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ID PMID Title PublicationDate abstract
15899050 Biomarkers of endothelial dysfunction, cardiovascular risk factors and atherosclerosis in 2005 Cardiovascular event rates are markedly increased in rheumatoid arthritis (RA), and RA atherogenesis remains poorly understood. The relative contributions of traditional and nontraditional risk factors to cardiovascular disease in RA await elucidation. The present study comprises three components. First, we compared biomarkers of endothelial dysfunction (vascular cell adhesion molecule [VCAM]-1, intercellular adhesion molecule [ICAM]-1 and endothelial leucocyte adhesion molecule [ELAM]-1) in 74 RA patients and 80 healthy control individuals before and after controlling for traditional and nontraditional cardiovascular risk factors, including high-sensitivity C-reactive protein (hs-CRP), IL-1, IL-6 and tumor necrosis factor-alpha. Second, we investigated the potential role of an extensive range of patient characteristics in endothelial dysfunction in the 74 RA patients. Finally, we assessed associations between biomarkers of endothelial dysfunction and ultrasonographically determined common carotid artery intima-media thickness and plaque in RA. The three biomarkers of endothelial dysfunction, as well as hs-CRP, IL-1, IL-6 and tumor necrosis factor-alpha, were higher in patients than in control individuals (P < 0.0001). Patients were also older, exercised less and had a greater waist circumference, blood pressure and triglyceride levels (P
17075601 Interleukin 6: from bench to bedside. 2006 Nov Interleukin (IL)-6 is a pleiotropic cytokine that has important roles in the regulation of the immune response, inflammation, and hematopoiesis. Disruption of IL-6 regulation might, however, affect the immune response and consequently induce immune-mediated inflammatory diseases such as rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease, and Crohn's disease. Overproduction of IL-6 also contributes, through its roles as a growth factor or an antiapoptotic factor, to the development of malignant diseases such as multiple myeloma and renal cancer. Progress in the study of IL-6 has increased our understanding of the pathological roles of this cytokine in these diseases and provided key evidence that antagonizing its activities can be used as a therapeutic strategy. The application of molecular biology techniques to design monoclonal antibodies as therapeutic agents has made it possible to regulate the IL-6 signal to successfully treat diseases that have so far proved refractory to conventional therapies. Blocking IL-6 actions by use of a humanized antibody, tocilizumab, which targets the IL-6 receptor, has been proven to be therapeutically effective for rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease and Crohn's disease. In this review, we discuss a paradigm of IL-6 from basic science to clinical use.
16641044 Factors associated with hyperhomocysteinaemia in Mexican patients with rheumatoid arthriti 2006 Mar BACKGROUND: Hyperhomocysteinaemia is a factor related to the development of atherosclerosis in rheumatoid arthritis (RA). However, Hispanics with RA develop high rates of coronary disease; there are no studies about the frequency and factors related to high levels of homocysteine in Mexican patients. OBJECTIVE: To evaluate the prevalence and characteristics associated with hyperhomocysteinaemia in Mexican patients with RA. METHODS: One hundred and fifty-two patients with RA were compared with 153 controls. The assessment in RA included clinical characteristics, disease activity (RADAR), functioning (HAQ-Di and global functional status), comorbidity, and radiological damage. Laboratory determinations included total serum homocysteine (tHcy), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and lipid profile. RESULTS: Median levels of homocysteine were higher in RA compared with controls (11.3 vs. 9.3, p<0.001). Twenty per cent of the patients with RA had hyperhomocysteinaemia (>15 micromol/L) compared with 6% in controls (p<0.001). There was statistical association between hyperhomocysteinaemia in RA with male gender (p<0.001), impairment in the global functional status (p = 0.004), higher radiological damage (p = 0.001), and CRP (p = 0.04). There was no association with RADAR, HAQ-Di, or RF, methotrexate dose or duration of use. In the adjusted multivariate model, the two variables associated with higher risk for hyperhomocysteinaemia were male gender (OR = 4.2, 95% CI 2 to 12, p = 0.006) and higher radiological damage (III-IV) (OR = 3.4, 95% CI 1.3 to 9, p = 0.01). CONCLUSIONS: Our data show a high prevalence of hyperhomocysteinaemia in Mexican patients with RA. More effort is required to evaluate and treat earlier this coronary risk factor.
16277578 Periodontitis and rheumatoid arthritis: a review. 2005 Nov Periodontitis and rheumatoid arthritis (RA) appear to share many pathologic features. In this review, the common pathologic mechanisms of these two common chronic conditions are explored. Emerging evidence now suggests a strong relationship between the extent and severity of periodontal disease and RA. While this relationship is unlikely to be causal, it is clear that individuals with advanced RA are more likely to experience more significant periodontal problems compared to their non-RA counterparts, and vice versa. A case is made that these two diseases could be very closely related through common underlying dysfunction of fundamental inflammatory mechanisms. The nature of such dysfunction is still unknown. Nonetheless, there is accruing evidence to support the notion that both conditions manifest as a result of an imbalance between proinflammatory and anti-inflammatory cytokines. As a result, new treatment strategies are expected to emerge for both diseases that may target the inhibition of proinflammatory cytokines and destructive proteases. The clinical implications of the current data dictate that patients with RA should be carefully screened for their periodontal status.
16095118 The genetic contribution of the TNFa11 microsatellite allele and the TNFb + 252*2 allele i 2005 Jul OBJECTIVES: The contribution of the microsatellite polymorphisms of TNFa and TNFb, and the TNFB + 252 (TNFB) dimorphism to the pathogenesis of rheumatoid arthritis (RA) was studied among Japanese patients. METHODS: The TNFa and TNFb microsatellite polymorphisms, and the TNFB dimorphism were determined in Japanese RA patients and normal subjects using electrophoresis followed by specific PCR amplification. HLA-DRB1*04 typing was carried out by the PCR-SSCP method. RESULTS: The allele frequency of TNFa11 showed a significant increase in RA with DRB1*0405 when compared to that in RA without DRB1*0405 (28.5% Vs 12.9%, respectively, p = 0.022). An association analysis indicated that TNFa11 was not primary, but secondary to the increase in HLA-DRB1*0405, because TNFa11 showed a strong positive association with HLA-DRB1*0405 in Japanese controls. The slight increase in the TNFb4 allele observed in RA with DRB1*0405 (50.0%) may be reflective of the increase in TNFa11 and DRB1*0405. In RA with DRB1*0405, the allele frequency of TNFB*2 significantly increased compared to that of normal controls (75.0% Vs 55.3%, respectively, p = 0.007) and compared to that of RA without DRB1*0405 (45.0%, p = 0.001). No significant positive association of TNFB*2 with HLA-DRB1*0405 or TNFa11 in Japanese controls might suggest that the increase in the TNFB*2 allele might not be secondary to the increase in DRB1*0405, and that TNFB*2 might contribute additively to DRB1*0405-positive RA in Japanese. CONCLUSION: TNFB*2 may contribute additively to Japanese RA with HLA-DRB1*0405, while TNFa11 and TNFb4 are not independent genetic markers of RA among Japanese.
17139663 Osteoporosis management in patients with rheumatoid arthritis: Evidence for improvement. 2006 Dec 15 OBJECTIVE: Osteoporosis in patients with rheumatoid arthritis (RA) is increasingly recognized as a major comorbidity. We examined past management patterns for glucocorticoid-induced osteoporosis and attempted to improve care through an educational intervention. The goal was to examine the frequency of osteoporosis management in patients with RA treated at a large academic rheumatology practice. METHODS: We performed a structured chart review on randomly selected patients seen during 2004 for RA. Osteoporosis management was defined as a bone mineral density test or receipt of a medication for osteoporosis in the prior 24 months. The frequency of osteoporosis management among our study group was assessed. We also examined how glucocorticoid dosage affected osteoporosis management in adjusted models. RESULTS: We reviewed the records for 193 patients, 99 had not used glucocorticoids in the prior 24 months, and 94 had used them. Of the total study population, 48% had received a bone mineral density test or medication for osteoporosis. Some form of osteoporosis management was present for 64% of patients taking > or =5 mg prednisone for > or =3 months compared with 38% for patients taking none (P = 0.002). Predictors of osteoporosis management included older age, female sex, glucocorticoid dosage, and prior osteoporosis diagnosis or fracture. CONCLUSION: The frequency of osteoporosis management appears to have increased compared with a prior chart review.
17013609 Role of amyloidosis in determining the prognosis of dialyzed patients with rheumatoid arth 2007 Feb The role of secondary amyloidosis in determining the prognosis of dialyzed patients with rheumatoid arthritis (RA) was examined in 22 patients with a mean age of 60.1 years included 21 renal amyloidosis. RA duration until the start of dialysis was 19.5 +/- 7.2 years and the observation period after introduction 27.1 +/- 26.4 months. Of the 14 dead cases, four died due to sepsis, three due to gastrointestinal tract bleeding, two due to congestive heart failure, and eight cases died within 5 months after starting dialysis. When comparing the eight survivors and the nine non-survivors who died within 2 years after the start of dialysis, the former patients showed significantly higher serum albumin, and lower electrocardiogram score and cardiothoracic ratios at the time of introduction to dialysis. The careful prevention and treatment of infection, cerebrovascular and/or gastrointestinal tract complications seem to be necessary to improve the prognosis of RA patients after the initiation of renal replacement therapy.
15759013 CUL1, a component of E3 ubiquitin ligase, alters lymphocyte signal transduction with possi 2005 May Ubiquitination affects various immune processes and E3 ubiquitin ligases (E3) play an important role in determining substrate specificity. We identified 11 human E3 ligase genes of potential importance in pathogenesis of autoimmune diseases by search of public databases and screened them for candidacy of biological investigation with case-control linkage disequilibrium tests on multiple SNPs in the genes using rheumatoid arthritis (RA) as a model of autoimmune diseases. Significant association with RA was observed in an SNP in intron 3 of Cullin 1 (CUL1) that affected transcriptional efficiency of the promoter activity in lymphocytic cell lines. Quantitative expression analysis revealed that CUL1 mRNA was highly detected in lymphoid tissues including spleen and tonsil, and was specifically expressed in T and B lymphocytes in fractionated peripheral leukocytes. Histological evaluation of tonsils indicated that CUL1 protein expression was relatively specific for maturing germinal centers. Suppression of CUL1 expression had influence on the phenotype of T-cell line, that is, it inhibited IL-8 induction, which is known to play an important role in the migration of inflammatory cells into the affected area seen in RA. Our data suggest that the regulation of CUL1 expression in immunological tissues may affect the susceptibility of RA via altering lymphocyte signal transduction.
16320324 Stromal cells and osteoclasts are responsible for exacerbated collagen-induced arthritis i 2005 Dec OBJECTIVE: Clinical trials using interferon-beta (IFNbeta) in the treatment of rheumatoid arthritis have shown conflicting results. We undertook this study to understand the mechanisms of IFNbeta in arthritis at a physiologic level. METHODS: Collagen-induced arthritis (CIA) was induced in IFNbeta-deficient and control mice. The role of IFNbeta was investigated in both the priming and effector phases of the disease. The effect of IFNbeta deficiency on synovial cells, macrophages, and fibroblasts from preimmunized mice was analyzed by flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assay. Differences in osteoclast maturation were determined in situ by histology of arthritic and naive paws and by in vitro maturation studies of naive bone marrow cells. The importance of IFNbeta-producing fibroblasts was determined by transferring fibroblasts into mice at the time of CIA immunization. RESULTS: Mice lacking IFNbeta had a prolonged disease with a higher incidence compared with control mice. IFNbeta deficiency was found to influence the effector phase, but not the priming phase, of arthritis. Compared with control mice, IFNbeta-deficient mice had greater infiltration of CD11b+ cells and greater production of tumor necrosis factor alpha in vivo, and their macrophages and fibroblasts were both more activated in vitro. Moreover, IFNbeta-deficient mice generated a greater number of osteoclasts in vitro, and mice immunized to induce arthritis, but not naive mice, had a greater number of osteoclasts in vivo compared with control mice. Importantly, IFNbeta-competent fibroblasts were able to ameliorate arthritis in IFNbeta-deficient recipients. CONCLUSION: Our data indicate that IFNbeta is involved in regulating the activation state of osteoclasts and stromal cells, including macrophages and fibroblasts, but that it has little effect on T cells.
16572289 Bcl-x(L) expression in vivo in rheumatoid synovium. 2006 Nov To examine the expression of the apoptosis regulatory protein, Bcl-x(L), in the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunohistochemistry for Bcl-x(L) was carried out on synovial samples from patients with RA and OA. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis were performed to qualitatively examine the expression of Bcl-x(L). Bcl-x(L) expression was detected in the lining, endothelium and inflammatory cells of both RA (n=20) and OA (n=10) samples. However, there was significantly more expression in the lining of RA synovium compared to OA (77 vs 61%, p<0.05). Many of the positive cells in the RA subsynovium were noted to be plasma cells. There was a significant correlation between Bcl-x(L) expression and the number of inflammatory cells in the subsynovium of RA and OA patients (r (s)=0.376, p<0.05, n=30). Age and disease duration did not correlate with Bcl-x(L) expression in rheumatoid patients. Bcl-x(L) may play a role in the extended survival of synoviocytes and inflammatory cells in rheumatoid synovium.
15231512 Influence of anti-tumour necrosis factor therapy on cardiovascular risk factors in patient 2005 Feb BACKGROUND: Tumour necrosis factor (TNF) is known to increase the concentrations of interleukin (IL) 6 and C reactive protein (CRP) and to induce proatherogenic changes in the lipid profile and may increase the cardiovascular risk of patients with rheumatoid arthritis (RA) and other inflammatory disorders. OBJECTIVE: To assess whether anti-TNF therapy modifies the cardiovascular risk profile in patients with RA. METHODS: The lipoprotein spectrum and the inflammation markers CRP and IL6 were investigated in 33 patients with RA treated with human anti-TNF monoclonal antibodies (D2E7, adalimumab, Humira) and 13 patients with RA given placebo, before and after 2 weeks' treatment. RESULTS: In the anti-TNF treated group, the mean (SD) concentrations of HDL-cholesterol were significantly higher after 2 weeks' treatment (0.86 (0.30) mmol/l v 0.98 (0.33) mmol/l, p<0.01), whereas LDL and triglyceride levels were not significantly changed. Additionally, a significant decrease in CRP (86.1 (54.4) mg/l v 35.4 (35.0) mg/l, p<0.0001), and IL6 (88.3 (60.5) pg/ml v 42.3 (40.7) pg/ml, p<0.001) concentrations was seen in this group. No changes in lipid profile, IL6, or CRP levels were seen in the placebo group. CONCLUSIONS: TNF neutralisation with monoclonal anti-TNF antibodies increased HDL-cholesterol levels and decreased CRP and IL6 levels after 2 weeks. Therefore this treatment may improve the cardiovascular risk profile of patients with RA.
16453283 CD28-dependent differentiation into the effector/memory phenotype is essential for inducti 2006 Feb OBJECTIVE: Interleukin-1 receptor antagonist (IL-1Ra)-deficient mice on a BALB/c background spontaneously develop a chronic inflammatory polyarthropathy closely resembling that of rheumatoid arthritis in humans. To elucidate the role of CD28 costimulatory signals in the development of this disease, we studied IL-1Ra/CD28-double-deficient mice. METHODS: We crossed IL-1Ra-deficient mice with CD28-deficient mice and observed the incidence and severity of arthritis. To investigate functions of IL-1Ra/CD28-double-deficient T cells, cells were stimulated with CD3 monoclonal antibody or allogeneic antigen-presenting cells (APCs) and their proliferative responses and levels of cytokine production were measured. RESULTS: Disease severity was lower in IL-1Ra/CD28-double-deficient mice than in mice that were deficient only in IL-1Ra, although incidence of arthritis was not affected by the presence or absence of CD28. When pathogenic IL-1Ra-KO T cells were transferred into nude mice, severe arthritis developed. Even though T cells from double-deficient mice showed the same diminished proliferative capacity as was seen in T cells from CD28-single-deficient animals, nude mice into which double-deficient T cells were transferred never developed arthritis. CONCLUSION: These findings indicate that IL-1Ra/CD28-double-deficient T cells can be activated by IL-1Ra-deficient activated APCs, resulting in induction of arthritis; however, these T cells did not induce the disease under normal conditions, because they did not differentiate into effector/memory phenotype.
16162882 Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. 2005 Sep 15 BACKGROUND: A substantial number of patients with rheumatoid arthritis have an inadequate or unsustained response to tumor necrosis factor alpha (TNF-alpha) inhibitors. We conducted a randomized, double-blind, phase 3 trial to evaluate the efficacy and safety of abatacept, a selective costimulation modulator, in patients with active rheumatoid arthritis and an inadequate response to at least three months of anti-TNF-alpha therapy. METHODS: Patients with active rheumatoid arthritis and an inadequate response to anti-TNF-alpha therapy were randomly assigned in a 2:1 ratio to receive abatacept or placebo on days 1, 15, and 29 and every 28 days thereafter for 6 months, in addition to at least one disease-modifying antirheumatic drug. Patients discontinued anti-TNF-alpha therapy before randomization. The rates of American College of Rheumatology (ACR) 20 responses (indicating a clinical improvement of 20 percent or greater) and improvement in functional disability, as reflected by scores for the Health Assessment Questionnaire (HAQ) disability index, were assessed. RESULTS: After six months, the rates of ACR 20 responses were 50.4 percent in the abatacept group and 19.5 percent in the placebo group (P<0.001); the respective rates of ACR 50 and ACR 70 responses were also significantly higher in the abatacept group than in the placebo group (20.3 percent vs. 3.8 percent, P<0.001; and 10.2 percent vs. 1.5 percent, P=0.003). At six months, significantly more patients in the abatacept group than in the placebo group had a clinically meaningful improvement in physical function, as reflected by an improvement from baseline of at least 0.3 in the HAQ disability index (47.3 percent vs. 23.3 percent, P<0.001). The incidence of adverse events and peri-infusional adverse events was 79.5 percent and 5.0 percent, respectively, in the abatacept group and 71.4 percent and 3.0 percent, respectively, in the placebo group. The incidence of serious infections was 2.3 percent in each group. CONCLUSIONS: Abatacept produced significant clinical and functional benefits in patients who had had an inadequate response to anti-TNF-alpha therapy.
15719700 Serum hyaluronic acid levels are elevated in arthritis patients, but normal and not associ 2005 BACKGROUND: Fibromyalgia syndrome (FM) is a disease with widespread chronic pain and many nonspecific symptoms. Hyaluronic acid (HA) is a disputed marker for the diagnosis of FM. The aim of the study is to clarify the discrepant results reported so far. METHODS: Serum concentrations of HA were measured with a radiometric assay (Pharmacia & Upjohn, Sweden) in 41 patients with FM (38 females), 48 with arthritis (35 females) and 31 control subjects (28 females). Correlations of HA levels with clinical parameters (duration of disease, age, gender, medication) and scores of disease severity (e.g. depression and pain) were calculated. If appropriate, partial correlations and analysis of covariance adjusted for confounding variables (e.g. age) were used. RESULTS: HA levels were confirmed to be age-related in the whole study group (r(s) = 0.54; P < 0.001) and each subgroup. Association between HA levels and gender, drug therapy, clinical or psychometric data could not be demonstrated in patients suffering from FM. Analyzing all study participants, HA levels were correlated with the pain disability index (PDI) (r(tau) = 0.27; P < 0.02) and, in arthritis patients only, with duration of disease (r(tau) = 0.82; P < 0.001). Moreover, analysis of covariance revealed that patients with FM had normal HA values as compared with control subjects and only patients with arthritis had significantly higher levels than both other groups. CONCLUSIONS: The present study with a quite large cohort including patients with arthritis and FM demonstrates that serum levels of HA in FM are neither elevated nor associated with any relevant clinical data of this disease and, therefore, have no diagnostic or prognostic value in Germans.
16331754 A phase 2 dose-finding study of PEGylated recombinant methionyl human soluble tumor necros 2005 Dec OBJECTIVE: In a phase 2 study, to assess the efficacy and safety of pegsunercept, a soluble tumor necrosis factor receptor type I, for the treatment of rheumatoid arthritis (RA). METHODS: Patients were randomized to receive weekly subcutaneous injections of placebo (n = 61) or active drug [400 microg/kg (n = 67) or 800 microg/kg (n = 66)] for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. Secondary efficacy measures included ACR50 and ACR70 responses, and changes in individual ACR components at Week 12. Safety assessments included summaries of adverse events including infectious episodes. RESULTS: Treatment with pegsunercept resulted in a significantly higher ACR20 response at Week 12 in the 800 microg/kg group (45%) compared with the placebo group (26%; p = 0.020). The treatment effect of pegsunercept (both doses) over the study period showed statistically significant improvement for most ACR components and health related quality of life, with the 800 microg/kg group showing greater clinical improvements in efficacy measures. The overall incidence of adverse events and infectious episodes was similar among the treatment and placebo groups. CONCLUSION: In this 12 week dose-finding study of 194 patients, weekly subcutaneous dosing with pegsunercept showed beneficial effects in improving the signs and symptoms of RA. It appeared to be safe and well tolerated in this small number of patients. Significant clinical improvements were seen in patients in the 800 microg/kg group; however, this dose may be suboptimal, and further evaluation of this product with higher doses or a more frequent dosing regimen is warranted.
15966394 [Cricoarytenoid arthritis diagnosed after tracheostomy in a rheumatoid arthritis patient]. 2005 Jun A 65-year-old woman was scheduled for total knee replacement. She had been suffering from rheumatoid arthritis for 22 years. She also had a history of occasional acute dyspnea, which had been diagnosed as asthmatic bronchitis. Preoperative examinations of the airway revealed limited neck flexion, a small jaw, and normal mouth opening. After epidural catheterization, anesthesia was induced with propofol, and a #3 laryngeal mask airway (LMA) was inserted. However, her lungs could not be ventilated through the LMA. Despite repeated attempts, proper placement of the LMA could not be achieved. Hence, a 7.0 mm ID armored endotracheal tube was inserted through an intubating LMA. Anesthesia was maintained with nitrous oxide and sevoflurane in oxygen. The surgery proceeded uneventfully. Five minutes after extubation, inspiratory dyspnea occurred. The patient's trachea was re-intubated nasally with a bronchofiberscope. Since the bronchofiberscopy revealed remarkable laryngeal edema, percutaneous tracheostomy was performed. On the 3 rd postoperative day, cricoarytenoid arthritis that had caused occasional airway obstruction was diagnosed, although her laryngeal edema disappeared. She went home with a permanent tracheostomy. Although cricoarytenoid arthritis is a common occurrence in patients with rheumatoid arthritis, the diagnosis can be difficult. A scrupulous preoperative evaluation and awareness of cricoarytenoid arthritis are necessary for optimal anesthetic management.
15794709 What to do with TNF failures. 2005 Mar The introduction of TNF inhibitors into the clinic for the treatment of patients with rheumatoid arthritis and other systemic inflammatory conditions has revolutionised the approach to these diseases. Despite the substantial efficacy of these agents, a subset of patients either does not respond or has a suboptimal clinical response. Defining what constitutes 'failure' of this type of therapy is important in both clinical research and practice. For patients who fail to respond to TNF inhibitors, a number of promising avenues targeting other aspects of the immune system are under study, and may be brought to the clinic in the near future.
17096696 A case report of leukocytapheresis for refractory leg ulcers complicated with rheumatoid a 2006 Oct Leukocytapheresis (LCAP) has recently been investigated for the treatment of drug-resistant rheumatoid arthritis (RA). In the present clinical study, we used LCAP in three patients with rheumatoid arthritis (RA), with drug-resistant leg ulcers. LCAP was carried out once a week for five weeks. Erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor titers and tender joint counts did not change when LCAP was used but the ulcers began to recede after the first treatment and, by the end of the fifth treatment, the ulcers had healed. The activated leukocytes that are the major part of the inflammation of skin ulcers are removed from the peripheral blood by LCAP. Thus, it is supposed that the activated leukocytes shift from the inflammatory skin ulcer to peripheral blood, causing the skin ulcer to recover. We hypothesize that LCAP is a useful treatment for refractory leg ulcers complicated with RA.
16573350 Abatacept. 2006 Abatacept (Orencia) is the first in a new class of biologics known as selective costimulation modulators. It inhibits full activation of T cells and interacts with other cell types to affect additional mediators of the inflammatory cascade. The clinical efficacy of abatacept in patients with active rheumatoid arthritis, despite prior treatment with methotrexate or anti-tumor necrosis factor-alpha (anti-TNFalpha) therapies, has been investigated in two randomized, double-blind, placebo-controlled, multicenter, phase III trials of 6 or 12 months' duration. In these trials, patients received intravenous abatacept (fixed-dose regimen based on bodyweight) or placebo in addition to background disease-modifying anti-rheumatic drugs (DMARDs) other than anti-TNFalpha therapies. Relative to placebo, abatacept significantly improved signs and symptoms of disease assessed using American College of Rheumatology (ACR) 20, 50, and 70 criteria and specific improvement in physical function as measured by the Health Assessment Questionnaire Disability Index at 6 months and significantly slowed structural damage progression in joints at 12 months. Improvements in ACR 20, 50, and 70 response rates were maintained at the final assessment in the 12-month trial. Abatacept infusions were generally well tolerated. Acute infusion-related reactions occurred in 9% of abatacept and 6% of placebo recipients in phase III trials. Integrated safety data from five clinical trials showed that serious adverse events were reported in 13.6% of abatacept and 12.3% of placebo recipients and the incidence of serious infections was 3.0% and 1.9%. Abatacept administered with background biologic DMARDs appears to be less well tolerated than abatacept plus background nonbiologic DMARDs.
16376247 Arthroscopic glenoid resurfacing with meniscal allograft: a minimally invasive alternative 2005 Dec The chronically painful arthritic glenohumeral joint recalcitrant to nonsurgical treatment modalities generally has been treated with an open arthroplasty type of procedure. Certain patients may benefit from a less invasive surgical technique in which a meniscal allograft is used to resurface the glenoid, resulting in decreased pain and increased function. We describe an arthroscopic method of glenoid resurfacing with a meniscal allograft to aid in the restoration of function by providing pain relief to patients debilitated by arthritic conditions of the glenohumeral joint.