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ID PMID Title PublicationDate abstract
25641894 A qualitative investigation of the barriers to help-seeking among members of the public pr 2015 Apr OBJECTIVE: Treating patients with rheumatoid arthritis (RA) within 3 months of symptom onset leads to significantly improved clinical outcomes. However, many people with RA symptoms wait a long time before seeking medical attention. To develop effective health interventions to encourage people to seek help early, it is important to understand what the general public knows about RA, how they would react to the symptoms of RA, and what might delay help-seeking. METHODS: Qualitative interviews were conducted with 38 members of the general public (32 women) without any form of inflammatory arthritis about their perceptions of RA symptoms and decisions to seek help were they to experience such symptoms. The interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis. RESULTS: A number of barriers and drivers to help-seeking were identified and grouped into 5 themes: perceived causes of symptoms; factors related to presentation, location, and experience of symptoms; perceived effect of symptoms on daily life; self-management of symptoms; and general practitioner-related drivers and barriers. CONCLUSION: To our knowledge, our study is the first to investigate barriers to and drivers of help-seeking in response to the onset of RA symptoms in individuals without a diagnosis of RA. It has revealed a number of additional factors (e.g., the importance of the location of the symptoms) besides those previously identified in retrospective studies of patients with RA. Together with the data from previous research, these findings will help inform future health interventions aimed at increasing knowledge of RA and encouraging help-seeking.
25566937 A genetic study on C5-TRAF1 and progression of joint damage in rheumatoid arthritis. 2015 Jan 8 INTRODUCTION: The severity of joint damage progression in rheumatoid arthritis (RA) is heritable. Several genetic variants have been identified, but together explain only part of the total genetic effect. Variants in Interleukin-6 (IL-6), Interleukin-10 (IL-10), C5-TRAF1, and Fc-receptor-like-3 (FCRL3) have been described to associate with radiographic progression, but results of different studies were incongruent. We aimed to clarify associations of these variants with radiographic progression by evaluating six independent cohorts. METHODS: In total 5,895 sets of radiographs of 2,493 RA-patients included in six different independent datasets from the Netherlands, Sweden, Spain and North-America were studied in relation to rs1800795 (IL-6), rs1800896 (IL-10), rs2900180 (C5-TRAF1) and rs7528684 (FCRL3). Associations were tested in the total RA-populations and in anti-citrullinated peptide antibodies (ACPA)-positive and ACPA-negative subgroups per cohort, followed by meta-analyses. Furthermore, the associated region C5-TRAF1 was fine-mapped in the ACPA-negative Dutch RA-patients. RESULTS: No associations were found for rs1800795 (IL-6), rs1800896 (IL-10) and rs7528684 (FCRL3) in the total RA-population and after stratification for ACPA. Rs2900180 in C5-TRAF1 was associated with radiographic progression in the ACPA-negative population (P-value meta-analysis = 5.85 × 10(-7)); the minor allele was associated with more radiographic progression. Fine-mapping revealed a region of 66Kb that was associated; the lowest P-value was for rs7021880 in TRAF1. The P-value for rs7021880 in meta-analysis was 6.35 × 10(-8). Previous studies indicate that the region of rs7021880 was associated with RNA expression of TRAF1 and C5. CONCLUSION: Variants in IL-6, IL-10 and FCRL3 were not associated with radiographic progression. Rs2900180 in C5-TRAF1 and linked variants in a 66Kb region were associated with radiographic progression in ACPA-negative RA.
25894998 The effect of vascular endothelial growth factor on osteoclastogenesis in rheumatoid arthr 2015 Vascular endothelial growth factor (VEGF) has angiogenic, inflammatory, and bone-destructive roles in rheumatoid arthritis (RA). We aimed to determine the unique role of VEGF in osteoclastogenesis in RA. VEGF-induced receptor activator of nuclear factor Ò¡B ligand (RANKL) expression was determined in RA synovial fibroblasts by real-time PCR, luciferase assays, and ELISA. Osteoclastogenesis in peripheral blood monocytes cultured with VEGF was assessed by determining the numbers of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. Synovial fluid RANKL was correlated with VEGF concentration in the RA patients. VEGF stimulated the expression of RANKL in RA synovial fibroblasts. The RANKL promoter activity was upregulated by VEGF in the synovial fibroblasts transfected with RANKL-reporter plasmids. The VEGF-induced RANKL expression was decreased by the inhibition of both VEGF receptors (VEGFR) 1 and 2, Src, protein kinase C (PKC) and p38 MAPK. VEGF induced osteoclast differentiation from monocytes in the absence of RANKL and this was decreased by the inhibition of VEGFR1 and 2, Src, PKC and p38 MAPK. On coculturing with VEGF-prestimulated RA synovial fibroblasts, the monocytes differentiated into osteoclasts, and the osteoclastogenesis decreased by inhibition of Src and PKC pathways. VEGF plays dual roles on osteoclastogenesis in RA: direct induction of osteoclastogenesis from the precursors and stimulation of RANKL production in synovial fibroblasts, which is mediated by Src and PKC pathways. The axis of VEGF and RANKL could be a potential therapeutic target for RA-associated bone destruction.
27749239 Treatment in rheumatoid arthritis and mortality risk in clinical practice: the role of bio 2016 Nov OBJECTIVES: To assess the mortality rate (MR) and the mortality risk of a rheumatoid arthritis (RA) inception cohort, with and without biologic agents (BAs). Other factors associated to mortality were also investigated. METHODS: Retrospective longitudinal study of RA patients, attending the rheumatology outpatient clinic of a tertiary Hospital (Madrid), collected over 5 years (2000-2004), and followed from the diagnosis of RA up to the patients' death, lost to follow-up or September 2013. The dependent variable was death and the independent variable was exposure to BAs. Covariables: sociodemographic, clinical and therapy variables. MR was expressed per 1,000 patient-years with the 95% confidence interval [CI]. BA influence on MR was analysed by multivariable Cox models. Clinical and therapy variables were used in a time-dependent manner. The results are expressed in hazard ratio (HR) and [CI]. RESULTS: We included 576 patients and 711 courses of therapy. 19.6% were taking BA, 86% disease-modifying anti-rheumatic drugs (DMARDs) (70% on methotrexate - MTX), and 12% were untreated. There were 133 deaths during 4,981.64 patient-years at risk. The MR for BA was 12.6 [6-26], for DMARDs was 22.3 [18.4-27.1], and for those without treatment was 89.1 [61.9-128.2]. The adjusted HR for mortality in those exposed to BA versus those not exposed was 0.75 [0.32-1.71]). Other variables independently associated with mortality were: age, rheumatoid factor, hospital admissions, Health Assessment Questionnaire (HAQ), and MTX use (HR: 0.44 [0.29-0.66]). CONCLUSIONS: BAs and standard DMARDs are more effective in decreasing mortality compared to no therapy. Patients exposed to Bas were not associated with a significant increase or decrease in mortality when compared to patients with non-biological DMARDs. The use of MTX remains the only drug that has independently shown a beneficial effect on mortality.
29071908 [Effect of Electroacupuncture Intervention on Inflammatory Reactions and Articular Synovia 2016 Jun 25 OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on inflammatory reactions and articular synovial nuclear factor kappa B (NF-κB) and TNF-α converting enzyme (TACE) protein expression in rheumatoid arthritis (RA) rats, so as to elucidate its anti-inflammatory mechanism. METHODS: Forty Sprague-Dawley (SD) rats were randomly divided into normal control, model, EA, and non-acupoint groups, with 10 rats in each group. The RA model was established by intradermal injection of bovine type Ⅱ collagen emulsified in incomplete Freund's adjuvant for 21 days. EA (2 Hz, 1 mA) was applied to bilateral "Zusanli" (ST 36), "Xuanzhong" (GB 39) and "Shenshu" (BL 23) for 15 min, once daily for 19 days, starting from the third day on after modeling. The sham acupoints (5 mm lateral to the above-mentioned acupoints) received the same stimulation to EA group. Paw swelling volume was detected using a water-filled glass mug, the serum C-reactive protein (CRP) and rheumatoid factor (RF) contents were assayed using velocity scatter turbidimetric method, and the plasma erythrocyte sedimentation rate (ESR) was assayed with Westergren method and VES-MATIC 20 ESR auto-analyzer and the expression levels of TACE and NF-κB proteins in the synovial tissue of knee joint were detected by Western blot. RESULTS: After RA modeling, the hind-paw volume was significantly bigger in the RA rats than in the normal rats (P<0.01), and remarkably lower in the EA group (not in the non-acupoint group) than in the model group (P<0.05). In addition, the plasma ESR, serum CRP and RF contents and the expression levels of NF-κB and TACE proteins in the synovial tissues were significantly increased in the model group compared with those in the normal group (P<0.01), and were obviously down-regulated in the EA group (P<0.05), but not in the non-acupoint group (P>0.05). CONCLUSIONS: EA can effectively improve the severity of articular inflammatory swelling and lo-wer ESR, serum CRP and RF contents and suppress synovial TACE/NF-κB protein signaling in RA rats.
26978266 Rheumatoid Arthritis and Incidence of Twelve Initial Presentations of Cardiovascular Disea 2016 INTRODUCTION: While rheumatoid arthritis is an established risk factor for cardiovascular disease (CVD), our knowledge of how the pattern of risk varies for different cardiovascular phenotypes is incomplete. The association between rheumatoid arthritis and the initial presentation of 12 types of CVDs were examined in a contemporary population of men and women of a wide age range. METHODS: CALIBER data, which links primary care, hospital and mortality data in England, was analysed. A cohort of people aged ≥18 years and without history of CVD was assembled and included all patients with prospectively recorded rheumatoid arthritis from January 1997, until March 2010, matched with up to ten people without rheumatoid arthritis by age, sex and general practice. The associations between rheumatoid arthritis and the initial presentation of 12 types of CVDs were estimated using multivariable random effects Poisson regression models. RESULTS: The analysis included 12,120 individuals with rheumatoid arthritis and 121,191 comparators. Of these, 2,525 patients with and 18,146 without rheumatoid arthritis developed CVDs during a median of 4.2 years of follow-up. Patients with rheumatoid arthritis had higher rates of myocardial infarction (adjusted incidence ratio [IRR] = 1.43, 95%CI 1.21-1.70), unheralded coronary death (IRR = 1.60, 95%CI 1.18-2.18), heart failure (IRR = 1.61, 95%CI 1.43-1.83), cardiac arrest (HR = 2.26, 95%CI 1.69-3.02) and peripheral arterial disease (HR = 1.36, 95%CI 1.14-1.62); and lower rates of stable angina (HR = 0.83, 95%CI 0.73-0.95). There was no evidence of association with cerebrovascular diseases, abdominal aortic aneurysm or unstable angina, or of interactions with sex or age. CONCLUSIONS: The observed associations with some but not all types of CVDs inform both clinical practice and the selection of cardiovascular endpoints for trials and for the development of prognostic models for patients with rheumatoid arthritis.
26573936 A nurse-led rheumatology clinic versus rheumatologist-led clinic in monitoring of patients 2015 Nov 16 BACKGROUND: Recommendations for rheumatology nursing management of chronic inflammatory arthritis (CIA) from European League Against Rheumatism (EULAR) states that nurses should take part in the monitoring patients' disease and therapy in order to achieve cost savings. The aim of the study was to compare the costs of rheumatology care between a nurse-led rheumatology clinic (NLC), based on person-centred care (PCC), versus a rheumatologist-led clinic (RLC), in monitoring of patients with CIA undergoing biological therapy. METHODS: Patients with CIA undergoing biological therapy (n = 107) and a Disease Activity Score of 28 ≤ 3.2 were randomised to follow-up by either NLC or RLC. All patients met the rheumatologist at inclusion and after 12 months. In the intervention one of two annual monitoring visits in an RLC was replaced by a visit to an NLC. The primary outcome was total annual cost of rheumatology care. RESULTS: A total of 97 patients completed the RCT at the 12 month follow-up. Replacing one of the two annual rheumatologist monitoring visits by a nurse-led monitoring visit, resulted in no additional contacts to the rheumatology clinic, but rather a decrease in the use of resources and a reduction of costs. The total annual rheumatology care costs including fixed monitoring, variable monitoring, rehabilitation, specialist consultations, radiography, and pharmacological therapy, generated € 14107.7 per patient in the NLC compared with € 16274.9 in the RCL (p = 0.004), giving a € 2167.2 (13 %) lower annual cost for the NLC. CONCLUSIONS: Patients with CIA and low disease activity or in remission undergoing biological therapy can be monitored with a reduced resource use and at a lower annual cost by an NLC, based on PCC with no difference in clinical outcomes. This could free resources for more intensive monitoring of patients early in the disease or patients with high disease activity. TRIAL REGISTRATION: The trial is registered as a clinical trial at the ClinicalTrials.gov (NCT01071447). Registration date: October 8, 2009.
27022244 Efficacy and safety of modified-release prednisone in patients with rheumatoid arthritis. 2016 The introduction of modified-release (MR) prednisone adds a drug with encouraging potential to the armamentarium of the rheumatologist. In particular, for patients experiencing a reduced quality of life due to prolonged morning stiffness, it is a promising therapeutic approach. Two clinical trials and one open-label observational study investigated the effectiveness of MR prednisone in reducing rheumatoid arthritis-related morning stiffness for both new and current users of corticosteroids. The efficacy and safety of MR prednisone use in rheumatoid arthritis patients are reviewed in this article. This includes pivotal trials as well as pathophysiological considerations and clinical implications.
24534758 Diagnostic delay in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing 2015 Mar BACKGROUND/PURPOSE: Early diagnosis of inflammatory rheumatic diseases is important in order to improve long-term outcome. We studied whether delay in diagnosis (time between onset of symptoms and establishment of diagnosis) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PSA) and ankylosing spondylitis (AS) changed from year 2000 to 2011. METHODS: Month and year of initial symptoms and diagnosis, gender, hospital, year of birth and date of first data entry were obtained for 13,721 patients with RA, PSA or AS who had been registered in the DANBIO registry. Time between symptom onset and diagnosis was modelled using generalised linear regression to predict the average duration for each calendar year of initial symptoms with adjustments for gender, year of birth and date of DANBIO entry. RESULTS: Patients with valid data (RA: 10,416 (73%); PSA: 1970 (68%); AS: 1335 (65%)) did not differ significantly from the whole DANBIO population, except more missing data in early years. The regression model showed that the mean duration from initial symptoms to diagnosis for RA, PSA and AS declined steadily from 30, 53 and 66 months (year 2000), respectively, to 3-4 months (year 2011). Sensitivity analyses including patients who were included after 2005, patients who had received biological treatment or had symptom onset less than 2 and 5 years prior to first entry into DANBIO showed similar results. CONCLUSION: Since the year 2000, a significant reduction in diagnostic delay was observed in this large cohort of patients with RA, PSA or AS, probably reflecting a stronger awareness of the importance of early diagnosis.
26379233 Reliability and Validity of Selected PROMIS Measures in People with Rheumatoid Arthritis. 2015 PURPOSE: To evaluate the reliability and validity of 11 PROMIS measures to assess symptoms and impacts identified as important by people with rheumatoid arthritis (RA). METHODS: Consecutive patients (N = 177) in an observational study completed PROMIS computer adapted tests (CATs) and a short form (SF) assessing pain, fatigue, physical function, mood, sleep, and participation. We assessed test-test reliability and internal consistency using correlation and Cronbach's alpha. We assessed convergent validity by examining Pearson correlations between PROMIS measures and existing measures of similar domains and known groups validity by comparing scores across disease activity levels using ANOVA. RESULTS: Participants were mostly female (82%) and white (83%) with mean (SD) age of 56 (13) years; 24% had ≤ high school, 29% had RA ≤ 5 years with 13% ≤ 2 years, and 22% were disabled. PROMIS Physical Function, Pain Interference and Fatigue instruments correlated moderately to strongly (rho's ≥ 0.68) with corresponding PROs. Test-retest reliability ranged from .725-.883, and Cronbach's alpha from .906-.991. A dose-response relationship with disease activity was evident in Physical Function with similar trends in other scales except Anger. CONCLUSIONS: These data provide preliminary evidence of reliability and construct validity of PROMIS CATs to assess RA symptoms and impacts, and feasibility of use in clinical care. PROMIS instruments captured the experiences of RA patients across the broad continuum of RA symptoms and function, especially at low disease activity levels. Future research is needed to evaluate performance in relevant subgroups, assess responsiveness and identify clinically meaningful changes.
25872674 [No evidence that diet has any influence on the aetiology of rheumatoid arthritis]. 2015 Apr 13 Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease affecting 0,5-1% of the population. Several genetic and environmental factors are implicated in the aetiology of RA. The only well-established environmental risk factor is tobacco smoking. In this review we examine data linking intake of fatty acids, meat, antioxidants and vitamin D with the risk of RA. Although there is some tendency to show a protective effect of fatty acids from fish on RA, generally, evidence on dietary risk factors is scarce with a lack of statistical significance and reproducibility.
26939612 Sustained moderate-to-high disease activity and higher Charlson score are predictors of in 2016 Mar OBJECTIVES: Rheumatoid arthritis (RA) guidelines have moved toward intensive treatment aimed at remission. Treatment and disease activity are predictors of infections; patients from developing countries have additional predictors that may further impact the infection spectrum. Our aim was to describe serious infection events (SIEs), predictors and impact on RA outcomes, in a cohort of Mexican Mestizo patients. METHODS: Up to February 2015, charts from 176 early RA patients were reviewed by a single data abstracter. SIEs were defined according to strict criteria. RA patients with ≥1 SIE up to last follow-up were considered cases. Descriptive statistics were used; cases and paired controls (no SIE up to last follow-up) were compared by uni-variate analysis and multiple logistic regression. RESULTS: The cohort contributed to 948 patient-years of follow-up. There were 34 SIEs in 15 patients, at a (mean±SD) follow-up of 5±4 years. Incidence rate of SIE was 8.7 infections per 100 patient-years. Twenty-four isolated SIE were present in 14 patients. The most frequent SIEs were complicated urinary tract infections and pneumonia (each, n=8) and soft-tissue infections (n=7). In the case-control analysis, higher Charlson score (OR: 2.04, 95%CI: 1.001-4.164, p=0.05) and higher cumulative DAS28 (OR: 3.08, 95%CI: 1.91-4.98, p=0.000) were predictors of SIE; in patients with at least moderate disease activity, risk of SIE increased with higher level of cumulative disease activity. However, SIEs did not impact subsequent DAS28, HAQ and SF-36. CONCLUSIONS: Comorbidity and cumulative disease activity increased serious infection risk in early RA patients treated with conventional drugs, but SIEs did not impact disease outcomes.
28011155 Soluble vascular endothelial (VE) cadherin and autoantibodies to VE-cadherin in rheumatoid 2017 Dec OBJECTIVES: The aim of this study was to investigate the clinical value of sVE and anti-vascular endothelial-cadherin antibodies (AAVE) in RA treated with etanercept or adalimumab combined with methotrexate. METHODS: This was an 18-month prospective multicenter study in which patients had active RA, requiring TNF antagonist. sVE rates and AAVE titers were measured respectively by dot blot and ELISA. The relationship of these biomarkers with parameters reflecting articular or systemic disease activity, progression of structural damage, and response or remission to treatment was analyzed. RESULTS: Forty-eight patients received TNF blocking agents. Variation of sVE rates were significantly correlated with that of C-reactive protein (CRP) levels at weeks 6, 12, 26 and 52. A significant decrease in sVE levels was observed in the group of patients exhibiting a decrease in CRP levels as compared to the patient group with unmodified CRP. AAVE at baseline were correlated with rheumatoid factor. Kinetics analysis of sVE levels and AAVE titers showed that their level were not associated with disease activity score and to methotrexate/adalimumab or etanercept response. CONCLUSIONS: sVE is a biomarker associated with systemic RA activity under anti-TNF. AAVE are related to autoantibodies usually associated to RA.
26178283 14-3-3η Autoantibodies: Diagnostic Use in Early Rheumatoid Arthritis. 2015 Sep OBJECTIVE: To describe the expression and diagnostic use of 14-3-3η autoantibodies in early rheumatoid arthritis (RA). METHODS: 14-3-3η autoantibody levels were measured using an electrochemiluminescent multiplexed assay in 500 subjects (114 disease-modifying antirheumatic drug-naive patients with early RA, 135 with established RA, 55 healthy, 70 autoimmune, and 126 other non-RA arthropathy controls). 14-3-3η protein levels were determined in an earlier analysis. Two-tailed Student t tests and Mann-Whitney U tests compared differences among groups. Receiver-operator characteristic (ROC) curves were generated and diagnostic performance was estimated by area under the curve (AUC), as well as specificity, sensitivity, and likelihood ratios (LR) for optimal cutoffs. RESULTS: Median serum 14-3-3η autoantibody concentrations were significantly higher (p < 0.0001) in patients with early RA (525 U/ml) when compared with healthy controls (235 U/ml), disease controls (274 U/ml), autoimmune disease controls (274 U/ml), patients with osteoarthritis (259 U/ml), and all controls (265 U/ml). ROC curve analysis comparing early RA with healthy controls demonstrated a significant (p < 0.0001) AUC of 0.90 (95% CI 0.85-0.95). At an optimal cutoff of ≥ 380 U/ml, the ROC curve yielded a sensitivity of 73%, a specificity of 91%, and a positive LR of 8.0. Adding 14-3-3η autoantibodies to 14-3-3η protein positivity enhanced the identification of patients with early RA from 59% to 90%; addition of 14-3-3η autoantibodies to anticitrullinated protein antibodies (ACPA) and/or rheumatoid factor (RF) increased identification from 72% to 92%. Seventy-two percent of RF- and ACPA-seronegative patients were positive for 14-3-3η autoantibodies. CONCLUSION: 14-3-3η autoantibodies, alone and in combination with the 14-3-3η protein, RF, and/or ACPA identified most patients with early RA.
25924447 [Clinical value of MDHAQ for disease activity assessment in patients with rheumatoid arthr 2015 Mar OBJECTIVE: To evaluate the clinical value of the mutidimensional health assessment questionnaire (MDHAQ) for disease activity assessment in patients with rheumatoid arthritis (RA). METHODS: A total of 100 RA patients were recruited in this study and completed the MDHAQ. Clinical data and involved joint function assessment were also collected. Routine assessment of patient index data 3 (RAPID3) was calculated using the MDHAQ. The correlations between RAPID3 and disease activity score 28 (DAS28), simplified disease activity index (CDAI), simplified disease activity index (SDAI) and clinical characteristics were analyzed. RESULTS: RAPID3 was correlated with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), swollen joints count, tender joints count and overall physician rating (P<0.05). The MDHAQ had a Cronbach's alpha coefficient of 0.821 and a KMO of 0.576. Bartlett's test of sphericity showed P<0.001. RAPID3 was also correlated with DAS28, CDAI and SDAI, with a coefficient of 0.743, 0.697 and 0.640 (P<0.001), respectively. CONCLUSION: MDHAQ is a reliable instrument for disease activity assessment in patients with RA. It is easy to administer in busy clinical settings.
25882452 Pain management in patients with rheumatoid arthritis. 2015 May 15 Rheumatoid arthritis (RA) is one of the most common inflammatory conditions in the United States affecting approximately 1 million adults. This article briefly reviews the evidence-based diagnosis of RA, mainstays of treatment to prevent joint destruction, and pain management.
25858044 Immuno-PET and Immuno-SPECT of Rheumatoid Arthritis with Radiolabeled Anti-Fibroblast Acti 2015 May One of the most prominent cell populations playing a role in rheumatoid arthritis (RA) is activated fibroblast-like synoviocytes. Among many other proteins, fibroblast-like synoviocytes dominantly express fibroblast activation protein (FAP). Because of the high expression of FAP in arthritic joints, radioimmunoimaging of activated fibroblasts with anti-FAP antibodies might be an attractive noninvasive imaging tool in RA. METHODS: SPECT and PET with (111)In- and (89)Zr-labeled anti-FAP antibody 28H1 was performed in mice with CIA. The radioactivity uptake in joints was quantified and correlated with arthritis score. RESULTS: Both (111)In-28H1 and (89)Zr-28H1 showed high uptake in inflamed joints, being 3-fold higher than that of the irrelevant isotype-matched control antibody DP47GS, clearly indicating specific accumulation of 28H1. Uptake of (111)In-28H1 ranged from 2.2 percentage injected dose per gram (%ID/g) in noninflamed joints to 32.1 %ID/g in severely inflamed joints. DP47GS accumulation ranged from 1.6 %ID/g in noninflamed tissue to 12.0 %ID/g in severely inflamed joints. Uptake of 28H1 in inflamed joints correlated with arthritis score (Spearman ρ, 0.69; P < 0.0001) and increased with severity of arthritis. CONCLUSION: SPECT/CT imaging with the anti-FAP antibody (111)In-28H1 specifically visualized arthritic joints with high resolution, and tracer accumulation correlated with the severity of the inflammation in murine experimental arthritis. Background uptake of the radiolabeled antibody was low, resulting in excellent image quality. (89)Zr-28H1 was less favorable for RA imaging because of an elevated bone uptake of (89)Zr. Future studies will focus on the potential role of 28H1 as a tool to monitor therapy response early on.
27306643 Paired Ig-Like Type 2 Receptor-Derived Agonist Ligands Ameliorate Inflammatory Reactions b 2016 Jul The paired immunoglobulin-like type 2 receptor (PILR) family consists of two functionally opposite members, inhibitory PILRα and activating PILRβ receptors. PILRs are widely expressed in various immune cells and interact with their ligands, especially CD99 expressed on activated T cells, to participate in immune responses. Here we investigated whether PILR-derived agonists inhibit β1 integrin activity as ligands for CD99. PILR-derived peptides as well as PILR-Fc fusion proteins prevented cell adhesion to fibronectin through the regulation of β1 integrin activity. Especially, PILRpep3, a representative 3-mer peptide covering the conserved motifs of the PILR extracellular domain, prevented the clustering and activation of β1 integrin by dephosphorylating FAK and vinculin, which are major components of focal adhesion. In addition, PILRpep3 inhibited transendothelial migration of monocytes as well as endothelial cell tube formation. Furthermore, upon intraperitoneal injection of PILRpep3 into mice with collagen-induced arthritis, the inflammatory response of rheumatoid arthritis was strongly suppressed. Taken together, these results suggest that PILR-derived agonist ligands may prevent the inflammatory reactions of rheumatoid arthritis by activating CD99.
27713619 Spotlight on sirukumab for the treatment of rheumatoid arthritis: the evidence to date. 2016 Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease primarily affecting synovial joints and is characterized by persistent high-grade systemic inflammation. Proinflammatory cytokines, particularly interleukin-6 (IL-6), are of crucial importance in the pathogenesis of the disease, driving both joint inflammation and extra-articular comorbidities. Tocilizumab, a humanized IL-6 receptor-inhibiting monoclonal antibody, has been the first, and, to date, the only, IL-6 inhibitor approved for the treatment of RA. Many studies have demonstrated the potency and effectiveness of tocilizumab in controlling disease activity and radiological progression of RA. These successful results have encouraged the development of novel IL-6 inhibitors, among which a promising agent is sirukumab (SRK), a human anti-IL-6 monoclonal antibody currently under evaluation in Phase II/III studies in patients with RA, systemic lupus erythematosus, giant-cell arteritis, and major depressive disorder. The evidence to date indicates SRK as an effective and well-tolerated new therapeutic tool for patients with active RA, with some preliminary data suggesting a specific beneficial impact on relevant systemic complications associated with the disease, such as depression and cardiovascular disease. Conversely, although pathophysiological considerations make plausible the hypothesis that IL-6 blockade with SRK may also be beneficial in the treatment of many diseases other than RA (either autoimmune or not), available clinical data in patients with systemic lupus erythematosus do not seem to support this view, also giving rise to potentially relevant concerns about drug safety. If large Phase III clinical trials currently in progress in patients with RA confirm the efficacy and tolerability of SRK, then in the long term, this drug could, in the near future, occupy a place in the treatment of the disease, potentially also opening the doors to a more extended use of SRK in a wide range of disorders in which IL-6 plays a key pathogenic role.
25585181 Treat to target in managing inflammatory arthritis. 2015 Jan Treating to target has been used in many areas of medicine, including diabetes mellitus and cardiovascular disease risk. This principle has now been applied to rheumatological conditions, notably inflammatory arthritis. This article discusses the role and importance of this management approach in inflammatory arthritis.