatment was 70%, 81%, 94%, 98% in the treated group, and 60%, 85%, 93%, 94% in the control, respectively, with insignificant difference found between the two groups (P > 0.05). Various indexes of RA were markedly improved in both two groups after treatment but the improvement in the treated group was better than that in the control group (P < 0.05). CONCLUSION: TGP combined MTX treatment shows favorable effect on RA, showing a quicker initiation with less side-effect and higher compliance.
18625616 Evaluating guidelines on continuation of anti-tumour necrosis factor treatment after 3 mon 2009 Jun OBJECTIVE: To study the adherence of rheumatologists to the Dutch guidelines for anti-tumour necrosis factor alpha (TNF-alpha) treatment. The secondary objective was to evaluate alternatives to the present guidelines with regard to the percentage of responders and costs. METHODS: The response (>1.2 DAS28 decrease) in patients who started on anti-TNF-alpha treatment for the first time was evaluated at 3 and 6 months after initiation. How many patients continued or discontinued their initial anti-TNF-alpha treatment was evaluated. Possible alternative guidelines were evaluated by means of a decision tree, with regard to the expected percentage of successfully (responders) and unsuccessfully treated patients and expected costs. RESULTS: At 3 months 56% (N = 306) and 44% (N = 233) of all 539 evaluable patients were classified as responders or non-responders, respectively. Despite the guidelines, most (81%) (N = 189) of the non-responders continued treatment. 37% of the non-responders who continued anti-TNF-alpha treatment were eventually classified as responders at 6 months. Decision analytical modelling showed that with equal expected costs all alternative strategies would result in more responders than according to theoretical full adherence with the guidelines. "Continuation in case of partial response" had the best trade-off between successfully treated patients (64%) and unsuccessfully treated patients (17%). CONCLUSION: There was suboptimal adherence to the Dutch guidelines for treatment with anti-TNF-alpha for rheumatoid arthritis patients. This seemed to be justified by the fact that a delayed response up to 6 months was shown. If treatment is continued despite a non-response at 3 months, this is only recommended in patients with at least a partial response (at least 0.6 DAS28 improvement).
17062647 Rheumatoid synovial endothelial cells produce macrophage colony-stimulating factor leading 2007 Apr OBJECTIVES: Periarticular osteoporosis and joint destruction are major complications in rheumatoid arthritis (RA), caused by osteoclast-mediated bone resorption. However, the mechanisms of monocyte/osteoclast maturation and role of RA endothelial cells (RAECs) in the control of osteoclastogenesis remain unclear. The present study was designed to determine the most important factors that influence monocyte accumulation and osteoclast formation among the many factors produced by RAEC. METHODS: We analysed the expression profiles of various genes in human endothelial cells from various organs (RA synovium, umbilical vein, skin, liver sinusoid, renal glomerulus and brain) using oligonucleotide microarrays. Specifically, up-regulated gene in RAECs was assessed by real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and immunostaining of RA synovia. Migration of monocytes was assessed by the chemotactic chamber EZ-TAXIScan. Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell (MNC) formation was observed by microscopy. RESULTS: Among many epithelial-expressed factors, macrophage colony-stimulating factor (M-CSF) gene was abundantly expressed specifically in RAECs. Genes of fibroblast growth factor-2, interleukin-6 and osteoprotegerin were also overexpressed in RAECs. Migration of monocytes and osteoclast formation in co-cultures promoted by culture supernatants of RAECs were inhibited by M-CSF neutralizing antibody. CONCLUSIONS: M-CSF produced by RAECs is involved in osteoclastogenesis from monocytes, migration and TRAP-positive MNC formation.
16835876 Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat model 2006 Oct Many studies have been carried out in recent years on the pharmacological effects of nigella sativa seeds that have uncovered their antiinflammatory and immunological effects. The objective of this study was to explore the antiinflammatory effects of thymoquinone on arthritis in rat models. Rats with arthritis induced by Freund's incomplete adjuvant were assigned into five groups: group 1: controls 0.9% NaCl (n = 7); group 2: 2.5 mg/kg thymoquinone (n = 7); group 3: 5 mg/kg thymoquinone (n = 7); group 4: Bacilli Chalmette Guerin (BCG) 6 x 10(5) CFU (n = 7); group 5: methotrexate 0.3 mg/kg (n = 7). Signs of inflammation on the claw and radiological signs were searched for and TNF-alpha and IL-1beta were measured. The results of control and other groups were compared. As a result, thymoquinone, confirmed clinically and radiologically, suppressed adjuvant-induced arthritis in rats.