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ID PMID Title PublicationDate abstract
20884656 Intensive lipid lowering in patients with rheumatoid arthritis and previous myocardial inf 2011 Feb OBJECTIVES: Documentation on secondary prevention with statins in RA patients with coronary heart disease (CHD) is limited, despite the increased risk of CHD in RA. Our objective was to describe the effect of statin treatment on lipid levels and cardiovascular disease (CVD) events in patients with RA who participated in the incremental decrease in endpoints through aggressive lipid lowering (IDEAL) study. METHODS: Patients with previous myocardial infarction (MI) were randomly assigned to atorvastatin 80 mg daily or simvastatin 20-40 mg daily and followed for 4.8 years. We focused on changes in lipid levels in the current exploratory analyses and used the composite secondary endpoint in the IDEAL study: any CVD event. Out of the 8888 patients in the IDEAL study, 87 had RA. RESULTS: RA patients had significantly lower baseline levels of total- and low-density lipoprotein (LDL) cholesterol than patients without RA; 4.8 + 1.0 vs 5.1 + 1.0 (P = 0.023) and 2.9 + 0.9 vs 3.1 + 0.9 mmol/l (P = 0.034) for total cholesterol and LDL, respectively. The lipid reductions with either simvastatin or atorvastatin were comparable. Cardiovascular events occurred in 23/87 (26.4%) of the RA patients compared with 2523/8801 (28.7%; P = 0.70) in the general IDEAL population. The occurrence of these events was not related to the duration of RA, age, gender or treatment assignment. CONCLUSION: Patients with RA and previous MI had comparable lipid-lowering effect and similar rates of cardiovascular events as those without RA, although the RA patients had lower baseline cholesterol levels than patients without RA.
20156946 Patient-derived joint counts are a potential alternative for determining Disease Activity 2010 May OBJECTIVE: To investigate the correlation between the Disease Activity Score using a 28-joint count (DAS28) based on physician-derived joint counts and the DAS28 based on patient-derived joint counts (Pt-DAS28) in rheumatoid arthritis (RA). METHODS: Data from a multicenter, open-label study investigating the immunogenicity of etanercept (ETN) were analyzed. ETN-naive patients with active RA received ETN 50 mg once weekly alone or with methotrexate (MTX). Joint counts were performed at baseline, Week 12, and Week 24 by the physician and patient independently. Patients received instruction in performing joint assessments. RESULTS: Of 447 patients enrolled (ETN, n = 218; ETN + MTX, n = 229), most were women (79%) and the mean age was 54.5 years. Correlation coefficients between DAS28 and Pt-DAS28 were > or = 0.57 at baseline, Week 12, and Week 24. At Week 24, 48%, 39%, and 12% of patients could be classified as having low, moderate, or high disease activity, respectively, using DAS28. Using Pt-DAS28, 43%, 39%, and 18% were similarly classified. Agreement in the category of disease activity classification occurred in 72% of patients (kappa = 0.55). At Week 24, 78% of patients using DAS28 and 72% of patients using Pt-DAS28 were classified as moderate or good European League Against Rheumatism responders. CONCLUSION: These results support the possible use of patient-derived tender and swollen joint counts to aid in the assessment of disease activity and clinical response in patients with RA.
20059371 Immigration check for neutrophils in RA lining: laminin alpha5 low expression regions act 2010 Mar OBJECTIVE: A correlation exists between the absence of alpha5-laminin and transit checkpoint fenestrations in vascular basement membranes. We hypothesized that similar laminin alpha5 low expression regions might exist in synovial lining, which, although lacking basement membrane, contains all basement membrane components in its interstitial matrix. METHODS: Laminin alpha4 and alpha5 chains and lactoferrin were stained using immunofluorescence and cathepsin G and neutrophil elastase using immunoperoxidase. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure laminin alpha4 and alpha5 mRNA copy numbers in cultured synovial fibroblasts, without/with tumour necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta). RESULTS: Laminin alpha4 and alpha5 chains were found in the intercellular matrix in synovial lining samples of trauma and revision total hip replacements. Laminin alpha5 was weaker in osteoarthritis (OA) and rheumatoid arthritis (RA), and RA synovial lining also contained local low expression areas. Double staining disclosed convergence of lactoferrin-degranulating neutrophils towards these laminin alpha5 low expression regions. In cultured OA synovial fibroblasts, laminin alpha5 mRNA decreased (p < 0.05) at 1 ng/mL TNFalpha and was not found at all in cultured resting or cytokine-stimulated RA fibroblasts. Degranulation of cathepsin G and neutrophil elastase was seen in neutrophils passing through blood vessels or synovial lining. CONCLUSIONS: Migrating neutrophils in RA seem to use laminin alpha5 chain low expression regions to exit synovial tissue to enter synovial fluid. Transmigrating neutrophils remodel the intercellular matrix by releasing their proteolytic granular contents to enhance these low expression checkpoints and/or to produce chemotactic stimuli. In RA fibroblasts this is facilitated by cytokine-mediated down-regulation or lack of laminin alpha5 synthesis.
19482674 Rheumatoid arthritis is caused by Proteus: the molecular mimicry theory and Karl Popper. 2009 Jun 1 Rheumatoid arthritis is a crippling and disabling joint disease affecting over 20 million people. It occurs predominantly in women and smokers, and affects the HLA-DR1/4 individuals who carry the "shared epitope" of amino acids EQRRAA. The cause of this disease was investigated by the methods of the philosopher of science Karl Popper who suggested that scientific research should be based on bold conjectures and critical refutations. The "Popper sequences" generate new facts which then change or alter the original problem. The new facts must then be explained by any new theory. Using the "molecular mimicry" model, it was found that Proteus bacteria possess an amino acid sequence ESRRAL in haemolysin which resembles the, shared epitope, and another sequence in urease which resembles type XI collagen. Antibodies to Proteus bacteria have been found in 14 different countries. It would appear that rheumatoid arthritis is caused by an upper urinary tract infection by Proteus bacteria. Anti-Proteus therapy should be assessed in the management of this disease separately or in conjunction with existing modalities of therapy.
20620945 Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cel 2010 Jun 25 Commensal microbes can have a substantial impact on autoimmune disorders, but the underlying molecular and cellular mechanisms remain largely unexplored. We report that autoimmune arthritis was strongly attenuated in the K/BxN mouse model under germ-free (GF) conditions, accompanied by reductions in serum autoantibody titers, splenic autoantibody-secreting cells, germinal centers, and the splenic T helper 17 (Th17) cell population. Neutralization of interleukin-17 prevented arthritis development in specific-pathogen-free K/BxN mice resulting from a direct effect of this cytokine on B cells to inhibit germinal center formation. The systemic deficiencies of the GF animals reflected a loss of Th17 cells from the small intestinal lamina propria. Introduction of a single gut-residing species, segmented filamentous bacteria, into GF animals reinstated the lamina propria Th17 cell compartment and production of autoantibodies, and arthritis rapidly ensued. Thus, a single commensal microbe, via its ability to promote a specific Th cell subset, can drive an autoimmune disease.
20535926 [Clinical study on active rheumatoid arthritis treated with simiao xiaobi decoction]. 2010 Mar OBJECTIVE: To observe the clinical efficacy and safety of Simiao Xiaobi Decoction (SXD) in treating active rheumatoid arthritis (RA) of humid pyretic toxic Bi-Zheng (HPTB) syndrome type. METHODS: One hundred and twenty RA patients were randomly assigned to 2 groups, 60 in the treatment group receiving SXD, and 60 in the control group receiving methotrexate, all were treated for 12 weeks. Clinical efficacy in patients was evaluated, referring to the criteria recommended by European League Against Rheumatoism (EULAR), in terms of effective rate, main symptoms, signs, scoring on symptom/sign by Chinese medicine scale and DAS28, physical and chemical indices, long-term outcome of patients and the average therapeutic effect initiating time. Meantime, the adverse reaction was recorded. RESULTS: The study was completed in 103 patients, 52 in the treated group and 51 in the control group. According to a per-protocol analysis, the effective rate was better in the treatment group than in the control group with marked difference in terms of Chinese and Western medicine respectively (92.3% vs 70.6% and 86.5% vs 62.7%, P<0.05). Superiorities in the treatment group were also seen in the improvements of main symptoms and signs, symptom/sign scores, DAS28 scores, and long-term outcome. Moreover, the average therapeutic effect initiating time was shorter (5.31 +/- 0.36 weeks vs 8.28 +/- 0.45 weeks), while the incidence of adverse reaction was less in the treatment group than in the control group (6.7% vs 43.3%, P<0.05). CONCLUSION: SXD can improve the joint symptoms and general condition of RA patients of HPTB type with shorter initiating time and less adverse reaction.
19734132 Effects of denosumab on bone mineral density and bone turnover in patients with rheumatoid 2010 May OBJECTIVES: To report results of subgroup analyses of bone mineral density (BMD) and bone turnover markers from a randomised, double-blind, placebo-controlled, phase II study of denosumab, an investigational RANKL inhibitor, in patients with rheumatoid arthritis (RA) concurrently receiving treatment with bisphosphonates or glucocorticoids. METHODS: Patients received subcutaneous placebo (n=75), denosumab 60 mg (n=71) or denosumab 180 mg (n=72) at baseline and 6 months. Assessments included dual x-ray absorptiometry scans of the lumbar spine and hip, and determination of levels of serum type I C-telopeptide (sCTx-I) and serum procollagen 1N-terminal peptide (P1NP). RESULTS: Denosumab treatment increased mean lumbar spine and hip BMD and reduced sCTx-I and P1NP compared with placebo through 12 months, regardless of baseline BMD or marker levels or concomitant bisphosphonate or glucocorticoid use. CONCLUSIONS: This study extends evidence that denosumab increases BMD and reduces bone turnover in patients with RA and may provide a new therapeutic option for reducing systemic bone loss in patients with RA.
19671821 The OMERACT ultrasound task force -- Advances and priorities. 2009 Aug This article reports the most recent work of the OMERACT Ultrasound Task Force (post OMERACT 8) and highlights of future research priorities discussed at the OMERACT 9 meeting, Kananaskis, Canada, May 2008. Results of 3 studies were presented: (1) assessing intermachine reliability; (2) applying the scoring system developed in the hand to other joints most commonly affected in rheumatoid arthritis (RA); and (3) assessing interobserver reliability on a deep target joint (shoulder). Results demonstrated good intermachine reliability between multiple examiners, and good applicability of the scoring system for the hand on other joints (including shoulder). Study conclusions were discussed and a future research agenda was generated, notably the further development of a Global OMERACT Sonography Scoring (GLOSS) system in RA, emphasizing the importance of testing feasibility and added value over standard clinical variables. Future disease areas of importance to develop include a scoring system for enthesitis and osteoarthritis.
21303493 Type I interferon in organ-targeted autoimmune and inflammatory diseases. 2010 A significant role for IFNα in the pathogenesis of systemic lupus erythematosus is well supported, and clinical trials of anti-IFNα monoclonal antibodies are in progress in this disease. In other autoimmune diseases characterized by substantial inflammation and tissue destruction, the role of type I interferons is less clear. Gene expression analysis of peripheral blood cells from patients with rheumatoid arthritis and multiple sclerosis demonstrate an interferon signature similar to but less intense than that seen in patients with lupus. In both of those diseases, presence of the interferon signature has been associated with more significant clinical manifestations. At the same time, evidence supports an anti-inflammatory and beneficial role of IFNβ locally in the joints of patients with rheumatoid arthritis and in murine arthritis models, and many patients with multiple sclerosis show a clinical response to recombinant IFNβ. As can also be proposed for type I diabetes mellitus, type I interferon appears to contribute to the development of autoimmunity and disease progression in multiple autoimmune diseases, while maintaining some capacity to control established disease - particularly at local sites of inflammation. Recent studies in both rheumatoid arthritis and multiple sclerosis suggest that quantification of type I interferon activity or target gene expression might be informative in predicting responses to distinct classes of therapeutic agents.
20498203 Lack of understanding in fibromyalgia and rheumatoid arthritis: the Illness Invalidation I 2010 Nov BACKGROUND: Patients with rheumatic diseases may face 'discounting' (denying and patronising) or 'lack of understanding' because of having symptoms without external clinical signs, but instruments to assess such invalidation experiences are lacking. OBJECTIVES: To develop and evaluate the Illness Invalidation Inventory (3*I), to compare invalidation experiences of two groups of patients who differ in visual signs and laboratory findings-rheumatoid arthritis (RA) and fibromyalgia-and to examine the association of invalidation with health status. METHODS: A questionnaire (eight items with respect to five sources: spouse, family, medical professionals, work environment and social services) was constructed. It was completed by 142 patients with RA and 167 patients with fibromyalgia. RESULTS: Principal axis factoring with oblimin rotation yielded two factors with high internal consistency (α>0.70): 'discounting' (five items) and 'lack of understanding' (three items). Patients with fibromyalgia experienced significantly more discounting and lack of understanding from their family, medical professionals, colleagues and social services than did patients with RA. Both patient groups experienced more invalidation from social services, colleagues and family than from medical professionals and spouses. More discounting and lack of understanding correlated with poorer mental well-being and social functioning in both patient groups. Discounting correlated with more physical disability and pain in patients with RA. CONCLUSIONS: The 3*I is a brief, reliable instrument for assessing patients' perceptions of invalidation from different sources, which differ between patient groups and are associated with health status. Future validation research should clarify the clinical impact of invalidation on treatment adherence and outcome.
19812889 Cutaneous vasculitis induced by TNF inhibitors: a report of three cases. 2010 Feb We describe 3 rheumatoid arthritis (RA) patients with anti-tumor necrosis factor (TNF) therapy-induced cutaneous vasculitis. Two cases were induced by infliximab and the other, in whom cutaneous vasculitis was found early at the start of therapy, was induced by etanercept. Skin biopsy was obtained in 2 patients, with histology-proven leukocytoclastic vasculitis. One patient spontaneously improved after cessation of the TNF inhibitor. Two patients required oral corticosteroid, the efficacy of which was observed to be excellent and rapid.
20345978 Cyclophilin-CD147 interactions: a new target for anti-inflammatory therapeutics. 2010 Jun CD147 is a widely expressed plasma membrane protein that has been implicated in a variety of physiological and pathological activities. It is best known for its ability to function as extracellular matrix metalloproteinase inducer (hence the other name for this protein, EMMPRIN), but has also been shown to regulate lymphocyte responsiveness, monocarboxylate transporter expression and spermatogenesis. These functions reflect multiple interacting partners of CD147. Among these CD147-interacting proteins cyclophilins represent a particularly interesting class, both in terms of structural considerations and potential medical implications. CD147 has been shown to function as a signalling receptor for extracellular cyclophilins A and B and to mediate chemotactic activity of cyclophilins towards a variety of immune cells. Recent studies using in vitro and in vivo models have demonstrated a role for cyclophilin-CD147 interactions in the regulation of inflammatory responses in a number of diseases, including acute lung inflammation, rheumatoid arthritis and cardiovascular disease. Agents targeting either CD147 or cyclophilin activity showed significant anti-inflammatory effects in experimental models, suggesting CD147-cyclophilin interactions may be a good target for new anti-inflammatory therapeutics. Here, we review the recent literature on different aspects of cyclophilin-CD147 interactions and their role in inflammatory diseases.
19379704 Evaluation of a biosensor immunoassay for simultaneous characterization of isotype and bin 2009 Jul 15 This article describes the simultaneous Biacore analysis of human anti-human antibodies (HAHAs) with respect to the binding region and the isotype by a combination of 11 single measurements per sample. The multiplexing single assay setup made efficient use of the four parallel flow cells on one biosensor chip by immobilization of full-length antibody and its constant (Fc) and antigen binding (Fab) fragments for differential binding analysis of anti-drug antibodies (ADAs). Thereby, a complete time-specific immunogenicity profile (intensity, isotype, specificity, and kinetics) of a patient could be obtained by assessing the response patterns of serially collected samples analyzed in a single measurement run. The use of functionally active standard conjugates allowed control of the assay performance throughout the whole procedure. The positive control standard conjugates mimicking polyclonal human ADAs of different isotypes were obtained by conjugating polyclonal rabbit antibodies against the therapeutic antibody to human immunoglobulin (Ig) M, IgG, or IgE. In this article, the qualification of the assay is demonstrated and the application of the methodology to six representative rheumatoid arthritis patients treated with the therapeutic humanized IgG1 antibody tocilizumab (anti-IL-6R) is shown to illustrate the versatility of the assay. The presented method allows one to differentiate specific ADAs from drug-unspecific responses (e.g., rheumatoid factors). In addition, the method can be used to discriminate between isotype responses of the IgG, IgM, and IgE types and, thereby, allows one to describe the time course of specific ADA formation and its disappearance on the single patient level.
20637072 The delivery of evidence-based preventive care for older Americans with arthritis. 2010 INTRODUCTION: Previous research suggests patients with rheumatoid arthritis (RA) may receive suboptimal care with respect to preventive tests and services. We evaluated the proportion of older Americans with RA, psoriatic arthritis (PsA), and osteoarthritis (OA) receiving these services and the specialty of the providers delivering this care. METHODS: Using data from 1999 to 2006 from the Medicare Chronic Conditions Warehouse, we identified persons age >/= 65 in the national 5% sample. Over the required five-year observation period, we identified tests and services recommended for older adults and the associated healthcare provider. Services of interest included dual energy x-ray absorptiometry (DXA), influenza and pneumococcal vaccination, hyperlipidemia lab testing, mammography and colonoscopy. RESULTS: After accounting for the sampling fraction, we identified 141,140 RA, 6,300 PsA, and 770,520 OA patients eligible for analysis. Over five years, a majority of RA, PsA, and OA patients were tested for hyperlipidemia (84%, 89% and 87% respectively) and received DXA (69%, 75%, and 52%). Only approximately one-third of arthritis patients received pneumococcal vaccination; 19% to 22% received influenza vaccination each year. Approximately 20% to 35% of arthritis patients never underwent mammography and colonoscopy over five years. Concomitant care from both a rheumatologist and a primary care physician was significantly associated with a greater likelihood of receiving almost all preventive tests and services. CONCLUSIONS: Among older Americans on Medicare, the absolute proportion of persons with arthritis receiving various recommended preventive services and screening tests was substantially less than 100%. Improved co-management between primary care and arthritis physicians may in part improve the delivery of preventive care for arthritis patients, but novel systematic interventions in this area are needed.
20361950 Dipeptidyl peptidase-IV in synovial fluid and in synovial fluid mononuclear cells of patie 2010 Aug 5 BACKGROUND: Dipeptidyl peptidase-IV (DPP-IV) enzymatic activity controls biological halftime of multiple local mediators. Its deregulation is associated with pathogenesis of several autoimmune diseases, including rheumatoid arthritis (RA). Although DPP-IV is the canonical representative of the group, a number of other proteins have been shown to have similar enzymatic activity. This study was aimed to identify the molecular source of DPP-IV activity in synovial fluid (SF) and fluid mononuclear cells (FMNC) in patients with RA and osteoarthritis (OA). In addition, the association of DPP-IV and the concentration of stromal cell-derived factor-1alpha (SDF), DPP-IV substrate, were evaluated. METHODS: DPP-IV activity was measured by the kinetic fluorimetric method. The expression of studied molecules in FMNC and their concentrations in SF were assayed using flow cytometry and ELISA respectively. RESULTS: DPP-IV activity in SF, dominantly derived from the canonical DPP-IV, does not significantly differ between RA and OA. However, a significantly lower DPP-IV activity and expression in FMNC was found in RA as opposed to OA patients. Negative correlation between SDF concentration in SF and the relative amount of CD3+CD26+ cells was observed. CONCLUSIONS: We report decreased presence of DPP-IV/CD26 in CD3+ FMNC in RA, which also may participate on impaired balance of SDF concentration in SF.
18647852 Residual inflammation after rituximab treatment is associated with sustained synovial plas 2009 Jun OBJECTIVE: To investigate the clinical effects of rituximab treatment in relation to immunological effects of rituximab on tissue-derived B lineage cells and repopulation of circulating B cells. METHODS: A total of 24 patients with rheumatoid arthritis (RA) were treated with 2x1000 mg rituximab and assessed clinically at 4, 12, 18 and 24 weeks using a 44-joint Disease Activity Score (DAS(44)). Synovial biopsies were analysed with immunohistochemistry at baseline and 12 weeks after treatment. Peripheral blood mononuclear cells were analysed by high sensitivity flow cytometry at all timepoints. RESULTS: In this study, a cohort of patients was dichotomised according to those who achieved a low disease activity score (DAS(44)<2.4: LoA group) and those with persistent disease activity (DAS(44)>2.4: HiA group) at any time after rituximab treatment. At baseline, the low activity (LoA) group had significantly lower DAS(44) scores (median 3.33, range 2.84 to 4.23) than the high activity (HiA) group (median 3.73, range 3.03 to 5.23; p = 0.022) and significantly less histological inflammation in synovium (median 6.7, range 1 to 15 vs 16.6, range 4 to 22; p = 0.036). DAS(44) scores before and after rituximab treatment were associated with synovial infiltration of CD79a+ CD20- B cells, morphologically resembling plasma cells. Following treatment with rituximab, the LoA group had significantly reduced repopulation of circulating pre-switched IgD+ B cells (median 0.044%, range 0.002 to 0.66 vs 0.45%, range 0.07 to 9.47; p = 0.006) and post-switched CD27+ B cells (median 0.17%, range 0.04 to 0.39 vs 0.67, range 0.08 to 2.05; p = 0.005) compared to the HiA group. CONCLUSION: The present study demonstrated that a low disease activity state following rituximab was associated with reduced infiltration of CD79a+ CD20- plasma cells in synovium and reduced B cell repopulation.
19331709 Modeling the cost-effectiveness of treatment of rheumatoid arthritis with rituximab using 2009 Apr OBJECTIVES: The aim of this study was to estimate the cost-effectiveness of rituximab in patients not responding adequately to the first tumor necrosis factor (TNF) inhibitor using a model constructed to predict resource consumption and health outcomes in a population-based registry of biological treatments in Southern Sweden (SSATG). METHODS: The model was developed as a discrete event simulation model, using SSATG data for the years 1999-2007. The data set included 1,903 patients with complete data on treatments (up to three treatment lines), functional capacity (HAQ), disease activity (DAS28), and utility (EQ-5D). Resource consumption was based on a regular population-based survey of patients in Southern Sweden. Rituximab was incorporated as second line treatment, using effectiveness data for the active group (N = 311) in a clinical trial comparing rituximab to placebo (REFLEX). It is thus compared to the mix of second line biologics used in SSATG. The analysis starts after failure of the first TNF inhibitor. Results are reported as costs (2008 euro) per quality-adjusted life-year (QALY; both discounted 3 percent), for the societal perspective in Sweden. RESULTS: Total costs in the rituximab strategy are estimated at 401,100 euro compared with 403,000 euro in the TNF-inhibitor arm. Total QALYs are 5.98 and 5.78, respectively. The findings were found to be robust in extensive sensitivity analysis. CONCLUSIONS: In our model, a strategy where rituximab is used as second line treatment after failure of the first TNF inhibitor provides a small saving (essentially due to the lower price of rituximab) and a QALY gain (due to better effect than the mix of second line TNF inhibitors).
19280942 [Recent progress in clinical trials for rheumatic diseases]. 2009 Mar Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that causes significant morbidity and mortality. RA patients should be started with DMARD represented by methotrexate (MTX) as early as possible. However, even use of MTX often fails to control disease activity and to prevent structural damage and, thereby, more effective treatment strategies are needed. Since TNF-alpha and IL-6 play a pivotal role in the pathological processes of RA, biologics targeting these cytokines with MTX, have revolutionized the treatment of RA, producing significant improvement in clinical, radiographic and functional outcomes not seen previously. However, even with these drugs the frequency and degree of responses are restricted. Therefore, new agents targeting cell surface molecules which are involved in cellular interaction and/or signaling on immune cells have been emerging, in order to increase response rates and to achieve high frequencies of remission or even cure. Two biologics abatacept, a CTLA4-Ig fusion protein, and rituximab, an anti-CD20 antibody, were launched in US and EU for the treatment of RA and many biologics are under the clinical trials from the similar concept. Thus, certain biologics have brought about paradigm shift in the treatment of rheumatic diseases, but an economical issue remains unsolved. In order to overcome the concern, low molecular weight chemical products have been rethought. Not a few agents targeting intracellular activation signaling in immune cells such as Jak and Syk are under clinical examinations and some of them appear to show wonderful results, which are comparable to biologics in the context of the treatment of rheumatic diseases. The prospects are here.
20436079 Uncoupling of collagen II metabolism in newly diagnosed, untreated rheumatoid arthritis is 2010 Jun OBJECTIVE: To investigate the relationship between markers of collagen II synthesis and degradation with disease activity measures, autoantibodies, and radiographic outcomes in a 4-year protocol on patients with early rheumatoid arthritis (RA) who are naïve to disease-modifying antirheumatic drugs. METHODS: One hundred sixty patients with newly diagnosed, untreated RA entered the Cyclosporine, Methotrexate, Steroid in RA (CIMESTRA) trial. Disease activity and radiograph status were measured at baseline and 4 years. The N-terminal propeptide of collagen IIA (PIIANP) and the cross-linked C-telopeptide of collagen II (CTX-II) were quantified at baseline by ELISA. PIIANP was also assayed at 2 and 4 years. Anticyclic citrullinated peptide (anti-CCP) was recorded at baseline. An uncoupling index for cartilage collagen metabolism was calculated from PIIANP and CTX-II measurements. RESULTS: PIIANP was low at diagnosis and 4 years on (p < 0.001), irrespective of treatment and disease activity. PIIANP was lowest in anti-CCP positive patients (p = 0.006), and there was a negative correlation between PIIANP and anti-CCP titers (rho = -0.25, p 0.002). CTX-II was increased (p < 0.001) and correlated positively with disease activity and radiographic progression, but not with anti-CCP (p = 0.93). The uncoupling index was not superior to CTX-II in predicting radiographic changes. CONCLUSION: These results suggest that cartilage collagen formation and degradation are unbalanced when RA is diagnosed. The different associations of collagen II anabolism (PIIANP) and collagen II degradation (CTX-II) with anti-CCP, synovitis, and radiographic progression indicate that at this early stage of RA, cartilage collagen degradation is mainly driven by synovitis, while anti-CCP antibodies may interfere with cartilage regeneration by inhibiting collagen IIA formation. Trial registration j.nr NCT00209859.
19640853 Lack of effect of TNFalpha blockade therapy on circulating adiponectin levels in patients 2010 Sep BACKGROUND: Adiponectin is an anti-inflammatory and potentially antiatherogenic molecule. Some recent reports suggest that tumour necrosis factor alpha (TNFalpha) blockade therapy increases circulating adiponectin levels, but data are sparse and inconsistent. METHODS: Data from a double-blind placebo controlled study of onercept in 126 patients with psoriatic arthritis (PsA) and from pre- and post-adalimumab treatment in 171 patients with rheumatoid arthritis (RA) were used to examine the effect of TNFalpha blockade therapy on adiponectin. RESULTS: Despite expected associations of adiponectin with gender and baseline high-density lipoprotein cholesterol and triglyceride, adiponectin levels did not change over time with TNFalpha blockade therapy in either group. The mean+/-SD absolute change in adiponectin levels was -0.23+/-4.6 microg/ml in patients with PsA treated with combined onercept 50 mg and onercept 100 mg (vs placebo, p=0.60) and 0.28+/-3.23 microg/ml in patients with RA treated with adalimumab (vs baseline, p=0.66). CONCLUSION: These results do not support a significant effect of TNFalpha blockade therapy on circulating adiponectin levels in patients with autoimmune disease.