Rheumatoid Arthritis: Netherlands

Landewé RB. · Department of InternalMedicine/Rheumatology, Maastricht University Medical Center, Care and Public Health Research Institute, Maastricht, The Netherlands. · Nat Clin Pract Rheumatol. · Pubmed #19030006 No free full text.

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Lecluse LL, Piskin G, Mekkes JR, Bos JD, de Rie MA. · Department of Dermatology, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands. · Br J Dermatol. · Pubmed #18627374 No free full text.

Abstract: Infliximab (Remicade; Schering-Plough, Kenilworth, NJ, U.S.A.) is a chimeric monoclonal antibody that acts as a tumour necrosis factor-alpha inhibitor. Infliximab is registered for the treatment of rheumatoid arthritis, psoriatic arthritis, Crohn disease, ulcerative colitis, ankylosing spondylitis and plaque-type psoriasis. Like other foreign protein-derived agents, infliximab may lead to infusion reactions during and after infusion. Infusion reactions occur in 3-22% of patients with psoriasis treated with infliximab. Most of these reactions are mild or moderate and only few are severe. Nevertheless, they may lead to discontinuation of treatment. As infliximab for psoriasis is prescribed as a last resort and is in most cases very effective, discontinuation of treatment is undesirable. With proper care and prevention of the infusion reactions the need to discontinue treatment with infliximab can be diminished. The objective of this article is to present a guideline for the management of infliximab-related infusion reactions, based on the best available evidence. This guideline can be used in patients with psoriasis as well as in dermatology patients receiving infliximab for off-label indications such as hidradenitis suppurativa or pyoderma gangrenosum.

Wulffraat NM, Kuis W, Petty R. · Department of Paediatric Immunology and Rheumatology, University Hospital for Children 'Het Wilhelmina Kinderziekenhuis', Utrecht, The Netherlands. · Rheumatology (Oxford). · Pubmed #10501434 links to  free full text

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Boers M. · Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. · Nat Clin Pract Rheumatol. · Pubmed #18446137 No free full text.

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van den Berg WB. · Rheumatology Research & Advanced Therapeutics, Radboud University, Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlandsw. · Nat Clin Pract Rheumatol. · Pubmed #18073726 No free full text.

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van Tuyl LH, Vlad SC, Felson DT, Wells G, Boers M. · VU University Medical Center, Amsterdam, The Netherlands. · Arthritis Rheum. · Pubmed #19405006 No free full text.

Abstract: OBJECTIVE: Due to advances in rheumatoid arthritis (RA) therapies over the last few years, an increasing proportion of patients are able to achieve a state of remission. However, the definition of remission is unclear. Currently, randomized controlled trials around the world use different remission definitions and consequently measure different aspects of a patient's disease state. The need for a uniform definition of remission is vital for research findings to be correctly interpreted. METHODS: The American College of Rheumatology (ACR) constituted a committee that included international clinical researchers, trialists, and clinical epidemiologists in order to redefine remission in RA. This group was asked to study current definitions of remission, explore the theoretical underpinning of the concept of remission, and develop a research agenda that would inform future work in the development of an ACR definition of remission. RESULTS: In its first meeting, the committee preferred to develop a strict definition, implying no or very low disease activity. Such a definition would need to be validated against long-term outcome, e.g., physical function and damage. CONCLUSION: The committee decided to consider both a definition for trials and a modified version for clinical practice. Since the first meeting, the ACR and the European League Against Rheumatism (EULAR) have decided to sponsor this initiative as an official ACR/EULAR collaboration.

Bruyn GA, Schmidt WA. · Department of Rheumatology, Medisch Centrum Leeuwarden, Leeuwarden, The Netherlands. · Best Pract Res Clin Rheumatol. · Pubmed #19393570 No free full text.

Abstract: Among the most important reasons for the increased use of ultrasound by rheumatologists is its feasibility to guide injections. Correct positioning of the needle in the targeted structure occurs much more frequently with ultrasound guidance than with conventional positioning without imaging. The sonographer can mark the skin above the structure, using ultrasound to localize this point and to estimate the depth of the structure. Alternatively, the sonographer might introduce the needle under direct sonographic visualisation, holding the probe in one hand and the needle in the other. The needle can be longitudinally parallel to the probe, with an angle of about 45 degrees to the probe. It can be introduced close to the middle of the probe or opposite the probe; the needle can be also depicted transversely. Ultrasound allows needle guidance in nearly all important structures of shoulders, elbows, hand, hips, knees and feet. Education involves training to coordinate probe and needle in sponges, chicken, cheese and other objects. Knowledge of anatomy, probe positioning and the ability to coordinate probe and needle are necessary when injecting patients with sonographic guidance. The rheumatologist might start with easy approaches in which the needle is parallel to the probe.

van der Zant FM, Boer RO, Moolenburgh JD, Jahangier ZN, Bijlsma JW, Jacobs JW. · Department of Nuclear Medicine, Hospital Medical Center Alkmaar, The Netherlands. · Clin Exp Rheumatol. · Pubmed #19327243 No free full text.

Abstract: OBJECTIVE: To perform a systemic review and meta-analysis on the effectiveness of radiosynoviorthesis (RSO). METHODS: A search of medical databases was conducted. Criteria for inclusion: articles in English, minimum follow-up of 6 months, specification of joint disease, reported outcome of at least 5 RSOs. The studies were scored for quality by the Oxford Centre of Evidenced-based Medicine Levels of Evidence, from 1 to 4. RESULTS: Twenty-one (21) studies were included (3 quality 1b, 5 2b and 13 4), analysing 169Erbium/186Rhenium-RSO used predominantly in small joints and 49 (1 quality 1b, 10 2b and 38 4) on 90Yttrium-RSO used predominantly in knee joints. The reported success rates of 169Erbium/186Rhenium-RSO ranged from 69-100% at 6 months, and from 54-100% at > or =12 months; for 90Yttrium they were 24-100% and 29-94%, res-pectively. Studies comparing the effect of RSO with that of glucocorticoid (GC) or saline injection alone were pooled. At 6 months, the pooled odds ratio favouring RSO of the knee with Yttrium over control is 4 (confidence interval (CI) 95% 1.2-14), p=0.02, but at 12 months the ratio was 1.7 (CI95% 0.69-4), p=0.26. For RSO of small joints with Erbium/Rhenium compared to controls, the pooled odds ratio at 6 months is 2 (CI95% 0.66-6), p=0.22 and at 12 months 2 (CI95% 1.09-3.5), p=0.03. CONCLUSION: Reported success rates of RSO are high, but differences in effect with GC injection are less evident, although there is marked heterogeneity in study design of the (small number of) comparative studies.

Klarenbeek NB, Allaart CF, Kerstens PJ, Huizinga TW, Dijkmans BA. · Department of Rheumatology, C-01-R, Leiden University Medical Center, PO Box 9600, Leiden 2300 RC, The Netherlands. · Curr Opin Rheumatol. · Pubmed #19318946 No free full text.

Abstract: PURPOSE OF REVIEW: To give an overview of recent strategy trials for the treatment of rheumatoid arthritis. RECENT FINDINGS: Strategy studies showed a clear benefit of dynamic result-driven treatment towards tight control of disease activity compared with 'usual care' in rheumatoid arthritis patients. In addition, treatment given after short symptom duration gives better outcomes than later initiation of treatment. In many trials, combination therapies, especially combinations with prednisolone or biologicals, were superior to monotherapies. Moreover, combination therapies were more effective if given early in the disease as compared with a delayed introduction, giving support to the window of opportunity hypothesis. In the BeSt study, initial combination therapy could be successfully discontinued in half of the patients, emphasizing that 'initial' would mean 'temporary'. Less evidence is available about initial combination in comparison with combination therapy with a shorter delay. Larger tight-controlled, goal-steered, dynamic strategy trials comparing initial combination therapy with a short-delay combination therapy will help to translate the use of initial (temporary) combination therapy into normal daily practice. SUMMARY: Treatment strategy trials have demonstrated that in the majority of patients with rheumatoid arthritis, the following approach is the most beneficial: goal-steered, dynamic treatment towards tight control of disease activity, including early introduction of (an) effective disease-modifying antirheumatic drug(s) in combination with prednisone or antitumor necrosis factor, which includes tapering of the medication if remission or low disease activity is achieved.

Cohen Tervaert JW. · Department of Internal Medicine, Division of Clinical and Experimental Immunology, Maastricht University Medical Center, Maastricht, The Netherlands. · Clin Exp Immunol. · Pubmed #19309350 No free full text.

Abstract: Premature atherosclerosis has been observed during the course of different systemic inflammatory diseases such as rheumatoid arthritis and sytemic lupus erythematosus. Remarkably, relatively few studies have been published on the occurrence of accelerated atherosclerosis in patients with vasculitis. In giant cell arteritis (GCA), mortality because of ischaemic heart disease is not increased. In addition, intima media thickness (IMT) is lower in patients with GCA than in age-matched controls. In contrast, IMT is increased significantly in Takayasu arteritis, another form of large vessel vasculitis occurring in younger patients. In Takayasu arteritis and in Kawasaki disease, a form of medium-sized vessel vasculitis, accelerated atherosclerosis has been well documented. In small vessel vasculitis because of anti-neutrophil cytoplasmic autoantibodies-associated vasculitis, cardiovascular diseases are a major cause of mortality. IMT measurements reveal conflicting results. During active disease these patients experience acceleration of the atherosclerotic process. However, when inflammation is controlled, these patients have atherosclerotic development as in healthy subjects. Several risk factors, such as diabetes and hypertension, are present more often in patients with vasculitis compared with healthy controls. In addition, steroids may be pro-atherogenic. Most importantly, many patients have impaired renal function, persistent proteinuria and increased levels of C-reactive protein, well-known risk factors for acceleration of atherosclerosis. Enhanced oxidation processes, persistently activated T cells and reduced numbers of regulatory T cells are among the many pathophysiological factors that play a role during acceleration of atherogenesis. Finally, autoantibodies that may be relevant for acceleration of atherosclerosis are found frequently in elevated titres in patients with vasculitis. Because patients have an increased risk for cardiovascular events, vasculitis should be treated with as much care as possible. In addition, treatment should be considered with angiotensin-converting-enzyme inhibitors and/or angiotensin receptor-1 blockers, statins and acetylsalicyl acid. Finally, classical risk factors for cardiovascular disease should be monitored and treated as much as possible.

Lebre MC, Tak PP. · Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands. · Hum Immunol. · Pubmed #19236901 No free full text.

Abstract: Dendritic cells (DC) comprise a complex network of heterogeneous antigen-presenting cells (APC) that are critical not only to the initiation and regulation of adaptive immunity (Th1/Th2/Th17 responses), but also to the maintenance of both central and peripheral tolerance (regulatory T cells, peripheral T-cell deletion). Previous work has clearly indicated a role for DC subsets in the pathogenesis of rheumatoid arthritis (RA). Therefore, utilizing these cells as therapeutic agents could be beneficial in the treatment of RA. However, it remains unclear which DC should be used for tolerance-inducing immunotherapy: myeloid, plasmacytoid, or both? This review summarizes the data obtained thus far concerning the functional characterization of several DC subsets in human RA and accordingly explores their potential use for immunotherapy.

Vliet Vlieland TP, Pattison D. · Leiden University Medical Center, Department of Orthopaedics and Department of Rheumatology, Leiden, The Netherlands. · Best Pract Res Clin Rheumatol. · Pubmed #19233050 No free full text.

Abstract: Non-pharmacological treatment modalities are often used as an adjunct to drug therapy in patients with rheumatoid arthritis (RA). The aim of this overview is to summarize the available evidence on the effectiveness of these modalities in early RA. The few available randomized controlled trials that have specifically investigated patients with early RA support the effectiveness of dynamic exercise and cognitive behavioural interventions, and to a lesser extent of joint protection programmes and foot orthoses. The effectiveness of multidisciplinary team-care programmes, specialist nurse care, electro-physical modalities (including passive hydrotherapy), wrist orthoses, and dietary interventions have not been studied in patients with early RA. Current recommendations on the usage of non-pharmacological treatment modalities in sets of guidelines on the management of early RA vary with respect to their scope, strength and level of detail. The results of this review indicate a need for further investigation into the most clinically effective and cost-effective strategies to deliver non-pharmacological treatment modalities as well as comprehensive arthritis care models in early RA.

Van Hemert FJ, Voermans C, Van Eck-Smit BL, Bennink RJ. · Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Q J Nucl Med Mol Imaging. · Pubmed #19182731 links to  free full text

Abstract: With growing interest in cell-based scintigraphic diagnosis or therapy monitoring, there is an increasing demand for non-invasive observation and quantification of cell trafficking in the preclinical and clinical setting. Monocytes are members of the human mononuclear phagocyte system originating from a myeloid precursor in the bone. Labeled monocytes are being used for investigation of pathogenesis like atherosclerosis and for monitoring of therapeutic intervention in inflammatory diseases like rheumatoid arthritis. Labeling mononuclear cells at high specific activity without affecting their biological functions allows (delayed) non-invasive imaging with g or PET cameras. Monocytes labeled before their final differentiation into macrophages or dendritic cells may reveal centers of inflammation in a patient and, thereby, contribute to scintigraphic diagnosis. Macrophages or dendritic cells may be in vitro cultured and by means of genetic transformation specified towards specific targets prior to re-injection, an approach with therapeutic potency. This review addresses issues on autologous monocytes, particularly their properties and labeling for non-invasive in vivo radionuclide imaging of chronic inflammation.

van Venrooij WJ, van Beers JJ, Pruijn GJ. · Department of Biomolecular Chemistry, Radboud University, Nijmegen, The Netherlands. · Ann N Y Acad Sci. · Pubmed #19076355 No free full text.

Abstract: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation of synovial joints. In most cases this will lead to the formation of pannus tissue, ultimately leading to joint destruction. Early diagnosis, coupled with aggressive use of disease-modifying antirheumatic drugs, has been shown to have a favorable effect on the course of the disease. Therefore, early and accurate diagnosis has become increasingly important. Several sets of criteria have been published to achieve such an early diagnosis, and all of them include measurement of antibodies directed to citrullinated peptides or proteins. This review summarizes our present knowledge about the most well-known and established test to measure these antibodies, the anti-CCP test, which measures antibodies directed to cyclic citrullinated peptides. We describe the current views on how these antibodies are generated and how genetic and environmental parameters are important in this process. The anti-CCP test is more specific than the commonly used RF test (95% versus less than 90%) and has a comparable sensitivity (more than 70%). These antibodies are detectable very early in the disease and are reported to predict the development of erosive RA. Increasing evidence supports a role for these antibodies in the pathology of the disease. In conclusion, testing for anti-CCP autoantibodies is widely accepted as an indispensable tool for diagnosis and early treatment in the management of rheumatoid arthritis patients.

Visser K, van der Heijde D. · Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. · Ann Rheum Dis. · Pubmed #19033290 links to  free full text

Abstract: OBJECTIVES: To review systematically the available literature on the optimal dosage and route of administration of methotrexate in patients with rheumatoid arthritis (RA), as an evidence base for generating clinical practice recommendations. METHODS: A systematic literature search was carried out in MEDLINE, EMBASE, Cochrane Library and American College of Rheumatology/European League Against Rheumatism meeting abstracts, searching for randomised controlled trials evaluating various dosages or routes of administration of methotrexate in RA. Articles that fulfilled predefined inclusion criteria were systematically reviewed and the quality was appraised. Effect sizes and odds ratios for clinical, radiological and toxicity outcomes were calculated and directly or indirectly compared between study groups using methotrexate in different dosages or by different routes. RESULTS: A total of 38 publications out of 1748 identified references was included in the review. Start doses of 25 mg/week or fast escalation with 5 mg/month to 25-30 mg/week were associated with higher clinical effect sizes and more (gastrointestinal) adverse events in comparison with doses of 5-15 mg/week or slow escalation. Starting with 15 mg/week subcutaneous versus oral methotrexate was associated with higher clinical efficacy but more withdrawal due to toxicity in early RA. In longstanding RA, after failure on 15-20 mg/week orally, a switch to 15 mg/week intramuscularly with subsequent dose escalation did not result in increased efficacy. CONCLUSIONS: Starting on methotrexate 15 mg/week orally, escalating with 5 mg/month to 25-30 mg/week, or the highest tolerable dose, with a subsequent switch to subcutaneous administration in the case of an insufficient response, seems to be the optimal evidence-based dosing and routing recommendation for methotrexate in RA.

Wenink MH, Han W, Toes RE, Radstake TR. · Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. · Handb Exp Pharmacol. · Pubmed #19031022 No free full text.

Abstract: Dendritic cells (DC) are the professional antigen presenting cells that protect us against invading organisms. On the other hand, they uphold tolerance thereby avoiding the initiation of autoimmunity. In performing these contrasting but essential tasks DC are unique and divide these processes in time and space. It is often thought that a loss of separation of these tasks underlies the breakthrough of tolerance leading to autoimmune conditions such as rheumatoid arthritis. In this review, we will focus on the evidence which points towards the implication of DC in the inflammatory process observed in RA and in experimental models of arthritis. Finally, we will conclude on future programs exploiting the capacity of DC to cure conditions such as RA.

Feitsma AL, van der Helm-van Mil AH, Huizinga TW, de Vries RR, Toes RE. · Department of Rheumatology, LUMC, Leiden, The Netherlands. · Ann Rheum Dis. · Pubmed #19022816 No free full text.

Abstract: Rheumatoid arthritis (RA) is a complex genetic disorder in which the HLA region contributes most to the genetic risk. HLA-DRB1 molecules containing the amino acid sequence QKRAA/QRRAA/RRRAA (ie, HLA-DRB1*0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001 and *1402) at position 70-74 in the third hypervariable region of the DRB1 chain are associated with susceptibility to RA. HLA-DRB1 molecules containing the amino acids "DERAA" (ie, HLA-DRB1*0103, *0402, *1102, *1103, *1301, *1302 and *1304) at the same position are associated with protection from RA. Interestingly, not only inherited but also non-inherited HLA-antigens from the mother can influence RA susceptibility. A protective effect of "DERAA"-containing HLA-DRB1 alleles as non-inherited maternal antigen (NIMA) has recently been described. The underlying mechanism of this protective effect is currently unknown, although a possible explanation is covered below. In this review, an overview of the current knowledge on protection against RA is given and the inherited and NIMA effect of "DERAA"-containing HLA-DRB1 alleles are compared.

Coenen MJ, Gregersen PK. · Department of Human Genetics of the Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. · Genes Immun. · Pubmed #18987647 No free full text.

Abstract: The field of genetics and autoimmune diseases is undergoing a rapid and unprecedented expansion with new genetic findings being reported at an astounding pace. It is now clear that multiple genes contribute to each of the major autoimmune disorders, with significant genetic overlaps among them. Rheumatoid arthritis (RA) is no exception to this, and emerging data are beginning to reveal the outlines of new diagnostic subgroups, complex overlapping relationships with other autoimmune disorders and potential new targets for therapy. This review describes the evolving genetic landscape of RA, with the full knowledge that our current view is far from complete. However, with the first round of genome-wide association scans now completed, it is reasonable to begin to take stock of the direction in which the major common genetic risk factors are leading us.

Grabiec AM, Tak PP, Reedquist KA. · Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. · Arthritis Res Ther. · Pubmed #18983693 links to  free full text

Abstract: Cellular activation, proliferation and survival in chronic inflammatory diseases is regulated not only by engagement of signal trans-duction pathways that modulate transcription factors required for these processes, but also by epigenetic regulation of transcription factor access to gene promoter regions. Histone acetyl transferases coordinate the recruitment and activation of transcription factors with conformational changes in histones that allow gene promoter exposure. Histone deacetylases (HDACs) counteract histone acetyl transferase activity through the targeting of both histones as well as nonhistone signal transduction proteins important in inflammation. Numerous studies have indicated that depressed HDAC activity in patients with inflammatory airway diseases may contribute to local proinflammatory cytokine production and diminish patient responses to corticosteroid treatment. Recent observations that HDAC activity is depressed in rheumatoid arthritis patient synovial tissue have predicted that strategies restoring HDAC function may be therapeutic in this disease as well. Pharmacological inhibitors of HDAC activity, however, have demonstrated potent therapeutic effects in animal models of arthritis and other chronic inflammatory diseases. In the present review we assess and reconcile these outwardly paradoxical study results to provide a working model for how alterations in HDAC activity may contribute to pathology in rheumatoid arthritis, and highlight key questions to be answered in the preclinical evaluation of compounds modulating these enzymes.

Takken T, Van Brussel M, Engelbert RH, Van Der Net J, Kuis W, Helders PJ. · Department of Pediatric Physical Therapy and Exercise Physiology, Wilhelmina Children's Hospital, UMC Utrecht, The Netherlands. · Eur J Phys Rehabil Med. · Pubmed #18762738 links to  free full text

Abstract: BACKGROUND: Exercise therapy is considered an important component of the treatment of arthritis. The efficacy of exercise therapy has been reviewed in adults with rheumatoid arthritis but not in children with juvenile idiopathic arthritis (JIA). OBJECTIVES: To assess the effects of exercise therapy on functional ability, quality of life and aerobic capacity in children with JIA. METHODS: Several electronic databases were searched up to October 2007 and references were tracked. The selection criteria were randomized controlled trials (RCTs) of exercise treatment in JIA. As for data collection and analysis, potentially relevant references were evaluated and all data were extracted by two review authors working independently. RESULTS: Three out of 16 identified studies met the inclusion criteria, with a total of 212 participants. All the included studies fulfilled at least seven of 10 methodological criteria. The outcome data of the following measures were homogenous and were pooled in a meta-analysis: functional ability (N=198; weighted mean difference [WMD] -0.07, 95% CI -0.22 to 0.08), quality of life (CHQ-PhS: N=115; WMD -3.96, 95% CI -8.91 to 1.00) and aerobic capacity (N=124; WMD 0.04, 95% CI -0.11 to 0.19). The results suggest that the outcome measures all favoured the exercise therapy but none were statistically significant. None of the studies reported negative effects of the exercise therapy. CONCLUSIONS: Overall, based on ''silver-level'' evidence there was no clinically important or statistically significant evidence that exercise therapy can improve functional ability, quality of life, aerobic capacity or pain. The included and excluded studies were all consistent about the adverse effects of exercise therapy; no short-term detrimental effects of exercise therapy were found in any study. Both included and excluded studies showed that exercise does not exacerbate arthritis. Although the short-term effects look promising, the long-term effect of exercise therapy remains unclear.

van der Leeden M, Steultjens MP, Terwee CB, Rosenbaum D, Turner D, Woodburn J, Dekker J. · Jan van Breemen Institute, Amsterdam, The Netherlands. · Arthritis Rheum. · Pubmed #18759256 No free full text.

Abstract: OBJECTIVE: To compose an inventory of instruments that have been described to measure foot function (i.e., pressure and/or gait parameters), foot pain, and foot-related disability in rheumatoid arthritis (RA), and to investigate the clinimetric quality of these measures. METHODS: A systematic search was conducted in Medline, CINAHL, EMBase, and Sportdiscus. Standardized criteria, extended with levels of evidence, were applied to assess the quality of the clinimetric studies and the properties (i.e., reliability, validity, and responsiveness) of the described instruments. RESULTS: A variety of measurement instruments were identified. Only 16 instruments have been studied for their measurement properties in RA patients: 7 for assessing foot function, 3 for measuring foot-related disability, and 6 for measuring both foot pain and foot-related disability. Thirteen instruments were rated for reliability, of which 10 were rated positively on different levels of evidence. No positive rating for absolute measurement error was applicable for any of the tests. Internal consistency was reported for 7 instruments; 3 assigned a positive rating. For 2 instruments, Rasch analysis was used to assess the methodologic quality. A positive rating was reported for goodness-of-fit only, not for item calibration. Seven instruments were rated for construct validity, and 3 assigned a positive rating. Only 2 instruments were rated positively for responsiveness. CONCLUSION: This review offers a basis for choosing the most appropriate instruments for measuring foot function, foot pain, and foot-related disability in RA patients, both for clinical practice and for research. Further research on the quality of these measures is urgently needed.

Aarden L, Ruuls SR, Wolbink G. · Sanquin Research at Central Laboratory for Blood Transfusion and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Plesmanlaan 125, Amsterdam, The Netherlands. · Curr Opin Immunol. · Pubmed #18619538 No free full text.

Abstract: To date, millions of people have been treated with therapeutic monoclonal antibodies (TmAbs) for various indications. It is becoming increasingly clear that TmAbs can be immunogenic, which may reduce efficacy or induce adverse effects. Over the years, the importance of antibody formation has been questioned and sometimes minimized, as few antibody responses to TmAbs (HACA or HAHA) were reported. However, the methods to detect and quantify such antibodies used in the past have been problematic. Only recently, methods have been developed that have adequate sensitivity and are not seriously disturbed by false-positive reactions caused by rheumatoid factors, natural antibodies to Fab or F(ab')2 fragments, or Fc interactions of IgG4. The large number of treated patients, in combination with these new assays, presents a unique opportunity to study the anti-antibody immune response in man, possibly allowing us to manipulate immunogenicity in the future.

Lafeber FP, Miossec P, Valentino LA. · Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. · Haemophilia. · Pubmed #18494686 No free full text.

Abstract: Haemophilic arthropathy, which shares some clinical and biological injury characteristics with rheumatoid arthritis, is characterized by two main features: chronic proliferative synovitis and cartilage destruction. It is the consequence of repeated extravasation of blood into joint cavities, but its exact pathogenesis, particularly with regard to early changes in the joint, is still incompletely understood. This review presents recent findings obtained in experiments performed in vitro and using animal models, which have improved our knowledge of the pathogenesis of haemophilic arthropathy. These experimental studies show that haemophilic arthropathy is a multifactorial event in which the deposit of iron in the joints appears to exert a central role. First, iron may promote the apoptosis of chondrocytes by catalysing the formation of oxygen metabolites; this may explain the fact that intra-articular blood exerts a directly harmful effect on cartilage before, and independent of synovial changes. Secondly, iron may also act on the synovial membrane by favouring its proliferation through the induction of proto-oncogenes involved in cellular proliferation and stimulation of inflammatory cytokines as well as abrogation of apoptosis. These two processes, one degenerative and cartilage-mediated, the other inflammatory and synovium-mediated could occur in parallel or sequentially. Overall, it may be expected that these experimental results will yield new therapeutic strategies capable of effectively preventing the occurrence of this still serious and common complication in patients with severe haemophilia.

van Eden W. · University of Utrecht, Institute of Infectious Diseases and Immunology, Yalelaan 1, 3584CL Utrecht, The Netherlands. · Curr Opin Investig Drugs. · Pubmed #18465663 No free full text.

Abstract: CBio Ltd, under license from the University of Queensland, is developing a recombinant form of chaperonin 10, known as XToll, for the potential anti-inflammatory treatment of rheumatoid arthritis, psoriasis and multiple sclerosis. All three indications have been evaluated in phase IIa clinical trials. By May 2005, a phase IIa trial for Crohn's disease had been terminated due to slow recruitment. The company has not disclosed plans for future development for this indication.

Gerlag DM, Tak PP. · Division of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. · Best Pract Res Clin Rheumatol. · Pubmed #18455687 No free full text.

Abstract: The analysis of synovial biomarkers is increasingly used in the context of innovative trial design in rheumatoid arthritis (RA). This approach, which is generally well tolerated by patients, has been used to provide insight into the pathogenesis of RA and the mechanism of action of therapy, as well as for screening purposes during early drug development.