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ID PMID Title PublicationDate abstract
28850025 Improved adalimumab dose decision with comprehensive diagnostics data. 2018 Jan OBJECTIVES: Monoclonal antibodies are important in the treatment of rheumatoid arthritis (RA). This is the first trial to monitor the effect of adalimumab dose escalation in persistently active RA. The aim of this study was to identify the response to adalimumab to improve the basis for making decision in relation to actual drug capacity in serum. METHODS: The disease activity of RA patients was assessed with CDAI and DAS28 before administration of additional 40 mg adalimumab one week after standard injection. Serum samples were analysed using the recoveryELISA technology, a combination of sandwich ELISA and competitive assay. The recoveryELISA measure the concentrations of free TNF-α, drug level, and the remaining active adalimumab in the patients' sera. An adalimumab concentration of 5.0-10.0 g/mL was defined as the targeted therapeutic window. RESULTS: Five of 8 patients achieved moderate EULAR response by dose escalation. The results of the free adalimumab and TNF-α neutralisation measurements allowed a separation of the cohort (n=17) into three groups. Group 1 represents 18% of the patients with free adalimumab level higher 30.0 μg/mL and TNF-α neutralisation above 95%. Group 2 (47%) consists of patients within the therapeutic window with balanced free adalimumab and TNF-α neutralisation values. Group 3 contains 35% of the cohort with low concentrations of free adalimumab and lowest remaining TNF-α-neutralisation capacity. Anti-drug antibodies were detected in four patients but did not prevent response to treatment. CONCLUSIONS: Drug and antigen monitoring using recoveryELISA may support dose decision to avoid unnecessary switch in medication or possible overtreatment.
26799059 Comparison of fetuin-A and transforming growth factor beta 1 levels in patients with spond 2017 Dec AIM: We investigated the serum transforming growth factor beta 1 (TGFβ1) and fetuin-A levels, and determined the relationships between these biomarkers and disease activity, mobility and radiologic progression in patients with spondyloarthropathy (SpA) and rheumatoid arthritis (RA). METHOD: The study included 55 patients with SpA and 38 patients with RA, together with 28 healthy subjects. In AS patients, we assessed disease activity using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), functional ability using the Bath Ankylosing Spondylitis Functional Index (BASFI), and mobility using the Bath Ankylosing Spondylitis Metrology Index (BASMI), radiologic progression using the Bath Ankylosing Spondylitis Radiology Index (BASRI). Serum fetuin-A and TGFβ1 were determined using enzyme-linked immunosorbent assay (ELISA) equipment. RESULTS: Fetuin-A was significantly higher in the axial SpA and RA groups than in healthy subjects (P < 0.01). Serum TGFβ1 and fetuin-A levels were similar in the peripheral SpA group and in healthy subjects. A significant positive correlation was found between the fetuin-A and TGFβ1 levels in the axial SpA, peripheral SpA, and RA groups (r = 0.293, P = 0.009; r = 0.215, P = 0.04; r = 0.223, P = 0.05, respectively). Significant correlations were found between fetuin-A and the BASMI and BASRI values in the axial SpA patients (r = 0.444, P = 0.031; r = 0.486, P < 0.001, respectively). CONCLUSION: We conclude that Fetuin-A may be one of the steps that can be active in disease progression in axial SpA patients.
27676131 Synovium-Derived MicroRNAs Regulate Bone Pathways in Rheumatoid Arthritis. 2017 Mar Articular bone erosion in rheumatoid arthritis (RA) is mediated by the interaction between inflammation and pathways regulating bone metabolism. Inflammation promotes osteoclastogenesis and also inhibits osteoblast function, further contributing to the persistence of erosions. MicroRNAs (miRNAs) are important regulators of skeletal remodeling and play a role in RA pathogenesis. We therefore determined the expression of miRNAs in inflamed synovial tissue and the role they play in pathways regulating osteoblast and osteoclast function. Using the serum transfer mouse model of RA in C57BL/6 mice, we performed Fluidigm high-throughput qPCR-based screening of miRNAs from nonarthritic and arthritic mice. Global gene expression profiling was also performed on Affymetrix microarrays from these same synovial samples. miRNA and mRNA expression profiles were subjected to comparative bioinformatics. A total of 536 upregulated genes and 417 downregulated genes were identified that are predicted targets of miRNAs with reciprocal expression changes. Gene ontology analysis of these genes revealed significant enrichment in skeletal pathways. Of the 22 miRNAs whose expression was most significantly changed (p < 0.01) between nonarthritic and arthritic mice, we identified their targets that both inhibit and promote bone formation. These miRNAs are predicted to target Wnt and BMP signaling pathway components. We validated miRNA array findings and demonstrated that secretion of miR-221-3p in exosomes was upregulated by synovial fibroblasts treated with the proinflammatory cytokine TNF. Overexpression of miR-221-3p suppressed calvarial osteoblast differentiation and mineralization in vitro. These results suggest that miRNAs derived from inflamed synovial tissues may regulate signaling pathways at erosion sites that affect bone loss and potentially also compensatory bone formation. © 2016 American Society for Bone and Mineral Research.
28061876 Salivary TNFα levels in groups of subjects with rheumatoid arthritis and chronic periodon 2017 Jan 7 BACKGROUND: Rheumatoid arthritis (RA) and chronic periodontitis are the most common chronic inflammatory diseases with significant pathological and clinical similarities. Numerous studies have indicated a relationship between rheumatoid arthritis and periodontal disease. The aim of this study was to compare the TNF-α levels in saliva among patients with Rheumatoid arthritis (RA) and chronic periodontitis as well as healthy subjects. METHODS: One hundred and seventy-one patients were enrolled in this cross-sectional study. Fifty-seven patients diagnosed of RA, 57 patients with chronic periodontitis and 57 healthy subjects. These patients have been examined with regard to TNF-α level from salivary samples. Their teeth were examined with regard to Plaque Index , Gingival Index, probing depth and clinical attachment level.All patients were non-smokers. RESULTS: The results revealed a significant difference in all periodontal parameters among the three groups. The chronic periodontitis group showed a significantly higher value in all clinical periodontal parameters in comparison to both the RA and healthy groups. No significant difference was found between salivary TNF-α level among the three study groups. CONCLUSIONS: Patients with chronic periodontitis had the highest periodontal indices. However there was no significant difference regarding the level of salivary TNF-α. Hence, suppression of proinflammatory cytokines might prove beneficial in suppressing periodontal diseases among RA patients.
28818831 Oral contraceptives, breastfeeding and the risk of developing rheumatoid arthritis: result 2017 Nov OBJECTIVES: To study whether oral contraceptive (OC) use or breastfeeding (BF) influence the risk of rheumatoid arthritis (RA), stratifying the cases by presence/absence of anticitrullinated protein antibodies (ACPA), and whether these factors interact with known risk factors in the development of ACPA-positive RA. METHODS: Women aged ≥18 years, participants in the population-based case-control Swedish Epidemiological Investigation of RA study (2641 cases/4251 controls), completed an extensive questionnaire regarding OC, BF and potential confounders. We calculated ORs, with 95% CIs, adjusted for age, residential area, smoking and alcohol consumption. Attributable proportion due to interaction (AP) was estimated to evaluate presence of interaction. RESULTS: Compared with never users, ever and past OC users had a decreased risk of ACPA-positive RA (OR=0.84 (95% CI 0.74 to 0.96); OR=0.83 (95% CI 0.73 to 0.95), respectively). No significant associations were found for ACPA-negative RA. Long duration of OC use (>7 years vs never use) decreased the risk of both ACPA-positive (p=0.0037) and ACPA-negative RA (p=0.0356).A history of long BF decreased the risk only of ACPA-positive RA in a dose-dependent manner (p=0.0086), but this trend did not remain after adjustments. A significant interaction was observed between the lack of OC use and smoking (AP=0.28 (95% CI 0.14-0.42)) on the risk of ACPA-positive RA. No interactions were found for BF. CONCLUSIONS: OC decreased the risk of RA, especially ACPA-positive RA, where an interaction with smoking was observed. A long duration of OC use decreased the risk of both disease subsets. We could not confirm an association between BF and a decreased risk of either ACPA-positive or ACPA-negative RA.
28286757 Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid 2017 Objective. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patients. Methods. Seventeen RA patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers, in vitro OC differentiation assays, and qRT-PCR for OC specific genes was performed. Results. After TNFi therapy, patients had reduced RANKL surface expression in B-lymphocytes and the frequency of circulating classical CD14(bright)CD16(-) monocytes was decreased. Serum levels of sRANKL, sRANKL/OPG ratio, and CTX-I were reduced in RA patients after TNFi treatment. Moreover, after exposure to TNFi, osteoclast differentiation and activity were decreased, as well as the expression of TRAF6 and cathepsin K. Conclusion. We propose that TNFi arrests bone loss and erosion, through two pathways: direct reduction of osteoclast precursor numbers and inhibition of intracellular signaling pathways acting through TRAF6.
28971528 M2 polarization of monocytes in ankylosing spondylitis and relationship with inflammation 2017 Dec The aim of this study was to evaluate the polarization of peripheral blood monocytes in the patients with ankylosing spondylitis (AS) and to determine the correlations between monocyte polarization and inflammation and structural damage. A total of 120 AS patients, 50 rheumatoid arthritis (RA) patients and 100 healthy controls were enrolled in the study. M1 (CD68+CD192+) and M2 (CX3CR1+CD163+) monocytes were characterized by flow cytometry. Demographic, clinical, radiographic and laboratory data were collected and analyzed. A large increase in M2 (CX3CR1+CD163+) monocytes was observed in AS, and M2/M1 ratio was 7.18 ± 6.12, 2.54 ± 3.14 and 35.61 ± 20.04 in control, RA and AS, respectively. The M2/M1 ratio correlated with modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) (r = 0.565; p < 0.001), ESR (r = -0.321; p < 0.001, CRP (r = -0.265; p < 0.001) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (r = -0.201; p = 0.028). Anti-TNF-α therapy induced a significant reduction in the percentage of M1 monocyte, ESR, CRP and BASDAI in AS patients. The present results demonstrated that M2 type polarized monocytes are predominant in the peripheral blood in AS and the M2/M1 ratio is correlated with structural damage (mSASSS), inflammatory biomarkers (ESR and CRP) and BASDAI.
28619044 Differing specificities and isotypes of anti-citrullinated peptide/protein antibodies in p 2017 Jun 15 BACKGROUND: To analyze differences in the recognition of anti-citrullinated peptide/protein antibody (ACPA) citrullinated epitopes and isotypes in patients with palindromic rheumatism (PR) and rheumatoid arthritis (RA). METHODS: ACPA fine specificities (citrullinated peptides of enolase, fibrin, and vimentin) and isotypes (IgG, IgM, and IgA) were analyzed in 54 patients with longstanding PR and 54 patients with established RA. RESULTS: CCP2 tested positive in 66.7% of patients with PR and RA. The ACPA distribution of fine specificities and isotypes differed between PR and RA patients. PR patients had a lower frequency of fine ACPA specificities than RA patients, which was significant in the case of a peptide derived from vimentin (PR 24.1% vs. 59.3% RA; p < 0.001). The mean number of ACPA specificities was lower in PR than in RA patients, and only 25.9% of PR patients recognized ≥2 additional specificities compared with 46.3% of RA patients. Significantly less isotype usage, especially IgA, was observed in PR patients. CONCLUSION: The ACPA immune response differed in patients with PR and RA, with fewer fine specificities and isotype usage in patients with PR. Some patients with PR may have impaired maturation of the B-cell response against citrullinated peptides with no progression to RA.
27787574 Outcome of knee revisions for osteoarthritis and inflammatory arthritis with postero-stabi 2017 Apr PURPOSE: Patients with rheumatoid arthritis (RA) and osteoarthritis (OA) may require revision total knee replacement. Few studies have compared post-operative complications, results and risk of re-revision in RA and OA patients. MATERIAL AND METHODS: Forty-five RA patients who had undergone revision TKA from 1998 to 2010 were selected and matched with 45 OA patients who had revision during the same period. Results of the use of a revision postero-stabilized implant in osteoarthritis were compared to results of its use in inflammatory arthritis. With a mean follow-up of ten years (range, 5-17 years) we determined differences in comorbidities, risk for peri-operative adverse events, functional and radiological results, and risk of subsequent re-revision, between patients suffering from OA versus RA. RESULTS: There were higher comorbidities, post-operative (<30 days) adverse events, and mortality at average ten years FU in RA than in OA patients. The mean overall changes in function scores were greater for the RA revision group when compared with the OA revision group. Taking steroids (Cox's regression, p = 0.001), and methotrexate or TNFα blockers (Cox's regression, p = 0.02) were not significant factors for radiolucent lines in RA and for loosening. At average ten years followup, patients with RA undergoing revision TKAs were not more likely to have a re-revision (4 among 45 patients; 9 %) than patients with OA undergoing revision in our department (7 patients; 15 %). CONCLUSIONS: Similar results for the knee were observed in these two forms of arthritis in spite of the fact that the initial local joint status and general health status are worse in inflammatory rheumatoid arthritis than in "degenerative" osteoarthritis. However, complications were more frequent with RA.
26965161 Hand pains in women and men in early rheumatoid arthritis, a one year follow-up after diag 2017 Feb Purpose This research analysed general pain intensity, hand pain at rest and hand pain during activity in women and men in early rheumatoid arhtritis (RA). Method Out of the 454 patients that were recruited into the Swedish early RA project "TIRA" the 373 patients (67% women) that remained at 12 months follow-up are reported here. Disease activity 28 joint score (DAS-28), disability (Health Assessment Questionnaire = HAQ) and pain (VAS) were recorded at inclusion and after 3 (M3), 6 (M6) and 12 (M12) months. General pain, hand pain during rest, hand pain during test of grip force as assessed by Grippit™, prescribed disease-modifying anti-inflammatory drugs (DMARDs) and hand dominance were recorded. Results DAS-28 and HAQ scores were high at inclusion and improved thereafter in both women and men. There were no significant differences between sexes at inclusion but women had higher DAS-28 and HAQ at all follow-ups. Women were more often prescribed DMARDs than were men. In both women and men all pain types were significantly lower at follow-up compared to at inclusion and women reported higher pain than men at follow-ups. The pain types differed significantly from each other at inclusion into TIRA, general pain was highest and hand pain during rest was lowest. There were no significant differences in hand pain related to hand dominance or between right and left hands. Conclusions Disease activity, disability and pain were high at inclusion and reduced over the first year. Despite more DMARDs prescribed in women than in men, women were more affected than were men. General pain was highest and not surprisingly hand pain during active grip testing was higher than hand pain during rest that was lowest in both sexes. Although our cohort was well controlled, it was evident that hand pain remains a problem. This has implications for rehabilitation and suggests potential ongoing activity limitations that should continue to receive attention from a multi-professional team. Implications for Rehabilitation General pain and hand pain remain a problem in RA despite today's early intervention and effective disease control with new era biologics. The extent of hand pain evidenced in our work gives a more detailed and comprehensive account of pain status. Higher hand pain during active grip testing than that during rest indicates a potential relationship to ongoing activity limitation. Hand pain assessment can help guiding multi-professional interventions directed to reduce hand pain and thereby probably reduce activity limitations.
28400572 Imaging atherosclerosis in rheumatoid arthritis: evidence for increased prevalence, altere 2017 Apr 11 In rheumatoid arthritis (RA), chronic inflammation is thought to drive increased cardiovascular risk through accelerated atherosclerosis. It may also lead to a more high-risk plaque phenotype. We sought to investigate carotid plaque phenotype in RA patients using Dynamic Contrast-Enhanced MRI (DCE-MRI) and Fludeoxyglucose Positron Emission Tomography(FDG-PET). In this pilot study, RA patients and age/sex-matched controls were evaluated for cardiovascular risk factors and carotid plaque on ultrasound. Subjects with plaque >2 mm thick underwent DCE-MRI, and a subgroup of patients had FDG-PET. Comparison of MRI findings between groups and correlation between clinical, serological markers and imaging findings was undertaken. 130 patients and 62 controls were recruited. Plaque was more prevalent in the RA group (53.1% vs 37.0%, p = 0.038) and was independently associated with IL6 levels (HR[95%CI]: 2.03 [1.26, 3.26] per quartile). DCE-MRI data were available in 15 patients and 5 controls. Higher prevalence of plaque calcification was noted in RA, despite similar plaque size (73.3% vs 20%, p = 0.04). FDG-PET detected plaque inflammation in 12/13 patients scanned and degree of inflammation correlated with hs-CRP (r = 0.58, p = 0.04). This study confirms increased prevalence of atherosclerosis in RA and provides data to support the hypothesis that patients have a high-risk plaque phenotype.
29153870 Factors associated with use of disease modifying agents for rheumatoid arthritis in the Na 2018 Apr OBJECTIVE: We examined the treatment patterns among adults with rheumatoid arthritis (RA) and identified factors influencing access to traditional and biological disease modifying antirheumatic drugs (DMARDs). METHODS: We analyzed visits recorded in the National Ambulatory Medical Care Survey from 2005 to 2014 with a RA diagnosis. The primary outcome was DMARD use (traditional and/or biological). We included prescriptions of all RA-related treatments such as traditional and biological DMARDs, glucocorticoids, gold preparations, immunosuppressants, and non-steroidal anti-inflammatory drugs. Covariates in the logistic regression models included age, gender, race/ethnicity, type of health care coverage, provider type, geographic region, and number of comorbidities. RESULTS: Among 1405 visits with a RA diagnosis, 60.4% (n = 807) were prescribed DMARDs and 23.8% (n = 334) biological DMARDs. In fully adjusted models, females have 1.57 times higher odds of any DMARD use (95% confidence interval (CI): 1.02-2.46). Also, Medicare beneficiaries as compared to privately insured have 2.31 times higher odds of receiving any DMARDs (95% CI: 1.40-3.82), while visits with specialist vs. general physician are 2.38 times more associated with any DMARD use (95% CI: 1.37-4.14). For biological DMARDs, Medicare beneficiaries were at 2.58 times higher odds (95% CI: 1.42-4.70) than privately insured, while visits with specialist are at 3.37 times higher odds than general physician (95% CI: 1.40-8.23). CONCLUSION: Visits with a specialist and Medicare beneficiaries were significantly associated with any DMARD or biological DMARD use. Additionally, contrary to prior evidence, race/ethnicity was not associated with any DMARD or biological DMARD use, which may indicate reduction in disparity of treatment access.
28340056 Neutrophil-derived mitochondrial DNA promotes receptor activator of nuclear factor κB and 2017 Jul 1 OBJECTIVES: Mitochondrial DNA (mtDNA) contains sequestered damage-associated molecular patterns that might be involved in osteoimmunological pathogenesis of RA. Here, we aimed to investigate the cellular source of mtDNA and its role in RANK ligand (RANKL) expression by RA SF neutrophils. METHODS: The gene expression signature of SF neutrophils was examined by proteomic quantitative analysis. Levels of mtDNA in circulating and SF neutrophils from RA patients and OA control subjects were assessed by real-time PCR. Purified neutrophils were challenged in vitro with Toll-like receptor agonists as well as mtDNA. RANKL expression by neutrophils was studied by flow cytometry. RESULTS: SF neutrophils from RA patients displayed a gene expression signature of oxidative stress. This stress signature was associated with the release of mtDNA in SF as observed by a significant increase of mtDNA in the SF of RA patients compared with OA patients. mtDNA in RA SF was correlated with systemic inflammation as assessed by CRP concentrations. We also showed that mtDNA drives neutrophil RANKL expression to the same extent as Toll-like receptor agonists. CONCLUSION: Our data identify SF neutrophils as a cellular source of mtDNA that leads to a subsequent expression of RANKL. This highlights the important role of neutrophils in RA osteoimmunology.
28946707 Efficacy of Bioactive Cyclic Peptides in Rheumatoid Arthritis: Translation from In Vitro t 2017 Sep 25 Using a novel drug discovery technology reported in previous issues of this journal cyclic peptides have been created which are able to down-regulate secretion of inflammatory cytokines, in vitro, by stimulated cells of the macrophage cell line J774. The cytokines in question, TNF-alpha and IL-6, are strongly implicated in etiology of diseases such as rheumatoid arthritis. Studies are reported here using the CAIA animal model for rheumatoid arthritis, which show that the peptides identified are indeed able to impact on inflammation of joints, induced in vivo. The results suggest that these peptides are effective at a dose which could be viable in man, and at which no adverse side effects are evident in the short term.
28584977 Andrographolide Benefits Rheumatoid Arthritis via Inhibiting MAPK Pathways. 2017 Oct Andrographolide (AD) is the main compound distributed in medicinal herb Andrographis paniculata and exhibits anti-inflammatory activity. AD has been used for the treatment of multiple inflammatory diseases. However, the therapeutic value of AD on human rheumatoid arthritis (RA) remains unclear. In this study, we investigated the effects of AD on collagen-induced arthritis (CIA) and human RA synovial fibroblasts (RA-SFs). CIA mice were treated with AD (dissolved in 0.5% CMC-Na, 100 mg/kg per day) or vehicle (0.5% CMC-Na) daily by oral gavage for 2 weeks. The arthritis severity and joint destruction were assessed. Serum anti-collagen II antibody (anti-CII Abs) and cytokines were determined by ELISA. TNFα-stimulated human RA-SFs were treated with varying doses of AD for in vitro investigation. Results showed that AD significantly attenuated the arthritis severity and joint damage. AD treatment significantly reduced the production of serum anti-CII, TNFα, IL-1β, and IL-6. In vitro, AD decreased the secretion of IL-1β and IL-6 from TNFα-stimulated RA-SFs in a dose-dependent manner. AD treatment reduced the TNFα-induced phosphorylation of p38 MAPK and ERK1/2 in a dose-dependent manner. Thus, our findings suggest that AD confers protective effects on autoimmune arthritis through inhibiting MAPK pathways.
28337018 Rheumatoid Arthritis Fibroblast-like Synoviocyte Suppression Mediated by PTEN Involves Sur 2017 Mar 23 Survivin is a proto-oncogene biomarker known for its anti-apoptotic and cell cycle regulating properties induced by the activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway. In the context of non-cancer pathology, such as rheumatoid arthritis (RA), survivin has emerged as a feature associated with severe joint damage and poor treatment response. Phosphatase and tensin homolog (PTEN) is a phosphatase antagonizing all classes of PI3K. The interplay between survivin oncogenic mechanisms and proliferation suppression networks in RA has remained largely elusive. This study investigated the effect of PTEN on survivin gene expression in rheumatiod arthritis fibroblast-like synoviocyte (RA-FLS). We showed for the first time that the suppression of RA-FLS was mediated by PTEN involving survivin silencing. Considering that survivin suppressants are currently available in clinical trials and clinical use, their effects in RA-FLS support a probably RA therapy to clinical practice.
28583648 Fluorescence optical imaging and 3T-MRI for detection of synovitis in patients with rheuma 2017 May OBJECTIVES: To address whether Indocyanine Green (ICG) enhanced fluorescence optical imaging (FOI) is more sensitive than magnetic resonance imaging (MRI) in the detection of synovitis of the wrist and finger joints in rheumatoid arthritis and to analyze the performance of FOI depending on the grade of synovitis. METHODS: Twenty patients with highly active rheumatoid arthritis (mean DAS28-ESR 5.25±1.0) and thirteen healthy volunteers underwent clinical examination, FOI and contrast-enhanced 3T-MRI. Joints were rated by three independent readers semiquantitatively (grade 0-3: no, low, moderate and high grade synovitis) and compared to a semiquantitative composite standard of reference (cSOR, grade 0-3) that incorporated clinical parameters, FOI and MRI results. RESULTS: 2.868 evaluations in 956 joints were performed. FOI had an overall sensitivity of 57.3% and a specificity of 92.1%, whereas MRI had a sensitivity of 89.2% and a specificity of 92.6%. The sensitivity of FOI increased with the degree of synovitis to 65.0% for moderate and severe synovitis (specificity 88.1%) and 76,3% for severe synovitis (specificity 80.5%). The performance of FOI decreased with the degree of synovitis with false negative results predominantly for mild (156/343, 45.5%) and moderate (160/343, 46.6%) synovitis and false positive FOI evaluations predominantly based on weak (grade 1) signals (133/163, 81,6%). CONCLUSION: FOI has a lower sensitivity than 3T-MRI in the detection of synovitis of the hand and finger joints. The diagnostic performance of FOI decreases with the degree of synovitis and with the strength of FOI signals.
28598681 Soluble CD206 plasma levels in rheumatoid arthritis reflect decrease in disease activity. 2017 Sep Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and infiltration by activated macrophages. TNFα is a central mediator in this process. The mannose receptor, CD206, is a scavenger receptor expressed by M2(A)-macrophages and dendritic cells. It is involved in collagen internalization and degradation. The soluble form has been suggested as a biomarker of M2(A)-macrophage activation. The aim of this study was to investigate sCD206 plasma levels in early RA patients initiating anti-TNFα treatment. Plasma levels of sCD206 were measured by ELISA in samples from 155 early RA patients with an average symptom duration of 3 months. Patients were randomized to 12 months' methotrexate and placebo (PLA) or methotrexate and adalimumab (ADA) treatment, followed by open-label treatment with disease-modifying anti-rheumatic drugs (DMARD) and if needed, ADA. Disease activity was assessed at baseline and after 3, 6, 12 and 24 months. Baseline plasma level of sCD206 in treatment naïve RA patients was 0.33 mg/L (CI: 0.33-0.38 mg/L) corresponding to the upper part of the reference interval for healthy controls (0.10-0.43 mg/L). In the PLA group, sCD206 levels decreased after 3 months, but did not differ from baseline after 6 months. In the ADA group, however, levels remained lower than baseline throughout the treatment period. In conclusion, initially, plasma sCD206 in early RA patients decreased in accordance with disease activity and initiation of DMARD treatment. Treatment with anti-TNFα preserved this decrease throughout the study period.
28012023 Oral to subcutaneous methotrexate dose-conversion strategy in the treatment of rheumatoid 2017 Feb Both the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) guidelines recommend the use of methotrexate (MTX) for the treatment of rheumatoid arthritis (RA) when there is no contraindication. While MTX is the foundation of RA therapy (Singh et al. in Arthritis Care Res 64:625-639,2012), absorption saturation compromises its oral bioavailability (BA). Differences in the relative BA of oral versus subcutaneous (SC) MTX demonstrate the need for guidance on successful dose-conversion strategies. This study was designed to compare MTX PK profiles as a result of MTX administration via three different treatment administrations: oral, SC MTX administered via an auto-injector (MTXAI) into the abdomen (MTXAI(ab)) and into the thigh (MTXAI(th)). In this paper, we establish a dose-conversion method based on the BA of MTX from oral and SC administration. SC administration provided higher exposure of MTX than the same dose given orally. Unlike the exposure limitations of oral MTX, dose-proportional exposure was seen with SC MTX.
28137914 Long-term dietary quality and risk of developing rheumatoid arthritis in women. 2017 Aug OBJECTIVES: To evaluate the association between long-term dietary quality, measured by the 2010 Alternative Healthy Eating Index, and risk of rheumatoid arthritis (RA) in women. METHODS: We prospectively followed 76 597 women in the Nurses' Health Study aged 30-55 years and 93 392 women in the Nurses' Health Study II aged 25-42 years at baseline and free from RA or other connective tissue diseases. The lifestyle, environmental exposure and anthropometric information were collected at baseline and updated biennially. Cumulative follow-up rates were more than 90% for both cohorts. The primary outcome was RA alone with two subtypes of the disease: seropositive and seronegative RA. RESULTS: During 3 678 104 person-years, 1007 RA cases were confirmed. In the multivariable-adjusted model, long-term adherence to healthy eating patterns was marginally associated with reduced RA risk. To assess potential effect modification by age at diagnosis, we stratified by age. Among women aged ≤55 years, better quality diet was associated with lower RA risk (HR(Q4 vs Q1): 0.67; 95% CI 0.51 to 0.88; p trend: 0.002), but no significant association was found for women aged >55 years (p interaction: 0.005). When stratifying by serostatus, the inverse association among those aged ≤55 years was strongest for seropositive RA (HR(Q4 vs Q1): 0.60; 95% CI 0.42 to 0.86; p trend: 0.003). CONCLUSIONS: A healthier diet was associated with a reduced risk of RA occurring at 55 years of age or younger, particularly seropositive RA.