Rheumatoid Arthritis: Austria

Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C, Bombardieri S, Choi H, Combe B, Dougados M, Emery P, Gomez-Reino J, Keystone E, Koch G, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Michaud K, O'Dell J, Paulus H, Pincus T, Richards P, Simon L, Siegel J, Smolen JS, Sokka T, Strand V, Tugwell P, van der Heijde D, van Riel P, Vlad S, van Vollenhoven R, Ward M, Weinblatt M, Wells G, White B, Wolfe F, Zhang B, Zink A, Felson D, Anonymous00358, Anonymous00359. · Medical University of Vienna, Vienna, Austria. · Arthritis Rheum. · Pubmed #18821648 No free full text.

Abstract: OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardized operating procedures, which use a three-step approach: 1) expert-based definition of relevant research questions (November 2006); 2) systematic literature search (November 2006 to May 2007); and 3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature, the expert panel recommended that each trial should report the following items: 1) disease activity response and disease activity states; 2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; 3) baseline disease activity levels (in general); 4) the percentage of patients achieving a low disease activity state and remission; 5) time to onset of the primary outcome; 6) sustainability of the primary outcome; 7) fatigue. CONCLUSION: These recommendations endorsed by EULAR and ACR will help harmonize the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

Machold KP, Brezinsek HP, Leeb BF, Pflugbeil S, Rainer F, Singer F, Skoumal M, Stamm TA, Herold M. · Klinische Abteilung für Rheumatologie, Medizinische Universität Wien, Wien, Austria. · Wien Klin Wochenschr. · Pubmed #18500599 No free full text.

This publication has no abstract.

Smolen JS, Aletaha D. · Division of Rheumatology, Medical University of Vienna, Vienna, Austria. · Nat Clin Pract Rheumatol. · Pubmed #18461061 No free full text.

This publication has no abstract.

Dejaco C, Duftner C, Wipfler E, Schirmer M. · Abteilung für Innere Medizin, Krankenhaus der Elisabethinen, Klagenfurt, Austria. · Wien Med Wochenschr. · Pubmed #19247593 No free full text.

Abstract: Abatacept is the first drug in a new class of disease-modifying anti-rheumatic drugs known as selective modulators of T-cell costimulation. The efficacy of abatacept in the treatment of rheumatoid arthritis (RA) has been shown in several clinical phase II and phase III trials, wherein abatacept was used in monotherapy, either in combination with methotrexate (MTX) after MTX-failure, in combination with MTX after failure of anti-TNF-alpha therapy or in combination with TNF-alpha blockers. In addition, the combination of abatacept/MTX was directly compared with infliximab/MTX. Current data on abatacept demonstrate an encouraging safety profile of this drug. The number of adverse events in patients on abatacept is comparable to that in patients treated with other biologics. Severe infections, however, are more common in abatacept-treated patients than in placebo-treated patients. Opportunistic infections are rare in patients with abatacept and the frequency of malignancies is not higher than expected in RA-patients. Additional studies are now warranted to get more information on rare adverse events and long-term unwanted effects.

Aletaha D, Huizinga TW. · Division of Rheumatology, Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria. · Best Pract Res Clin Rheumatol. · Pubmed #19233051 No free full text.

Abstract: Many early arthritis clinics have been started in the past decade. A major objective of these clinics is to improve our understanding of early arthritis in its undifferentiated form and to help provide guidance, recommendations, or criteria for diagnostic and therapeutic decision-making in patients with such presentation. Increasingly, they will allow aspects of pathogenesis - including autoantibodies and potential genetic markers - to be included in the set of clinical predictors that a rheumatologist is presented with. From an analytical perspective, usually logistic regression modelling is used to identify the best predictors of potentially long-lasting and/or erosive disease. Classification tree analysis might be another way to analyse data, and has the advantage that the results are easier to interpret than statistical parameters. In the past, many such projects have been published, none of which has achieved widespread use. Currently, the American College of Rheumatology and the European League Against Rheumatism are in the process of defining new criteria for rheumatoid arthritis that will allow earlier diagnosis and treatment of patients and definition of patients with early disease for inclusion in clinical trials.

Smolen JS, Aletaha D, Steiner G. · Division of Rheumatology, Department of Internal Medicine 3, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. · Ann Rheum Dis. · Pubmed #19139203 No free full text.

Abstract: Rheumatoid arthritis (RA) is characterised by both inflammation, as manifested by pain and swelling, and destruction of the joints. Unequivocal evidence indicates that disease activity, and thus the inflammatory response, is linked to joint damage. From this viewpoint we suggest that, vice versa, joint damage might be a cause of the active disease process, thus leading to a vicious cycle of events. The background to this notion stems from the known autoimmune response in RA, the potential of cartilage and bone breakdown products to elicit inflammation and notions that in joints that have undergone surgery with cartilage removal RA does not flare. However, the clinical evidence for this relationship is still to be provided as proof of the concept.

Leibbrandt A, Penninger JM. · IMBA, Institute for Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria. · Ann N Y Acad Sci. · Pubmed #19076348 No free full text.

Abstract: Bone-related diseases, such as osteoporosis and rheumatoid arthritis, affect hundreds of millions of people worldwide and pose a tremendous burden to health care. By deepening our understanding of the molecular mechanisms of bone metabolism and bone turnover, it became possible over the past years to devise new and promising strategies for treating such diseases. In particular, three tumor necrosis factor (TNF) family molecules, the receptor activator of NF-kappaB (RANK), its ligand RANKL, and the decoy receptor of RANKL, osteoprotegerin (OPG), have attracted the attention of scientists and pharmaceutical companies alike. Genetic experiments revolving around these molecules established their pivotal role as central regulators of osteoclast development and osteoclast function. RANK-RANKL signaling not only activates a variety of downstream signaling pathways required for osteoclast development, but crosstalk with other signaling pathways also fine-tunes bone homeostasis both in normal physiology and disease. In addition, RANKL and RANK have essential roles in lymph node formation, establishment of the thymic microenvironment, and development of a lactating mammary gland during pregnancy. Consequently, novel drugs specifically targeting RANK, RANKL, and their signaling pathways in osteoclasts are expected to revolutionize the treatment of various ailments associated with bone loss, such as arthritis, periodontal disease, cancer metastases, and osteoporosis.

Smolen JS, Aletaha D, Grisar J, Redlich K, Steiner G, Wagner O. · Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. · Arthritis Res Ther. · Pubmed #18557991 links to  free full text

Abstract: Rheumatoid arthritis is a heterogeneous disease with respect to clinical manifestations, serologic abnormalities, joint damage and functional impairment. Predicting outcome in a reliable way to allow for strategic therapeutic decision-making as well as for prediction of the response to the various therapeutic modalities available today, especially biological agents, would provide means for optimization of care. In the present article, the current information on biological and clinical markers related to disease activity and joint damage as well as for predictive purposes is reviewed. It will be shown that the relationship of many biomarkers with disease characteristics is confounded by factors unrelated to the disease, and that only few biomarkers exist with some predictive value. Moreover, clinical markers appear of equal value as biomarkers for this purpose, although they likewise have limited capacity in these regards. The analysis suggests the search for better markers to predict outcomes and therapeutic responsiveness in rheumatoid arthritis needs to be intensified.

Scheinecker C, Redlich K, Smolen JS. · Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. · Immunity. · Pubmed #18400186 No free full text.

Abstract: Biological therapies targeting cytokines, T cells, or B cells have improved outcomes of inflammatory diseases. However, many issues remain open: What is the best target? How well can response be predicted? How can cure be achieved?

Smolen JS, Aletaha D. · Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Austria. · Curr Opin Rheumatol. · Pubmed #18388523 No free full text.

Abstract: PURPOSE OF REVIEW: To describe the importance of assessing disease activity in general, aiming for significant improvement particularly low disease activity and remission, and the value of employing simplified instruments toward this end in rheumatoid arthritis RECENT FINDINGS: Various instruments have either been newly developed, validated or assessed in the recent two years. Additional insights relate to the frequency of attainment of low disease activity and remission in clinical trials and clinical practice, as well as to therapeutic strategies, which involve comprehensive and tight evaluation of disease activity in the adaptation of therapy, including biologicals. All studies assessing these instruments reveal that simplified scores perform at least similar compared with more complex indices, and often better, in the evaluation of disease activity and response to treatment. SUMMARY: Simplified indices can be routinely used in clinical practice and trials and adaptation of therapy on the basis of tight control of disease activity will lead to improved outcomes of rheumatoid arthritis.

Brezinschek HP, Hofstaetter T, Leeb BF, Haindl P, Graninger WB. · Division of Rheumatology, Department of Internal Medicine, Medical University Graz, Graz, Austria. · Curr Opin Rheumatol. · Pubmed #18388521 No free full text.

Abstract: PURPOSE OF REVIEW: The aim of this study is to highlight the recent findings on the use of methotrexate and/or TNFalpha-blockers in adult patients with rheumatoid arthritis and their effects on the immune response to various vaccines. RECENT FINDINGS: Regarding influenza vaccination, methotrexate monotherapy is not associated with a decreased response, whereas the use of etanercept and infliximab in combination with methotrexate may cause lower titers and lower response rates. Concerning pneumococcal vaccination, methotrexate seems to impair responsiveness. The concomitant use of adalimumab and methotrexate is also associated with decreased response, whereas the concomitant use of etanercept or infliximab seems not to have an effect on response rates. As immunological pathways seem to play a major role, T-cell-dependent pneumococcal vaccines are designed to achieve higher response rates and protective titers. SUMMARY: Patients with rheumatic disorders are more likely to develop preventable infectious diseases, which underlines the importance of adequate immunoprotective titers. Several studies have shown that the combination of methotrexate and certain TNFalpha-blockers are affecting the responsiveness to vaccines. Further findings indicate that the response also depends on what type of vaccine is used.

Trieb K. · Department of Orthopaedics, Klinikum Kreuzschwestern Wels, Wels, Austria. · J Hand Surg Am. · Pubmed #18261675 No free full text.

Abstract: Wrist involvement is common in rheumatoid arthritis and affects up to 50% of patients within the first 2 years after the onset of the disease, including bilateral involvement. It is a progressive disease that destroys the articular cartilage and surrounding soft tissues, thus leading to severe deformities. Radiological changes are characteristic and include narrowing of the joint line, cysts, and periarticular osteoporosis. Clinical changes are characterized by different scoring systems, indicating different therapeutic options. Surgical orthopedic treatment options include joint-preserving techniques to prevent further damage (radiosynoviorthesis, synovectomy, or axial correction with tendon transfers in earlier stages) and joint replacing techniques to restore function (arthrodesis, resection arthroplasty or total joint arthroplasty in later stages). This article reviews pathologic changes in the rheumatoid hand and their surgical treatment alternatives.

Zenz R, Eferl R, Scheinecker C, Redlich K, Smolen J, Schonthaler HB, Kenner L, Tschachler E, Wagner EF. · Ludwig Boltzmann Institute for Cancer Research, Währinger Strasse 13a, A-1090 Vienna, Austria. · Arthritis Res Ther. · Pubmed #18226189 links to  free full text

Abstract: Activator protein 1 (AP-1) (Fos/Jun) is a transcriptional regulator composed of members of the Fos and Jun families of DNA binding proteins. The functions of AP-1 were initially studied in mouse development as well as in the whole organism through conventional transgenic approaches, but also by gene targeting using knockout strategies. The importance of AP-1 proteins in disease pathways including the inflammatory response became fully apparent through conditional mutagenesis in mice, in particular when employing gene inactivation in a tissue-specific and inducible fashion. Besides the well-documented roles of Fos and Jun proteins in oncogenesis, where these genes can function both as tumor promoters or tumor suppressors, AP-1 proteins are being recognized as regulators of bone and immune cells, a research area termed osteoimmunology. In the present article, we review recent data regarding the functions of AP-1 as a regulator of cytokine expression and an important modulator in inflammatory diseases such as rheumatoid arthritis, psoriasis and psoriatic arthritis. These new data provide a better molecular understanding of disease pathways and should pave the road for the discovery of new targets for therapeutic applications.

Sipos W, Pietschmann P, Rauner M. · II. Medical Clinic, University of Veterinary Medicine Vienna, Veterinärplatz 1, A-1210 Vienna, Austria. · Curr Med Chem. · Pubmed #18220768 No free full text.

Abstract: For many bone and joint diseases in humans, including postmenopausal osteoporosis, rheumatoid arthritis, and ankylosing spondylitis, an immune-mediated etiology has either been proven or is considered as a co-factor in pathogenesis. The identification of the receptor activator of nuclear factor kappaB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG)-interplay and the in-depth characterization of the signaling pathways induced upon RANK activation, including molecules such as TNF receptor-associated factor 6 (TRAF6), nuclear factor-kappaB (NF-kappaB), and signal transducer and activator of T cells (STAT)-3, now promise to give the opportunity to target osteoclastogenesis specifically. Additionally, many byways influencing osteoclastogenesis have been elucidated, thus giving rise to additional therapeutic approaches. These are based mainly upon the effects of diverse cytokines on osteoclast differentiation with interleukin (IL)-17 and interferone (IFN)-gamma being most prominent at the moment. The same applies for the recently established signaling pathways in osteoblastogenesis, which have attracted much attention in the recent years. In this respect, much attention has been attributed towards bone morphogenetic proteins (BMPs) and the Wnt signaling cascade. In this review, an overview on the key molecules, which (could) serve as promising targets for novel therapeutic interventions with the aim of enhancing osteoblast formation or suppressing osteoclast development, is given. Further on, antibody-based therapeutical schemes as well as methodologically novel, albeit predominantly theoretical at the moment, strategies in the fight against immune-mediated osteopathologies are discussed.

Smolen J, Aletaha D. · Division of Rheumatology, Internal Medicine III, Medical University of Vienna, Vienna, Austria. · Eur J Health Econ. · Pubmed #18157733 No free full text.

Abstract: As part of the investigation into the burden of rheumatoid arthritis (RA) and the access to treatment, this article reviews the medical aspects of the disease. RA is mediated by a variety of pathogenic events which culminate in the activation of B-cells, T-cells and other cell populations and lead to secretion of proinflammatory cytokines. These events result in signs and symptoms of active disease, such as pain and swelling, joint damage and disability, the three cornerstones of the clinical expression of RA. Active disease leads to joint damage and both to disability, whereby joint destruction is associated with the irreversible portion of disability. The diagnosis of RA is based on characteristic clinical and laboratory features, however, these may not be obvious in early disease. Therapy aims at interfering with disease activity, ideally leading to remission, as well as at retarding, ideally holding or even healing, joint destruction. This can be achieved by using disease modifying anirheumatic drugs (DMARDs). Among the chemical DMARDs, methotrexate is the anchor drug, although there exist many more such agents. Among the biological compounds, TNF-inhibitors have been in use for more than one decade, and co-stimulation blockade and B-cell targeted therapy have been recent additions to the armamentarium. Therapeutic outcome can be predicted by clinical means.

Dittrich E, Schmaldienst S, Derfler K. · Klinische Abteilung für Nephrologie und Dialyse, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Osterreich. · Wien Klin Wochenschr. · Pubmed #17939280 No free full text.

This publication has no abstract.

Müllner M, Vamvakas S, Rietschel M, van Zwieten-Boot BJ. · Austria Medicines and Medical Devices Agency/AGES PharmMed, Vienna, Austria. · Int J Clin Pharmacol Ther. · Pubmed #17907590 No free full text.

Abstract: OBJECTIVE: There is concern that patients included in trials do not represent the true patient population and women in particular may selectively be excluded. We looked at trial data submitted to the European Medicines Agency (EMEA) by drug companies to achieve marketing authorization in Europe between 2000 and 2003. METHODS: We reviewed the EMEA database and included the main studies for the risk/benefit assessment (pivotal trials) submitted between 2000 and 2003. RESULTS: In pivotal trials submitted to the EMEA there was no, or generally clinically negligible, evidence for gender bias; however, women were underrepresented in hypertension, diabetes and hepatitis B trials, and overrepresented in rheumatoid arthritis and allergic conjunctivitis. CONCLUSIONS: In trials submitted for marketing authorization to the EMEA gender bias was not a serious problem.

De Zordo T, Mlekusch SP, Feuchtner GM, Mur E, Schirmer M, Klauser AS. · Department of Radiology II, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. · Eur J Radiol. · Pubmed #17768022 No free full text.

Abstract: The purpose of this review is to describe the spectrum of sonographic findings in rheumatic diseases with respect to the diagnostic potential using US contrast media which prove activity or inactivity in synovial tissue where new treatment regimes target. Synovial activity can be found in non-erosive and erosive forms of primary and secondary osteoarthritis, and in inflammatory forms of joint diseases like rheumatoid arthritis and peripheral manifestations of spondyloarthritis including, ankylosing spondylitis, Reiter's syndrome, psoriatic arthritis and enteropathic arthritis. It can also be present in metabolic and endocrine forms of arthritis, in connective tissue arthropathies like systemic lupus erythematosus or scleroderma and in infectious arthritis. Ultrasound should be used as first-line imaging modality in suspected early cases of RA and other forms of arthritis, whereas contrast-enhanced ultrasound (CEUS) can further enable for sensitive assessment of vascularity which correlates with disease activity.

Aletaha D, Strand V, Smolen JS, Ward MM. · Department of Rheumatology, Internal Medicine III, Medical University of Vienna, Austria. · Ann Rheum Dis. · Pubmed #17644550 No free full text.

Abstract: BACKGROUND: Physical function in rheumatoid arthritis (RA) has reversible and irreversible components, and is typically assessed by the Health Assessment Questionnaire Disability Index (HAQ). Since irreversible components are expected to increase with longer duration of RA and reduce the ability for improvement in physical function, we analysed responsiveness of HAQ scores in patient populations with differing RA durations in randomised controlled trials (RCTs). METHODS: Data from all RCTs published between 1980 and 2005 that reported changes from baseline in HAQ at 6 and/or 12 months were analysed. Treatments were grouped as "biologics", or "traditional" disease modifying antirheumatic drugs (DMARDs), and "placebo". We computed effect sizes of HAQ in each trial, and contrasted the association between these effects and duration of RA among treatment groups using regression models. RESULTS: We identified 42 RCTs with complete data for the statistical models. The models indicate that discrimination of functional improvement between active drug groups and placebo is reduced in patients with a longer duration of RA (p = 0.02 for the change in discrimination over time). The placebo-adjusted HAQ responses decreased on average by 0.37 per year of RA duration. CONCLUSION: Responsiveness in HAQ scores is inversely associated with mean disease duration in RA. This impacts assessment of physical function, a key outcome measure in RCTs and practice, and impacts the ability to discriminate active treatment from placebo.

Smolen JS. · Department of Rheumatology, Medical University of Vienna, Vienna, Austria. · J Rheumatol Suppl. · Pubmed #17611974 No free full text.

Abstract: The recently approved therapies abatacept and rituximab have significantly improved treatment options for patients with rheumatoid arthritis, especially for patients who have an inadequate response to tumor necrosis factor inhibitors. This article reviews the latest efficacy and safety data for both abatacept and rituximab. One-year data from abatacept and rituximab clinical trials show significantly better efficacy and reduction in radiographic damage for these therapies compared with placebo. In addition, repeated courses of rituximab confer continued efficacy for patients. The safety profile of these therapies shows that infusion reactions and infections are the most commonly reported important adverse events. Premedication with corticosteroids reduces the infusion reactions to rituximab.

Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P. · Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. · Lancet. · Pubmed #17570481 No free full text.

Abstract: Rheumatoid arthritis is characterised by pain, swelling, and destruction of joints, with resultant disability. Only disease-modifying antirheumatic drugs can interfere with the disease process. In the past few years, biological agents, especially inhibitors of tumour necrosis factor, have allowed for hitherto unseen therapeutic benefit, although even with these drugs the frequency and degree of responses are restricted. Therefore, new agents are needed, and three novel biological compounds for treatment of rheumatoid arthritis have already been used in practice or are on the horizon: rituximab (anti-CD20), abatacept (cytotoxic T-lymphocyte antigen 4 immunoglobulin), and tocilizumab (anti-interleukin 6 receptor). We discuss the targets of these drugs, the roles of these targets in the pathogenesis of rheumatoid arthritis, and the efficacy and adverse effects of these agents from clinical trial data. Novel therapeutic strategies in conjunction with optimised disease assessment for better treatment of rheumatoid arthritis and an outlook into potential future targets are also presented.

Gartlehner G, Hansen RA, Jonas BL, Thieda P, Lohr KN. · Ludwig Boltzmann Institute for Health Technology Assessments, Garnisongasse 7/20, 1090, Vienna, Austria. · Clin Rheumatol. · Pubmed #17570009 No free full text.

Abstract: Biologics are an important therapeutic option for treating patients with juvenile idiopathic arthritis (JIA). In adults, they are associated with rare but severe adverse events such as serious infections and malignancies. We reviewed systematically the evidence on the efficacy and safety of biologics for the treatment of JIA. We searched electronic databases up to August 2006. We limited evidence to prospective studies for efficacy but included retrospective observational evidence for safety. Outcomes of interest were clinical response, radiographic progression, quality of life, and adverse events. One randomized controlled trial (RCT) and 11 uncontrolled prospective studies provided data on efficacy; three additional studies assessed safety. The only RCT and six uncontrolled trials support the general efficacy of etanercept for the treatment of JIA. Internal and external validity of these studies are limited. The evidence on other biologic agents such as adalimumab, abatacept, anakinra, infliximab, rituximab, and tocilizumab is sparse or entirely missing. Because of the lack of sound long-term safety data, evidence is insufficient to draw firm conclusions about the balance of risks and benefits of any biologic agent for the treatment of JIA. Clinicians have to be aware of the lack of evidence supporting a long-term net benefit when considering biologics for patients with JIA.

Steiner G. · Department of Rheumatology, Internal Medicine III, Medical University of Vienna, Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna and Ludwig Boltzmann Institute for Rheumatology, Vienna, Austria. · Clin Rev Allergy Immunol. · Pubmed #17426358 No free full text.

Abstract: Rheumatoid arthritis (RA) is not only the most severe of all joint diseases but also the most common systemic autoimmune disease affecting approximately 1% of the world-wide adult population. RA is characterized by the presence of autoantibodies in serum and synovial fluid distinguishing the disease from other arthritides such reactive arthritis or osteoarthritis. Since the historical description of rheumatoid factor (RF), which is an autoantibody directed to immunoglobulin G, numerous additional autoantibodies have been discovered in sera of RA patients. These antibodies may be directed to cartilage components, stress proteins, enzymes, nuclear proteins and, most importantly, citrullinated proteins such as fibrin or vimentin. In contrast to other antibodies including RF, anti-citrullinated protein antibodies are targeted almost exclusively by RA patients thus being the most specific serological markers of RA. Even though most other antibodies are not used for diagnostics, they may contribute to the patholophysiology of RA by forming immune complexes in the joint. Furthermore, autoreactive T-cells in serum and synovial fluid may initiate or enhance the disease process via production of proinflammatory cytokines leading to autoantibody secretion, stimulation of macrophages and activation of bone resorbing osteoclasts. Identification of novel autoantigens, particularly citrullinated proteins, and the characterization of the cellular and molecular processes underlying the autoimmune reactions against them has provided new insights into the complex pathogenesis of RA. This has made possible the development of novel therapeutic concepts that may allow to treat the disease more effectively in its early stages where the chances are highest to interrupt the deleterious processes.

Pieringer H, Stuby U, Biesenbach G. · Section of Rheumatology, 2nd Department of Medicine, General Hospital Linz, Linz, Austria. · Semin Arthritis Rheum. · Pubmed #17204310 No free full text.

Abstract: OBJECTIVES: To review published data on the perioperative management of antirheumatic treatment and perioperative outcome in patients with rheumatoid arthritis (RA). METHODS: The review is based on a MEDLINE (PubMed) search of the English-language literature from 1965 to 2005, using the index keywords "rheumatoid arthritis" and "surgery". As co-indexing terms the different disease-modifying antirheumatic drugs (DMARDs) as well as nonsteroidal anti-inflammatory drugs (NSAIDs) and "glucocorticoids" were used. In addition, citations from retrieved articles were scanned for additional references. Furthermore, because the number of published articles is so limited, relevant abstracts presented at congresses were included in the analysis. RESULTS: Continuation of methotrexate (MTX) appears to be safe in the perioperative period. Only a limited number of studies address the use of leflunomide and the results are conflicting. Because of the very long drug half-life, its discontinuation would need to be of long duration and is probably not necessary. Data on hydroxychloroquine do not show increased risks of infection. Regarding sulfasalazine, there are no studies from which definite answers could be drawn on whether it should be withheld perioperatively. Preliminary data show that the risk of infections during treatment with TNF-blocking agents may be lower than initially expected. The only available recommendation (Club Rhumatismes et Inflammation, CRI) suggests discontinuing the drugs before surgery for several weeks, depending on the risk of infection and the drug used. They should not be restarted until wound healing is complete. To avoid the antiplatelet effect during surgery, NSAIDs other than aspirin should be withheld for a duration of 4 to 5 times the drug half-life. Patients with chronic glucocorticoid therapy and suppressed hypothalamic-pituitary-adrenal (HPA) axis need perioperative supplementation. CONCLUSIONS: While continuation of MTX likely is safe, data on other DMARDs are sparse. In particular, more data on the perioperative use of the biologic agents are needed.

Rauner M, Sipos W, Pietschmann P. · Ludwig Boltzmann Institute of Aging Research, Vienna, Austria. · Int Arch Allergy Immunol. · Pubmed #17191007 links to  free full text

Abstract: Osteoimmunology is an interdisciplinary research field combining the exciting fields of osteology and immunology. An observation that contributed enormously to the emergence of osteoimmunology was the accelerated bone loss caused by inflammatory diseases such as rheumatoid arthritis. Receptor activator of nuclear factor kappaB ligand (RANKL), which is the main regulator of osteoclastogenesis, was found to be the primary culprit responsible for the enhanced activation of osteoclasts: activated T cells directly and indirectly increased the expression of RANKL, and thereby promoted osteoclastic activity. Excessive bone loss is not only present in inflammatory diseases but also in autoimmune diseases and cancer. Furthermore, there is accumulating evidence that the very prevalent skeletal disorder osteoporosis is associated with alterations in the immune system. Meanwhile, numerous connections have been discovered in osteoimmunology beyond merely the actions of RANKL. These include the importance of osteoblasts in the maintenance of the hematopoietic stem cell niche and in lymphocyte development as well as the functions of immune cells participating in osteoblast and osteoclast development. Furthermore, research is being done investigating cytokines, chemokines, transcription factors and co-stimulatory molecules which are shared by both systems. Research in osteoimmunology promises the discovery of new strategies and the development of innovative therapeutics to cure or alleviate bone loss in inflammatory and autoimmune diseases as well as in osteoporosis. This review gives an introduction to bone remodeling and the cells governing that process and summarizes the most recent discoveries in the interdisciplinary field of osteoimmunology. Furthermore, an alternative large animal model will be discussed and the pathophysiological alterations of the immune system in osteoporosis will be highlighted.