Rheumatoid Arthritis: USA

Furst DE, Halbert RJ, Bingham CO, Fukudome S, Anderson L, Bonafede P, Bray V, Cohen SB, Sherrer YR, St Clair EW, Tesser JR, Weinblatt M, Dubois RW. · Geffen School of Medicine, University of California at Los Angeles, 1000 Veteran Ave Rm 32-59, Los Angeles, CA 90095-1670, USA. · Rheumatology (Oxford). · Pubmed #18178593 No free full text.

Abstract: OBJECTIVES: There is a lack of agreement on assessing disease activity in patients with RA and determining when the RA treatment should be changed or continued. A panel of rheumatologists was convened to develop guidelines to assess adequacy of disease control, focusing on the use of disease-modifying anti-rheumatic drugs. METHODS: The Research and Development/University of California in Los Angeles (RAND/UCLA) Appropriateness Method was used to evaluate disease control adequacy. After a literature review, 108 scenarios were developed to simulate situations most likely to be encountered in clinical practice and rated on a 9-point scale by a 10-member expert panel. RESULTS: Final appropriateness rankings for the scenarios were as follows: 37% 'appropriate', 48% 'inappropriate', and 16% 'neutral'. The panelists felt that patients with disease control in the 'appropriate' range have adequate control with their current therapy, whereas those in the 'inappropriate' range should be considered for a change in therapy. Those in 'neutral' areas should have their therapy reviewed carefully. The panelists recommended that the clinically active joint count should be considered the most important decision factor. In patients with no clinically active joints, regardless of other factors no change in therapy was felt to be warranted. Patients with five or more active joints should be considered inadequately treated, and in patients with one to four active joints other variables must be considered in the decision to change therapy. CONCLUSION: These preliminary guidelines will assist the clinician in determining when a patient's clinical situation warrants therapy escalation and when continuing the current regimen would be appropriate.

Khanna D, Arnold EL, Pencharz JN, Grossman JM, Traina SB, Lal A, MacLean CH. · Division of Immunology, University of Cincinnati and VAMC, OH, USA. · Semin Arthritis Rheum. · Pubmed #16461068 No free full text.

Abstract: OBJECTIVE: To describe the scientific evidence that supports each of the explicit process measures in the Arthritis Foundation's Quality Indicator Set for Rheumatoid Arthritis. METHODS: For each of the 27 measures in the Arthritis Foundation's Quality Indicator set, a comprehensive literature review was performed for evidence that linked the process of care defined in the indicator with relevant clinical outcomes and to summarize practice guidelines relevant to the indicators. RESULTS: Over 7500 titles were identified and reviewed. For each of the indicators the scientific evidence to support or refute the quality indicator was summarized. We found direct evidence that supported a process-outcome link for 15 of the indicators, an indirect link for 7 of the indicators, and no evidence to support or refute a link for 5. The processes of care described in the indicators for which no supporting/refuting data were found have been assumed to be so essential to care that clinical trails assessing their importance have not, and probably never will be, performed. The process of care described in all but 2 of the indicators is recommended in 1 or more practice guidelines. CONCLUSION: There are sufficient scientific evidence and expert consensus to support the Arthritis Foundation's Quality Indicator Set for Rheumatoid Arthritis, which defines a minimal standard of care that can be used to assess health care quality for patients with rheumatoid arthritis.

Newsome G, Anonymous00109. · North Georgia College & State University, Dahlonega, GA, USA. · J Am Acad Nurse Pract. · Pubmed #12426799 No free full text.

Abstract: Rheumatoid arthritis (RA) is a progressive polyarthritis that is responsible for over nine million office visits annually. It is likely that most nurse practitioners will care for one or more patients with RA because approximately 1% of the adult population is affected by this disabling disorder. The guideline reviewed in this month's column describes the recommended care of patients who have been previously diagnosed with RA.

Furst DE, Cush J, Kaufmann S, Siegel J, Kurth R. · UCLA Medical School, Los Angeles, USA Presbyterian Hospital, Dallas, USA. · Ann Rheum Dis. · Pubmed #12379625 links to  free full text

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Anonymous00188. · American College of Rheumatology, 1800 Century Place, Suite 250, Atlanta, GA 30345, USA. · Arthritis Rheum. · Pubmed #11840435 No free full text.

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Lu CY, Macneill P, Williams K, Day R. · Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, Massachusetts, USA. · Aust New Zealand Health Policy. · Pubmed #18489760 links to  free full text

Abstract: ABSTRACT: Access to "high cost medicines" through Australia's Pharmaceutical Benefits Scheme (PBS) is tightly regulated. It is inherently difficult to apply any criteria-based system of control in a way that provides a fair balance between efficient use of limited resources for community needs and equitable individual access to care. We suggest, in relation to very high cost medicines, that the present arrangements be re-considered in order to overcome potential inequities. The biological agents for the treatment of rheumatoid arthritis are used as an example by which to discuss the ethical issues associated with the current scheme. Consideration of ethical aspects of the PBS and similar programs is important in order to achieve the fairest outcomes for individual patients, as well as for the community.

Pincus T, Yazici Y, Sokka T. · Department of Medicine, Division of Rheumatology, New York University Hospital for Joint Diseases, New York, NY 10003, USA. · Nat Clin Pract Rheumatol. · Pubmed #18461062 No free full text.

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Weisman MH. · Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · Nat Clin Pract Rheumatol. · Pubmed #18431369 No free full text.

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Pisetsky DS. · Division of Rheumatology and Immunology at the Duke University Medical Center, Durham, NC, USA. · Nat Clin Pract Rheumatol. · Pubmed #18382480 No free full text.

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Hwang A, Gupta S, Liang MH. · Brown University, USA. · Nat Clin Pract Rheumatol. · Pubmed #18227830 No free full text.

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Griffin WS. · Geriatric Research, Education and Clinical Center, Neurobiology, Physiology, and Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. · J Neuroinflammation. · Pubmed #18186919 links to  free full text

Abstract: Tumor necrosis factor-alpha (TNF) is one of a number of systemic and immunomodulating cytokines that generally act to promote acute-phase reactions but can drive degenerative changes when chronically elevated. Traditional focus on TNF has been directed at these inflammation-related functions. Of particular relevance to intersections between neuroinflammation and neurodegeneration is the ability of TNF to increase expression of interleukin-1 (IL-1), which in turn increases production of the precursors necessary for formation of amyloid plaques, neurofibrillary tangles, and Lewy bodies. More recent data have revealed that TNF, one of the few gliotransmitters, has strikingly acute effects on synaptic physiology. These complex influences on neural health suggest that manipulation of this cytokine might have important impacts on diseases characterized by glial activation, cytokine-mediated neuroinflammation, and synaptic dysfunction. Toward such manipulation in Alzheimer's disease, a six-month study was conducted with 15 probable-Alzheimer patients who were treated weekly with perispinal injection of Etanercept, an FDA-approved TNF inhibitor that is now widely used for treatment of rheumatoid arthritis and other systemic diseases associated with inflammation. The results demonstrated that perispinal administration of etanercept could provide sustained improvement in cognitive function for Alzheimer patients. Additionally, the authors were impressed by the striking rapidity with which these improvements occurred in the study patients. An example of this rapid improvement is presented in this issue as a case report by Tobinick and Gross. Such rapid gain of function inspires speculation about the role of gliotransmission or other equally rapid synaptic events in the relationship of TNF to Alzheimer-impacted neurophysiology. Because of the inability of large molecules such as etanercept to cross the blood brain barrier following conventional systemic administration, it is likely that the more direct drug delivery system pioneered by Tobinick also contributed to the effectiveness of the treatment. If so, this system could be useful in drug delivery to the brain in other neural disorders, as well as in animal research studies, many of which currently employ delivery strategies that inflict damage to neural cells and thus engender neuroinflammatory responses.

Radstake TR, Bucala R. · Department of Medicine and Pathology, Yale University School of Medicine, The Anlyan Center, S525, 300 Cedar Street, New Haven, CT 06520-8031, USA. · Curr Rheumatol Rep. · Pubmed #17915086 No free full text.

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Diamond B. · Division of Rheumatology, Columbia University Medical Center, New York, USA. · Curr Opin Rheumatol. · Pubmed #17762602 No free full text.

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Aletaha D. · National Institutes of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA. · Arthritis Res Ther. · Pubmed #16542465 links to  free full text

Abstract: Several pooled indices for the assessment of rheumatoid arthritis disease activity are available to rheumatologists. Face and criterion validity of these instruments can be assessed by determining the association of their measurements with opinions of physicians. Several confounding aspects must be considered in such analyses, especially blinding of the person(s) making the decisions to the instruments being studied and to the objective of the study in general. From several studies in the literature, there is currently no evidence that any one of the available composite indices is better or worse than any other. The choice of index in clinical practice should ideally be based on practical considerations related to the needs of the rheumatologist in the respective health care setting.

Firestein GS. · Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, La Jolla, California, USA. · Arthritis Res Ther. · Pubmed #15987499 links to  free full text

Abstract: Studies of cytokine expression in rheumatoid arthritis have provided key insights into the pathogenesis of disease and have offered clues for effective therapy. Patterns of T-cell products in chronic rheumatoid synovitis suggest that T helper type 1 cells contribute to the perpetuation of disease. However, there is no guarantee that the mechanisms of late disease are identical to very early rheumatoid arthritis. Evaluation of the cytokine profile at the earliest time points after onset of symptoms could identify novel targets that prevent progression to chronic arthritis.

Moser B, Hudson BI, Schmidt AM. · Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, NY, USA. · Arthritis Res Ther. · Pubmed #15987496 links to  free full text

Abstract: The receptor for advanced glycation endproducts (RAGE) interacts with distinct ligand families linked to the inflammatory response. Studies in animal models suggest that RAGE is upregulated in the inflamed joint and that blockade of the receptor, using a ligand decoy soluble form of RAGE (sRAGE), attenuates joint inflammation and expression of inflammatory and tissue-destructive mediators. In this issue of Arthritis Research & Therapy, Rille Pullerits and colleagues reported that plasma levels of sRAGE were reduced in subjects with rheumatoid arthritis compared with healthy controls or subjects with non-inflammatory joint disease. These findings suggest the possibility that levels of sRAGE might be a biomarker of inflammation. Not resolved by these studies, however, is the intriguing possibility that endogenously higher levels of sRAGE might be linked to a lower incidence of arthritis or to the extent of inflammation. Nevertheless, although 'cause or effect' relationships may not be established in this report, fascinating insights into RAGE, inflammation and human arthritis emerge from these studies.

Peterfy CG. · Synarc, Inc., San Francisco, California 94105, USA. · J Rheumatol. · Pubmed #15088286 links to  free full text

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Marmor MF. · Stanford University School of Medicine, California 94305-5308, USA. · Clin Exp Rheumatol. · Pubmed #15083878 No free full text.

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Goronzy JJ, Weyand CM. · Departments of Medicine and Immunology, Mayo Clinic, Rochester, MN, USA. · Arthritis Res Ther. · Pubmed #12723978 links to  free full text

Abstract: Depleting B cells with anti-CD20 monoclonal antibodies emerges as a new therapeutic strategy in autoimmune diseases. Preliminary clinical studies suggest therapeutic benefits in patients with classic autoantibody-mediated syndromes, such as autoimmune cytopenias. Treatment responses in rheumatoid arthritis have opened the discussion about whether mechanisms beyond the removal of potentially pathogenic antibodies are effective in B-cell depletion. B cells may modulate T-cell activity through capturing and presenting antigens or may participate in the neogenesis of lymphoid microstructures that amplify and deviate immune responses. Studies exploring which mechanisms are functional in which subset of patients hold the promise of providing new and rational treatment approaches for autoimmune syndromes.

Hochberg MC. · Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA. · Arthritis Res Ther. · Pubmed #12716445 links to  free full text

Abstract: Cyclooxygenase (COX)-2 selective inhibitors have been shown to have comparable efficacy to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Large outcome studies have shown that patients with OA and RA not taking low-dose aspirin have fewer symptomatic and complicated upper GI events when treated with COX-2 selective inhibitors than with nonselective NSAIDs. When used in recommended dosages, there is no convincing evidence that patients treated with COX-2 selective inhibitors have an increased incidence of cardiovascular thrombotic events, including non-fatal myocardial infarction, than patients treated with either placebo or nonselective NSAIDs other than naproxen. Co-therapy with low-dose aspirin is recommended in patients with OA and RA at increased risk for cardiovascular events; the need for gastroprotective therapy in such patients is controversial.

Krane SM. · Department of Medicine, Harvard Medical School, Center for Immunology and Inflammatory Diseases, Charlestown, Massachusetts, USA. · Arthritis Res Ther. · Pubmed #12716440 links to  free full text

Abstract: Irreversible destruction of joint structures is a major feature of osteoarthritis and rheumatoid arthritis. Fibrillar collagens in bone, cartilage and other soft tissues are critical for optimal joint form and function. Several approaches can be used to ascertain the role of collagenases, matrix metalloproteinases, in proteolysis of joint collagens in arthritis. These approaches include identifying spontaneous genetic disorders of the enzymes and substrates in humans and animals, as well as engineering mutations in the genes that encode these proteins in mice. Insights gained from such studies can be used to design new therapies to interrupt these catabolic events.

Wu T, Mohan C. · Department of Internal Medicine (Rheumatology), University of Texas Southwestern Medical School, Dallas, TX 75390-8884, USA. · Endocr Metab Immune Disord Drug Targets. · Pubmed #19519464 No free full text.

Abstract: Autoimmunity affects a substantial fraction of our population. In patients with autoimmune disease, the immune system recognizes self-tissues as foreign. Common autoimmune diseases include rheumatoid arthritis, diabetes mellitus, lupus and multiple sclerosis. Though different target organs may be affected in different autoimmune diseases, aberrations in adaptive or innate immunity underlie all of these diseases. Abnormal functioning, differentiation and/or activation of T-cells, B-cells and myeloid cells have been documented in various autoimmune diseases. More recent studies have also detailed anomalous activation of various signaling axes including various MAPK, AKT, NF-kappaB, Bcl-2 family members, and JAK/STAT molecules in these cells, in the context of systemic autoimmunity. Among these, one molecular pathway that appears to be particularly attractive for therapeutic targeting is the PI3K/AKT/mTOR axis. In this review, we summarize how the AKT axis affects multiple molecular processes in autoimmune diseases and discuss the potential of targeting this axis in these diseases.

Pernis AB. · Department of Medicine, Columbia University, New York, NY 10032, USA. · J Intern Med. · Pubmed #19493058 No free full text.

Abstract: Recent work has implicated a novel Th effector cell subset, the Th17 cell subset, in the development of both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) because of the ability of Th17 cells to produce cytokines like IL-17 and IL-21 that can drive both inflammatory and humoral responses. In this review, we will discuss recent studies that have begun elucidating the factors that regulate the development of Th17 cells and provide a brief overview of the role of Th17 cells in RA and SLE.

Rothstein TL, Guo B. · Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA. · J Intern Med. · Pubmed #19493057 No free full text.

Abstract: Receptor crosstalk: reprogramming B cell receptor signalling to an alternate pathway results in expression and secretion of the autoimmunity-associated cytokine, osteopontin (Review). J Intern Med 2009; 265: 632-643.Intracellular signalling emanating from the B-cell antigen receptor is considered to follow a discrete course that requires participation by a set of mediators, grouped together as the signalosome, in order for downstream events to occur. Recent work indicates that this paradigm is true only for naïve B cells. Following engagement of the IL-4 receptor, a new, alternate pathway for B-cell receptor (BCR)-triggered intracellular signalling is established that bypasses the need for signalosome elements and operates in parallel with the classical, signalosome-dependent pathway. Reliance on Lyn and sensitivity to rottlerin by the former, but not the latter, distinguishes these two pathways. The advent of alternate pathway signalling leads to production and secretion by B cells of osteopontin (Opn). As Opn is a polyclonal B-cell activator that is strongly associated with a number of autoimmune diseases including lupus and rheumatoid arthritis, this novel finding is likely to be clinically relevant. Our results highlight the potential role of B-cell-derived Opn in immunity and autoimmunity and suggest that stress-related IL-4 expression might act to strengthen immunoglobulin secretion at the risk of autoantibody formation. Further, these results illustrate receptor crosstalk in the form of reprogramming, whereby engagement of one receptor (IL-4R) produces an effect that persists after the original ligand (IL-4) is removed and results in alteration of the pathway, and outcome, of signalling via a second receptor (BCR) following its activation.

Sarkar PK, Patel N, Furie RA, Talwar A. · Department of Pulmonary Medicine, North Shore University Hospital and Long Island Jewish Medical Center, North Shore Long Island Jewish Health System, New York, USA. · Indian J Chest Dis Allied Sci. · Pubmed #19445445 No free full text.

Abstract: Sjögren's syndrome (SS) is a complex autoimmune exocrinopathy with multifactorial pathogenesis and multisystem manifestation. It is called primary Sjögren's syndrome (PSS) when the manifestations are seen without any other co-existent rheumatic diseases. The incidence of respiratory system involvement varies widely in the reported medical literature, partly due to lack of a universal agreement over the diagnostic criteria of the disease and the type of study methods employed. Respiratory system manifestations are protean; upper airway symptoms are very common and so is the complaint of dry cough. The PSS patients may develop interstitial lung diseases (ILDs) such as usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), lymphocytic interstitial pneumonia (LIP), bronchiolitis obliterans and organising pneumonia (BOOP), etc. They may also develop the whole spectrum of lymphoproliferative disorders of the lung ranging from LIP to follicular bronchiolitis, nodular lymphoid hyperplasia and low-grade lymphomas. Therapeutic options include symptomatic and supportive measures and corticosteroids as the mainstay of the treatment for ILDs occurring in these patients. In recent years, rituximab (anti-CD20) has emerged as a promising treatment for this disease, though data from controlled trials are still lacking. Pulmonary involvement may be a source of significant morbidity in these patients, though only rarely, it is the cause of death.