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ID PMID Title PublicationDate abstract
23393485 Payers Have Biologic Alternative for Patients With Moderate to Severe Rheumatoid Arthritis 2006 Dec Earlier biologic therapies for rheumatoid arthritis represented a breakthrough in treatment of the disease, but there are still some patients who do not respond adequately to them. The market entry of abatacept, which allows for consistent dosing and predictable drug-acquisition costs, presents patients, physicians, and third-party payers with an effective alternative - the first therapy proven to be effective in patients with inadequate response to DMARDs such as methotrexate or anti-TNF-alpha therapies.
24692770 Abatacept for the treatment of rheumatoid arthritis: A review. 2007 Nov BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory disease affecting synovial joints. Patients with persistent, active disease have traditionally been treated with disease-modifying antirheumatic drugs (DMARDs) (eg, methotrexate) or biologic agents (eg, tumor necrosis factor [TNF] antagonists). However, patients may discontinue these treatments due to toxicity, infection, or lack of efficacy. Two additional biologic therapies-rituximab and abatacept-are currently available for TNF-antagonist inadequate responders. Abatacept is also indicated for inadequate responders to traditional DMARDs. OBJECTIVES: The aims of this review was to provide an overview of the issues surrounding the treatment of RA patients experiencing inadequate responses to current treatment and to discuss the current and future impact of abatacept on the RA treatment armamentarium. METHODS: The MEDLINE, EMBASE, and BIOSIS databases were searched (search dates: January 1, 2000-September 19, 2007) using the terms abatacept or CTLA-4 or Orencia with rheumatoid arthritis. Full text articles in English were selected for relevance, and only articles presenting primary clinical trial data from randomized, placebo-controlled, clinical trials of abatacept were included. This review focused on the Phase III trials of abatacept in methotrexate and/or TNF-antagonist inadequate responders, as these trials had the largest number of patients and the longest study durations. RESULTS: The literature search initially yielded 848 papers. A total of 12 articles fulfilled the inclusion criteria. Abatacept is a novel agent that has been reported to reduce the signs and symptoms of RA in patients with active RA with an inadequate response to DMARDs and/or TNF-antagonist treatment. In both of these patient populations, treatment with abatacept was found to provide clinically meaningful health-related quality-of-life benefits, such as improvements in physical function, activity limitation, sleep, and fatigue. Abatacept was reported to have a consistent safety and tolerability profile, with a low rate (3.5%-4.2%) of discontinuation due to adverse events. CONCLUSION: The efficacy and tolerability data from Phase III clinical trials suggest that abatacept is an effective and generally well tolerated treatment option for RA patients with an inadequate response to methotrexate and/or TNF antagonists.
18667798 Neuroendocrine dysfunction in Sjogren's syndrome. 2008 Interactions among the immune, nervous and endocrine systems, which are mediated by hormones, neuropeptides, neurotransmitters, cytokines and their receptors, appear to play an important role in modulating host susceptibility and resistance to inflammatory disease. The neuroendocrine system has two main components: the central and the peripheral. The central compartment is located in the locus ceruleus, the brainstem centers of the autonomic system and the paraventricular nucleus; the peripheral mainly consists of the sympathetic/adrenomedullary system, the hypothalamic-pituitary-adrenal axis (HPA), the hypothalamic-pituitary-gonadal (HPG) axis, and the neuroendocrine tissue located in several organs throughout the body. Hormones and neuropeptides may influence the activities of lymphoid organs and cells via endocrine and local autocrine/paracrine pathways or alter the function of different cell types in target organs. Recent studies highlighted alterations of the neuroendocrine system in systemic autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus and Sjogren's syndrome (SS). SS, a prototype autoimmune disorder, has a wide clinical spectrum, extending from organ involvement (autoimmune exocrinopathy) to systemic disease and B cell lymphoma. In SS, several functions of the neuroendocrine system are impaired. First, the HPA axis appears to be disturbed, since significantly lower basal ACTH and cortisol levels were found in patients with SS and were associated with a blunted pituitary and adrenal response to ovine corticotropin-releasing factor compared to normal controls. Second, HPG axis is also involved, since lack of estrogens is associated with human disease and the development of autoimmune exocrinopathy in several experimental models. Finally, exocrine glands are enriched with neuroendocrine-related molecules, adjacent to local autoimmune lesions. Certain clinical manifestations of the disease, including the sicca manifestations, easy fatigue, fibromyalgia and psychological disturbances can be very well explained by mechanisms directly related to disturbances of the neuroendocrine axis. On the other hand, the molecular and biochemical effects of the inflammatory molecules or cell-to-cell interaction, observed during the local or systemic autoimmune injury with cells and mediators of the neuroendocrine system, are largely unexplored.
16626905 Septic arthritis due to Roseomonas mucosa in a rheumatoid arthritis patient receiving infl 2006 Aug We report a case of septic arthritis due to Roseomonas mucosa in a rheumatoid arthritis patient receiving infliximab therapy. This is the first report of septic arthritis due to R. mucosa, and infliximab therapy might be a predisposing factor because this infection was never reported in the pre-anti-tumor necrosis factor alpha therapy period.
16651968 Orthognathic surgery in juvenile rheumatoid arthritis patients. 2006 May BACKGROUND: Mandible advancement osteotomy in juvenile rheumatoid arthritis patients for class II anterior open-bite malocclusion is controversial; however, there is no literature discussing outcomes of surgery in this group of patients. An evaluation of such outcomes was undertaken at The Hospital for Sick Children. METHODS: A retrospective chart review revealed that eight patients with juvenile arthritis underwent orthognathic surgery during a period of 5 years. All of the patients had a bilateral sagittal split osteotomy of the mandible, six had a simultaneous Le Fort I osteotomy, and four had an additional advancement genioplasty. The age of the patients at the time of surgery ranged between 17 and 22 years (mean, 18 years), with three male patients and five female patients. The patients were under follow-up for a minimum of 8 months after surgery, and measurements were performed studying preoperative and postoperative lateral cephalometric radiographs. RESULTS: All patients have an improved occlusion and improved facial aesthetics. One patient continued to suffer from temporomandibular joint pain. The mean mandible advancement was 9.6 mm (range, 3.9 to 18.3 mm). The mean mandible relapse after surgery was 2.1 mm (range, 1 to 3.1 mm). No exacerbation of the juvenile rheumatoid arthritis was encountered as a result of the surgical procedure. CONCLUSIONS: Orthognathic surgery in juvenile rheumatoid arthritis patients improves the patient's occlusion, facial aesthetics, and therefore quality of life. The relapse rate postoperatively did not significantly affect the clinical outcome, and the authors recommend orthognathic surgery for this patient population. Future presurgical plans in this patient population will include a small posterior open bite and positioning the incisors edge to edge to allow for some postoperative relapse.
18940623 Sjögren syndrome: a review for the maxillofacial surgeon. 2008 Nov Sjögren syndrome is a multisystemic condition that predominantly involves the salivary and lacrimal glands. Also known as sicca complex, the disease often is underdiagnosed and poorly understood. This article provides a comprehensive review on Sjögren syndrome, with an emphasis on diagnosis and treatment modalities.
18525352 The pathobiology of psoriatic synovium. 2008 Jul PURPOSE OF REVIEW: Psoriatic arthritis pathogenesis is incompletely understood and the pathophysiologic role of the synovium is only beginning to be elucidated. Currently, approaches similar to those applied to rheumatoid arthritis are being applied to psoriatic arthritis synovia. RECENT FINDINGS: Synovitis is being re-examined along with efforts to better characterize the clinical phenotype and improve patient stratification. The dermatological perspective brings an alternative view of autoimmunity and the role of innate immunity. A pathogenetic basis for the differing roles of skin and synovium is suggested by a landmark animal study that demonstrated a psoriasis-like skin disease coupled with a T cell and B cell dependent arthritis. The histopathology of the synovio-entheseal complex has been described. Systematic methods for evaluating synovitis have been developed and cross-sectional evaluations of psoriatic arthritis synovia in the context of other arthritides have been performed. Fresh looks at psoriatic arthritis synovia suggest similarity to rheumatoid arthritis synovia. SUMMARY: Research into the pathophysiology of psoriatic arthritis is at an early, yet promising stage. Instruments are being developed to characterize and stratify psoriatic arthritis. The role of synovia remains unclear, but we now have a better understanding of the pathology of innate and adaptive immunity and are reminded that psoriatic arthritis is a systemic disease.
20477627 What does the immunogenetic basis of rheumatoid arthritis teach us about the immunobiology 2006 Sep Rheumatoid arthritis is a chronic inflammatory autoimmune disease in which, although the exact etiology is unknown, the contribution from genetic factors is approximately 60%. major histocompatibility complex alleles make the largest contribution to this genetic effect. The remainder is probably made up of an, as yet undefined, number of genes ( approximately 50-200) with low disease penetrance. Recent advances in genetic technology are now enabling us to start to identify some of these more moderate risk-conferring candidate genes. Evidence from functional studies of such genes is beginning to provide insight into the exact nature of the pathways and processes involved in disease susceptibility and expression. In this review, we will discuss how a growing number of genetic polymorphisms might underpin the immunological and molecular anomalies characteristic of rheumatoid arthritis. Specifically, we will focus on one particular pathway, T-cell activation, with an emphasis on the genetic polymorphism that influences antigen presentation and recognition in antigen-presenting cells, as well as those genes that influence the thresholds of antigen-receptor signaling in T lymphocytes.
20528442 Cost-effectiveness of tumor necrosis factor-alpha antagonists in rheumatoid arthritis, pso 2007 Apr The treatment of chronic arthritic diseases has undergone some dramatic changes over the past few years. In particular, a new class of drugs called the tumor necrosis factor-alpha antagonists has transformed the management of rheumatoid arthritis, and decision makers are now consid1ering their use in psoriatic arthritis and ankylosing spondylitis. Whilst short-term clinical trials suggest that tumor necrosis factor-alpha antagonists improve physical function and pain linked to disease activity, this class of drug has generated controversy owing to its substantial cost. Pharmacoeconomic studies conclude that tumor necrosis factor-alpha antagonists result in significant increases in health-related quality of life; however, the cost-effectiveness of this class of drug remains uncertain, particularly in the treatment of psoriatic arthritis and ankylosing spondylitis. This paper reviews pharmacoeconomic analyses examining the cost-effectiveness of tumor necrosis factor-alpha inhibitors in rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis.
21794411 [Cognition and perception deficits in fibromyalgia and rheumatoid arthritis]. 2007 May INTRODUCTION: Cognitive disturbance in patients with fibromyalgia and rheumatoid arthritis is today a topic of a great clinical interest, largely due to the fact that these persons often complain about cognitive problems. OBJECTIVE: This study is aimed to assess the visuospatial memory, attention and perceptive capacities in chronic pain patients. MATERIAL AND METHODS: Groups were constituted by fibromyalgia patients and rheumatoid arthritis patients, as well as a control group. All the subjects completed a battery of visual and spa-tial memory, speed of processing, working memory, attention, orientation and visuoperceptive abilities. A cognitive reserve measurement was obtained. RESULTS: Results show that chronic pain patients displayed worse cognitive performance than controls. Moreover, arthritis patients execute poorly when compared to the group of fibromyalgia in tasks that demand visuoperceptive integration and visuomotor processing. Patients suffering fibromyalgia obtained worse punctuations than those with arthritis in spatial memory and spatial orientation tasks. CONCLUSIONS: Both groups developed important cognitive deficits, which cannot be explained by the collateral effects of such pathologies, because cognitive profiles are not similar and appear from the beginning of the disease.
20477048 Tocilizumab for the treatment of rheumatoid arthritis. 2008 Mar Tocilizumab is a humanized anti-human IL-6 receptor antibody that specifically inhibits the biological activity of IL-6 by competitively inhibiting the binding of IL-6 to the IL-6 receptor. Clinical trials have shown that tocilizumab 8 mg/kg administered by monthly infusion not only improves clinical signs and symptoms of refractory rheumatoid arthritis but also suppresses radiographic progression. In regard to safety, the most common adverse event was nonsevere infection, such as nasopharyngitis, although the incident rate of adverse events was slightly higher than that of disease-modifying antirheumatic drug treatment. Studies have shown that there is no specific infection or prolongation of infection related to tocilizumab treatment. Tocilizumab is a promising therapeutic agent with statisfactory efficacy and safety for rheumatoid arthritis.
18466514 Mapping a gene for rheumatoid arthritis on chromosome 18q21. 2007 Although single chi-square analysis of the North American Rheumatoid Arthritis Consortium (NARAC) data identifies many single-nucleotide polymorphisms (SNPs) with p-values less than 0.05, none remain significant after Bonferroni correction. In contrast, CHROMSCAN evades heavy Bonferroni correction and auto-correlation between SNPs by using composite likelihood to model association across all markers in a region and permutation to assess significance. Analysis by CHROMSCAN identifies a 36-kb interval that includes the most significant SNP (msSNP) observed in a 10-Mb target suggested by linkage. Unexpectedly, stratification by gender and age of onset shows that association evidence comes almost entirely from females with age of onset less than 40. Combining evidence from a meta-analysis of linkage studies and three subsets of the NARAC data provides significant evidence for a determinant of rheumatoid arthritis in a 36-kb interval and illustrates the principle that estimates of location and its information are more powerful than estimates of p-values alone.
21794444 [Use of glucocorticosteroids in rheumatoid arthritis. How and when should steroids be used 2007 Nov Glucocorticoids (GC) are a mainstay of the therapy in rheumatoid arthritis (RA). Currently, and despite their extensive use, the discussion about the benefits and adverse effects of low dose GC in the management of RA persists. In recent years, a number of clinical trials have attempted to establish the benefits of long-term GC use as a disease-modifying antirheumatic drug in RA, and to define their side effects. Results of these clinical trials provide solid evidence that low-dose GC can inhibit radiographic damage in early RA, and that side effects of GC, when used in that clinical framework, are limited to hyperglycaemia, cataracts, and transient weight gain.
18360618 Etanercept in the treatment of rheumatoid arthritis. 2007 Mar Etanercept (ETN) is the first anti-tumor necrosis factor (TNF) agent to be approved for the treatment of rheumatoid arthritis (RA). Over the last 8 years, several clinical trials have shown its efficacy and safety in established and early RA, as well as a monotherapy or in combination with methotrexate. ETN not only reduces the signs and symptoms of RA, but also retards the progression of radiographic damage and improves the quality of life and function of patients. Its safety profile has been predictable since the first clinical trials with no new major safety concerns. Beyond its efficacy in RA, ETN is also indicated for the treatment of psoriatic arthritis. This current report reviews the evidence and the data in RA and psoriatic arthritis (PsA).
17768196 Synovectomy of the hip in patients with juvenile rheumatoid arthritis. 2007 Sep BACKGROUND: There is a lack of data on the functional effect of open hip synovectomy in a large number of patients with juvenile rheumatoid arthritis evaluated with a validated assessment tool. METHODS: Between 1985 and 1997, sixty-seven open hip-joint synovectomies were carried out in fifty-six patients with juvenile rheumatoid arthritis. Fifty-five hips (82%) had radiographic changes that were stage III or higher according to the system of Larsen et al. Hip function was evaluated preoperatively and after a mean of fifty months with the Merle d'Aubigné hip score. RESULTS: Sixty-five (97%) of the sixty-seven hips were available for follow-up. The mean total Merle d'Aubigné hip score (and standard error of the mean) was significantly improved from 9.5 +/- 2.5 points at baseline to 16.3 +/- 1.0 points at the time of follow-up (p < 0.001). The individual scores for pain, mobility, and walking ability were significantly increased as well (all p < 0.001). Eighty-five percent of the hips were observed to have a very great or great improvement in function. A concomitant soft-tissue release was performed in seven hips, and nine hips required surgical dislocation. Surgical complications included two superficial wound hematomas that did not require intervention; osteonecrosis of the femoral head was not observed. Five hips required total hip arthroplasty during the follow-up period. Thus, the survival rate for the hips was 94% at a mean of four years following the synovectomy. CONCLUSIONS: Open hip synovectomy in patients with juvenile rheumatoid arthritis is a safe procedure that can improve hip-joint function for up to five years.
17874245 Results of bilateral combined hip and knee arthroplasty in very young patients with juveni 2008 Mar INTRODUCTION: We evaluated the long-term outcomes for combined, bilateral total knee and hip arthroplasty performed on a group of very young patients with juvenile rheumatoid arthritis. MATERIALS AND METHODS: Six consecutive patients with a mean age of 14 years at the time of hip replacement and 16 years at knee replacement were analyzed. Five of the six patients were wheelchair dependent pre-operatively. All knee components had uncemented fixation, while the hip replacements were a mixed group of cemented and uncemented prostheses. RESULTS: Clinical and radiographic follow-up at a mean duration of 13.8 years for the hips and 17.3 years for the knees demonstrated four of the six patients were unlimited community ambulators, one a limited community ambulator and the remaining patient a household ambulator. Failure, defined as revision of any of the components or definite radiographic loosening, occurred in three knees (two patients) and five hips (three patients). CONCLUSIONS: These good long-term functional results in a relatively very young population indicate that an early and aggressive approach to multiple joint disease is an appropriate option at a young age for patients with juvenile rheumatoid arthritis with severe disability and pain refractory to conservative management.
22589621 The prevalence of bronchopulmonary infection among patients with rheumatoid arthritis vers 2008 Apr A high frequency of bronchopulmonary infections complicating rheumatoid arthritis has been described in reports of case series. This study was undertaken to confirm and compare these finding in patients with RA and control. 117 patients with RA and 103 patients with OA/soft tissue rheumatism as controls. Study subjects were studied using their medical records available from hospitals' casenotes and GP data base. Details of all documented bronchopulmonary infections for the preceding year including lower and upper respiratory tract infections were recorded. Details of hospital admissions due to bronchopulmonary infection, antibiotic usage and functional capacity were also recorded. Mean age for RA was 56 and 59 for control. There were 34 males and 83 females in RA group, however, 14 males and 55 females in control group. There were at least 1 episodes of BPI in 66.7% (p<0.05) patients with RA and 48.5% in control. 69.2% (p<0.05) of subgroup patients with RA were noted to have poorer functional capacity compared to 50% in control. More RA patients with BPI (15%) (p<0.05) were admitted to hospital compared to control (3.8%). Significance findings were noted in terms of prevalence of BPI in RA patients compared to controls as well as patients with RA have severe course of BPI warranting hospitalization. RA patients with poorer functional capacity also noted to have high incidence of BPI.
18564403 Paradoxical effects of tumour necrosis factor-alpha in adjuvant-induced arthritis. 2008 Anti-tumour necrosis factor (TNF)alpha therapy is highly effective in rheumatoid arthritis and it is surprising, therefore, that a recent study showed that intraperitoneal administration of recombinant TNFalpha reduced the severity of adjuvant-induced arthritis and decreased IFNgamma expression in cultured draining lymph node cells. Furthermore, in untreated arthritic rats, maximal TNFalpha expression in draining lymph node cells coincided with spontaneous disease remission, suggesting a role for endogenous TNFalpha in recovery from arthritis. If confirmed in further studies, these findings suggest that, in addition to its well-established pro-inflammatory properties, TNFalpha may also play a disease-limiting role in this model of rheumatoid arthritis by suppressing effector T cell responses.
21938809 Choosing Medications for Rheumatoid Arthritis: Clinician's Guide . 2007 This guide summarizes evidence comparing the effectiveness and safety of disease-modifying antirheumatic drugs (DMARDs) and corticosteroids used for rheumatoid arthritis (RA). It does not address other drugs that are no longer commonly used as first-line treatment for RA, such as azathioprine, chloroquine, cyclosporine, gold, and penicillamine. It also does not discuss analgesics, such as acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids.
17062441 Long-term follow-up of patients with adult-onset Still's disease. 2006 Sep OBJECTIVE: To evaluate the long-term outcome of patients with adult-onset Still's disease (AOSD). METHODS: Eleven patients with AOSD who were regularly followed-up during the past 13 years, even after discontinuation of treatment, were evaluated for the long-term prognosis of the disease and its possible complications. RESULTS: No exacerbation of the symptoms was noted during therapy. Only two of the 11 patients exhibited relapse of the systemic disease after discontinuation of treatment. Both patients had previously been on corticosteroids and responded well to reinitiation of therapy. Progressive deforming arthritis was not noted in any patient. Hepatic failure, central nervous system involvement, renal involvement or systematic amyloidosis did not complicate the course of any of the patients. CONCLUSIONS: Long-term prognosis of AOSD may be benign in a significant subset of patients. Further studies should clarify characteristics of the subset of patients for whom disease-modifying therapy is warranted.