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ID PMID Title PublicationDate abstract
16462521 Imaging outcomes and their role in determining outcomes in osteoarthritis and rheumatoid a 2006 Mar PURPOSE OF REVIEW: This review describes the advances in knowledge of outcomes that have occurred recently as a result of imaging research in both osteoarthritis and rheumatoid arthritis. RECENT FINDINGS: Recent imaging advances in osteoarthritis have offered insights into fundamental questions including the cause of pain and reasons for disease progression. Although ongoing disease modification clinical drug trials in osteoarthritis mostly use standardized plain radiographs to monitor structural changes in the joint, magnetic resonance imaging is rapidly evolving as a method of monitoring joint structure and with time may become the preferred method of monitoring this feature in osteoarthritis clinical trials. The past decade has seen major advances in the treatment of rheumatoid arthritis in which imaging determines whether individual agents or therapeutic regimens are structure modifying. Although conventional radiography remains the gold standard for assessing structural progression in rheumatoid arthritis, growing work on the performance metrics of magnetic resonance imaging has resulted in its increasing use in trials. Ultrasonography shows preliminary promise as a useful outcome measure. SUMMARY: Recent advances in imaging are improving our understanding of the etiopathogenesis and treatment of persons with osteoarthritis and rheumatoid arthritis. Complex challenges face us over the coming years as clinicians and researchers grapple with the use of these new techniques, the insights they may provide, and their clinical application.
17109060 Prognostic factors of radiographic progression in early rheumatoid arthritis: a two year p 2007 Jul The objective of the study was to analyze the prognostic factors of radiographic progression in a series of patients with early rheumatoid arthritis (RA) after 2 years of therapy with a structured algorithm using disease-modifying antirheumatic drugs (DMARDs) and very low doses of oral glucocorticoids. One hundred and five patients (81% female) with early RA (disease duration <2 years) treated with the same therapeutic protocol using gold salts and methotrexate in a step-up strategy, together with methylprednisolone (4 mg/day), were followed up for 2 years. The outcome variable was radiographic progression after 2 years of DMARD therapy using the modified Larsen method. Clinical, biological, immunogenetic, and radiographic data were analyzed at study entry and after 1 and 2 years of follow-up. Radiographic progression (increase of four or more units in the Larsen score) was observed in 32% of patients after 2 years of follow-up. The percentage of erosive disease increased from 18.3% at baseline to 28.9% at 12 months and 44.6% at 24 months, in spite of a significant improvement in disease activity. New erosions appeared in 33% of patients after 2 years. Several baseline parameters were associated with radiographic progression in the univariate analysis: shared epitope (SE) homozygozity, HLA-DRB*04 alleles, female gender, hemoglobin, erythrocyte sedimentation rate, and anticyclic citrullinated peptide antibodies (anti-CCP). In the multivariate analysis, female gender [odds ratio (OR) 5.5, 95% confidence interval (CI): 1.1-28.2, p = 0.04], DRB1*04 alleles (OR 3.1, 95% CI 1.1-9, p = 0.03) and, marginally, anti-CCP antibodies (OR 3.6, 95% CI 0.9-14.5, p = 0.06), were associated with progression. Female patients with both DRB1*04 alleles and anti-CCP antibodies showed the highest scores in radiographic progression. The presence, but not the titer, of anti-CCP antibodies predicted progression. The positive predictive value of the multivariate model for progression was only 53.9% whereas the negative predictive value was 80.3%. In a series of early RA patients treated with a structured algorithm using DMARDs and very low doses of glucocorticoids, radiographic progression was observed in one third of patients after 2 years. Female gender, DRB1*04 alleles (rather than the SE), and the presence of anti-CCP antibodies at baseline (independently of the titer) were the most important predictors of progression. The utility of these parameters in clinical practice is limited by their relatively low positive predictive value.
16249224 Incidence of lymphoma in a large primary care derived cohort of cases of inflammatory poly 2006 May OBJECTIVE: To determine the risk of lymphoma in a primary care derived cohort of new onset cases of inflammatory polyarthritis and assess the contribution of disease severity and standard immunosuppressive treatment. DESIGN: Prospective cohort study. METHODS: 2105 subjects with new onset inflammatory polyarthritis were recruited to the Norfolk Arthritis Register (NOAR) and followed annually for (median) 8.4 years. Occurrence of lymphoma was determined by annual morbidity review and linkage to the central hospital database serving the NOAR area. Cases of lymphoma were verified by record review. Standardised incidence ratios (SIRs) for lymphoma were calculated compared with the local, age, sex, and calendar year expected rates. Stratified analyses were undertaken for various markers of disease severity and treatment history. RESULTS: There were 11 cases of lymphoma during 15,548 person years of follow up, the majority of which were of large B cell type. Compared with the local population the SIR was 2.4 (95% confidence interval, 1.2 to 4.2). The risks in cases classified as rheumatoid arthritis, ever rheumatoid factor positive, or ever treated with DMARDs were all higher, the highest risk group being those treated with methotrexate: SIR = 4.9 (1.8 to 10.6). CONCLUSIONS: There was a doubling in risk of lymphoma in new onset cases of inflammatory polyarthritis. Patients with the most severe disease were twice as likely as other patients to develop lymphoma. These results need to be taken into account when considering reported increased risks of lymphoma compared to background population risk in users of new biological agents.
16100342 Attenuated response to purified protein derivative in patients with rheumatoid arthritis: 2005 Sep BACKGROUND: The purified protein derivative (PPD) skin test is the only widely used method which detects latent tuberculosis infection (LTBI) and is dependent on a normal T cell function. In rheumatoid arthritis (RA) the T cell function is altered, which may result in an inability to develop an adequate PPD reaction. OBJECTIVES: To evaluate the response to PPD in patients with RA and to compare it with that of control subjects. METHODS: 112 patients with RA and 96 healthy controls were studied. PPD 5 U was applied using the Mantoux method, and skin reaction was measured at 72 hours. The reaction was considered negative for PPD <5 mm. RESULTS: There were no significant differences in age, sex, history of bacille Calmette-Guerin vaccination, or tuberculosis contact between the two groups. The median size of the PPD induration in the patients with RA was significantly less than that in the control group (4.5 v 11.5 mm, p<0.01). 79 (70.6%) patients with RA compared with 25 (26%) of the control group had a negative reaction to PPD (p<0.01), a response not influenced by disease activity or duration of disease in the patients with RA. CONCLUSION: A PPD skin test is not an appropriate test for recognising LTBI in patients with RA in our population.
16670824 Radiographic study of joint destruction patterns in the rheumatoid elbow. 2007 Apr Knowledge of the pattern of joint destruction is important for planning the therapeutic approach to rheumatoid arthritis (RA) of the elbow. Accordingly, we carried out a large-scale radiographic study with the objective of elucidating the joint destruction pattern in rheumatoid elbows. From 2001 through 2003, we examined and took plain X-rays of both elbows of 193 RA patients (i.e., 386 elbows), consisting of 18 men and 175 women, with a mean age of 57.0 years. Radiographic images of the elbow joints were used to classify the degree of bone loss in various zones on the elbow joint surface into four grades of severity, and joint destruction was compared between the left and right elbows. In addition, correlation in the extent of bone loss between each of the zones of the same elbow and differences in the extent of bone loss were analyzed statistically. The results showed direct correlations for destruction of the elbow joint surface among the zones for the left and right elbow joints and in the same elbow joint. However, more severe destruction was observed on the radial side of the humeral trochlea, and it was surmised that destruction of the elbow joint must begin at that site and gradually spread mediolaterally. In addition, in the same elbow joint, the correlation in the degree of bone loss between the trochlea of humerus and the trochlear notch was especially strong, indicating that the bone destruction at both sites represented mirror lesions. We conclude that when performing radiographic diagnosis of the joint damage in the rheumatoid elbow, knowledge of this pattern of joint destruction will be useful for assessing whether there is joint destruction in the initial stage and for deciding the therapeutic approach.
16465612 Rheumatoid arthritis: inflammation and bone loss. 2006 Jan Chronic synovial inflammation is usually accompanied by bone erosion. Due to resulting structural damage, bone erosion is a major reason for disability in RA patients. Anti-rheumatic drug therapy is focussed not only on the control of synovial inflammation but also on preserving bone from structural damage. Bone erosion in arthritis is a consequence of synovial osteoclast formation. Therapeutic approaches which interfere with synovial osteoclastogenesis and/or osteoclast activation are therefore of great interest. This review describes the mechanism of inflammatory bone loss, describes its cellular and molecular players and gives insights in current therapeutic tools to inhibit this process.
16705047 Macrophage migration inhibitory factor and glucocorticoid sensitivity. 2006 Aug Glucocorticoids (GCs) are widely used in the treatment of inflammatory diseases including rheumatoid arthritis (RA). Treatment with GC is associated with significant dose-dependent side-effects. The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) has emerged in recent years as a candidate factor which could regulate GC sensitivity. MIF is induced by GC, and is able to override anti-inflammatory actions of GCs. In this review, we summarize the pro-inflammatory actions of MIF with respect to RA, describe the interactions between MIF and GC and examine new evidence, which identifies MIF as a specific target for steroid sparing.
16300475 The therapeutic potential of CXCR4 antagonists in the treatment of HIV infection, cancer m 2005 Dec CXCR4 is the receptor of the chemokine CXCL12, which is involved in progression and metastasis of several types of cancer cells, HIV infection and rheumatoid arthritis. The authors developed selective CXCR4 antagonists, T22 and T140, initially as anti-HIV agents, which inhibit T cell line-tropic (X4-) HIV-1 infection through their specific binding to CXCR4. Recently, T140 analogues have also been shown to inhibit CXCL12-induced migration of breast cancer cells, leukaemia T cells, pancreatic cancer cells, small cell lung cancer cells, chronic lymphocytic leukaemia B cells, pre-B acute lymphoblastic leukaemia cells and so on in vitro. Biostable T140 analogues significantly suppressed pulmonary metastasis of breast cancer cells and melanoma cells in mice. Furthermore, these compounds significantly suppressed the delayed-type hypersensitivity response induced by sheep red blood cells and collagen-induced arthritis, which represent in vivo mouse models of arthritis. Thus, T140 analogues proved to be attractive lead compounds for chemotherapy of these problematic diseases. This article reviews recent research on T140 analogues, referring to several other CXCR4 antagonists.
16893550 Soluble human leukocyte antigen: a diagnostic indicator of rheumatoid arthritis? 2006 Aug 31 Early stage rheumatoid arthritis (RA) is often difficult to diagnose because initial symptoms are non-specific. To aid diagnosis, suitable serological diagnostic markers are sought. Elevated levels of soluble MHC class II (soluble human leukocyte antigen; sHLA-DR) in human serum have been associated with rheumatoid and 'rheumatoid-like' autoimmune diseases. As a result, sHLA-DR has been suggested as a specific marker of RA. However, reported levels of sHLA-DR in sera of healthy donors vary significantly and the mechanism of release of HLA-DR into serum is poorly understood. Investigations into the diagnostic potential of this molecule necessitate the development of a sensitive and specific sHLA-DR assay. We have investigated multiple ELISA setups to develop such an assay and false positive signal has been carefully removed using a combination of isotype-matched controls and immuno-depletion. sHLA-DR levels in sera of RA patients were not significantly different from those in healthy donors which suggests sHLA-DR has limited utility in the diagnosis of RA. In RA patients, we detected high levels of sHLA-DR in aspirated synovial fluid (SF), but this did not correlate with sHLA-DR levels in serum.
16331790 Reconciling subject differences in recruitment to clinical trials and clinical practice. 2005 Dec The special interest group on Reconciling Subject Differences was centered around the issue that the results from randomized clinical trials do not predict response to therapies in clinical practice, and around the hypothesis that this might be explained by differences in subjects selected for clinical trials compared to those treated in routine practice.
16582690 Synovial cell activation. 2006 May PURPOSE OF REVIEW: Modern molecular biology offers a unique opportunity to gain a comprehensive picture of gene expression in a disease state. This review presents recent findings in the field of synovial fibroblast biology contributing to knowledge of the pathogenesis of rheumatoid arthritis. RECENT FINDINGS: Recently it has become apparent that innate immune response pathways play a critical role in driving synovial activation and contribute significantly to the turnover of leukocytes in the synovial compartment. In addition, microparticles have been identified as a new class of potent mediators, broadening the known spectrum of cell-derived modulators in the joint. Numerous research groups gained new insights into detailed molecular mechanisms leading to the invasiveness of rheumatoid arthritis synovial fibroblasts, the disturbance in the regulation of apoptosis, and synovial cell-cell and cell-matrix interactions. SUMMARY: The key role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis has been highlighted by the fact that these cells not only are the main executors of cartilage and bone destruction but also modulate numerous interactions in rheumatoid joints. Moreover, it has become evident that integration of a large body of information is indispensable to get a comprehensive outlook on synovial activation in the pathology of rheumatoid arthritis.
16331756 Factors affecting rheumatoid arthritis patients' decisions to participate in clinical tria 2005 Dec OBJECTIVE: To delineate the personal, psychosocial, and disease-related factors that may influence rheumatoid arthritis (RA) patients' decisions to participate in clinical trials. METHODS: A total of 191 patients with RA were asked to participate in this survey. The questionnaire collected information on demographics, RA disease-related factors, and the importance of several factors that might influence patients' willingness to participate in clinical trials. Patients were then asked if they would consider participating in a hypothetical study. RESULTS: Participants were 88% female with a mean age of 40.5 years. The ethnic composition was 57% Hispanic, 25% Caucasian, 12% Asian, and 6% African American, with 71% having a family income < $20,000/year. Factors that patients considered important for participation in a clinical study included: the opportunity to help others, the possibility of improved health, early access to new therapy, the availability of free treatments, unknown side effects of the study drug, and the need to stop current therapy. There were strong correlations between the rank order importance weights between Hispanics and Caucasians, suggesting fundamental similarities in preferences. The most important factor was the opportunity to help others. In general, the more important factors were associated with preferences for trial participation. CONCLUSION: This questionnaire identified factors that may affect RA patients' willingness to participate in a study. Patient participation in trials is driven by diverse factors that include altruism and the opportunity for healthcare and improved health. Consideration of these factors may facilitate the inclusion of more diverse patient populations into trials and enhance the applicability of trial results.
16265691 Static wrist splint use in the performance of daily activities by individuals with rheumat 2005 Nov OBJECTIVE: In individuals with rheumatoid arthritis (RA), to identify the influence of wrist splint wear on pain, work performance, endurance, perceived task difficulty, and perceived splint benefit while performing various upper limb tasks. METHODS: This crossover study included 30 individuals with wrist involvement. Pain, work performance, endurance, and perceived task difficulty were assessed with the splint on and off. Using a work simulator, participants performed 14 tasks, 10 assessing work performance and 4 assessing endurance. A visual analog scale (VAS) was used to rate pain, task difficulty, and perceived splint benefit. RESULTS: With the splint on, pain was significantly lower in 5 tasks, as was perceived difficulty in task performance. Work performance did not differ significantly with the splint on versus off. While mean endurance scores were always better with the splint on, differences reached significance on only one task. The task with greatest overall perceived splint benefit was "chopping with a knife." CONCLUSION: Results revealed that for most tasks, there was generally a positive effect of splint use on hand function; however, perceived splint benefit was marginal. For most tasks splint use improved or did not change pain levels, did not interfere with work performance, increased or maintained endurance, and did not increase perceived task difficulty. The findings suggest that wrist splint prescription is not a simple process; clinicians and clients need to work together to determine the daily wear pattern that maximizes benefit and minimizes inconvenience according to the client's individual needs.
16902778 [Update on rheuma-orthopedics - role and therapeutic options]. 2006 Nov Orthopaedic treatment options for rheumatological patients have been further developed over recent years. For orthopaedic treatment, a range of different interventions are offered: orthoses and special technical aids as well as injections for joints and tendons, or surgery. Surgical interventions cover joint preservation, restitution and arthrodeses. Improvements in equipment and surgical procedures also make minimally invasive interactions possible for rheumatoid diseases. Thus, postoperative morbidity has been reduced significantly. Improvement in function, reduction of pain and prevention of recurrent local inflammation are primary. Considering these aims, arthrodeses are restricted to special indications. Joint preservation and restitution are the predominant measures used. The various procedures are discussed.
17064873 Autoantibodies in rheumatoid arthritis: a review. 2006 Dec Emerging insights into the importance of B cells in the pathogenesis of rheumatoid arthritis (RA) as highlighted by the efficacy of B cell depletion is one factor that has contributed to the upsurge of interest in the potential role of autoantibodies both as disease markers and with respect to a pathogenic role. Since the initial description of rheumatoid factor (RF), a large number of both disease-specific and non-specific autoantibodies have been described in patients with RA including antibodies to type II collagen (CII), immunoglobulin binding protein (BiP) and antibodies directed at citrullinated peptides (anti-CCP) and other citrullinated proteins such as vimentin (anti-Sa) . Despite some overlap the serological profile of RA does appear to be distinct from other diseases such as SLE . Although the precise mechanisms responsible for the formation of these antibodies have not been well defined their presence must reflect the interaction between T and B cells believed to be relevant to the pathogenesis of RA. The specificity of the association of such factors as anti-CCP and anti-BiP with RA may reflect unique pathogenic events leading to the processing and presentation of the "cryptic self" . Ease of measurement and stability make autoantibodies attractive diagnostic and prognostic markers particularly in early disease when it may be difficult to distinguish self-limiting synovitis from persistent disease . The purpose of this article is to provide an overview of the current state of knowledge of the spectrum of autoantibodies thus far characterised in individuals with rheumatoid arthritis, and discuss their diagnostic, prognostic and pathogenetic relevance.
16357447 Clinical significance of anti-CCP antibodies in rheumatoid arthritis. 2005 Nov A number of novel autoantibodies have been recently described in rheumatoid arthritis (RA), and their clinical significance and possible pathogenic roles have been discussed. In particular, new autoantibodies to citrullinated proteins such as filaggrin and its circular form (cyclic citrullinated peptide: CCP) are especially noteworthy because of their high sensitivity and high specificity. There are many studies that anti-CCP antibodies may serve as a powerful serologic marker for early diagnosis of RA and prognostic prediction of joint destruction. Anti-citrullinated protein antibodies are locally produced in RA joints, and citrullinated proteins (most are fibrins) are localized in RA synovial tissue. This finding strongly suggests a possibility that local citrullination of intraarticular proteins might be the initial event leading to autoantibody production in RA. Genetic factors such as a gene polymorphism of the citrullinating enzyme, PADI, might be associated with the breakage of self-tolerance and induction of autoimmunity against citrullinated proteins.
15242865 A multicentre, randomised, double blind, placebo controlled phase II study of subcutaneous 2005 Jan OBJECTIVE: To assess the efficacy of interferon beta (IFN beta) in combination with methotrexate in treatment of patients with rheumatoid arthritis. METHODS: 209 patients with active rheumatoid arthritis, who had been on methotrexate for at least six months and at a stable dose for four weeks before study entry, were randomised in double blind fashion to receive placebo (0.05 ml or 0.5 ml), IFN beta 2.2 microg (0.05 ml), or IFN beta 44 microg (0.5 ml), given subcutaneously three times weekly for 24 weeks. The primary efficacy measure was a change in radiological scores at week 24. The secondary endpoint was the proportion of patients who met the ACR 20% improvement criteria at the end of the study. Synovial biopsy specimens were obtained before and after treatment from a subset of patients. Immunohistochemistry was used to detect the presence of inflammatory cells and the results were measured by digital image analysis. Collagen crosslinks were measured in urine at different times throughout the study. RESULTS: Analysis of radiological scores and clinical variable showed no changes in any of the groups, and there were no differences between the groups. On microscopic analysis of synovial tissue there was no significant change in the scores for infiltration by inflammatory cells after IFN beta treatment. Urinary levels of collagen crosslinks were unchanged between the treatment groups. CONCLUSIONS: At the doses tested, treatment with IFN beta three times weekly in combination with methotrexate did not have a clinical or radiological effect in patients with rheumatoid arthritis.
16937542 Development of ulcerative colitis during the course of rheumatoid arthritis: Association w 2006 Aug 28 A 56-year-old woman with a 29-year history of rheumatoid arthritis (RA) was admitted to the hospital, complaining of high fever, abdominal pain and severe bloody diarrhea. Colonoscopy revealed friable and edematous mucosa with spontaneous bleeding, diffuse erosions and ulcers extending from the rectum to the distal transverse colon. Histopathological findings of rectal biopsies were compatible with ulcerative colitis (UC). Being diagnosed as having severe active left-side UC, she was successfully treated with intravenous methylprednisolone followed by prednisolone and leukocytapheresis. Laboratory tests revealed low serum and saliva IgA levels, which might play a role in the development of UC. To our knowledge, this is the first case of UC occurring during the course of RA, accompanied by selective IgA deficiency.
17013822 Assessing utility values in rheumatoid arthritis: a comparison between time trade-off and 2006 Oct 15 OBJECTIVE: To compare the utility values and quality-adjusted life years (QALYs) obtained by the Time Trade-Off instrument (TTO) and the EuroQol-5D (EQ-5D) in patients with rheumatoid arthritis (RA); to analyze the association between utility values and Disease Activity Score 28 (DAS28) and Health Assessment Questionnaire (HAQ). METHODS: We conducted a longitudinal, prospective, 1-year study of RA patients selected randomly from 10 rheumatology clinics. TTO and EQ-5D were administered at 4 scheduled visits. RESULTS: The study sample comprised 300 RA patients (82% women, mean age 59 years, mean disease duration 10.3 years). A total of 260 patients completed both the TTO and the EQ-5D at baseline, and the mean +/- SD TTO scores were significantly higher than the EQ-5D scores (0.81 +/- 0.22 versus 0.53 +/- 0.35, P < 0.0001). The intraclass correlation coefficient (ICC) for the utility methods was 0.19. Data about changes in both TTO and EQ-5D scores during the study year were available in 163 patients. These changes tended to be larger in the TTO scores than the EQ-5D scores (mean +/- SD 0.05 +/- 0.25 versus -0.005 +/- 0.35, P = 0.054). The ICC for the mean changes in the utility scores was 0.24. Patients obtained a mean +/- SD of 0.04 +/- 0.20 QALYs based on TTO scores and 0.004 +/- 0.27 based on EQ-5D scores (P = 0.12). At baseline, the EQ-5D scores were highly correlated with the HAQ (r = -0.74) and moderately correlated with the DAS28 (r = -0.47), whereas the TTO correlated poorly with both the HAQ and DAS28. Correlation between the mean change in the EQ-5D and in the HAQ was moderate (r = -0.55). CONCLUSION: TTO and EQ-5D do not yield the same utility values. The results suggest that the EQ-5D is more representative of RA status than the TTO, a valuable conclusion when addressing economic evaluations in RA.
15761729 Digital radiogrammetry as a new diagnostic tool for estimation of disease-related osteopor 2005 Aug OBJECTIVES: To investigate the potential of a new osteogeometric technology based on digital X-ray radiogrammetry (DXR) as a diagnostic tool for quantification of severity-dependent osteoporosis, and to distinguish between inflammation-mediated and corticoid-induced variations of bone mineralisation in patients suffering from rheumatoid arthritis. METHODS: Ninety-six patients (duration of disease: <18 months) underwent retrospective calculations of bone mineral density (DXR-BMD) and metacarpal index (MCI) by DXR, which were calculated from plain radiographs of the non-dominant hand. For comparison, pQCT-calculated BMD (total, cortical-subcortical and trabecular partition of bone tissue) was done on the distal radius. Severity was classified using Ratingen Score by two independent radiologists, and divided into three main groups. In addition, the patients were separated into those with corticoid medication (n=44; 5 mg/day over a half year period) and a control group (n=52) without any corticoid therapy. RESULTS: Correlations between DXR-BMD and MCI versus pQCT parameters were all significant (0.36