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ID PMID Title PublicationDate abstract
14765862 Premature wear and osteolysis in an HA-coated, uncemented total hip arthroplasty. 2004 Jan The ABG I cementless hip prosthesis has demonstrated unacceptably high rates of wear and osteolysis in our patients. We performed a retrospective study of 97 hips implanted between 1992 and 1998. Radiographic analysis revealed high rates of wear of the polyethylene liner with marked peri-acetabular osteolysis. Clinical examination indicated that many of these patients were initially asymptomatic. Wear-related problems have required ten hips to be revised and a furher 13 are awaiting revision. This gives a failure rate of 24% at a mean follow-up of 69 months. Contributing factors are likely to include poor wear characteristics of the polyethylene liners which were gamma irradiated in air, and increased wear debris caused by a poor fit of the polyethylene liner within the shell. We believe that all ABG I implants should be immediately reviewed and remain under careful, long-term follow-up.
15115702 Relationships between platelets and inflammatory markers in rheumatoid arthritis. 2004 May AIM OF THE STUDY: To investigate platelets and different inflammatory markers in conjunction with a substantial inflammatory reaction. We used individuals with active rheumatoid arthritis (RA) as an experimental cohort. METHODS: We selected 16 patients with active RA having at least one affected joint. On day 1, platelet and neutrophil counts together with C-reactive protein (CRP) were determined. We further analysed platelet volume (MPV) and plasma levels of thrombopoietin (TPO), P-selectin, myeloperoxidase and interleukin 6 (IL-6). After 2 years when all patients failed to show any swollen joints all analyses were repeated. RESULTS AND CONCLUSIONS: As expected platelet count, CRP and IL-6 were elevated in active RA. The measures correlated with each other thus reflecting the same characteristic of the inflammatory response. The neutrophil count, MPV and myeloperoxidase also mirror disease activity. They failed to correlate with other activity markers thus providing unique information. MPV and myeloperoxidase on day 1 correlated with recovery values. Therefore, they could be suitable to use when following the inflammatory reaction over a long period of time.
15495938 [Blockade of chemokines in chronic inflammatory diseases]. 2004 Sep 4 Chemokines form a relatively new family of chemotactic cytokines that seem to play a central role in the migration and activation of leukocytes in a wide variety of immune-mediated disorders. Specific therapy targeted against these proteins may well become an effective treatment in many of these disorders. The efficacy and safety of chemokine blockade is currently being investigated in clinical trials on patients with HIV infection, multiple sclerosis, rheumatoid arthritis and other chronic inflammatory disorders. The first results have been reported in patients with rheumatoid arthritis and these seem to confirm the potency of this treatment.
15225369 CD25brightCD4+ regulatory T cells are enriched in inflamed joints of patients with chronic 2004 CD25+CD4+ regulatory T cells participate in the regulation of immune responses. We recently demonstrated the presence of CD25brightCD4+ regulatory T cells with a capacity to control T cell proliferation in the joints of patients with rheumatoid arthritis. Here, we investigate a possible accumulation of these regulatory T cells in the inflamed joint of different rheumatic diseases including rheumatoid arthritis. The studies are also extended to analyze whether cytokine production can be suppressed by the regulatory T cells. Synovial fluid and peripheral blood samples were obtained during relapse from 36 patients with spondyloarthropathies, 21 adults with juvenile idiopathic arthritis and 135 patients with rheumatoid arthritis, and the frequency of CD25brightCD4+ T cells was determined. Of 192 patients, 182 demonstrated a higher frequency of CD25brightCD4+ T cells in synovial fluid than in peripheral blood. In comparison with healthy subjects, the patients had significantly fewer CD25brightCD4+ T cells in peripheral blood. For functional studies, synovial fluid cells from eight patients were sorted by flow cytometry, and the suppressive capacity of the CD25brightCD4+ T cells was determined in in vitro cocultures. The CD25brightCD4+ T cells suppressed the production of both type 1 and 2 cytokines including interleukin-17, as well as proliferation, independently of diagnosis. Thus, irrespective of the inflammatory joint disease investigated, CD25brightCD4+ T cells were reduced in peripheral blood and enriched in the joint, suggesting an active recruitment of regulatory T cells to the affected joint. Their capacity to suppress both proliferation and cytokine secretion might contribute to a dampening of local inflammatory processes.
15701214 Benefits of transdermal fentanyl in patients with rheumatoid arthritis or with osteoarthri 2004 Dec OBJECTIVES: To evaluate the effectiveness and safety of transdermal fentanyl (TDF) for the treatment of pain associated with rheumatoid arthritis (RA) or osteoarthritis of the knee or hip (OA), which was not adequately controlled by non-opioid analgesics and/or weak opioids. METHODS: The study design incorporated a 1-week run-in period when current analgesic medications were optimised, a 28-day treatment period and a 1-week taper-off period. Patients with RA (n = 104) and OA (n = 159) started treatment with TDF 25 microg/h. Patches were replaced every 72 h, with the option to up-titrate until adequate pain control was achieved. Metoclopramide was taken during the first treatment week and as needed thereafter. RESULTS: 203 patients completed the treatment phase, 90 entered the taper-off phase. 25 microg/h was the most frequently used maximum dose (51%). Pain control was increased from 4% to 29% of patients during run-in. The number of patients reaching adequate pain control in the first treatment week was increased to 75%, and increased further to 88% on day 28 and to 80% at endpoint. From baseline (screening) to endpoint, there were significant reductions in pain (p < 0.001) on the Wisconsin Brief Pain Inventory, and significant improvements in quality of life (Short-Form-36: physical p < 0.001; mental health p < 0.05). Eighty per cent of the patients (n = 134) assessed the treatment favourably; nausea and vomiting were the most common adverse events, mainly occurring at treatment initiation. Efficacy of metoclopramide appeared limited. TDF could be initiated in patients pre-treated with non-opioid analgesics or weak opioids and tapered off without major complications. CONCLUSIONS: TDF significantly improved pain control and quality of life, and was well tolerated in patients with RA or knee/hip OA who continued to experience pain on their current analgesic treatment. Treatment could be discontinued without issues. Nausea and vomiting was usually mild during treatment initiation. Patients' well being could be further accommodated by optimising prophylactic treatment.
12088269 Soluble HLA-II expression in African-Americans. 2002 Jun OBJECTIVE: In this study we evaluated the contribution of major histocompatibility complex (MHC) genes to soluble histocompatibility antigen class II (sHLA-II) secretion in African American patients with rheumatoid arthritis (RA). METHODS: A sensitive enzyme-linked immunoassay was used to quantitate sHLA-II in the serum of 7 patients with RA, as well as 28 of their kinships and 49 HLA typed normal African American individuals. RESULTS: Mean sHLA-II values were higher in patients with RA than those in healthy African American individuals (p < 0.05). There were variations in concentrations in individual patients but these were unrelated to any apparent clinical event. The proportion of unaffected family members with detectable levels of sHLA-II was not significantly different than those in normal controls. Neither specific HLA-haplotype, or HLA-allele(s) correlated with high or low sHLA-II secretion. CONCLUSIONS: Our data suggest that sHLA-II molecules are not regulated by MHC linked genes but may be regulated by non-MHC linked genes and racial background may reflect genetic heterogeneity of the expression of this soluble HLA material. These observations contrast with previous observations concerning soluble HLA class I (sHLA-I) molecules in a described population sample which were almost the precise reverse.
16225773 Analysis of accumulating clonotypes of T cell in joints of a spontaneous murine model of r 2004 Aug SKG mouse, as a model of spontaneous rheumatoid arthritis (RA) bred recent years, is similar to the patients with RA. We analyzed the clonotypes of T cell infiltrating into joints of SKG mice in initial stage and late stage of RA by using reverse transcriptase-polymerase chain reaction (RT-PCR) and subsequent single-strand conformation polymorphism (SSCP). The results indicated that the percentages of clonotypes TCR Vbeta2 and Vbeta8.2 of T cell clonotypes increased obviously to 72.3% and 60.2%, respectively. Mice number with identical TCR Vbeta2 and Vbeta8.2 clonotypes also clearly increased in late stage of disease to 100% and 75%, respectively. These results mean that T cells with TCR Vbeta2 and Vbeta8.2 clonotypes probably play an important role in RA progression of SKG mouse. Sequencing of the extracted DNA verified that common bands on SSCP gel were derived from the same T cell clones among samples from different joints. The results we obtained implied that RT-PCR/SSCP method was a sensitive and credible method for analyzing T cell clonotypes. When the T cells of SKG mouse were adoptively transferred to a nude mouse, it was verified that the T cells infiltrating into joints were related to morbid formation of RA.
15605214 [Frequency of terminally differentiated fibroblasts in the synovial membrane of rheumatoid 2004 Dec The metabolic activation of synovial fibroblasts (SF) and their expression of matrix degrading enzymes and inflammatory cytokines contributes to the pathology of rheumatoid arthritis (RA). It is remarkable that SF of RA patients do not proliferate at higher rates when compared to SF of other patients, but they are resistant to apotposis inducing signals. The chronic inflammation in RA causes fibrosis of the synovial tissue and fibrosis has been associated with terminal differentiation. Therefore we investigated if there are increased numbers of terminally differentiated fibroblasts in the RA synovium and if there is a correlation between terminal differentiation of SF and increased levels of expression of interleukins and matrix metalloproteinases. We analyzed specimen of four RA patients, two patients with osteoarthritis (OA) and two healthy donors suffering from joint injuries. By use of RT-PCR techniques we examined mRNA expression of two genes in SF which are associated with terminal differentiation, p16INK4a and p21-cip. In addition, we labelled differentiated fibroblasts using the SA-beta-galaktosidase assay and investigated differences in protein expression patterns of factor PIVa and the tropomyosin 1 and 2 molecules. We report that the number of terminally differentiated fibrolasts are not increased in the synovial membrane of RA patients. On the contrary we show that the synovia of the much younger patients has higher levels of terminally differentiated fibroblasts. Consequently, the fibrosis of synovial tissues in RA patients at later stages of disorder is not associated with proliferation and differentiation of the fibroblasts but rather a consequence of chronic inflammation.
14688068 T cells accumulating in the inflamed joints of a spontaneous murine model of rheumatoid ar 2004 Jan Although a number of studies have revealed that T cells expand clonally in the joints of patients suffering from rheumatoid arthritis (RA), the kinetics of T cell clonality in multiple joints of an individual throughout progression of the disease is not known. By employing a TCR beta chain gene-specific RT-PCR and subsequent single-strand conformation polymorphism, which enables us to monitor T cell clonality, we analyzed transgenic mice (Tg) carrying the human T cell leukemia virus type I env-pX region. These mice spontaneously develop destructive progressive arthritis similar to RA as they age. In the early stage, the majority of accumulating T cell clones differed in each of four affected feet analyzed. However, in the advanced stage, many of the clones were common to all four feet. The total number of distinct clones gradually decreased as the disease progressed. When splenocytes from arthritic elder Tg were adoptively transferred into either nude mice or young Tg, the clones common to all four feet of the donor were detected again in four feet of the recipients. These findings suggest that, as arthritis progresses, the T cell clones accumulating in the arthritic joints are gradually restricted to certain common clonotypes, some of which are arthrotropic.
11953974 Influence of hypoxia and reoxygenation on cytokine-induced production of proinflammatory m 2002 Apr OBJECTIVE: Articular cartilage is an avascular tissue that functions at a lower oxygen tension than do most tissues. With mobilization, arthritic joints may undergo cycles of hypoxia and reoxygenation. The goal of this study was to determine the effects of hypoxia and reoxygenation on cytokine-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in articular cartilage. METHODS: Porcine cartilage explants were incubated at 37 degrees C for 72 hours in either 1% O(2) (hypoxia) or 20% O(2) (normoxia) in media supplemented with interleukin-1alpha (IL-1alpha) or tumor necrosis factor alpha (TNFalpha), with or without the NO synthase 2 (NOS2) selective inhibitor 1400W. Culture media were then removed and replaced with freshly prepared media and incubated for a further 24 hours in normoxia. RESULTS: NO levels were significantly higher in explants supplemented with IL-1alpha and TNFalpha compared with controls, in both hypoxia and normoxia. Compared with normoxia, hypoxia decreased IL-1alpha- and TNFalpha-induced NO production significantly. Reoxygenation of hypoxic explants resulted in sustained significant NO production in response to either cytokine. However, comparably high levels of NO production were not sustained in explants cultured continuously in normoxia. Although IL-1alpha alone did not significantly increase PGE(2) production, significant PGE(2) superinduction occurred in cartilage stimulated with IL-1alpha and the NOS2 inhibitor 1400W compared with stimulation with IL-1alpha alone in hypoxia, but not in normoxia. CONCLUSION: Oxygen tension significantly affects cytokine-induced proinflammatory mediator production in articular cartilage. Furthermore, hypoxia alters NO mediation of PGE(2) production. Hypoxia and reoxygenation can affect cytokine-induced proinflammatory mediator production, suggesting that oxygen tension may influence inflammation associated with cartilage injury and disease.
12413559 Post-processing water-fat imaging technique for fat suppression in a low-field MR imaging 2002 Nov PURPOSE: To evaluate the feasibility of the phase difference-based post-processing water-fat imaging method for fat suppression at low-field in imaging of arthritic joints. MATERIALS AND METHODS: Thirty joints (wrist, 10; elbow, 10; knee, 10) in 30 patients with rheumatoid arthritis were imaged using a 0.23T MRI unit. Contrast-enhanced T1-weighted (T1w) three-dimensional (3D) gradient-echo (GRE) images with and without fat suppression along with short inversion time inversion-recovery (STIR) images were evaluated by two radiologists. Contrast-enhanced T1w 3D GRE images and corresponding post-processed fat-suppressed images were scored for conspicuity and delineation of enhancing synovial hypertrophy. The uniformity of fat suppression was evaluated between T1w 3D GRE fat-suppressed images and STIR images, and general image quality was estimated for all of the three techniques by consensus. For a quantitative analysis, the enhancing synovial hypertrophy-to-fat contrast-to-noise (CNR) values for the T1W 3D GRE images with and without fat suppression were measured. For comparison, synovial bright signal-to-fat CNR values for the STIR images were measured. RESULTS: The post-processing water-fat imaging technique for fat suppression was successfully applied in all examinations. Conspicuity and delineation of enhancing tissue were superior in fat-suppressed T1w 3D GRE images compared to non-fat-suppressed images (P < 0.0001). As expected, the enhancing synovial hypertrophy tissue-to-fat CNRs were significantly higher in fat-suppressed T1w 3D GRE images compared to non-fat-suppressed images (P < 0.0001). General image quality was assessed to be best in non-fat-suppressed images, and the difference was significant compared to fat-suppressed images (P < 0.05) and STIR images (P < 0.05). CONCLUSION: The phase difference-based post-processing water-fat imaging technique for fat suppression can be successfully used at low-field, and it provides high-quality fat suppression images in imaging of arthritic joints.
12375270 Antimicrobial peptides are expressed and produced in healthy and inflamed human synovial m 2002 Nov The objective of this study was to determine the expression and production of antimicrobial peptides by healthy and inflamed human synovial membranes. Deposition of the antimicrobial peptides lysozyme, lactoferrin, secretory phospholipase A(2) (sPA(2)), matrilysin (MMP7), human neutrophil alpha-defensins 1-3 (HNP 1-3), human beta-defensin 1 (HBD-1), and human beta-defensin 2 (HBD-2) was determined by immunohistochemistry. Expression of mRNA for the antimicrobial peptides bactericidal permeability-increasing protein (BPI), heparin binding protein (CAP37), human cationic antimicrobial protein (LL37), human alpha-defensin 5 (HD5), human alpha-defensin 6 (HD6), HBD-1, HBD-2, and human beta-defensin 3 (HBD-3) was analysed by reverse transcription polymerase chain reaction (RT-PCR). RT-PCR revealed CAP37 and HBD-1 mRNA in samples of healthy synovial membrane. Additionally, HBD-3 and/or LL37 mRNA was detected in synovial membrane samples from patients with pyogenic arthritis (PA), osteoarthritis (OA) or rheumatoid arthritis (RA). BPI, HD5, HD6, and HBD-2 mRNAs were absent from all samples investigated. Immunohistochemistry identified lysozyme, lactoferrin, sPA(2), and MMP7 in type A synoviocytes of all samples. HBD-1 was only present in type B synoviocytes of some of the samples. Immunoreactive HBD-2 peptide was only visible in some inflamed samples. HNP1-3 was detected in both healthy and inflamed synovial membranes. The data suggest that human synovial membranes produce a broad spectrum of antimicrobial peptides. Under inflammatory conditions, the expression pattern changes, with induction of HBD-3 in PA (LL37 in RA; HBD-3 and LL37 in OA) as well as down-regulation of HBD-1. HBD-3 holds therapeutic potential in PA as it has a broad spectrum of antimicrobial activity and accelerates epithelial healing. However, caution is appropriate since defensins also promote fibrin formation and cell proliferation - key elements in joint infection. Clarification of the role of antimicrobial peptides in OA and RA will require further investigation.
11817585 Stimulation of matrix metalloprotease 3 release from human chondrocytes by the interaction 2002 Jan OBJECTIVE: The chemokine family of secreted proteins regulates cellular activities through interaction with G protein-coupled chemokine receptors. The aim of this study was to analyze the role of a chemokine stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 in rheumatoid arthritis (RA) and osteoarthritis (OA) by examining their gene expression in joint cartilage and synovium and by determining the effect of their interaction on the release of matrix metalloproteases (MMPs) from chondrocytes. METHODS: SDF-1 protein levels in synovial fluid from the knee joints of 58 RA patients, 55 OA patients, and 60 control patients without arthritis were quantified by enzyme-linked immunosorbent assay. SDF-1 and CXCR4 messenger RNA (mRNA) levels in chondrocytes and synovial fibroblasts were determined by reverse transcriptase-polymerase chain reaction. Isolated human chondrocytes were stimulated with 100 ng/ml of SDF-1, and the response was analyzed by quantifying the release of MMPs 1 and 3. RESULTS: We found that the concentration of SDF-1 in synovial fluid increased 3.57-fold in OA patients and 10.71-fold in RA patients compared with normal controls. The source of SDF-1 in synovial fluid was synovium, since SDF-1 mRNA was synthesized by synovial fibroblasts but not by chondrocytes. Conversely, CXCR4 was expressed by chondrocytes but not by synovial fibroblasts. The interaction of SDF-1, which was abundant in synovial fluid from RA and OA patients, with CXCR4-positive chondrocytes resulted in a specific elevation of the release of the cartilage matrix-degrading enzyme MMP-3 (stromelysin 1). CONCLUSION: Our findings suggest a novel mechanism by which synovial cells induce degradation of cartilage matrix through SDF-1 signaling in RA and OA.
15580350 Ochronotic arthritis: case reports and review of the literature. 2005 Aug Alkoptunuria is an inherited autosomal recessive metabolic disorder which is caused by the lack of homogentisic acid-oxidase enzyme. It is associated with various systemic abnormalities and related to the deposition of homogentisic acid pigment in connective tissues. These pigmentary changes are termed "ochronosis". We describe two patients with ochronotic arthritis who presented with advanced degenerative changes in the lumbo-sacral spine, knee and hip. The literature, differential diagnosis and management of this rare condition are reviewed in this article.
11808967 Reliability, validity, and responsiveness of severity of dyspepsia assessment (SODA) in a 2002 Jan OBJECTIVES: We aimed to assess the Severity of Dyspepsia Assessment (SODA) scales as measures of change in dyspepsia-related health in a blinded, randomized, controlled trial in arthritis patients treated with nonsteroidal anti-inflammatory drugs. METHODS: Three thousand nine hundred seven arthritis patients completed SODA at baseline and weeks 4, 13, 26, and 52 and/or at early termination. Using baseline and 4-wk data, reliability was evaluated with Cronbach's a and the intraclass correlation coefficient (ICC). Dyspepsia adverse events were defined based on a combined set of World Health Organization Adverse Reaction Terminology terms. The ability of SODA to measure change in dyspepsia-related health was evaluated by comparing SODA change scores by dyspepsia adverse event severity level and withdrawal status. Responsiveness was further evaluated by the area under the curve (AUC) from receiver operating characteristic curves using withdrawal due to dyspepsia as the criterion. RESULTS: The SODA scales--Pain Intensity (alpha = 0.93), Non Pain Symptoms (alpha = 0.82), and Satisfaction (alpha = 0.89)--demonstrated excellent internal consistency reliability using baseline data. Reproducibility was fair to good: Pain Intensity ICC = 0.49, Non Pain Symptoms ICC = 0.61, and Satisfaction ICC = 0.45. SODA change scores (4-wk score - baseline score) increased, or worsened, with increasing dyspepsia severity and differentiated between adjacent levels of dyspepsia severity for eight of nine adjacent comparisons (p < 0.05). SODA change scores also differentiated between those who did and did not withdraw (p < 0.001). Responsiveness was highest with the Pain Intensity scale (AUC = 0.78), followed by the Non Pain Symptoms (AUC = 0.74) and Satisfaction (AUC = 0.75) scales. CONCLUSIONS: SODA is a reliable, valid instrument for use as a measure of dyspepsia tolerability in future clinical trials involving cyclo-oxygenase-2-specific and/or traditional nonsteroidal anti-inflammatory drugs.
12571843 Transcription factor early growth response 1 activity up-regulates expression of tissue in 2003 Feb OBJECTIVE: To investigate the regulatory potential of early growth response 1 (Egr-1) on tissue inhibitor of metalloproteinases 1 (TIMP-1) expression in synovial fibroblasts. METHODS: Egr-1 and TIMP-1 transcripts were detected by in situ hybridization in synovial tissue. Egr-1-regulated TIMP expression was studied in immortalized fibroblast lines using gel retardation assays, RNase protection analysis, reporter gene studies using the human TIMP-1 promoter, and by enzyme-linked immunosorbent assay. RESULTS: TIMP-1 and Egr-1 were coexpressed in synovial fibroblasts of inflamed joints, and Egr-1 activated the expression of TIMP-1. Egr-1 binding to a recognition sequence in the TIMP-1 promoter was demonstrated in gel retardation and reporter gene assays. Since the same DNA sequence was also recognized by the transcription factor Sp-1, our results suggest that the expression of TIMP-1 in synovial fibroblasts may be differentially regulated by Egr-1 and Sp-1. In addition, fibroblasts expressing Egr-1 at high levels were found to express increased levels of TIMP-2 and TIMP-3 messenger RNA. CONCLUSION: The enhanced expression of Egr-1 may regulate the activity of matrix metalloproteinases in synovial fibroblasts by enhancing the expression of the TIMP-1, -2, and -3 genes.
12033987 A multinational randomized, controlled, clinical trial of etoricoxib in the treatment of r 2002 May 22 BACKGROUND: Etoricoxib is a highly selective COX-2 inhibitor which was evaluated for the treatment of rheumatoid arthritis (RA). METHODS: Double-blind, randomized, placebo and active comparator-controlled, 12-week study conducted at 67 sites in 28 countries. Eligible patients were chronic NSAID users who demonstrated a clinical worsening of arthritis upon withdrawal of prestudy NSAIDs. Patients received either placebo, etoricoxib 90 mg once daily, or naproxen 500 mg twice daily (2:2:1 allocation ratio). Primary efficacy measures included direct assessment of arthritis by counts of tender and swollen joints, and patient and investigator global assessments of disease activity. Key secondary measures included the Stanford Health Assessment Questionnaire, patient global assessment of pain, and the percentage of patients who achieved ACR20 responder criteria response (a composite of pain, inflammation, function, and global assessments). Tolerability was assessed by adverse events and routine laboratory evaluations. RESULTS: 1171 patients were screened, 891 patients were randomized (N = 357 for placebo, N = 353 for etoricoxib, and N = 181 for naproxen), and 687 completed 12 weeks of treatment (N = 242 for placebo, N = 294 for etoricoxib, and N = 151 for naproxen). Compared with patients receiving placebo, patients receiving etoricoxib and naproxen showed significant improvements in all efficacy endpoints (p<0.05). Treatment responses were similar between the etoricoxib and naproxen groups for all endpoints. The percentage of patients who achieved ACR20 responder criteria response was 41% in the placebo group, 59% in the etoricoxib group, and 58% in the naproxen group. Etoricoxib and naproxen were both generally well tolerated. CONCLUSIONS: In this study, etoricoxib 90 mg once daily was more effective than placebo and similar in efficacy to naproxen 500 mg twice daily for treating patients with RA over 12 weeks. Etoricoxib 90 mg was generally well tolerated in RA patients.
12535392 Short-term low-dose corticosteroids vs placebo and nonsteroidal antiinflammatory drugs in 2003 BACKGROUND: The effect of low dose corticosteroids, equivalent to 15 mg prednisolone daily or less, in patients with rheumatoid arthritis has been questioned. We performed a systematic review of trials which compared corticosteroids with placebo or non-steroidal, anti-inflammatory drugs. OBJECTIVES: To determine whether short-term (i.e. as recorded within the first month of therapy), oral low-dose corticosteroids (corresponding to a maximum of 15 mg prednisolone daily) is superior to placebo and non-steroidal, anti-inflammatory drugs in patients with rheumatoid arthritis. SEARCH STRATEGY: Medline Silverplatter, The Cochrane Controlled Trials Register, reference lists and a personal archive. Date of last search May 2002. SELECTION CRITERIA: All randomised studies comparing an oral corticosteroid (not exceeding an equivalent of 15 mg prednisolone daily) with placebo or a non-steroidal, anti-inflammatory drug were eligible if they reported clinical outcomes within one month after start of therapy. For adverse effects, long-term trials and matched cohort studies were also selected. DATA COLLECTION AND ANALYSIS: Decisions on which trials to include were made independently by two observers based on the methods sections of the trials. Standardised mean difference (random effects model) was used for the statistical analyses. MAIN RESULTS: Ten studies, involving 320 patients, were included. Prednisolone had a marked effect over placebo on joint tenderness (standardised mean difference 1.31, 95% confidence interval 0.78 to 1.83), pain (1.75, 0.87 to 2.64) and grip strength (0.41, 0.13 to 0.69). Measured in the original units, the differences were 12 tender joints (6 to 18) and 22 mm Hg (5 to 40) for grip strength. Prednisolone also had a greater effect than non-steroidal, anti-inflammatory drugs on joint tenderness (0.63, 0.11 to 1.16) and pain (1.25, 0.26 to 2.24), whereas the difference in grip strength was not significant (0.31, -0.02 to 0.64). Measured in the original units, the differences were 9 tender joints (5 to 12) and 12 mm Hg (-6 to 31). The risk of adverse effects, also during moderate- and long-term use, seemed acceptable. REVIEWER'S CONCLUSIONS: Prednisolone in low doses (not exceeding 15 mg daily) may be used intermittently in patients with rheumatoid arthritis, particularly if the disease cannot be controlled by other means. Since prednisolone is highly effective, short-term placebo controlled trials studying the clinical effect of low-dose prednisolone or other oral corticosteroids are no longer necessary.
15039494 Improvement in health utility among patients with rheumatoid arthritis treated with adalim 2004 Jun OBJECTIVES: To compare health-related quality of life (HRQoL), as measured by health utility, in patients with rheumatoid arthritis (RA) treated with adalimumab (a human anti-tumour necrosis factor (anti-TNF) monoclonal antibody) plus methotrexate or placebo plus methotrexate. METHODS: HRQoL data were obtained in two randomized, double-blind, placebo-controlled, multidose clinical trials conducted in the United States and Canada. The Health Utilities Index Mark 3 (HUI3) was administered in both studies at baseline, at the end of the study and at two time points in between. Patients' HUI3 scores were compared with population norm scores. Change in HUI3 was defined as the end-of-study score minus the baseline score. Utility gained throughout the study was measured by area under the utility curve and expressed as quality-adjusted life years (QALYs). Statistical testing adjusted for confounders and used the Dunnett test to account for multiple comparisons. RESULTS: Patients' utility scores at baseline were low (range of treatment group means 0.38-0.44) compared with population norms (0.88). HUI3 mean changes from baseline scores for adalimumab-treated patients were 0.22 and 0.21 in the two trials, whereas placebo patients' changes were 0.04 and 0.07. The rate of QALYs gained per year in the treatment group compared with the placebo group were 0.145 in the ARMADA trial and 0.104 in the DE019 trial. All gains were clinically important and statistically significant. CONCLUSIONS: Treatment with adalimumab plus methotrexate provides clinically important and statistically significant improvements in HRQoL as measured by health utility in patients with RA. This translates into measurable and important gains in QALYs.
15242866 Anti-tumour necrosis factor alpha therapy in rheumatoid arthritis: an update on safety. 2004 Dec Anti-TNFalpha therapy may have associated risks of serious infection, congestive heart failure, malignancy, and multiple sclerosis. The magnitude of these risks is difficult to assess. This article reviews publications on the current knowledge about the safety of these agents.