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ID PMID Title PublicationDate abstract
17343248 Health economic issues in rheumatoid arthritis. 2006 Nov The objectives of treatment in rheumatoid arthritis (RA) are to reduce temporary symptoms due to inflammatory activity and, more importantly, to preserve function. The introduction of potent disease-modifying anti-rheumatic drugs (DMARDs) in recent years has increased the opportunities for effective treatment. However, these treatments come at a substantially higher cost than traditional DMARDs and therefore compete with other essential interventions for limited resources. They have triggered a debate on whether they represent an efficient use of resources, which patients should be treated, when, and for how long. Cost-effectiveness analysis attempts to estimate the trade-offs involved in these decisions and to provide information that can help in making them. However, in chronic progressive diseases, health gains and any potential associated economic benefits are often most evident in the long-term. As a consequence, the impact of new treatments has to be estimated using models that can project available knowledge, such as results from clinical trials or short-term follow-up studies in clinical practice, into the future. These models also allow scenarios to be explored that provide the best value for money, for example by defining subgroups for which treatment is most effective, or criteria that define when treatment should be stopped. Economic evaluation in RA has a long tradition, with the first study performed about 20 years ago. However, with the recent drug introductions, the field has witnessed an explosion of economic studies. Modelling techniques have become more sophisticated to overcome concerns about their validity. At the same time, they may appear less transparent, making it difficult for non-specialists to understand the details. This article, rather than reviewing all published models and comparing them, attempts to illustrate the inputs required for such studies, and the influence that different approaches and datasets can have on the results.
15914465 Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis. 2005 Jun Methotrexate administered weekly in low doses is a mainstay in the therapy of rheumatoid arthritis. Although originally developed as a folate antagonist for the treatment of cancer, its mechanism of action in the therapy of rheumatoid arthritis remains less clear. Several mechanisms have been proposed including inhibition of T cell proliferation via its effects on purine and pyrimidine metabolism, inhibition of transmethylation reactions required for the prevention of T cell cytotoxicity, interference with glutathione metabolism leading to alterations in recruitment of monocytes and other cells to the inflamed joint, and promotion of the release of the endogenous anti-inflammatory mediator adenosine. These mechanisms of action and the role of methotrexate in the suppression of rheumatoid arthritis are reviewed.
16496073 [Measuring disease activity for rheumatoid arthritis]. 2006 Mar Rheumatoid arthritis (RA) is the most common systemic inflammatory joint disease. It can be treated effectively with disease modifying antirheumatic drugs, and the currently propagated treatment strategy is to treat RA consequently, and revise the therapeutic approach frequently on the basis of proper disease activity evaluation. In the current review, we focus on the instruments and measures used in the assessment of RA disease activity. We will first consider the so-called core set measures of activity, prividing comprehensive overviews on joint count scales, global scales, pain scales, biomarkers, and functional assessment instruments. The second part of the review focuses on the value of composite measures of disease activity; a term under which we subsume activity indices using various formulae, self-assessment tools of disease activity, and response criteria. Among the inflammatory rheumatic diseases, RA is the one for which the most intensive research is done, and usually instruments that work for RA are further tested for other joint diseases. However, there is still a research agenda for the assessment of disease activity, even for RA. One important aspect is to assess the reliability and utility of all available instruments, including the very low end of disease activity, since remission has become an achievable goal. Another focus of disease activity assessment is to derive measures that work in clinical trials and in daily practice, but are also well understood by patients and physicians. This will further improve our ability to care for patients with RA consequently.
17122688 Emerging new therapies in rheumatoid arthritis: what's next for the patient? 2006 Nov Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by an inflammation of the synovial membranes and progressive joint destruction, leading to significant impairment of physical function and quality of life. Rheumatoid arthritis imposes a substantial economic burden on both patients and society. The recent introduction of new biologic therapies for the treatment of RA reflects the application of knowledge obtained from advancements in the understanding of disease immunopathology. This article reviews emerging new therapies for RA, focusing on those that will be administered by infusion, and highlights the important role of the infusion nurse in providing optimal patient care.
16909710 Cytokine network and its manipulation in rheumatoid arthritis. 2006 Jun Studies of the inflammatory process in the inflamed synovium from rheumatoid arthritis patients have shown an intricate network of molecules involved in its initiation, perpetuation and regulation trial balances the pro- and anti-inflammatory process. This system is self-regulating though the action of anti-inflammatory and pro-inflammatory cytokines cytokine receptor antagonists and naturally occurring antibodies cytokines. Inflammatory synovitis in rheumatoid arthritis (and possibly in other inflammatory arthritidies) appears to be the result of an imbalance in the cytokine network with either an excess production of pro-inflammatory cytokines or from inadequacy of the natural anti-inflammatory mechanisms. Using this knowledge the newer therapeutic approaches to RA and other inflammatory arthritides are being aimed at correcting this imbalance. Monoclonal antibodies to INF-alpha (humanised form of this is called infliximab), soluble TNF-alpha receptors (etanercept) are already in clinical use and adalimumab (humanised TNF-alpha antibody). IL-1Ra is undergoing clinical trials. Other promising therapeutic agents that could regulate the cytokine network are in various stages of laboratory and clinical evaluation. These studies promise to yield therapeutic targets that could dramatically change the way inflammatory diseases would he treated in the future. The now established efficacy of infliximab and etanercept in inflammatory arthritides could be considered just a glimpse of the exciting scenario of the future.
16602022 [Planning of orthopedic surgery for rheumatoid arthritis]. 2006 May The inflammatory process in rheumatoid arthritis is progressive and ends in destruction of the cartilage. Subsequent instability and mutilation of the joint might happen. The classification of destruction can be done by X-rays and assessment of the clinical picture. Depending on the radiologic stage different therapy concepts, ranging from conservative to operative, are established. It is the aim of surgery to restore motion and function in a painless joint. Surgery can be done to prevent the joint from further destruction or to replace the joint after resection. Different concepts based on radiologic findings are presented in this review.
15588977 Therapeutic strategies in early rheumatoid arthritis. 2005 Feb Rheumatoid arthritis (RA) therapy rests primarily on the use of disease-modifying antirheumatic drugs (DMARDs). It has been unequivocally shown that DMARD therapy early in the course of RA retards progression of damage and disability to a larger degree compared with delayed institution; the most effective DMARD is methotrexate (MTX). Moreover, combination therapy including intermediate to high doses of glucocorticoids and combinations of MTX with tumour necrosis factor blockers are more effective than monotherapies. However, early DMARD treatment requires early referral of patients and early diagnosis. This is hampered by the current lack of classification criteria for early RA, since the aim is to prevent destruction from occurring, while RA is typically characterized by the presence of erosions. Novel treatment strategies and therapeutic agents allow us to aim for remission rather than improvement of disease activity. Whether a 'window of opportunity' exists during which effective therapy might lead to cure is still an open issue and will be the focus of clinical trials in the near future.
16757672 Proteomics: applications to the study of rheumatoid arthritis and osteoarthritis. 2006 Jun The study of both DNA and protein technologies has been marked by unprecedented achievement over the last decade. The completion of the Human Genome Project in 2003 is representative of a new era in genomics; likewise, proteomics research, which has revolutionized the way we study disease, offers the potential to unlock many of the pathophysiologic mechanisms underlying the clinical problems encountered by orthopaedic surgeons. These new fields are extending our approach to and investigation of the etiology and progression of musculoskeletal disorders, notably rheumatoid arthritis and osteoarthritis. Advances in proteomics technology may lead to the development of biomarkers for both rheumatoid arthritis and osteoarthritis. Such biomarkers would improve early detection of these diseases, measure response to treatment, and expand knowledge of disease pathogenesis.
16622478 B-cell targeting in rheumatoid arthritis and other autoimmune diseases. 2006 May B-cell-targeted therapy for autoimmune disease emerged from theoretical proposition to practical reality between 1997 and 1998, with the availability of the B-cell-depleting monoclonal antibody rituximab. Since then, a score of autoantibody-associated disorders have been treated, with most convincing evidence of efficacy seen in subjects with rheumatoid arthritis. Several classes of B-cell-targeted agent are now under investigation. From the outset, a major goal of B-cell targeting has been the re-establishment of some form of immunological tolerance. In some subjects, the observed improvement of disease for years following therapy fuels hope that this goal might ultimately be achievable.
17009815 The distal radioulnar joint in rheumatoid arthritis. 2006 Aug Rheumatoid arthritis (RA) involves the wrist in up to 80% of cases; up to 95% of patients have signs of wrist arthritis after 12 years of disease. The distal radioulnar joint (DRUJ) is involved in 31% to 75% of these patients and is often the first compartment of the wrist involved. The inflammatory sequence of events leads to the "caput ulnae syndrome" described by Backdahl in 1963. Extensor tendon ruptures are frequently associated. The presence of the "scallop" sign on radiographs is an alerting sign for tendon attrition. The gold standard in treatment remains resection of the distal ulnar head, known as Darrach's procedure. The most frequent complication is instability of the proximal ulnar stump. In order to restore stability or to prevent instability, several stabilisation techniques have been reported with free tendon grafts, the extensor carpi ulnaris, the flexor carpi ulnaris, the joint capsule and the pronator quadratus muscle. There is no evidence that stabilisation of the proximal ulnar stump during the initial operation gives better results. Another drawback of ulnar head resection is the progression of ulnar translation of the carpus. There are however several surveys showing that this ulnar translocation is the consequence of the disease rather than the result of the Darrach procedure. Several features such as an increased radial slope (> 23 degrees) and/or destruction of the ulnar corner of the distal radial epiphysis have been mentioned as predictive elements for further ulnar slide of the carpus. The Sauvé Kapandji procedure is in these cases a useful alternative choice. Another advantage of this technique is that it provides a larger surface so that other (radial) procedures can be more easily combined (Chamay partial radiocarpal fusion, wrist prosthesis).
16932625 Cytokine networks--towards new therapies for rheumatoid arthritis. 2005 Nov Success achieved so far in the blockade of tumor necrosis factor and interleukin (IL)-1 in rheumatoid arthritis exemplifies the feasibility and potential therapeutic application of antagonizing cytokine signaling. Despite these advances, there remains a considerable unmet clinical need in this field. A number of preclinical development programs are ongoing to target a variety of cytokines that are central to immune regulation and tissue-matrix destruction in rheumatoid arthritis. Evidence indicates that IL-6 antagonists might represents a useful approach and preliminary data similarly identify IL-15 as an intriguing target. Numerous additional cytokines are under investigation at the preclinical stage, including IL-12-IL-23, IL-17 and IL-18. As therapeutic goals move from disease control towards remission induction, development of the capacity for cytokine targeting to modify the underlying immune dysregulation remains a major priority.
16670812 [Pregnancy in patients with rheumatoid arthritis and inflammatory spondylarthropathies]. 2006 May The activity of a rheumatic disease can be influenced by pregnancy and puerperium. Prospective studies have shown an improvement in joint involvement in rheumatoid arthritis in two thirds to three quarters of pregnancies. After birth, an exacerbation is common. In spondylarthropathies there is no relevant change in disease activity. The fetal outcome is not impaired in patients with rheumatoid arthritis and inflammatory spondylarthropathies. Every pregnancy in women with a rheumatic disease should be considered as high-risk, and such pregnancies require close collaboration between rheumatologists and obstetricians.
15588975 How to predict prognosis in early rheumatoid arthritis. 2005 Feb In early rheumatoid arthritis (RA), the objectives of therapeutic strategies are to obtain remission and prevent joint destruction as early as possible. These goals may be reached with conventional disease-modifying antirheumatic drugs (DMARDs) or with biological agents. In clinical practice, initial treatments are usually chosen according to the degree of disease activity at baseline, and adapted according to a step-up strategy. A more elegant therapeutic approach would be to choose the most appropriate treatment based on the prognosis of RA. Therefore, prognostic stratification could improve the relative roles and benefits of initial DMARD or biological therapy for early RA. For RA with a severe prognosis, a combination of DMARDs or biologicals could be initiated as the first-line therapy. However, we need to know how to predict outcome in early RA for this type of strategy. This review attempts to answer this question by reporting the most reliable prognostic factors and some predictive models proposed for classification into benign, mild and severe RA.
16567358 Synovial fibroblasts: key players in rheumatoid arthritis. 2006 Jun Rheumatoid arthritis (RA) is a chronic autoimmune-disease of unknown origin that primarily affects the joints and ultimately leads to their destruction. The involvement of immune cells is a general hallmark of autoimmune-related disorders. In this regard, macrophages, T cells and their respective cytokines play a pivotal role in RA. However, the notion that RA is a primarily T-cell-dependent disease has been strongly challenged during recent years. Rather, it has been understood that resident, fibroblast-like cells contribute significantly to the perpetuation of disease, and that they may even play a role in its initiation. These rheumatoid arthritis synovial fibroblasts (RASFs) constitute a quite unique cell type that distinguishes RA from other inflammatory conditions of the joints. A number of studies have demonstrated that RASFs show alterations in morphology and behaviour, including molecular changes in signalling cascades, apoptosis responses and in the expression of adhesion molecules as well as matrix-degrading enzymes. These changes appear to reflect a stable activation of RASFs, which occurs independently of continuous exogenous stimulation. As a consequence, RASFs are no longer considered passive bystanders but active players in the complex intercellular network of RA.
15833077 Infliximab for the treatment of early rheumatoid arthritis. 2005 Mar Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease characterised predominately by polyarthritis with frequent progression to permanent joint damage and disability. Evidence shows that starting treatment with disease-modifying antirheumatic drug (DMARD) therapy early in the course of disease can slow radiographic progression of RA compared with a more delayed approach. Moreover, in the early stages of RA, treatment with a combination of methotrexate (MTX), a traditional DMARD, and a biologic with tumour necrosis factor (TNF)-alpha blocking activity has proven to be more effective than using MTX alone. Among the approved TNF-alpha inhibitors, infliximab is a chimeric monoclonal antibody with high affinity and specificity for its target cytokine. It binds to soluble TNF monomers and trimers, as well as membrane-bound TNF-alpha, forming a stable complex which prevents TNF-alpha from binding to its receptor and triggering a biological response. The combination of MTX and infliximab therapy has shown superior clinical outcomes compared with MTX monotherapy in early RA, as well as greater protection against joint damage and physical disability. Although infliximab therapy has been associated with side effects, including serious infections, this drug can be administered with an acceptable margin of safety for several years by appropriate selection of patients, screening for latent and active tuberculosis, and monitoring of patients for infection and other toxicities. The knowledge of the benefits of infliximab therapy for early RA affords groundwork for developing more effective treatment strategies that can minimise disease progression over the long term.
17083761 Remission and radiographic progression in rheumatoid arthritis. 2006 Nov Complete remission, defined as the presence of clinical as well as radiographic remission, is the ultimate goal of treatment of rheumatoid arthritis (RA). Functional disability in patients with low disease activity is associated with joint inflammation and joint damage. Despite the methodologic problems of scoring radiographs, studies show that radiographic progression is an important outcome measure, and conventional radiography remains the best available method to assess it. Whether radiographic progression is entirely dependent on the presence of joint inflammation is a matter of debate; some evidence suggests that radiologic progression may continue in patients who appear clinically to be in remission. The potential availability of more effective drugs in the near future presents a need to further define and monitor progression of joint damage by more reliable methods. Better diagnosis of joint damage will assist in our quest to attain and document full remission in RA. Some newer techniques that provide direct assessments of metabolic activity in the inflamed joint appear to predict radiographic progression before it can be detected by conventional methods. Until these techniques are validated and assessed for predictive value, we would advocate that radiographic progression be added to existing criteria for clinical remission, in order to define remission in RA more comprehensively.
16973111 Genetic markers of treatment response in rheumatoid arthritis. 2006 Oct Rheumatoid arthritis patients exhibit a considerable interindividual variability in response to drug treatment. Although many disease-related and demographic factors have been studied to predict treatment outcome, the effective disease-modifying antirheumatic drug (DMARD) therapy is not yet allocated based on factors that predict efficacy. Individual genetic characteristics are thought to play an important role in treatment response; therefore, current research aims to identify these genetic predictors for clinical response. Pharmacogenetic studies are beginning to provide results, which suggests that personalized treatment maximization of DMARD efficacy and minimization of adverse drug reactions are feasible.
15838231 Rheumatoid arthritis: non-tumor necrosis factor targets. 2005 May PURPOSE OF REVIEW: The treatment of rheumatoid arthritis has been revolutionised in recent years with the advent of biologic treatments. The purpose of this review is to outline new treatments that target the inflammatory pathway in rheumatoid arthritis other than tumor necrosis factor-alpha. RECENT FINDINGS: As the use of anti-tumor necrosis factor-alpha treatment has become more widespread, the number of patients in whom this treatment is unsuccessful has also accumulated. Contraindications such as infection and cardiac failure further add to the number of patients who need alternative treatment. A better understanding of the inflammatory pathway in rheumatoid arthritis has led to interest in other therapeutic targets. Promising treatments such as interleukin-6 antagonists (MRA), CTLA4Ig (abatacept), and anti-B cell therapy (rituximab) have already been tested in randomized controlled trials over the past year. Other cytokines have been identified and have been shown to be of benefit in animal models, including interleukin-15, interleukin-17, and interleukin-18, and clinical trials of these agents are currently under way. SUMMARY: For patients with rheumatoid arthritis that does not respond to anti-tumor necrosis factor-alpha treatment, the promising alternatives MRA, abatacept, and rituximab have been tested. It is hoped that these agents will become available shortly.
17083762 Is remission in rheumatoid arthritis associated with radiographic healing? 2006 Nov The precondition for joint damage in rheumatoid arthritis (RA) is inflammation, and the precondition for healing is absence of inflammation. A systematic search for healing phenomena in RA patients in remission has not yet been undertaken. In reports of patients in whom healing was observed, clinical and laboratory data have not been published in part due to space restrictions. However, this preliminary review of the existing literature about repair supports the thesis that a strong association may exist between remission and repair. Several reports indicate that patients in whom radiographic repair was seen were in clinical remission. In most reports clinical response to treatment was very good, and in groups of patients in which scoring was done, evidence of repair was seen in patients with strong inhibition or halt of radiographic progression. In contrast, healing is unlikely to be detected in patients with persistent clinically active disease and/or moderate or strong radiographic progression. In most reports clinical response to treatment was very good, and in groups of patients in which scoring was done, evidence of repair was seen in patients with strong inhibition or halt of radiographic progression. In contrast, healing is unlikely to be detected in patients with persistent clinically active disease and/or moderate or strong radiographic progression.
15899059 Gastrin-releasing peptide, substance P and cytokines in rheumatoid arthritis. 2005 Many studies have shown that modulation of cytokine function is effective in ameliorating symptoms of rheumatoid arthritis. Neuropeptides have recently been shown to have powerful effects on the production and release of cytokines and have also been shown to exert potent proinflammatory and anti-inflammatory effects in animal models of inflammatory diseases. An analysis of cytokine and neuropeptide content of synovial fluid from patients with rheumatoid arthritis has revealed a significant correlation between two neuropeptides, bombesin/gastrin-releasing peptide and substance P, and the proinflammatory cytokine interleukin-6 as well as the erythrocyte sedimentation rate. These findings provide further evidence for a role of neuropeptides and cytokines in the pathophysiology of rheumatoid arthritis, as well as suggesting additional approaches for the development of novel therapeutic interventions.