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ID PMID Title PublicationDate abstract
18383423 Determinants of the use of wrist working splints in rheumatoid arthritis. 2008 Apr 15 OBJECTIVE: To gain insight into the determinants of the use of wrist working splints among patients with rheumatoid arthritis (RA). METHODS: A qualitative descriptive study was performed among 18 patients with RA who recently received a fabric wrist working splint because of pain due to arthritis of the wrist. Patients were interviewed at home using semistructured in-depth interviews. Interviews were audiotaped and transcribed verbatim and analyzed using the framework approach. RESULTS: The majority of patients indicated that their splint use was dependent on the seriousness of the symptoms (pain, swelling, or tingling feelings) they perceived. Important reasons to wear the splint were reduction of symptoms, wrist support, and immobilization of the wrist. Important reasons to stop wearing the splint were reduced functional abilities using the splint and the performance of dirty or wet activities. CONCLUSION: The reasons for patients to wear and not wear wrist working splints are related to intentional decisions of the patients, which are primarily based on perceived benefits and barriers of splint wearing. The results of this study have been used to develop educational and behavioral strategies to increase adherence to wearing wrist working splints.
17133580 The functional variant of the inhibitory Fcgamma receptor IIb (CD32B) is associated with t 2006 Dec OBJECTIVE: Fcgamma receptors (FcgammaRs) recognize immune complexes (ICs) and coordinate the immune response by modulating the functions of dendritic cells (DCs). The purpose of this study was to unravel the role of the inhibitory FcgammaRIIb in rheumatoid arthritis (RA) by studying the effect of the FCGR2B 695T>C polymorphism on susceptibility to RA, severity of the disease, and DC function. METHODS: Genotyping was performed in RA patients (n = 246) and healthy blood donors (n = 269). The patients' demographic data, disease severity, and disease progression were assessed over a followup of 6 years. DCs were cultured for flow cytometry to determine the expression of FcgammaRs. For detection of FcgammaRIIb (CD32B), a unique anti-FcgammaRIIb antibody (2B6-fluorescein isothiocyanate [FITC]) was used. The capacity for antigen uptake by DCs was studied by assessing the uptake of FITC-labeled ICs. Levels of cytokine production by DCs were measured during lipopolysaccharide-mediated cell activation in the presence and absence of ICs. RESULTS: Although no role of the FCGR2B variant in RA susceptibility was demonstrated, this variant was associated with a nearly doubled rate of radiologic joint damage during the first 6 years of RA. Multiple regression analysis showed that FCGR2B was by far the strongest predictor of joint damage identified to date. DCs from patients carrying this variant failed to display the inhibitory phenotype normally observed upon IC-mediated triggering of inflammation and displayed diminished FcgammaRII-mediated antigen uptake compared with wild-type DCs. However, the levels of FcgammaRs were not affected, suggesting that the FCGR2B variant alters the function rather than regulation of proteins. CONCLUSION: This study is the first to show that a single genetic variant, the FCGR2B 695T>C polymorphism, is a critical determinant of disease severity in RA and radically changes DC behavior. Our results underscore the key role of DCs in the progression of RA and reveal FcgammaRIIb as an important potential therapeutic target in RA and other autoimmune conditions.
17322487 Decrease of fructosamine levels during treatment with adalimumab in patients with both dia 2007 Mar Tumour necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine which has been closely linked to obesity and insulin resistance. We present two cases of patients with rheumatoid arthritis (RA) and concomitant diabetes mellitus, who showed a marked decrease of fructosamine levels after initiating therapy with adalimumab, a TNFalpha-blocking agent, for active RA. This finding may implicate that TNFalpha blockade causes better glycaemic control in RA patients with concomitant diabetes, possibly by improving insulin resistance.
17350968 Circulating levels of the chemokine CCL18 but not CXCL16 are elevated and correlate with d 2007 Oct BACKGROUND: Antigen-presenting cells (APC) and T cells are considered to play a significant role in the pathogenesis of rheumatoid arthritis (RA). CCL18 and CXCL16 are two chemokines that facilitate T cell attraction by APC, of which a role in the pathogenesis of RA has been suggested. OBJECTIVE: To compare the circulating levels of CXCL16 and CCL18 in RA with controls and to investigate the relation of CXCL16 and CCL18 with RA disease activity and joint damage. METHODS: Circulating CCL18 and CXCL16 levels were determined in 61 RA patients with a follow-up of 6 years and a group of 41 healthy controls with ELISA. Chemokine levels were correlated with demographic data, disease activity (DAS28) and joint damage (modified Sharp score). In addition, serum CCL18 and CXCL16 levels from a cohort of 44 RA patients treated with anti-TNF-alpha were correlated with disease activity. RESULTS: CCL18 levels in serum were significantly elevated in RA patients compared with controls, while serum CXCL16 levels were not. In contrast to CXCL16, serum CCL18 was positively correlated with disease activity. Both CCL18 and CXCL16 levels decreased upon treatment with anti-TNF-alpha. Neither CCL18 nor CXCL16 correlated with joint damage and progression. CONCLUSION: Here, we show, for the first time, that circulating CCL18 and not CXCL16 levels are elevated in RA patients as compared with controls and correlate with disease activity in RA. More knowledge regarding the regulation and function of both CCL18 and CXCL16 is essential to value their role in RA.
18501558 The development of targeted therapies in rheumatoid arthritis. 2008 Nov The therapy of rheumatoid arthritis has been revolutionised by advances in the understanding of disease at a cellular and molecular level accompanied by the technology to target specific mediators of disease. Proposed therapeutic targets from in vitro and animal models however have frequently resulted in unexpected outcomes in clinical trials. These have included have included cytokines, chemokines, the T cell receptor trimolecular complex, T cells and B cells. The most successful strategies have resulted from a close dialogue between clinical and laboratory work. The key stages in the development of these agents and remaining unanswered questions are reviewed.
17064527 [Study of the proteins associated with Sa antigen]. 2006 Jul 18 OBJECTIVE: To study the proteins associated with Sa antigen, a target of the anti-Sa antibodies specific for rheumatoid arthritis, and to elucidate the nature of these proteins. METHODS: Sa antigen was extracted from fresh human placental tissue by anion exchange chromatography and subjected to SDS-PAGE electrophoresis. Serum samples were collected from 155 patients with connective tissue diseases, including rheumatoid arthritis (71 cases), ankylosing spondylitis (11 cases), psoriatic arthritis (7 cases), reactive arthritis (7 cases), juvenile idiopathic arthritis (4 cases), osteoarthritis (5 cases), polymyalgia rheumatica (6 cases), gout (6 cases), systemic lupus erythematous (7 cases), Sjogren's syndrome (10 cases), adult onset Still's disease (3 cases) and Sa antibodies were detected by immunoblotting. The gel bands corresponding to the stained bands were excised, trypsin-digested in gel, and analyzed by LC-ESI-MS/MS. Once identified, the protein was recombinate and expressed in Escherichia coli, and the antibodies were detected by immunoblotting. Then the protein was citrullinated to detect the antibodies again. RESULTS: Immunoblotting showed anti-Sa antibodies, band (s) with apparent molecular weight of 50 000 (and) 55 000, in 34 of the 71 patients of rheumatoid arthritis and 4 of the 84 patients of other rheumatic diseases, with a sensitivity rate of 47.9% and a specificity rate of 95.2%. The target protein was identified as vimentin. The positive rate of anti-vimentin antibody was statistically different between the RA patients and the patients with other rheumatic diseases (P = 0.005), with a sensitivity rate of 36.6% and a specificity rate of 83.3%, respectively. But there was no obvious correlation between anti-vimentin antibody and anti-Sa antibodies (Kappa = 0.316). The positive rate of anti-citrullinated vimentin antibody was significantly higher in the RA patients than in the patients with other rheumatic diseases (P < 0.01), with a sensitivity rate of 49.3%. There was a high correlation between anti-citrullinated vimentin antibody and anti-Sa antibodies (Kappa = 0.746), albeit a low specificity rate (86.9%). CONCLUSION: Citrullinated vimentin is closely correlated with Sa antigen.
16414468 Shoulder arthroplasty in Olmsted County, Minnesota, 1976-2000: a population-based study. 2006 Jan Because little information is currently available on the epidemiology of shoulder arthroplasty, this study was designed to evaluate the characteristics of patients undergoing this procedure and changes in practice patterns. Residents of Olmsted County, Minnesota, who underwent shoulder arthroplasty between 1976 and 2000 were identified (98 residents, 112 procedures). A relatively lower initial rate of shoulder arthroplasty was followed by a statistically significant steady increase (P < .0001), with an age- and sex-adjusted annual operative incidence rate of 1.4 per 100,000 person-years (1976-1980) to 10.1 per 100,000 person-years (1996-2000). Increased utilization of shoulder arthroplasty during the last decade was mainly a result of its application in osteoarthritis. A significant need exists for examination of utilization patterns for shoulder arthroplasty. An aging population and an increased demand and awareness by the public regarding interventions to improve quality of life will shape the future of arthroplasty, reinforcing the need for future studies of this nature.
18666383 Clinical pharmacogenomics of thiopurine S-methyltransferase. 2006 Jan Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (6-MP), thioguanine and azathioprine (AZA). These drugs are used to treat conditions such as acute lymphoblastic leukemia, inflammatory bowel disease, rheumatoid arthritis, and organ transplant rejection. This review highlights the polymorphisms of TPMT gene and their clinical impact on the use of thiopurine drugs. To date, there are 18 known mutational TPMT alleles. The three main TPMT alleles, namely TPMT *2, *3A and *3C, account for 80 - 95% of the intermediate and low enzyme activity. The TPMT gene exhibits significant genetic polymorphisms among all ethnic groups studied. Patients who inherited very low levels of TPMT activity are at greatly increased risk for thiopurine-induced toxicity such as myelosuppression, when treated with standard doses of these drugs, while subjects with very high activity may be undertreated. Moreover, clinical drug interactions may occur due to TMPT induction or inhibition. Identification of the TPMT mutant alleles allows physicians to tailor the dosage of the thiopurine drugs to the genotype of the patient or to use alternatives, improving therapeutic outcome.
18037337 Forkhead box protein 3: essential immune regulatory role. 2008 CD4+CD25+ regulatory T (Treg) cells play a crucial role in maintaining self-tolerance and preventing autoimmune disease. The transcription factor forkhead box protein 3 (Foxp3) has been identified as a molecular marker for Treg cells. Foxp3 is highly expressed in lymphoid tissue and several signalling pathways influence its expression. It plays an essential role in the development and function of Treg cells. Mutations in Foxp3 are responsible for the scurfy (sf) mutant mouse, and for autoimmune human diseases including the X-linked fatal "immune dysregulation, polyendocrinopathy, enteropathy, X-linked" (IPEX), autoimmune colitis and rheumatoid arthritis. Recent studies have also revealed an important and novel anti-atherogenic role for Treg cells and consequently for Foxp3. These data open up potential novel therapeutic avenues for the management of atherosclerosis.
17040961 Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum. 2007 Apr BACKGROUND: Resistin is a newly identified adipocytokine which has demonstrated links between obesity and insulin resistance in rodents. In humans, proinflammatory properties of resistin are superior to its insulin resistance-inducing effects. OBJECTIVES: To assess resistin expression in synovial tissues, serum and synovial fluid from patients with rheumatoid arthritis, osteoarthritis and spondylarthropathies (SpA), and to study its relationship with inflammatory status and rheumatoid arthritis disease activity. METHODS: Resistin expression and localisation in synovial tissue was determined by immunohistochemistry and confocal microscopy. Serum and synovial fluid resistin, leptin, interleukin (IL)1beta, IL6, IL8, tumour necrosis factor alpha, and monocyte chemoattractant protein-1 levels were measured. The clinical activity of patients with rheumatoid arthritis was assessed according to the 28 joint count Disease Activity Score (DAS28). RESULTS: Resistin was detected in the synovium in both rheumatoid arthritis and osteoarthritis. Staining in the sublining layer was more intensive in patients with rheumatoid arthritis compared with those with osteoarthritis. In rheumatoid arthritis, macrophages (CD68), B lymphocytes (CD20) and plasma cells (CD138) but not T lymphocytes (CD3) showed colocalisation with resistin. Synovial fluid resistin was higher in patients with rheumatoid arthritis than in those with SpA or osteoarthritis (both p<0.001). In patients with rheumatoid arthritis and SpA, serum resistin levels were higher than those with osteoarthritis (p<0.01). Increased serum resistin in patients with rheumatoid arthritis correlated with both CRP (r=0.53, p<0.02), and DAS28 (r=0.44, p<0.05), but not with selected (adipo) cytokines. CONCLUSION: The upregulated resistin at local sites of inflammation and the link between serum resistin, inflammation and disease activity suggest a role for resistin in the pathogenesis of rheumatoid arthritis.
18032542 The role of HLA-DRB1 shared epitope alleles in predicting short-term response to leflunomi 2007 Dec OBJECTIVES: To investigate the role of shared epitope (SE) alleles in the short-term clinical response to leflunomide for the treatment of active RA. METHODS: In an open-label, multi-centre study of 16-weeks duration, 93 patients (82% female) fulfilling ARA 1987 RA criteria were treated with leflunomide (100 mg loading dose for 3 days, then 20 mg/day as the maintenance dose). The primary efficacy criterion was the response status according to the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score-28 (DAS28) activity measure. SE determinations have been undertaken by polymerase chain reaction and sequence-specific oligonucleotide genotyping methods. RESULTS: The mean (s.d.) Disease Activity Score-28 (DAS28) was 5.1 (1.3) before the treatment, which was significantly decreased after 16 weeks [3.0 (1.1), P < 0.001]. According to the EULAR response criteria, 55 patients (59.1%) were classified as good responders. SE was positive in 51 (54.8%) of the patients, with 13 (13.9%) having SE homozygosity or carrying any two SE alleles. Among SE-positive patients, 68.6% (35/51) were good responders, compared with 47.6% (20/42) in SE negatives (P = 0.04). No difference was present according to SE hetero- or homozygosity (68.4 vs 69.2%). RF was also present significantly more frequently in the SE-positive group compared with negatives (78.4 vs 57.1%, P = 0.03). However, no significant difference was observed in the prevalence of RF positivity in patients with a good clinical response (72.7 vs 63.2%, P = 0.32). CONCLUSIONS: The results suggest that HLA-DRB1 SE presence may favourably affect the outcome of leflunomide monotherapy in an unselected group of RA patients with an active disease and naive to leflunomide.
17538753 Diastolic function abnormalities in rheumatoid arthritis: relation with duration of diseas 2007 Jun INTRODUCTION: There are limited studies on the prevalence of diastolic dysfunction in rheumatoid arthritis (RA) from the Indian subcontinent. The aim of this study was to evaluate left ventricular filling abnormalities in patients with RA without clinically-evident cardiovascular manifestations, and to correlate it with disease duration. METHODS: 45 patients affected with RA according to the American Rheumatism Association criteria, were selected without evidence of cardiac disease, and compared with age- and sex-matched control subjects. All patients and the control group were submitted to M-mode, two-dimensional and Doppler echocardiography. The following diastolic parameters were evaluated: peak of early diastolic (E) and late diastolic (A) mitral flow velocity, E/A ratio, isovolumic relaxation time (IVRT), ejection fraction and fractional shortening. RESULTS: In RA patients, left ventricular filling abnormalities were found characterised by a reduced E/A ratio (mean [SD] 0.98 [0.22] versus controls 1.09 [0.11]; p-value equals 0.004), prolonged IVRT (75.77 [8.12] ms versus 70.43 [2.94] ms; p-value equals 0.001) and increased late diastole flow velocity (76.91 [11.61] cm/s versus 70.11 [5.32] cm/s; p-value equals 0.001). In the group of patients, a negative correlation was found between E/A ratio and disease duration (Pearson correlation, r equals -0.56, p-value equals 0.001), indicating diastolic dysfunction with increasing disease duration. A strong correlation was also found between IVRT and disease duration (r equals 0.66, p-value equals 0.01) and also between late diastolic flow velocity and disease duration (r equals 0.61, p-value equals 0.001). CONCLUSION: The present study confirms a high frequency of left ventricular diastolic dysfunction characterised by impaired E/A ratio, prolonged IVRT and increased late diastole flow velocity in patients with RA without evident cardiovascular disease. The correlation between transmitral flow alteration and disease duration suggests a subclinical myocardial involvement with disease progression. This may be relevant to the high incidence of cardiovascular deaths observed in patients with RA.
16465651 Single-blind randomized trial of combination antibiotic therapy in rheumatoid arthritis. 2006 Feb OBJECTIVE: To determine the potential clinical efficacy of combination antibiotic therapy in treating rheumatoid arthritis (RA). METHODS: Twenty-one patients with active RA despite second-line treatment were randomized to receive either combination antibiotic therapy (treatment group, n = 11) or no additional therapy (control group, n = 10). Antibiotic therapy was given for 12 months and comprised oral tetracycline 250 mg twice daily, 3 times per week, and intravenous clindamycin infused on 5 consecutive days (300, 300, 600, 600, and 900 mg) followed by weekly infusions of 900 mg for 3 weeks and then fortnightly infusions for the remainder of the 12 months. The primary outcome measure was the American College of Rheumatology 20% (ACR20) response at the end of the initial treatment period of 12 months. RESULTS: Five patients in the treatment group (45%) achieved an ACR20 response at 1 year compared to none in the control group (p = 0.04). Eight patients in the treatment group and 1 in the control group had a greater than 20% improvement in tender joint count (p = 0.008). There were also significant differences between the groups in physician and patient global assessments. Nine patients in the treatment group completed the 6 months' followup; of these, 3 sustained the ACR20 response. CONCLUSION: Combined antibiotic therapy with intravenous clindamycin and oral tetracycline may be useful in the management of active RA. A double-blind, placebo-controlled trial of therapy is justified.
17394223 Experiences of mothers living with inflammatory arthritis. 2007 Apr 15 OBJECTIVE: To describe the impact of chronic, inflammatory arthritis on parenting and to develop a conceptual framework for subsequent study of mothering. METHODS: A qualitative, grounded theory design guided data collection and analysis. In-depth interviews were conducted with a purposive sample of 12 women with either rheumatoid arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, or systemic lupus erythematosus who were mothers of at least 1 child living at home. Transcripts were analyzed using a systematic approach of coding and forming concepts and key categories to construct an explanatory framework. Peer checking and member checking enhanced analytical rigor. RESULTS: Analysis of participants' experiences resulted in 4 interrelated categories describing the impact of arthritis on their role as mothers: participation in mothering tasks, best described as "sometimes I can, sometimes I can't"; different types and levels of support from others; the influence of the mother's arthritis on the family; and the challenge of balancing energy and fatigue. Individuals' arthritis story, life stage, their children's developmental stage, and daily routine described the context in which mothers experienced elements of each of the 4 main categories. CONCLUSION: Inflammatory arthritis has a dramatic impact on the experience of motherhood, with both positive and negative influences. The perspectives shared by study participants may inform practice regarding problem identification and adaptive strategies, and the explanatory model generated from the data proposes hypotheses for further study.
16456308 Targeting rheumatoid tenosynovial angiogenesis with cytokine inhibitors. 2006 May Proliferation and invasion of the tenosynovial lining of tendons in patients with rheumatoid arthritis can result in tendon damage and rupture, leading to decreased hand function. Angiogenesis is an important process in rheumatoid joint disease; however, the role of angiogenesis in tendon disease is unknown. Our aim was to determine whether rheumatoid tenosynovial lining could produce angiogenic proteins, and if inhibition of tumor necrosis factor-alpha and interleukin-1 could decrease vascular endothelial growth factor production. Samples of encapsulating and invasive tenosynovial lining taken from the same hand and wrist synovial lining were harvested from 58 patients with rheumatoid arthritis having wrist surgery. Ex vivo samples were studied to quantify vascularity, angiogenic protein production under normoxic and hypoxic conditions, and the effect of inhibiting tumor necrosis factor-alpha and interleukin-1 on vascular endothelial growth factor production. Rheumatoid tenosynovial lining was more vascular than rheumatoid joint synovial lining and produced high levels of angiogenic factors such as vascular endothelial growth factor, interleukin-1beta, fibroblast growth factor-2, and angiopoietin-2. Hypoxia induced an increase in production of vascular endothelial growth factor by ex vivo tenosynovial lining cells. Inhibition of the cytokines interleukin-1 and tumor necrosis factor-alpha effectively reduced vascular endothelial growth factor production by tenosynovial samples. LEVEL OF EVIDENCE: Therapeutic study. Level II (Prospective comparative study). See the Guidelines for Authors for a complete description of levels of evidence.
16385496 Contribution of congestive heart failure and ischemic heart disease to excess mortality in 2006 Jan OBJECTIVE: Although mortality among patients with rheumatoid arthritis (RA) is higher than in the general population, the relative contribution of comorbid diseases to this mortality difference is not known. This study was undertaken to evaluate the contribution of congestive heart failure (CHF) and ischemic heart disease (IHD), including myocardial infarction, to the excess mortality in patients with RA, compared with that in individuals without RA. METHODS: We assembled a population-based inception cohort of individuals living in Rochester, Minnesota, in whom RA (defined according to the criteria of the American College of Rheumatology [formerly, the American Rheumatism Association]) first developed between 1955 and 1995, and an age- and sex-matched non-RA cohort. All subjects were followed up until either death, migration from the county, or until 2001. Detailed information from the complete medical records was collected. Statistical analyses included the person-years method, cumulative incidence, and Cox regression modeling. Attributable risk analysis techniques were used to estimate the number of RA deaths that would be prevented if the incidence of CHF was the same in patients with RA and non-RA subjects. RESULTS: The study population included 603 patients with RA and 603 subjects without RA. During followup, there was an excess of 123 deaths among patients with RA (345 RA deaths occurred, although only 222 such deaths were expected). The mortality rates among patients with RA and non-RA subjects were 39.0 and 29.2 per 1,000 person-years, respectively. There was a significantly higher cumulative incidence of CHF (but not IHD) in patients with RA compared with non-RA subjects (37.1% versus 27.7% at 30 years of followup, respectively; P < 0.001). The risk of death associated with either CHF or IHD was not significantly different between patients with RA and non-RA subjects. If the risk of developing CHF was the same in patients with RA and individuals without RA, the overall mortality rate difference between RA and non-RA hypothetically would be reduced from 9.8 to 8.0 excess deaths per 1,000 person-years; that is, 16 (13%) of the 123 excess deaths could be prevented. CONCLUSION: CHF, rather than IHD, appears to be an important contributor to the excess overall mortality among patients with RA. CHF contributes to this excess mortality primarily through the increased incidence of CHF in RA, rather than increased mortality associated with CHF in patients with RA compared with non-RA subjects. Eliminating the excess risk of CHF in patients with RA could significantly improve their survival.
16353227 Power Doppler assessment of overall disease activity in patients with rheumatoid arthritis 2006 Jan PURPOSE: To examine synovial vascularity and flow patterns in hand and wrist joints--metacarpophalangeal (MCP) joints and ulnar stiloid (USTL) regions--of patients with rheumatoid arthritis (RA) using power Doppler sonography (PDUS) and spectral Doppler analysis and to assess the accuracy of PDUS in detecting overall disease activity in RA patients. METHODS: Two hundred forty MCP joints and 48 USTL regions in 24 RA patients were examined. Patients were categorized into 2 groups--active and inactive--according to the American College of Rheumatology remission criteria. Resistance indexes (RIs) were measured. RESULTS: Flow signals were detected in 50 MCP joints (in 13 patients) and 24 USTL regions (in 16 patients) and spectral analysis was performed in 46 MCP joints (12 patients) and 23 USTL regions (16 patients). The sensitivity and specificity of PDUS in detecting disease activity in RA were 92% and 40%, respectively. There was a negative correlation between flow signal number and RI, with higher scores of flow signals corresponding to lower RIs. CONCLUSION: PDUS appears to be a reliable method for assessing inflammatory activity in rheumatoid synovium.
17582315 [Cost of rheumatoid arthritis in france: comparison leflunomide/etanercept]. 2007 Mar Treatment of rheumatoid arthritis was deeply modified with the availability since 1999 of anti-TNFalpha. The clinical superiority of these drugs compared to traditional treatments is proven, but can one make the assumption that the cost of these innovative treatments is partially compensated by a reduction of consumption of other health resources? A retrospective observational study was carried out in the Midi-Pyrenees area, from the point of view of health insurance, to compare the consumed health resources between two cohorts of patients, one treated by etanercept (Enbrel) and the other by leflunomide (Arava). Two hundred and fifty three patients were included in the etanercept cohort and 539 in the leflunomide cohort. The average annual PR cost for a patient treated with etanercept is 13 936 euro and 5 764 euro for a patient treated with leflunomide. The health costs avoided by recourse to etanercept do not compensate the high cost of this drug.
16957889 Course of damage to the hallux over 5 years after forefoot resection arthroplasty in rheum 2007 Aug A retrospective study of 34 feet from 20 consecutive patients with rheumatoid arthritis was performed to investigate the development of damage to the hallux over 5 years after forefoot resection arthroplasty. Radiographically we analysed changes in two valgus angles and the interphalangeal joint (IP) damage of the hallux. These parameters were measured preoperatively, 12 months postoperatively, and at the latest follow-up. Although the average HVA (between the first metatarsal and the proximal phalanx) significantly decreased from 38.7 degrees preoperatively to 8.66 degrees postoperatively, the angle increased to 23.0 degrees during the first 12 months following surgery. Further deterioration of the angle at the last follow-up was not detected (25.3 degrees ; P=0.252). The average IPV (between the proximal phalanx and the distal phalanx) angle significantly increased from 6.65 degrees preoperatively to 12.1 degrees 12 months postoperatively and thereafter slightly increased to 13.3 degrees at the latest follow-up. The average of the Sharp/van der Heijde score of the IP joint significantly increased from 5.71 preoperatively to 8.58 12 months postoperatively and thereafter slightly increased to 9.65 at the latest follow-up. The deterioration and destruction process of the hallux after resection arthroplasty occurred soon after surgery, and the progression of the deformity was temporary.
18066613 Photodynamic therapy using talaporfin sodium for synovial membrane from rheumatoid arthrit 2008 Jun We investigated the efficacy of photodynamic therapy (PDT) using talaporfin sodium as a new method of synovectomy for rheumatoid arthritis (RA). We first used RA synovial membrane (RASM) for in vitro and in vivo study. The RASM was obtained from patients with RA during total knee replacement. In the in vitro study, RA fibroblast-like synoviocytes (RASCs) obtained from the RASM were examined by fluorescent microscopy to measure the intracellular localization of talaporfin sodium. The cells were then subjected to PDT, and their viability was examined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium inner salt assay. In the in vivo assay, RASM was obtained as described above, grafted onto severe combined immunodeficiency (SCID) mice and subjected to PDT. The damaged area of RASM was evaluated histologically at 1 day after PDT. Next, we performed a separate experiment using rats with collagen-induced arthritis (CIA). After intra-articular injection of talaporfin sodium, the concentration of talaporfin sodium accumulated in the CIA synovial membrane (CIASM) was compared with that in cartilage, periarticular muscle, and skin. We then performed PDT with intra-articular injection of talaporfin sodium and intra-articular irradiation. The damaged area of the CIASM was measured at 1 day after the PDT, and the articular histological and radiological changes of the ankle were observed at 56 days after the PDT. In RASM, talaporfin sodium accumulated in lysosomes in vitro, and the phototoxicity to RASCs in vitro and to RASM grafted onto SCID mice in vivo depended on the concentration of talaporfin sodium and the laser energy. In CIA rats, there was a greater accumulation of talaporfin sodium in the CIASM than in normal tissue. The CIASM was selectively damaged at 1 day after the PDT, and the bone and cartilage destruction were ameliorated at 56 days after the PDT. In conclusion, PDT using talaporfin sodium might be a new method for synovectomy in patients with RA.