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ID PMID Title PublicationDate abstract
23242182 Investigation of rheumatoid arthritis genetic susceptibility markers in the early rheumato 2013 Feb OBJECTIVE: The TRAF1 genetic region conferring susceptibility to rheumatoid arthritis (RA) has been reported to associate with radiological damage. We aimed to test RA genetic susceptibility markers for association with a continuous measure of radiological damage over time using longitudinal modeling techniques. METHODS: Sixty-seven RA susceptibility variants were genotyped in 474 patients in the Early Rheumatoid Arthritis Study (ERAS) using Sequenom MassArray technology. Correlation between genetic markers and Larsen score was assessed longitudinally using zero-inflated negative binomial regression to include repeat measurements in the same individual at different timepoints. Genetic markers associated with radiological damage in ERAS were tested using the same modeling techniques on previously published data from the Norfolk Arthritis Register (NOAR). RESULTS: The single marker associated longitudinally with Larsen score in ERAS (p = 0.02) and in NOAR (p = 0.04) was rs2900180 at the TRAF1 locus. Analysis of individual timepoints in ERAS showed that rs2900180 displays its effect primarily on the extent of Larsen score early in the disease course. Combined longitudinal analysis of the 2 cohorts suggests further association of several loci with Larsen score (KIF5A, PTPN22, AFF3, TAGAP) and therefore a significant accumulation of RA severity markers among RA susceptibility markers (p = 0.016). CONCLUSION: The marker rs2900180 is associated with the extent of radiological damage in the ERAS cohort. This represents the second independent study correlating rs2900180 at the TRAF1 locus with radiological severity in RA. Replication in a large dataset is required to establish the role of other RA susceptibility loci in disease severity.
24482016 Anatomical location of erosions at the metatarsophalangeal joints in patients with rheumat 2014 May OBJECTIVE: The aim of this study was to identify the anatomical location of erosions at the MTP joints in patients with RA using high-resolution 3T MRI. METHODS: In 24 patients with RA, the more symptomatic forefoot was imaged using 3T MRI. T1-weighted, intermediate-weighted and T2-weighted fat-suppressed sequences were acquired through the MTP joints, together with three-dimensional volumetric interpolated breath-hold examination (3D VIBE) and T1-weighted fat-suppressed post-gadolinium contrast sequences. Images were scored for bone erosion in the distal and proximal part of the MTP joints using the RA MRI scoring (RAMRIS) system. The base of the proximal phalanx and the head of the metatarsal were divided into quadrants to determine the location of erosions (octants) in the dorsal-medial, dorsal-lateral, plantar-medial and plantar-lateral regions. RESULTS: Seventeen females and seven males with a mean age of 55.5 years and disease duration of 10.6 years (range 0.6-36) were included. Eighteen patients were RF positive, the mean 44-joint DAS for CRP and ESR (DAS44CRP and DAS44ESR) were 2.5 (s.d. 0.8) and 2.6 (s.d. 0.9), respectively. In this cohort of patients with RA, irrespective of MTP joint location, octants located in the proximal part (metatarsal) of the joint and the plantar aspect of the joint were more eroded. CONCLUSION: This is the first study to report the anatomical location of erosions at the MTP joints in patients with RA. We noted that erosions were more commonly seen on the plantar aspect of the metatarsal head in RA, supporting the hypothesis of a relationship between biomechanical demands and bone changes in the forefoot.
24701713 [Best practice use of corticosteroids in rheumatoid arthritis]. 2014 Mar 12 Since the 50s oral glucocorticoids including prednisone are used in the management of rheumatoid arthritis due to their efficacy and the limited availability of the other treatments in the past. Thereafter numerous studies confirmed the usefulness of prednisone in controlling clinical inflammatory manifestations and the progression of radiographic damage. Sixty years later the position of prednisone in the treatment strategy of rheumatoid arthritis is still controversial, considering the presence of numerous side effects and the availability of other effective treatments. If prednisone can be reasonably used in some situations either as bridging therapy in combination with other treatments or in case of flare, its long-term use should be avoided.
23137833 Influence of resveratrol on rheumatoid fibroblast-like synoviocytes analysed with gene chi 2013 Feb 15 Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that primarily attacks joints and is therefore a common cause of chronic disability and articular destruction. The hyperplastic growth of RA-fibroblast-like synoviocytes (FLSs) and their resistance against apoptosis are considered pathological hallmarks of RA. The natural antioxidant resveratrol is known for its antiproliferative and pro-apoptotic properties. This study investigated the effect of resveratrol on RA-FLS. RA-FLS were isolated from the synovium of 10 RA patients undergoing synovectomy or joint replacement surgery. RA-FLS were first stressed by pre-incubation with interleukin 1beta (IL-1β) and then treated with 100 μM resveratrol for 24h. In order to evaluate the influence of resveratrol on the transcription of genes, a Gene Chip Human Gene 1.0 ST Array was applied. In addition, the effect of dexamethasone on proliferation and apoptosis of RA-FLS was compared with that of resveratrol. Gene array analysis showed highly significant effects of resveratrol on the expression of genes involved in mitosis, cell cycle, chromosome segregation and apoptosis. qRT-PCR, caspase-3/7 and proliferation assays confirmed the results of gene array analysis. In comparison, dexamethasone showed little to no effect on reducing cell proliferation and apoptosis. Our in vitro findings point towards resveratrol as a promising new therapeutic approach for local intra-articular application against RA, and further clinical studies will be necessary.
24119062 Potential of a 70 kDa IL-10-like factor in synovial fluid from rheumatoid arthritis patie 2016 Feb AIM: To elucidate the role of polymorphonuclear leukocytes (PMNs) in joint destruction during the inflammatory process in rheumatoid arthritis (RA) as related to superoxide generation. METHODS: Superoxide generation by human peripheral PMNs was measured by using a water-soluble formazan dye, 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium salt, under PMN stimulation with N-formylmethionyl-leucyl-phenylalanine (fMLP) and cytochalasin B. Factors in synovial fluids (SF) from RA patients that may augment PMN superoxide generation were characterized via high-performance liquid chromatography and isoelectric focusing. RESULTS: The formazan dye allowed measurement of superoxide generated in the xanthine-xanthine oxidase system and by PMNs stimulated by cytochalasin B and fMLP in the presence of the intermediate electron transporter phenazine methosulfate. By using chromatography and electrophoresis, an RA-SF protein with an apparent molecular size of 70 kDa and an isoelectric point of 8.3 was isolated and was demonstrated to increase superoxide generation by PMNs. The factor was heat-labile and susceptible to protease treatment. This enhancing activity of the factor was absorbed by human PMNs and was somewhat immunoadsorbed with a specific monoclonal antibody against interleukin (IL)-10. CONCLUSION: The 70-kDa protein factor in RA-SF increased superoxide generation by human PMNs, which suggests the possibility of its being related to IL-10. This factor may have a pathological role in RA joint destruction caused by PMNs and coinciding with rheumatoid inflammation, which suggests that PMNs, via superoxide generation, play an important role in RA joint destruction. IL-10 therefore likely has biological activity toward PMNs during synovial inflammatory chain reactions in RA.
24061933 Comparison of the 1987 American College of Rheumatology and the 2010 American College of R 2014 Mar Performance of rheumatoid arthritis (RA) classification by the 2010 American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria, compared to the 1987 ACR criteria, has not been assessed in population-based cohorts in which disease identification is by mailed questionnaire. Women followed in the Nurses' Health Study and Nurses' Health Study II cohorts self-reported new doctor-diagnosed RA on biennial questionnaires. Two RA experts reviewed medical records of 128 new RA self-reports to obtain individual 1987 and 2010 criteria and arrived at a consensus opinion. We compared agreement in classification by the two criteria sets (kappa), and calculated sensitivity and specificity, with reviewers' opinion as gold standard. Ninety-eight (77%) participants were classified as RA by reviewers' consensus opinion; 98 (77%) fulfilled 1987 criteria, while 79 (63%) fulfilled 2010 criteria. Seventy-two (56%) were classified as RA by both sets, 21 (16%) by neither, 26 (20%) by only 1987 criteria, and 9 (7%) by only 2010 criteria. Kappa for concordance was 0.36 (95% CI 0.20-0.53). Compared to reviewer's opinion, sensitivity and specificity were 0.93 and 0.77 for 1987 criteria, and 0.79 and 0.87 for 2010 criteria. Participants fulfilling 1987 criteria only were more likely to be seronegative. In these prospective population-based cohorts, significant discordance between 1987 ACR and 2010 ACR/EULAR criteria for classifying RA exists. Using the 2010 ACR/EULAR criteria alone had decreased sensitivity, and seronegative RA cases would be excluded in particular. Combined use of both will be necessary to maximize inclusion and allow sensitivity analyses.
24757143 Endogenous myeloperoxidase is a mediator of joint inflammation and damage in experimental 2014 Apr OBJECTIVE: Myeloperoxidase (MPO) is implicated as a local mediator of tissue damage when released extracellularly in many chronic inflammatory diseases. The purpose of this study was to explore the role of endogenous MPO in experimental rheumatoid arthritis (RA). METHODS: K/BxN serum-transfer arthritis was induced in C57BL/6 wild-type (WT) and MPO knockout (MPO(-/-) ) mice, and disease development was assessed. MPO activity was measured in joint tissues from mice with or without K/BxN arthritis. Collagen-induced arthritis (CIA) was induced in WT and MPO(-/-) mice, and disease development and immune responses were examined. MPO expression was assessed in synovial biopsy samples from patients with active RA, and the effect of MPO on synovial fibroblasts was tested in vitro. RESULTS: MPO was up-regulated in the joints of mice with K/BxN arthritis, and MPO deficiency attenuated the severity of the disease without affecting circulating cytokine levels. In CIA, MPO(-/-) mice had enhanced CD4+ T cell responses and reduced frequency of regulatory T cells in the lymph nodes and spleen, as well as augmented interleukin-17A and diminished interferon-γ secretion by collagen-stimulated splenocytes, without an effect on circulating anticollagen antibody levels. Despite enhanced adaptive immunity in secondary lymphoid organs, CIA development was attenuated in MPO(-/-) mice. Intracellular and extracellular MPO was detected in the synovium of patients with active RA, and human MPO enhanced the proliferation and decreased the apoptosis of synovial fibroblasts in vitro. CONCLUSION: MPO contributes to the development of arthritis despite suppressing adaptive immunity in secondary lymphoid organs. This suggests distinct effects of local MPO on arthritogenic effector responses.
23322466 Tocilizumab inhibits structural joint damage and improves physical function in patients wi 2013 Feb OBJECTIVE: To assess radiographic progression, physical function, clinical disease activity, and safety in patients with rheumatoid arthritis (RA) who had inadequate response to methotrexate (MTX) and who were treated with tocilizumab-MTX or MTX during Year 2 of a 2-year study. METHODS: During Year 1, patients were randomized to placebo-MTX, 4 mg/kg tocilizumab-MTX, or 8 mg/kg tocilizumab-MTX. During Year 2, patients continued the initial double-blind treatment or switched to open-label 8 mg/kg tocilizumab-MTX. Co-primary endpoints at Week 104 were mean change from baseline in Genant-modified Total Sharp Score (GmTSS) and adjusted mean area under the curve (AUC) for change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI). Signs and symptoms of RA and safety were also evaluated. RESULTS: At Week 104, mean change from baseline in GmTSS was significantly lower for patients initially randomized to tocilizumab-MTX 4 mg/kg (0.58; p = 0.0025) or 8 mg/kg (0.37; p < 0.0001) than for patients initially randomized to placebo-MTX (1.96). Adjusted mean AUC of change from baseline in HAQ-DI was also significantly lower in patients initially randomized to tocilizumab-MTX 4 mg/kg (-287.5; p < 0.0001) or 8 mg/kg (-320.8; p < 0.0001) than in patients initially randomized to placebo-MTX (-139.4). Signs and symptoms of RA were maintained or showed improvement. No new safety signals were noted. CONCLUSION: Compared with placebo-MTX, tocilizumab-MTX significantly inhibited structural joint damage and improved physical function in patients with RA who previously had inadequate response to MTX. An extension of this study is continuing and will provide additional longterm efficacy and safety data. National Clinical Trials registry NCT00106535.
24459221 Changes in physical activity measured by accelerometry following initiation of DMARD thera 2014 May OBJECTIVE: The aim of this study was to assess changes in habitual physical activity levels in response to DMARD therapy in RA patients. METHODS: Eighteen drug-naive RA patients were prospectively assessed at baseline and following 3 months of DMARD therapy for habitual physical activity by accelerometry, disease activity using the clinical disease activity index (CDAI) and functional disability using the modified HAQ (mHAQ). Baseline physical activity was also compared with an equal number of healthy control participants matched for age, sex and BMI. RESULTS: Following 3 months of DMARD therapy, in parallel with significant improvements in CDAI scores (P < 0.001) and HAQ scores (P < 0.001), accelerometry measures in the RA cohort showed that the average activity counts in sedentary thresholds decreased (P = 0.012), while average activity counts within higher-intensity thresholds increased (P = 0.039). Multiple regression analysis showed that the change in moderate activity was associated with a decrease in CRP (β = - 0.922, P = 0.026) while the decrease in sedentary activity and increase in moderate activity were associated with decreased morning stiffness of the joints (β = 0.694, P = 0.035 and β = -0.927, P = 0.024, respectively). At baseline, RA patients were less physically active than control participants in the morning (P = 0.048) and in the late afternoon (P = 0.016), but these diurnal differences were no longer significant after the DMARD intervention. CONCLUSION: These findings suggest that accelerometry may potentially be a viable objective method of assessing changes in physical disability in response to various disease-modifying drugs.
23607571 Repair of erosions in patients with rheumatoid arthritis treated with etanercept: magnetic 2013 OBJECTIVES: To monitor repair of bone erosions using magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) during etanercept combination therapy. METHOD: The study population comprised 29 RA patients [biologic-naïve, 28-joint Disease Activity Score (DAS28) ≥ 3.2] starting etanercept combination therapy with disease-modifying anti-rheumatic drugs (DMARDs) and completing the 1-year study period with the same treatment. Clinical and laboratory assessments and MRI of the hand were performed at baseline and at 1 year. MRI findings were scored by two readers using the Rheumatoid Arthritis MRI Scoring System (RAMRIS). Both readers were blind to the chronological order of the MRI scans, the identity of the patients, and clinical and other imaging data. Tenosynovitis was also scored. The intra- and inter-reader intraclass correlation coefficients (ICCs) were calculated, along with the sensitivity to change with the smallest detectable difference (SDD). Repair of erosions was defined as a RAMRIS score of at least 1 point lower than baseline. RESULTS: The mean RAMRIS score for erosions did not change but all other inflammatory MRI parameters decreased significantly. In 19 patients, the RAMRIS score for erosions remained unchanged after 1 year. In five patients the score decreased after 1 year, although the decrease exceeded the SDD in only one patient (3.4%). CONCLUSIONS: Etanercept combined with DMARDs stopped the progression of erosions, as measured by the RAMRIS, in 82.8% of our RA patients and occasional repair of bone erosions occurred after 1 year of treatment.
23505228 The 158VV Fcgamma receptor 3A genotype is associated with response to rituximab in rheumat 2014 Apr OBJECTIVE: The polymorphism 158V/F of Fc fragment of IgG (FCGR) type 3A may influence the response to rituximab (RTX) in rheumatoid arthritis (RA). We investigated the FCG3A polymorphism in a large cohort of RA patients treated with RTX, also by considering the possible loss of response from month +4 to +6 after RTX and the presence of established predictors of response. METHODS: The study analysed 212 RA patients. European League Against Rheumatism (EULAR) response was evaluated at months +4 and +6 after the first RTX infusion. The FCGR3A polymorphism was analysed by PCR followed by Sanger sequencing. RESULTS: The FCGR3A genotypes were associated with EULAR response (good or moderate) at month +6 (response in 34/38 (89.5%) VV vs 70/106 (66%) VF and in 51/77 (66.2%) FF patients; p=0.01), but not at month +4 (response in 32/37 (86.5%) VV vs 69/102 (67.6%) VF and 53/73 (72.6%) FF patients; p=0.09). Loss of response was observed only in VF and FF carriers ((VV vs VF vs FF: 0/37 (0%) vs 11/102 (10.8%) vs 12/73 (16.4%); p=0.02)). Probability of response at month +6 was very high when at least two of the three following items selected by multivariate analysis were present: positive rheumatoid factor and/or anticyclic citrullinated peptide antibodies, previous treatment with ≤ 1 anti-tumor necrosis factor (TNF) agent, and 158VV FCGR3A genotype (p<0.0001; OR 7.9, 95% CI 4.1 to 15.1). CONCLUSIONS: The 158VV FCGR3A genotype was associated with response to RTX in a large cohort of RA patients. Patient genotyping may be helpful to plan RTX treatment, and may be integrated with clinical predictors.
25192895 Association of IL-18 promoter gene polymorphisms with rheumatoid arthritis: a meta-analysi 2014 Dec Interleukin-18(IL-18) plays a potential pathological role in rheumatoid arthritis (RA). The conclusions of the published reports on the relationship between single-nucleotide polymorphisms -607C/A (rs1946518) and -137G/C (rs187238) located in the IL-18 gene promoter and RA risk remain controversial. This meta-analysis was performed to evaluate the association between IL-18 gene promoter (-607A/C and -137C/G) polymorphisms and RA using (1) allele, (2) codominant, (3) dominant, and (4) recessive models. Literature search was conducted up to January, 2013, in PubMed, EMBASE, Spring-link, Web of Science, Wanfang (Chinese) and China National Knowledge Infrastructure (CNKI). A total of 10 studies from eight articles involving 2,662 cases and 2,168 controls for -607A/C polymorphism and 9 studies from six articles involving 1,331 cases and 1,468 controls for -137C/G polymorphism were considered in the meta-analysis. For the relationship of IL-18 -607A/C polymorphism with RA risk, significant association was observed in allele model (OR = 0.778, 95 % CI = 0.633-0.955) and dominant model (OR = 0.618, 95 % CI = 0.466-0.819). However, no significant association could be observed between -137C/G polymorphism and RA risk under all genetic models (allele model: OR = 0.940, 95 % CI = 0.777-1.138; codominant model: OR = 1.079, 95 % CI = 0.574-2.029; dominant model: OR = 0.913, 95 % CI = 0.779-1.069; recessive model: OR = 1.133, 95 % CI = 0.586-2.190). In the subgroup analysis by ethnicity, significant result was also found in Asian populations but not found in Caucasian populations for the relationship of IL-18 -607A/C polymorphism with RA risk; while no obvious association was found between IL-18 -137C/G polymorphism and RA risk. This meta-analysis indicates that IL-18 -607A/C polymorphism in promoter region may be associated with RA risk.
23574524 Biologic therapy in rheumatoid arthritis. 2013 Biologic therapies have notably improved the treatment of RA, making disease remission a realistic goal. After more than ten years of experience, the safety issues associated with these drugs are well characterized and can be avoided with careful patient selection and tight clinical control. Although the different biologic drugs (anti-TNF agents, anti-IL-6, anti-B cells and anti-costimulation of T-cells) have apparently different mechanisms of action, all biologic agents have demonstrated similar efficacy. In addition results of the combination of two biologic therapies have shown no additive clinical effects, although there is an increased risk of infection. Therefore, further research is needed to optimize the use of these and future targeted therapies in RA.
25259409 Cellular energy metabolism in T-lymphocytes. 2015 Jan Energy homeostasis is a hallmark of cell survival and maintenance of cell function. Here we focus on the impact of cellular energy metabolism on T-lymphocyte differentiation, activation, and function in health and disease. We describe the role of transcriptional and posttranscriptional regulation of lymphocyte metabolism on immune functions of T cells. We also summarize the current knowledge about T-lymphocyte adaptations to inflammation and hypoxia, and the impact on T-cell behavior of pathophysiological hypoxia (as found in tumor tissue, chronically inflamed joints in rheumatoid arthritis and during bone regeneration). A better understanding of the underlying mechanisms that control immune cell metabolism and immune response may provide therapeutic opportunities to alter the immune response under conditions of either immunosuppression or inflammation, potentially targeting infections, vaccine response, tumor surveillance, autoimmunity, and inflammatory disorders.
25295284 Cytokine-mediated bone destruction in rheumatoid arthritis. 2014 Bone homeostasis, which involves formation and resorption, is an important process for maintaining adequate bone mass in humans. Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation and bone loss, leading to joint destruction and deformity, and is a representative disease of disrupted bone homeostasis. The bone loss and joint destruction are mediated by immunological insults by proinflammatory cytokines and various immune cells. The connection between bone and immunity has been intensely studied and comprises the emerging field of osteoimmunology. Osteoimmunology is an interdisciplinary science investigating the interplay between the skeletal and the immune systems. The main contributors in osteoimmunology are the bone effector cells, such as osteoclasts or osteoblasts, and the immune cells, particularly lymphocytes and monocytes. Physiologically, osteoclasts originate from immune cells, and immune cells regulate osteoblasts and vice versa. Pathological conditions such as RA might affect these interactions, thereby altering bone homeostasis, resulting in the unfavorable outcome of bone destruction. In this review, we describe the osteoclastogenic roles of the proinflammatory cytokines and immune cells that are important in the pathophysiology of RA.
25481426 Lifestyle modifications to improve musculoskeletal and bone health and reduce disability-- 2014 Jun This review covers the evidence relating to lifestye modification in the big three musculoskeletal conditions: osteoarthritis, osteoporosis and rheumatoid arthritis. Lifestyle is of considerable importance in the first two and there is emerging evidence for rheumatoid arthritis despite it not traditionally being considered a lifestyle disease.
24832837 Budget impact analysis of biosimilar infliximab (CT-P13) for the treatment of rheumatoid a 2014 May The first biosimilar monoclonal antibody (infliximab, CT-P13) was registered by the European Medicines Agency in 2013 for the treatment of several inflammatory conditions including rheumatoid arthritis (RA). Biosimilar infliximab is first being marketed in the Central and Eastern European countries. This paper presents the estimated budget impact of the introduction of biosimilar infliximab in RA over a 3-year time period in six selected countries, namely Bulgaria, the Czech Republic, Hungary, Poland, Romania and Slovakia. A prevalence-based model was constructed for budget impact analysis. Two scenarios were compared to the reference scenario (RSc) where no biosimilar infliximab is available: biosimilar scenario 1 (BSc1), where interchanging the originator infliximab with biosimilar infliximab is disallowed, and only patients who start new biological therapy are allowed to use biosimilar infliximab; as well as biosimilar scenario 2 (BSc2), where interchanging the originator infliximab with biosimilar infliximab is allowed, and 80% of patients treated with originator infliximab are interchanged to biosimilar infliximab. Compared to the RSc, the net savings are estimated to be €15.3 or €20.8 M in BSc1 and BSc2, respectively, over the 3 years. If budget savings were spent on reimbursement of additional biosimilar infliximab treatment, approximately 1,200 or 1,800 more patients could be treated in the six countries within 3 years in the two biosimilar scenarios, respectively. The actual saving is most sensitive to the assumption of the acquisition cost of the biosimilar drug and to the initial number of patients treated with biological therapy. The study focused on one indication (RA) and demonstrated that the introduction of biosimilar infliximab can lead to substantial budget savings in health care budgets. Further savings are expected for other indications where biosimilar medicines are implemented.
23292482 Felty's syndrome without rheumatoid arthritis? 2013 May Felty's syndrome (FS) is characterized by neutropenia and splenomegaly in patients with seropositive (RF+, anti-CCP+) rheumatoid arthritis (RA). As a result of neutropenia, affected persons are increasingly susceptible to infections. In the majority of patients, FS appears in the course of long-standing and well-established RA. Manifestations of FS without clinical but only with laboratory features of RA are extremely rare. We present a case of severe neutropenia and mild splenomegaly in a patient with high titers of RF and anti-CCP. For 4 years, patient's neutropenia remained asymptomatic. The neutropenia reduction to agranulocytosis was followed by successful methotrexate-corticosteroid therapy. Efficacy of the standard anti-RA therapy confirmed autoimmune mechanism of the Felty's neutropenia. The most important lesion from our case is to recognize this condition in the range of autoimmune rheumatic diseases without delay. We reviewed literature with non-articular FS.
25178409 The association of radiographic progression with serum R-spondin 1 (RSPO1) levels or Dickk 2014 OBJECTIVES: To investigate the clinical implications of serum levels of R-spondin 1 (RSPO1), a natural antagonist for Dickkopf-1 (DKK1), and of DKK1/RSPO1 ratios in rheumatoid arthritis (RA) patients. METHOD: Serum DKK1 and RSPO1 levels were measured in 102 RA patients and 39 age- and gender-matched healthy controls. In addition, DKK1 and RSPO1 levels were determined prior to and 3 months after anti-tumour necrosis factor alpha (anti-TNF-α) therapy in 15 RA patients. Clinical and laboratory data and baseline radiographs of the hands and feet were obtained. Serial radiographs were evaluated in 83 RA patients. Radiographic joint damage was assessed by the modified Sharp/van der Heijde score (SHS). RESULTS: Serum RSPO1 levels were significantly reduced whereas serum DKK1 levels and DKK1/RSPO1 ratios were significantly increased in RA patients compared with controls (all p < 0.0001). Anti-TNF-α treatment significantly suppressed DKK1/RSPO1 ratios (p < 0.01). In contrast to DKK1 or RSPO1 levels, the ratios were significantly associated with erosive disease, elevated acute phase reactants, Disease Activity Score in 28 joints (DAS28) > 3.2, and radiographic progression rate (all p < 0.05). Although the RA patients with radiographic progression exhibited significantly increased DKK1 and reduced RSPO1 levels (p < 0.05), only the DKK1/RSPO1 ratio (log-transformed) was found to be a significant predictor of subsequent radiographic progression [odds ratio (OR) 2.07, p < 0.01]. CONCLUSIONS: In this study, the presence of RSPO1 in the circulation was shown for the first time. Our results suggest that the serum DKK1/RSPO1 ratio represents a better predictor of structural progression than either DKK1 or RSPO1 levels alone in RA patients.
24241033 Work disability and state benefit claims in early rheumatoid arthritis: the ERAN cohort. 2014 Mar OBJECTIVE: RA is an important cause of work disability. This study aimed to identify predictive factors for work disability and state benefit claims in a cohort with early RA. METHODS: The Early RA Network (ERAN) inception cohort recruited from 22 centres. At baseline, and during each annual visit, participants (n = 1235) reported employment status and benefits claims and how both were influenced by RA. Survival analysis derived adjusted hazard ratios (aHRs) and 95% CIs to predict associations between baseline factors and time until loss of employment due to RA or a state benefits claim due to RA. RESULTS: At baseline, 47% of participants were employed and 17% reported claiming benefits due to RA. During follow-up, loss of employment due to RA was reported by 10% (49/475) of the participants and 20% (179/905) began to claim benefits. Independent predictors of earlier work disability were bodily pain (aHR 2.45, 95% CI 1.47, 4.08, P = 0.001) and low vitality (aHR 1.84, 95% CI 1.18, 2.85, P = 0.007). Disability (aHR 1.28, 95% CI 1.02, 1.61, P = 0.033), DAS28 (aHR 1.48, 95% CI 1.05, 2.09, P = 0.026) and extra-articular disease (aHR 1.77, 95% CI 1.17, 2.70, P = 0.007) predicted earlier benefits claims. CONCLUSION: Work disability and benefits claims due to RA were predicted by different baseline factors. Pain and low vitality predicted work disability. Baseline disability, extra-articular disease manifestations and disease activity predicted new benefits claims due to RA. Future research on interventions targeting these factors could investigate job retention and financial independence.