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ID PMID Title PublicationDate abstract
26061065 CD8+ T Cells Specific to Apoptosis-Associated Antigens Predict the Response to Tumor Necro 2015 CD8+ T cells specific to caspase-cleaved antigens derived from apoptotic T cells (apoptotic epitopes) represent a principal player in chronic immune activation, which is known to amplify immunopathology in various inflammatory diseases. The purpose of the present study was to investigate the relationship involving these autoreactive T cells, the rheumatoid arthritis immunopathology, and the response to tumor necrosis factor-α inhibitor therapy. The frequency of autoreactive CD8+ T cells specific to various apoptotic epitopes, as detected by both enzyme-linked immunospot assay and dextramers of major histocompatibility complex class I molecules complexed with relevant apoptotic epitopes, was longitudinally analyzed in the peripheral blood of rheumatoid arthritis patients who were submitted to etanercept treatment (or other tumor necrosis factor inhibitors as a control). The percentage of apoptotic epitope-specific CD8+ T cells was significantly higher in rheumatoid arthritis patients than in healthy donors, and correlated with the disease activity. More important, it was significantly more elevated in responders to tumor necrosis factor-α inhibitor therapy than in non-responders before the start of therapy; it significantly dropped only in the former following therapy. These data indicate that apoptotic epitope-specific CD8+ T cells may be involved in rheumatoid arthritis immunopathology through the production of inflammatory cytokines and that they may potentially represent a predictive biomarker of response to tumor necrosis factor-α inhibitor therapy to validate in a larger cohort of patients.
25807089 An examination of the mechanisms involved in secondary clinical failure to adalimumab or e 2015 Apr BACKGROUND: Biological therapies against tumor necrosis factor α have revolutionized the treatment of several inflammatory rheumatic diseases. However, 30% of responders will present a clinical failure after having controlled the disease for at least 6 months (secondary clinical failure). Biological therapies may induce an unwanted immune response, which may alter the bioavailability of the drug causing a loss of clinical response. OBJECTIVE: The objective of this study was to assess the correlation between secondary clinical failure (based on Disease Activity Score in 28 Joints or Bath Ankylosing Spondylitis Disease Activity Index) and the type of mechanism involved in failure (based on drug levels) in patients with inflammatory arthropathies treated with anti-tumor necrosis factor α. METHODS: Drug and antidrug antibodies (ADAs) serum levels were determined by enzyme-linked immunosorbent assay immediately before drug administration in patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis who presented secondary clinical failure after at least 6 months of treatment with adalimumab (ADL) or etanercept (ETN). RESULTS: Thirty-six patients with secondary clinical failure were recruited: 63.88% had rheumatoid arthritis, 22.22% had psoriatic arthritis, and 13.88% had ankylosing spondylitis; 58.33% did not respond to ADL, whereas 41.66% did not to ETN. None of the patients treated with ETN showed either subtherapeutic drugs levels or ADAs (failure due to a primary mechanism) whereas it was found that 23.80% of the patients treated with ADL had subtherapeutic drug levels for reasons attributable to immunogenicity (failure due to a secondary mechanism; P = 0.000048). CONCLUSIONS: We suggest the utility of measuring drug and ADA levels in patients with secondary clinical failure to ADL for a better optimization and rational use, but not in patients who fail to ETN.
25440158 The durability of abatacept as a first and subsequent biologic and improvement in HAQ from 2015 Apr OBJECTIVES: Assessment of the effectiveness of newer biologics such as abatacept is essential in real-world practice. METHODS: RA patients administered infusions of abatacept via the Orencia Response Program network with at least one follow-up evaluation were included. The number needed to treat (NNT) to improve HAQ by at least the minimal clinically important difference (MID ≥ 0.22) and abatacept survival and differences between biologic-naïve and TNFi-experienced patients were assessed. RESULTS: Among 2929 patients enrolled, 1771 (60.5%) were eligible for analysis (mean age was 57.6 years, disease duration was 16.5 ± 11.0 (SD) years, 77.2% were female, and 79.2% had past TNFi), with mean follow-up of 13.8 ± 12.3 (SD) months. Half had comorbidities including hypertension (17%), diabetes (8.4%), asthma (6.0%), hypothyroidism (5.7%), and hyperlipidemia (4.0%). Mean (SE) durability of treatment was 26.8 (0.53) months, where 66% were receiving abatacept at 12 months and 53% at 24 months. Patient survival was longer where abatacept was the first biologic vs. post-TNFi (P = 0.0001). In the use of abatacept as a first biologic, 70% achieved MID in HAQ vs. 71% if post-TNFi (P = 0.65) with NNT to improve one patient with at least MID of HAQ was 1.4. CONCLUSIONS: Abatacept is effective in improving HAQ in RA both pre and post first biologic in real-world patients with comorbidities. For those still on abatacept, HAQ continued to improve over the first 2 years. The durability of abatacept is better as a first biologic, but NNT to improve HAQ patients on treatment is the same post-DMARDs and post-TNFi. For treatment durability and HAQ MID achievement, abatacept use as a first biologic is better.
28502136 CD4+ CD25+ CD127low Regulatory T Cells as Indicator of Rheumatoid Arthritis Disease Activi 2016 Jun Rheumatoid arthritis (RA) is an autoimmune disease characterized by disturbed immune regulation, inducing a progressive cartilage and bone destruction. Despite enrichment of T regulatory cell (T-regs) in synovial fluid, conflicting results are reported concerning T-regs in peripheral blood (PB) of RA patients. To determine possible correlation between the frequency of PB CD4+ CD25+CD127low (T-regs) with RA disease activity. Forty females with RA, classified according to the Disease Activity Score 28 (DAS-28), as highly active, mild-moderate or low disease activity; and 20 age and sex matched healthy controls, were enrolled to study CD4+ CD25+ CD127low T- regs in PB by flow cytometry. Active RA patients had lower frequency of the CD4+ CD25+ CD127low T- regs compared to those with mild-moderate or low disease activity (P <0.001). The frequencies of the T- regs showed negative correlation with the DAS-28 (P<0.01). In conclusion, CD4+ CD25+ CD127low T-regs is significantly lower in highly active RA patients compared to patients with lower activity or controls.
26063950 Vitamin D Is a Good Marker for Disease Activity of Rheumatoid Arthritis Disease. 2015 AIM: This study was conducted to find out the optimal vitamin D cutoff point in predicting activity of RA disease. MATERIALS AND METHODS: One hundred and two rheumatoid arthritis Saudi patients of both genders were recruited in this study. Vitamin D as 25-hydroxy-vitamin D [25(OH)D] was measured and serum level less than 20 ng/mL defined as deficient patient. Disease activity was measured based on the disease activity score index of a 28-joint count (DAS28) using serum erythrocyte sedimentation rate levels. Receiver operating characteristic (ROC) curves were used to determine the optimal vitamin D cutoff points for identifying disease activity. RESULTS: It has been observed that vitamin D levels were lower (P < 0.05) in patients with high disease activity. A significant inverse correlation between serum 25(OH)D levels and DAS28 (r = -0.277, P = 0.014) was shown. ROC curves results showed that vitamin D less than 12.3 ng/mL predicted high disease activity, and vitamin D more than 17.9 ng/mL predicted low disease activity, with good sensitivity and accuracy results regarding vitamin D. CONCLUSION: Study results concluded that vitamin D is a good predictor of RA disease activity in Saudi patients.
25701769 Basilar Invagination: Case Report and Literature Review. 2015 Jun BACKGROUND: Basilar invagination is a rare clinical condition characterized by upward protrusion of the odontoid process into the intracranial space, leading to bulbomedullary compression. It is often encountered in adults with rheumatoid arthritis. Transoral microscopic or endonasal endoscopic decompression may be pursued, with or without posterior fixation. We present a case of basilar invagination with C1-C2 autofusion and discuss an algorithm for choice of anterior versus posterior approaches. CASE DESCRIPTION: A 47-year-old woman with rheumatoid arthritis presented with severe occipital and cervical pain, dysphagia, hoarseness, and arm paresthesias. Findings on magnetic resonance imaging revealed moderate cranial settling with the odontoid indenting the ventral medulla but no posterior compression. Computed tomography demonstrated bony fusion at C1-C2 without lateral sag. Given autofusion of C1-C2 in proper occipitocervical alignment and the absence of posterior compression, the patient underwent endoscopic endonasal odontoidectomy without further posterior fusion, with satisfactory resolution of symptoms. CONCLUSION: Endoscopic endonasal odontoidectomy offers a safe and effective method for anterior decompression of basilar invagination. Preoperative assessment for existing posterior fusion, absence of posterior compression, and preservation of the anterior C1 ring during operative decompression help stratify the need for lone anterior approach versus a combined anterior and posterior treatment.
26792814 Comparative effects of biologics on cardiovascular risk among older patients with rheumato 2016 Oct OBJECTIVES: To compare the coronary heart disease risk among patients with rheumatoid arthritis (RA) initiating common biologic disease-modifying antirheumatic drugs of different mechanisms. METHODS: We conducted a retrospective cohort study of patients with RA enrolled in Medicare, a public health plan covering >90% of US residents 65 years or older, from 2006 to 2012 who (1) initiated a biologic, (2) had complete medical and pharmacy coverage for at least 12 months before biologic initiation and (3) were free of coronary heart disease at the time of initiation. We compared the incidence rates (IRs) of (1) acute myocardial infarction (AMI) and (2) a composite outcome of AMI or coronary revascularisation and used multivariable adjusted Cox regression models to examine the associations between the type of biologic and the two outcomes. RESULTS: We identified 47 193 eligible patients with RA with mean age 64 (SD 13) years; 85% were women. Crude IRs for AMI ranged from 5.7 to 8.8 cases per 1000 person-years (PYs). AMI risk was significantly elevated among antitumour necrosis factor (anti-TNF) initiators overall (adjusted HR (aHR) 1.3; 95% CI 1.0 to 1.6) and individually among etanercept (aHR 1.3; 95% CI 1.0 to 1.8) and infliximab (aHR 1.3; 95% CI 1.0 to 1.6) compared with abatacept initiators. Crude IRs for the composite outcome ranged from 7.6 to 14.5 per 1000 PYs. Tocilizumab initiators were at reduced risk of the composite outcome compared with abatacept initiators (aHR 0.64, 95% CI 0.41 to 0.99). DISCUSSION: Findings from this observational study of patients with RA suggested that anti-TNF biologics may be associated with higher AMI risk compared with abatacept.
27888342 Putting recommendations into practice: Australian rheumatologists' opinions on leflunomide 2017 Apr Leflunomide is the most recently introduced conventional disease-modifying anti-rheumatic drugs in Australia. It has several unique methods for initiation, unique monitoring recommendations and a distinctive cessation protocol in the event of serious toxicity. The aim of this study was to evaluate initiation and monitoring practices of Australian rheumatologists using leflunomide. A survey was emailed twice, approximately 3 months apart to 332 rheumatologist members of the Australian Rheumatology Association. Wave analysis was used to assess evidence of non-response bias. The response rate to the survey was 20% and there was no difference between the responses of waves 1 and 2. Fifty percent of the respondents indicated that 20 mg once daily was the initial dose of leflunomide that they most commonly prescribed, 45% indicated 10 mg once daily, whilst only 3% preferred to initiate leflunomide at 100 mg daily for 2-3 days followed by 10 mg once a day as recommended when first marketed. Of the responders, 12% had used doses above 20 mg daily and 70% had used alternate daily dosing with leflunomide. In a patient taking leflunomide with an ALT or AST >3 times the ULN on two or more blood tests, 75% of responders indicated they would stop leflunomide immediately and 20% would follow cessation by administering a cholestyramine washout. The choice of initial leflunomide dose among responding Australian rheumatologists varied considerably, although most preferred not to use the loading dose. Despite the recommendation of clinical guidelines, the use of a cholestyramine washout procedure for hepatic toxicity is not universal.
27712078 Extracellular Proteome and Citrullinome of the Oral Pathogen Porphyromonas gingivalis. 2016 Dec 2 Porphyromonas gingivalis is an oral pathogen associated with the inflammatory disease periodontitis. Periodontitis and P. gingivalis have been associated with rheumatoid arthritis. One of the hallmarks of rheumatoid arthritis is the loss of tolerance against citrullinated proteins. Citrullination is a post-translational modification of arginine residues, leading to a change in structure and function of the respective protein. This modification, which is catalyzed by peptidylarginine deiminases (PADs), plays a role in several physiological processes in the human body. Interestingly, P. gingivalis secretes a citrullinating enzyme, known as P. gingivalis PAD (PPAD), which targets bacterial and human proteins. Because the extent of P. gingivalis protein citrullination by PPAD was not yet known, the present study was aimed at identifying the extracellular proteome and citrullinome of P. gingivalis. To this end, extracellular proteins of two reference strains, two PPAD-deficient mutants, and three clinical isolates of P. gingivalis were analyzed by mass spectrometry. The results uncovered substantial heterogeneity in the extracellular proteome and citrullinome of P. gingivalis, especially in relation to the extracellular detection of typical cytoplasmic proteins. In contrast, the major virulence factors of P. gingivalis were identified in all investigated isolates, although their citrullination was shown to vary. This may be related to post-translational processing of the PPAD enzyme. Altogether, our findings focus attention on the possible roles of 6 to 25 potentially citrullinated proteins, especially the gingipain RgpA, in periodontitis and rheumatoid arthritis.
25833292 Brief Report: Autocrine Cytokine-Mediated Deficiency of TRAIL-Induced Monocyte Apoptosis i 2015 Jul OBJECTIVE: Dysregulated apoptosis of monocytes is a pathogenic feature of rheumatoid arthritis (RA). The aim of this study was to investigate the role of TRAIL and TRAIL-induced apoptosis in patients with RA. METHODS: Cell surface expression and serum concentrations of TRAIL were determined in 63 patients with RA, and TRAIL-induced monocyte apoptosis was quantified. Surface expression of TRAILR-1, TRAILR-2, TRAILR-3, TRAILR-4, CXCR1, and CXCR2 was determined, and intracellular signal transduction was investigated. In 8 patients with RA, clinical and laboratory parameters of disease activity were investigated longitudinally, before and after initiation of treatment with tumor necrosis factor (TNF) inhibitors. RESULTS: Serum concentrations of both TRAIL and interleukin-8 (IL-8) were increased in patients with RA, while cell surface expression of the TRAIL receptors TRAILR-1, TRAILR-2, TRAILR-3, and TRAILR-4 was diminished. TRAIL-induced monocyte apoptosis was significantly decreased in RA due to increased TRAIL-induced IL-8 secretion by RA monocytes. The combined effect of TRAIL and IL-8 on monocytes resulted in activation of antiapoptotic pathways, including p42/44 MAPK and p38. Susceptibility to TRAIL-induced apoptosis was restored in RA monocytes after 3 months of TNF inhibition. CONCLUSION: In RA, circulating monocytes with the potential to produce proinflammatory cytokines appear to have defects in several pathways of apoptosis induction, among which is a deficiency in TRAIL-induced apoptosis. Although this resistance to apoptosis might contribute to perpetuation of the disease, it remains to be determined whether specific induction of apoptosis could be therapeutically beneficial.
26897854 [The Laboratory Medicine of Lipid Mediators]. 2015 Oct Lysophospholipids such as lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P), and lysophosphatidylserine (LysoPS) are attracting attention as second-generation lipid mediators. We have pursued the clinical introduction of the assays of lysophospholipids and related proteins, and in this review, the clinical application of the assay of LPA and autotaxin(ATX), which produces LPA from lysophosphatidylcholine through its lysophospholipase D activity, is mainly described. The assay of ATX is promising as a useful laboratory test, especially for the diagnosis and staging of liver fibrosis
27881258 Cost-Effectiveness Analysis of Tocilizumab in Comparison with Infliximab in Iranian Rheuma 2016 May OBJECTIVES: To analyze the cost-effectiveness of two common treatment strategies in Iran, comparing infliximab plus methotrexate with tocilizumab plus methotrexate in patients with rheumatoid arthritis with inadequate response to traditional disease-modifying antirheumatic drugs. METHODS: A multistage Markov decision model was applied to assess the incremental cost-effectiveness ratio (ICER) of a tocilizumab-containing regimen versus an infliximab-containing regimen over a 5-year time period. In the case of no response, we assumed that patients switched to the next treatment (adalimumab, rituximab, or supportive care) in sequence for each strategy. We considered major cost items, such as direct medical costs and direct nonmedical costs, from a payer (patients and third-party payers) perspective. A deterministic sensitivity analysis was conducted to assess the robustness of the model results over the uncertainty of key parameters. RESULTS: In the base-case analysis, the ICER of the tocilizumab-containing regimen was US $60,800 per quality-adjusted life-year as compared to the infliximab-containing regimen. In the sensitivity analysis, changes in the price of the drugs by generic substitution, in utility scores, and in discount rate did not change our overall conclusions. Among all inputs to the primary study and the sensitivity analyses, however, the price of tocilizumab had the most impact on the ICER. CONCLUSIONS: Although tocilizumab and methotrexate provide a larger gain in quality-adjusted life-years, their current price is quite high as compared with those of our other interventions. Therefore, a regimen containing tocilizumab is not cost-effective as compared with an infliximab-containing regimen for patients with rheumatoid arthritis in Iran.
27585422 Regulatory CD4+ T-Cell Subsets and Anti-Citrullinated Protein Antibody Repertoire: Potenti 2016 OBJECTIVE: Seropositive arthralgia patients (SAP) are at high risk of developing rheumatoid arthritis (RA). This prospective study aimed to determine whether altered peripheral regulatory T-cells (Tregs) and defined subsets, besides a broadened anti-citrullinated protein antibody (ACPA) response, may qualify as biomarkers for RA development in SAP. METHODS: Thirty-four consecutive SAP were prospectively assessed every 6 months for minimally 2 years. At inclusion, peripheral Treg (CD4+CD25+FoxP3+) numbers and subsets, defined as CD45RA+FoxP3low naive Tregs (Fr I), CD45RA-FoxP3high activated Tregs (Fr II) and CD45RA-FoxP3low non-Tregs (Fr III), were compared to age- and sex-matched healthy controls (HC, n = 16) and treatment-naive RA patients (n = 12). SAP that developed RA were compared to non-switchers and analyzed for Treg numbers and Treg subsets at inclusion. Also, Treg numbers and subsets were compared in switched SAP before and at diagnosis. To assess the ACPA repertoire, IgG and IgA reactivity was measured against citrullinated peptides from fibrinogen, α-enolase and vimentin. RESULTS: Treg numbers were similar between HC, SAP and RA patients. Although the bonafide Treg subsets Fr I and Fr II were comparable between groups, Fr III was increased in SAP compared to HC (p = 0.01). Fourteen (41%) SAP developed RA during follow-up. Their Treg numbers and subsets were comparable to non-switched SAP. At RA diagnosis, Treg numbers in switched SAP were similar to 6 months before. Switched SAP displayed a more diverse IgG ACPA repertoire compared to non-switched SAP (p = 0.046) and showed more IgA reactivity than non-switched SAP reaching significance for Fib1 only (p = 0.047). CONCLUSION: Numbers of Total Treg and bonafide Treg subsets are not indicative for RA development in SAP, opposed to the ACPA repertoire.
26905069 The Challenge of Treating Early-Stage Rheumatoid Arthritis: The Contribution of Mixed Trea 2016 Apr BACKGROUND: Use of biologic drugs is approved for treatment in rheumatoid arthritis (RA), both in established disease and at the early stage of RA (ERA). Identification of ERA and an early therapeutic strategy would lead to greater clinical improvement. Only a few indirect comparisons of the efficacy of different biologic agents in established RA have been performed and, to date, no studies reporting direct comparisons have been performed in ERA. OBJECTIVE: The aim of this study was to compare, by use of a mixed treatment comparison (MTC), the efficacy profiles of biologic agents in ERA. METHODS: An extensive literature search was performed to identify results of randomized, controlled trials (RCTs) evaluating biologic agents at licensed doses to treat patients affected by ERA. The primary end points for the analysis were the American College of Rheumatology 20% improvement (ACR20), ACR50, and ACR70 responses from baseline to various times of follow-up. WinBUGS 1.4 software (MRC Biostatistics Unit, Cambridge, UK) was used to perform the analyses. The MTC results are reported as the relative risk of a response for every single treatment coadministered with methotrexate, versus methotrexate plus placebo, which was used as a comparator in all RCTs. RESULTS: Ten scientific papers met the study inclusion criteria and were included in the analysis. Data on the use of infliximab, adalimumab, etanercept, abatacept, golimumab, and rituximab were included. No studies reported on the use of certolizumab pegol or tocilizumab in ERA. All biologic agents coadministered with methotrexate proved to be more efficacious than methotrexate plus placebo in inducing ACR20, ACR50, and ACR70 responses. The biologic agent characterized by the highest probability of inducing an ACR70 response was adalimumab (33.28%). Etanercept was the biologic agent with the highest probability of inducing ACR20 and ACR50 responses, in comparison with all other biologic agents, with probability rates of 62.95 and 37.1%, respectively. CONCLUSION: In our analysis, adalimumab proved to be the biologic agent with the highest probability of inducing an ACR70 response in patients affected by ERA, while etanercept was the biologic agent with the highest probability of inducing ACR50 and ACR20 responses.
27805584 Generation of Induced-pluripotent Stem Cells Using Fibroblast-like Synoviocytes Isolated f 2016 Oct 16 Mature somatic cells can be reversed into a pluripotent stem cell-like state using a defined set of reprogramming factors. Numerous studies have generated induced-Pluripotent Stem Cells (iPSCs) from various somatic cell types by transducing four Yamanaka transcription factors: Oct4, Sox2, Klf4 and c-Myc. The study of iPSCs remains at the cutting edge of biological and clinical research. In particular, patient-specific iPSCs can be used as a pioneering tool for the study of disease pathobiology, since iPSCs can be induced from the tissue of any individual. Rheumatoid arthritis (RA) is a chronic inflammatory disease, classified by the destruction of cartilage and bone structure in the joint. Synovial hyperplasia is one of the major reasons or symptoms that lead to these results in RA. Fibroblast-like Synoviocytes (FLSs) are the main component cells in the hyperplastic synovium. FLSs in the joint limitlessly proliferate, eventually invading the adjacent cartilage and bone. Currently, the hyperplastic synovium can be removed only by a surgical procedure. The removed synovium is used for RA research as a material that reflects the inflammatory condition of the joint. As a major player in the pathogenesis of RA, FLSs can be used as a material to generate and investigate the iPSCs of RA patients. In this study, we used the FLSs of a RA patient to generate iPSCs. Using a lentiviral system, we discovered that FLSs can generate RA patient-specific iPSC. The iPSCs generated from FLSs can be further used as a tool to study the pathophysiology of RA in the future.
25924444 [CCL19/IL-1beta positive feedback loop involved in the progress of inflammation in rheumat 2015 Mar OBJECTIVE: To explore the function and mechanism of CCL19 in the pathogenesis of rheumatoid arthritis. METHODS: Synovial fibroblasts were collected from 5 cases of rheumatoid arthritis. Peripheral blood mononuclear cells (PBMCs) were obtained from 5 healthy people by Ficoll-Hypaque density gradien centrifugation. The cells were stimulated with IL-1beta, TNF-alpha, IL-17 and other cytokines, and then the expression of CCL19 was detected by RT-PCR. The cells also were treated with different concentration of CCL19, then the expressions of IL-1beta, TNF-alpha were detected by RT-PCR, the expressions of p-ERK, p-p38 were detected by western blot. RESULTS: IL-1beta promoted the CCL19/CCR7 expression in both synovial fibroblasts and PBMCs. CCL19 upregulated the expression of IL-10 in both synovial fibroblasts and PBMCs. The stimulation of CCL19 also increased its receptor CCR7 expression. CCL19 activated p-ERK and p-p38 in PBMCs. CONCLUSION: The positive feedback loop between CCL19 and IL-1 participate in the development of rheumatoid arthritis.
25212046 Proapoptotic activity of a monomeric smac mimetic on human fibroblast-like synoviocytes fr 2015 Feb Inhibitors of apoptosis proteins (IAPs) block cell death in response to diverse stimuli. The mitochondrial protein, second mitochondria-derived activator of caspase (Smac), negatively regulates IAP inhibition of caspase activity. We investigated the proapoptotic activity of a synthetic Smac (Smac 066) on fibroblast-like synoviocytes (FLS) derived from patients with active rheumatoid arthritis (RA). We found that Smac 066 induced significant apoptosis in all RA-FLS samples. Furthermore, IAPs, which are upregulated in RA-FLS, were downregulated by Smac 066. This suggested that IAPs upregulation was responsible for RA-FLS sensitivity to Smac 066. Next, we analysed caspase activation and found that Smac 066 was associated with caspase 8 and caspase 3 activities. We then investigated the mechanism underlying Smac 066 downregulation of IAPs in RA-FLS with an apoptotic pathway array. Interestingly, Smac 066 significantly upregulated IGFBP-5, a protein involved in differentiation, apoptosis, and osteoblastic activation. Smac 066 may represent a new therapeutic approach to RA treatment.
26872745 Clinical features of organizing pneumonia associated with rheumatoid arthritis. 2016 Nov OBJECTIVES: To clarify the clinical features of organizing pneumonia (OP) associated with rheumatoid arthritis (RA) and to determine whether development of OP is related to RA activity. METHODS: A cross-sectional study was conducted, in which medical records of 499 consecutive RA patients who visited our hospital during one month were reviewed. OP was diagnosed by pathological findings by trans-bronchial biopsy or by clinical features (typical computed tomography findings, no causative agents, good response to glucocorticoids, and lack of response to antibiotics). RESULTS: Among 499 patients, OP was found in 19 patients and the estimated prevalence was 1.9-4.8%. No differences in clinical features were noted between the OP and non-OP groups. The mean age of OP development was 57.2 years and the period from the onset of RA to OP ranged from -4 to +34 years. Although 14 patients presented OP after the onset of RA, two developed OP before RA and three developed OP simultaneously with RA. Patients receiving tumor necrosis factor inhibitors also developed OP. RA disease activity just before onset of OP was low in 8 of 14 RA cases. At the onset of OP, only two patients showed exacerbations of arthritis, whereas most patients presented with fever and serum C-reactive protein (CRP) elevations. Glucocorticoids were effective for OP in all patients who received them. Relapse occurred in 4 of 19 cases. CONCLUSIONS: OP develops in approximately 4% of RA patients, which occurs independently from arthritis activity and at any time in RA patients.
27134251 Magnetic Resonance Imaging Bone Edema at Enrollment Predicts Rapid Radiographic Progressio 2016 Jul OBJECTIVE: To clarify whether magnetic resonance imaging (MRI) bone edema predicts the development of rapid radiographic progression (RRP) in the Nagasaki University Early Arthritis Cohort of patients with early-stage rheumatoid arthritis (RA). METHODS: Patients with early-stage RA (n = 76) were enrolled and underwent 1.5-T MRI of both wrists and finger joints. Synovitis, bone edema, and bone erosion were evaluated using the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS). RRP was defined as an annual increment > 3 at 1 year by the Genant-modified Sharp score of plain radiographs. A multivariate logistic regression analysis was performed to establish the risk factors for RRP. RESULTS: Median disease duration at enrollment was 3 months. RRP was found in 12 of the 76 patients at 1 year. A univariate analysis revealed that matrix metalloprotease-3, RAMRIS bone edema score, and RAMRIS bone erosion score were associated with RRP. Multivariate logistic regression analyses demonstrated that the RAMRIS bone edema score at enrollment (5-point increase, OR 2.18, 95% CI 1.32-3.59, p = 0.002) was the only independent predictor of the development of RRP at 1 year. A receiver-operating characteristic analysis identified the best cutoff value for RAMRIS bone edema score as 5. RRP was significantly rare among the patients with a RAMRIS bone edema score < 5 at enrollment (2 from 50 patients). CONCLUSION: Our findings suggest that MRI bone edema is closely associated with the development of RRP in patients with early-stage RA. Physicians should carefully control the disease activity when MRI bone edema is observed in patients with early RA.
26603893 Validation and internal consistency of the Swedish version of the Valued Life Activities s 2016 Dec OBJECTIVE: The objective was to create a linguistically and culturally validated Swedish version of the Valued Life Activities scale. The aim was also to describe its content and concurrent validity and its internal consistency in persons with rheumatoid arthritis. METHODS: The Valued Life Activities scale was translated to Swedish and culturally adapted. In order to describe the content validity, both the Swedish and original Valued Life Activities scale were linked to the International Classification of Functioning, Disability and Health. The concurrent validity and internal consistency were evaluated in 737 patients with rheumatoid arthritis. To establish concurrent validity, the scale was correlated to disease activity, activity limitations, and life satisfaction. Internal consistency was assessed with Cronbach's alpha. RESULTS: The equivalence of meaning between the Swedish and the original Valued Life Activities scale was ensured by harmonization review. Content validity was high when linked to the International Classification of Functioning, Disability and Health. Concurrent validity showed a strong correlation with the activity limitations (r = 0.87), moderate with life satisfaction (r = -0.61), and weak with disease activity (r = 0.38). Internal consistency was excellent (Cronbach's alpha = 0.97). CONCLUSIONS: The Swedish Valued Life Activities scale has been tested in a large and well-characterized sample and found to be a linguistically valid and culturally adapted self-reported measure of participation. Content validity of the Valued Life Activities scale was excellent, concurrent validity strong, and the internal consistency excellent. Since both individual preferences and International Classification of Functioning, Disability and Health concepts of disability are taken into account, the Swedish Valued Life Activities scale appears to be a promising new scale addressing important aspects of participation.