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ID PMID Title PublicationDate abstract
27084908 The Reporting of Patient-reported Outcomes in Studies of Patients with Rheumatoid Arthriti 2016 Jul OBJECTIVE: Patient-reported outcomes (PRO) in rheumatoid arthritis (RA) provide important information regarding disease effect. The study objective was to assess the frequency of PRO use in recent RA studies and compare results with a previous systematic review (SR) in 2005-2007. METHODS: An SR was performed in PubMed MEDLINE (January 2015). Publications were identified using these MEdical Subject Headings terms: "arthritis, rheumatoid" with a limitation to "humans," "all adults: 19+ years," "English," "published in the last 2 years," and "clinical trials." All studies were assessed, whatever their designs. All PRO reported in publications were classified according to general domains of health by 2 authors. Statistics were descriptive. RESULTS: Two hundred fifty articles were analyzed. Of them, 113 (45.2%) were randomized controlled trials; 138 different PRO were reported. The most frequent PRO, similar to the 2007 SR, were function (68.0%), pain (40.0%), patient's global assessment (49.2%), and health-related quality of life (18.4%). Fatigue (14.4%), morning stiffness (10.0%), psychological status (9.6%), productivity losses (6.4%), utility (5.2%), sleep disturbance (2.4%), and coping (2.0%) were rarely reported. Although frequent domains were reported using well-validated questionnaires, the others were reported using heterogeneous questionnaires. CONCLUSION: The PRO collected and reported in RA studies are remarkably consistent with those seen in 2005-2007, and reflect the existing RA Core Set measures. Other domains of health prioritized by patients including fatigue, psychological status, productivity losses, sleep disturbance, and coping remain rarely reported. Further, heterogeneity in outcome measures used presents challenges in interpreting true disease effect and response to therapy.
26543327 Symmetric Dimethylarginine Is Not Associated with Cumulative Inflammatory Load or Classica 2015 Symmetric dimethylarginine (SDMA) indirectly inhibits nitric oxide (NO) synthesis and predicts cardiovascular and all-cause mortality in high-risk patients. The aim of our study was to investigate the associations of cumulative inflammatory burden (assessed by serial measurements of inflammatory markers) and classical cardiovascular (CV) disease risk factors with SDMA in RA patients. 201 RA patients (155 females, median age 67 (59-73)) were assessed at baseline (2006). Classical CV disease risk factors were recorded and systemic inflammation was determined by the measurement of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). At follow-up (2012) SDMA levels were measured by enzyme-linked immunosorbent assay. Mean SDMA levels in RA population were 0.40 (0.40-0.53) μmol/L. No significant association between SDMA and cumulative inflammatory load was established in the analysis. SDMA levels were not found to be significantly related to CV disease risk factors. We explored the potential relationship between SDMA and cumulative inflammatory burden in patients with RA and obtained negative results. SDMA did not relate to CV disease risk factors in our population and its clinical significance as a surrogate marker of endothelial dysfunction in patients with RA remains to be determined.
30641624 [The Real World Study on Evaluating the Effect of Chinese Medicine Combined Western Medici 2016 Nov Objective To observe the curative effect of Chinese medicine (CM) combined West- ern medicine (WM) in treating rheumatoid arthritis (RA) patients. Methods Totally 351 RA patients were allocated into two groups by their willingness, 52 cases in the control group and 299 cases in the combination group. Treatment of WM mainly included non-steroidal anti-inflammatory drugs, glucocorti- coids, and anti-rheumatic drugs. And treatment based on syndrome differentiation of CM was adopted. Four diagnostic information of CM, joint pain, tenderness, swelling index, laboratory indices, and treat- ment expenses were observed. Disease activity score 28 (DAS28) , quality of life score [health assessment questionnaire (HAQ) ] , and efficacy of disease were assessed. Results After 2-3 months of treatment, the total effective rate was higher in the combination group than in the control group (P < 0. 05). After 6-12 months of treatment, the total effective rate, DAS28, and HAQ score were better in the combination group than in the control group (P <0. 05). There was no statistical difference in use of Western drugs, total expenses of hospitalization, total expenses of outpatient service between the two groups (P >0. 05). Patients who were treated by combined treatment, or having higher DAS obtained better effects after 2-3 months of treatment (P <0. 05). Patients who were treated by combined treatment, or having lower DAS obtained better effects after 6-12 months of treatment (P <0. 05). Conclusions Real world study (RWS) observed that combined CM and WM could get more significant effect. It also could effectively reduce disease activity, improve patients' QOL, with no economic burdens added.
26613769 Clinical factors, anticitrullinated peptide antibodies and MRI-detected subclinical inflam 2016 Oct INTRODUCTION: Patients with clinically suspect arthralgia (CSA) have, according to their rheumatologists, an increased risk of rheumatoid arthritis (RA), but their actual outcome is unexplored. This longitudinal study investigated (1) progression from CSA to clinically detectable arthritis and (2) associations of clinical factors, serological factors (among which are anticitrullinated peptide antibodies (ACPAs)) and MRI-detected subclinical inflammation with arthritis development. METHODS: 150 patients with CSA were followed for ≥6 months. At baseline, clinical and serological data were collected and unilateral 1.5 T-MRI of metacarpophalangeal (MCP), wrist and metatarsophalangeal (MTP) joints was made. MRI scoring was done according to the RA MRI scoring system. Subclinical MRI inflammation was defined based on MRI results of 193 symptom-free persons. RESULTS: During follow-up (median=75 weeks, IQR=41-106 weeks), 30 patients developed clinical arthritis; 87% did so <20 weeks after inclusion. In multivariable analyses, age, localisation of initial symptoms in small and large joints (compared with small joints only), C-reactive protein level, ACPA-positivity and subclinical MRI inflammation significantly associated with arthritis development; ACPA and MRI inflammation were most strongly associated (HR (95% CI) respectively, 6.43 (2.57 to 16.05) and 5.07 (1.77 to 14.50)). After 1-year follow-up, 31% of the patients with MRI inflammation and 71% of the ACPA-positive patients with MRI inflammation had progressed to arthritis. Forty-three per cent of the patients that developed arthritis within 1 year were ACPA-negative; 78% of them had subclinical MRI inflammation at baseline. When MRI inflammation was absent arthritis development was infrequent (6% in all patients with CSA and 3% in ACPA-negative patients with CSA). CONCLUSIONS: Subclinical MRI inflammation precedes clinical arthritis with a few months. Subclinical MRI inflammation is, independent of other factors such as ACPA, associated with arthritis development.
26754993 Rheumatoid arthritis and the risk of dementia: A systematic review and meta-analysis. 2016 Jan BACKGROUND: The association between chronic inflammation and dementia has been identified in several epidemiologic studies. However, the data on rheumatoid arthritis (RA), one of the most common chronic inflammatory disorders, remains unclear. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of cohort, case-control, and cross-sectional studies that compared the risk of dementia in patients with RA versus non-RA controls. Data from each study were combined using random-effect, generic inverse variance method of DerSimonian and Laird to calculate the pooled risk ratio (RR) and 95% confidence interval (CI). RESULTS: Three cohort studies and two cross-sectional studies were identified and included in the meta-analysis. We found a significantly increased risk of dementia among patients with RA, with the pooled risk ratio of 1.61 (95% CI, 1.10-2.37). The statistical heterogeneity was high, with an I2 of 91%. CONCLUSIONS: Our study demonstrated a statistically significant increase in the risk of dementia among patients with RA.
26659718 Identification of an immunodominant peptide from citrullinated tenascin-C as a major targe 2016 Oct OBJECTIVES: We investigated whether citrullinated tenascin-C (cTNC), an extracellular matrix protein expressed at high levels in the joints of patients with rheumatoid arthritis (RA), is a target for the autoantibodies in RA. METHODS: Citrullinated sites were mapped by mass spectrometry in the fibrinogen-like globe (FBG) domain of tenascin-C treated with peptidylarginine deiminases (PAD) 2 and 4. Antibodies to cyclic peptides containing citrullinated sites were screened in sera from patients with RA by ELISA. Potential cross-reactivity with well-established anticitrullinated protein antibody (ACPA) epitopes was tested by inhibition assays. The autoantibody response to one immunodominant cTNC peptide was then analysed in 101 pre-RA sera (median 7 years before onset) and two large independent RA cohorts. RESULTS: Nine arginine residues within FBG were citrullinated by PAD2 and PAD4. Two immunodominant peptides cTNC1 (VFLRRKNG-cit-ENFYQNW) and cTNC5 (EHSIQFAEMKL-cit-PSNF-cit-NLEG-cit-cit-KR) were identified. Antibodies to both showed limited cross-reactivity with ACPA epitopes from α-enolase, vimentin and fibrinogen, and no reactivity with citrullinated fibrinogen peptides sharing sequence homology with FBG. cTNC5 antibodies were detected in 18% of pre-RA sera, and in 47% of 1985 Swedish patients with RA and 51% of 287 North American patients with RA. The specificity was 98% compared with 160 healthy controls and 330 patients with osteoarthritis. CONCLUSIONS: There are multiple citrullination sites in the FBG domain of tenascin-C. Among these, one epitope is recognised by autoantibodies that are detected years before disease onset, and which may serve as a useful biomarker to identify ACPA-positive patients with high sensitivity and specificity in established disease.
27863504 B-cell imaging with zirconium-89 labelled rituximab PET-CT at baseline is associated with 2016 Nov 18 BACKGROUND: B cells are key players in the pathogenesis of rheumatoid arthritis (RA). Although successful in 50-60% of patients with RA, anti-B-cell therapy given as rituximab could be more efficient by identifying potential responders prior to treatment. Positron emission tomography (PET) using radiolabeled rituximab for B-cell imaging might provide the means to fulfil this unmet clinical need. The objective of this study was to investigate the association between biodistribution of zirconium-89 ((89)Zr)-rituximab on PET-computed tomography (CT) and clinical response in patients with RA. METHODS: We included 20 patients with RA who were starting rituximab treatment. At the first intravenous (i.v.) therapeutic dose, patients were also injected with (89)Zr-rituximab, followed by PET-CT. European League Against Rheumatism (EULAR) response criteria were applied to determine response at week 24. PET-CT was analyzed visually and quantitatively. Lymph node (LN) biopsies were performed at 0 and 4 weeks to correlate B-cell counts with imaging data. RESULTS: PET-positive hand joints (range 1-20) were observed in 18/20 patients. Responders had significantly higher (89)Zr-rituximab uptake in PET-positive hand joints than non-responders (median target-to-background (T/B)) ratios (IQR) were 6.2 (4.0-8.8) vs. 3.1 (2.2-3.9), p = 0.02). At T/B ≥4.0, positive and negative predictive values for clinical response were respectively 90% and 75%. Quantitative (89)Zr-rituximab hand joint uptake on PET correlated inversely with CD22(+) B-cell count in LN tissue at 4 weeks of treatment (r = 0.6, p = 0.05). In addition, the CD22(+) B-cell count in LN correlated positively with quantitative LN PET data at baseline, supporting the specificity of B-cell imaging on PET. CONCLUSIONS: Non-invasive B-cell imaging by (89)Zr-rituximab PET-CT has promising clinical value to select RA responders to rituximab at baseline. (89)Zr-rituximab PET-CT may also hold promise for monitoring anti-B-cell therapies in other B-cell driven autoimmune diseases, such as systemic lupus erythematosus and Sjögren's disease.
27667787 Tolerogenic dendritic cells generated with dexamethasone and vitamin D3 regulate rheumatoi 2017 Jan Tolerogenic dendritic cells (tolDC) are a new immunotherapeutic tool for the treatment of rheumatoid arthritis (RA) and other autoimmune disorders. We have established a method to generate stable tolDC by pharmacological modulation of human monocyte-derived DC. These tolDC exert potent pro-tolerogenic actions on CD4(+) T cells. Lack of interleukin (IL)-12p70 production is a key immunoregulatory attribute of tolDC but does not explain their action fully. Here we show that tolDC express transforming growth factor (TGF)-β1 at both mRNA and protein levels, and that expression of this immunoregulatory cytokine is significantly higher in tolDC than in mature monocyte-derived DC. By inhibiting TGF-β1 signalling we demonstrate that tolDC regulate CD4(+) T cell responses in a manner that is at least partly dependent upon this cytokine. Crucially, we also show that while there is no significant difference in expression of TGF-βRII on CD4(+) T cells from RA patients and healthy controls, RA patient CD4(+) T cells are measurably less responsive to TGF-β1 than healthy control CD4(+) T cells [reduced TGF-β-induced mothers against decapentaplegic homologue (Smad)2/3 phosphorylation, forkhead box protein 3 (FoxP3) expression and suppression of (IFN)-γ secretion]. However, CD4(+) T cells from RA patients can, nonetheless, be regulated efficiently by tolDC in a TGF-β1-dependent manner. This work is important for the design and development of future studies investigating the potential use of tolDC as a novel immunotherapy for the treatment of RA.
25911222 Increased risk of mycobacterial infections associated with anti-rheumatic medications. 2015 Jul RATIONALE: Anti-tumour necrosis factor (TNF) agents and other anti-rheumatic medications increase the risk of TB in rheumatoid arthritis (RA). Whether they increase the risk of infections with nontuberculous mycobacteria (NTM) is uncertain. OBJECTIVES: To determine the effect of anti-TNF therapy and other anti-rheumatic drugs on the risk of NTM disease and TB in older patients with RA. METHODS: Population-based nested case-control study among Ontario seniors aged ≥67 years with RA who were prescribed at least one anti-rheumatic medication between 2001 and 2011. We identified cases of TB and NTM disease microbiologically and identified drug exposures using linked prescription drug claims. We estimated ORs using conditional logistic regression, controlling for several potential confounders. MEASUREMENTS AND MAIN RESULTS: Among 56 269 older adults with RA, we identified 37 cases of TB and 211 cases of NTM disease; each case was matched to up to 10 controls. Individuals with TB or NTM disease were both more likely to be using anti-TNF therapy (compared with non-use); adjusted ORs (95% CIs) were 5.04 (1.27 to 20.0) and 2.19 (1.10 to 4.37), respectively. Exposure to leflunomide and other anti-rheumatic drugs with high immunosuppressing potential also were associated with both TB and NTM disease, while oral corticosteroids and hydroxychloroquine were associated with NTM disease. CONCLUSIONS: Anti-TNF use is associated with increased risk of both TB and NTM disease, but appears to be a relatively greater risk for TB. Several other anti-rheumatic drugs were also associated with mycobacterial infections.
27481908 Gaps in Addressing Cardiovascular Risk in Rheumatoid Arthritis: Assessing Performance Usin 2016 Nov OBJECTIVE: Cardiovascular disease (CVD) is a major comorbidity for patients with rheumatoid arthritis (RA). This study sought to determine the performance of 11 recently developed CVD quality indicators (QI) for RA in clinical practice. METHODS: Medical charts for patients with RA (early disease or biologic-treated) followed at 1 center were retrospectively reviewed. A systematic assessment of adherence to 11 QI over a 2-year period was completed. Performance on the QI was reported as a percentage pass rate. RESULTS: There were 170 charts reviewed (107 early disease and 63 biologic-treated). The most frequent CVD risk factors present at diagnosis (early disease) and biologic start (biologic-treated) included hypertension (26%), obesity (25%), smoking (21%), and dyslipidemia (15%). Performance on the CVD QI was highly variable. Areas of low performance (< 10% pass rates) included documentation of a formal CVD risk assessment, communication to the primary care physician (PCP) that patients with RA were at increased risk of CVD, body mass index documentation and counseling if overweight, communication to a PCP about an elevated blood pressure, and discussion of risks and benefits of antiinflammatories in patients at CVD risk. Rates of diabetes screening and lipid screening were 67% and 69%, respectively. The area of highest performance was observed for documentation of intent to taper corticosteroids (98%-100% for yrs 1 and 2, respectively). CONCLUSION: Gaps in CVD risk management were found and highlight the need for quality improvements. Key targets for improvement include coordination of CVD care between rheumatology and primary care, and communication of increased CVD risk in RA.
26251154 [Successful second cord blood transplantation (CBT) for late graft failure associated with 2015 Jul A 64-year-old woman underwent reduced-intensity conditioning cord blood transplantation (RIC-CBT) for refractory acute myeloid leukemia (AML). A 6/6 antigen-level HLA-identical cord blood from a male infant was transfused. After successful engraftment with complete donor chimerism, the patient developed mixed chimera (XX 8.8%) on day 82. Tapering of tacrolimus was started on day 96. Bone marrow chimerism analysis showed a decreasing recipient cell population (XX 2.2%) on day 117 and tacrolimus was discontinued with no clinical signs of GVHD on day 123. However, pancytopenia with agranulocytosis was detected on day 138. She was diagnosed as having secondary graft failure associated with Coombs-positive immune hemolytic anemia and immune thrombocytopenia (ITP). At the same time, the percentage of recipient T cell chimerism in peripheral blood was about 50% and the B cell population showed lambda light chain restriction. On day 180, she received a second RIC-CBT due to lack of improvement of agranulocytosis. A single dose of rituximab was administered on day - 11 before the second CBT to eliminate the activated B cells. Prompt neutrophil engraftment was achieved and both hemolytic anemia and ITP also showed resolution. She is currently well (30 months after the second CBT), showing normal blood cell counts and complete second donor chimerism of marrow cells.
26026281 Epigenetic dynamics in immunity and autoimmunity. 2015 Oct A tightly synchronized and spatial-temporal interaction among regulatory proteins within genomic DNA and chromatin is essential for cellular commitment and differentiation. During development and activation of the immune system, a complex regulatory network that involves induction of lineage instructive transcription factors, installation or removal of histone modifications and changes in DNA methylation patterns locally orchestrate the three-dimensional chromatin structure and determine immune cell fate and immune responses. In autoimmune diseases, disease associated epigenetic marks and dynamic changes control the dysregulated immune system, thus determining the disease development and clinical phenotype. In this review, we introduce the dynamic epigenetic regulation of DNA and histones, summarize the epigenetic regulatory mechanisms in the development and differentiation of some important immune cell subsets and provide new insights for the pathogenesis of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and Type 1 diabetes. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.
25295920 Validity and responsiveness of a self-administered foot evaluation questionnaire in rheuma 2015 May OBJECTIVES: A self-administered foot evaluation questionnaire (SAFE-Q) was developed by the Japanese Society for Surgery of the Foot (JSSF). The aim of this study is to evaluate the validity and responsiveness of the SAFE-Q in patients with rheumatoid arthritis (RA). METHODS: In total, 180 patients with RA answered the SAFE-Q. Of 180 patients, 34 answered the SAFE-Q twice, preoperatively and postoperatively, to assess responsiveness. Construct validity was tested by comparing the 5 SAFE-Q subscales and the JSSF standard rating system for the RA foot and ankle scale (JSSF-RA), a Japanese version of the Health Assessment Questionnaire (JHAQ), disease activity score in 28 joints (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI). Responsiveness was examined by calculating the standardized response mean (SRM) and effect size (ES) 3 months after surgery. RESULTS: There were moderate correlations between the SAFE-Q and the JSSF-RA and JHAQ. Conversely, a low correlation was observed between the SAFE-Q and DAS28, SDAI, and CDAI. The responsiveness was high, with an SRM of 0.9 and ES of 0.7 for pain subscales. CONCLUSION: SAFE-Q is a useful tool for assessing the foot and ankle in RA patients.
27801596 Comparative usability study for a certolizumab pegol autoinjection device in patients with 2017 Jan OBJECTIVES: To compare the usability of a new certolizumab pegol (CZP) autoinjector with the adalimumab, etanercept, and golimumab devices in patients with rheumatoid arthritis. METHODS: Two identical studies were performed in 2013 and 2016; patients performed a simulated self-injection with the CZP autoinjector and the most up-to-date device versions at the time in a randomized, consecutive sequence. The primary end point was the ranking of the four autoinjectors in order of preference. Device usability and intuitiveness were assessed across a range of secondary and exploratory end points. RESULTS: The 2013 and 2016 study populations included 76 patients each; a significant majority (2013: 67%; 2016: 59%) ranked the CZP autoinjector as their most preferred device (p < 0.001). Most patients agreed that the CZP autoinjector was easier to use, start, and manipulate, and were more willing to use it than the comparator devices (p < 0.001 for all pairwise comparisons with CZP). Likert score differences also favored the CZP autoinjector regarding how easy it was to determine injection completion. The CZP autoinjector was associated with a low rate of use error. CONCLUSIONS: In both studies, the CZP autoinjector was the preferred choice compared to the alternative devices and was associated with a high level of patient satisfaction.
28004828 Analysis of CXCR5(+)Th17 cells in relation to disease activity and TNF inhibitor therapy i 2016 Dec 22 Th17 and TfH cells are thought to promote tissue inflammation and autoantibody production, respectively, in autoimmune diseases including rheumatoid arthritis (RA). TfH cells that co-express Th17 markers (CXCR5(+)Th17) encompass both of these pathogenic functions, and are increased in some human autoimmune settings including juvenile dermatomyositis. We investigated CXCR5(+)Th17 cells in RA subjects with stable or active disease and before and after TNF inhibitor therapy. CXCR5(+)Th17 cell frequency was increased in RA compared to healthy controls, but other helper T cell subsets were not different. CXCR5(+)Th17 cells correlated with disease activity in subjects with active RA prior to initiation of TNF inhibitor therapy. Baseline CXCR5(+)Th17 cells also correlated with numbers of swollen joints as late as one year post-therapy. CXCR5(+)Th17 cell frequencies were unaltered by TNF blockade and in fact remained remarkably stable within individuals. We conclude that CXCR5(+)Th17 cells are not a direct target of TNF blockade and therefore cannot serve as a biomarker of current disease activity. However, basal CXCR5(+)Th17 cell frequency may indicate underlying differences in disease phenotype between patients and predict ultimate success of TNF inhibitor therapy.
26087654 Interleukin-23 in early disease development in rheumatoid arthritis. 2015 OBJECTIVES: To investigate the levels of interleukin (IL)-23 in patients with early rheumatoid arthritis (eRA) and the effect of anti-tumour necrosis factor (anti-TNF)-α treatment on IL-23 levels. METHOD: Treatment-naïve eRA patients from the OPERA cohort were included (n = 151). Patients were randomized to methotrexate (MTX) plus adalimumab (ADA; n = 75) or MTX plus placebo-ADA (PLA; n = 76). Plasma samples were obtained at baseline and at months 3, 6, and 12 together with values for C-reactive protein (CRP), the 28-joint Disease Activity Score based on CRP (DAS28CRP), scores on the Clinical Disease Activity Index (CDAI) and the Simplified Disease Activity Index (SDAI), visual analogue scale (VAS) for pain/fatigue/physician global and total Sharp/van der Heijde score (TSS). IL-23 was measured at each time point. RESULTS: IL-23 levels decreased significantly in the ADA group from 20.6 pg/mL (IQR 13.1-32.7 pg/mL) at baseline to 18 pg/mL (IQR 7.2-25.0 pg/mL) at 12 months (p < 0.01). No significant decrease in IL-23 level was observed in the PLA group. No associations between baseline IL-23 levels and measures of disease activity (DAS28CRP, CRP, CDAI, or SDAI) at 12 or 24 months were present in the treatment groups. Baseline IL-23 correlated inversely with changes in TSS and symptom duration before diagnosis. CONCLUSIONS: Our data show increased baseline levels and a significant decrease in IL-23 levels in eRA patients treated with anti-TNF-α. The inverse correlation with duration of symptoms before diagnosis supports the importance of IL-23 in the preclinical disease development of RA.
27281130 Myeloperoxidase as a Target for the Treatment of Inflammatory Syndromes: Mechanisms and St 2016 Inflammation is an initial response of the body to a harmful stimuli and it is achieved by the increased movement of leukocytes (especially granulocytes) from blood into injured tissues. It is required for healing wounds and infections. Despite their indispensable role in microbial killing, the inflammation reactions may also cause diseases to a host such as hay fever, atherosclerosis, and rheumatoid arthritis. The enzymes and oxidizing species released during the inflammatory process can cause damages to the host tissues which lead to inflammatory syndromes. The role of myeloperoxidase (MPO) in the inflammatory reactions is well documented. It contributes in killing the pathogens but it is also implicated in several inflammatory syndromes such as Parkinson's disease, Alzheimer's disease and atherosclerosis. Thus, this enzyme has attracted more attention of the scientists and it has become a target for drug designing. In the last decade, several reversible and irreversible MPO inhibitors were identified as very high potent inhibitors such as fluoroalkylindole, aromatic hydroxamic acid, thioxanthine and benzoic acid hydrazide derivatives. In this review, we tried to illustrate the MPO inhibitors and highlight their structure activity relationship (SAR). In this paper we also discussed the mechanism of the inhibitory effect of the most potent compounds.
25896020 Deficiency of cathepsin K prevents inflammation and bone erosion in rheumatoid arthritis a 2015 May 22 Using rheumatoid arthritis (RA) and periodontitis mouse models, we demonstrate that RA and periodontitis share many pathological features, such as deregulated cytokine production, increased immune-cell infiltration, increased expression of Toll-like receptors (TLRs), and enhanced osteoclast activity and bone erosion. We reveal that genetic deletion of cathepsin K (Ctsk) caused a radical reduction in inflammation and bone erosion within RA joint capsules and periodontal lesions, a drastic decrease in immune-cell infiltration, and a significant reduction in osteoclasts, macrophages, dendritic and T-cells. Deficiency of Ctsk greatly decreased the expression of TLR-4, 5, and 9 and their downstream cytokines in periodontal gingival epithelial lesions and synovial RA lesions. Hence, Ctsk may be targeted to treat RA and periodontitis simultaneously due to its shared osteoimmune role.
27409294 On-demand ultrasonography assessment in the most symptomatic joint supports the 8-joint sc 2017 Mar OBJECTIVES: To investigate whether on-demand ultrasonography (US) assessment alongside a routine examination is useful in the management of rheumatoid arthritis (RA). METHODS: US was performed in eight (bilateral MCP 2, 3, wrist and knee) joints as the routine in a cumulative total of 406 RA patients. The most symptomatic joint other than the routine joints was additionally scanned. Power Doppler (PD) and gray-scale images were scored semiquantitatively. Eight-joint scores were calculated as the sum of individual scores for the routine joints. RESULTS: The most symptomatic joint was found among the routine joints in 209 patients (Group A) and in other joints in 148 (Group B). The PD scores of the most symptomatic joint correlated well with the 8-joint scores in Group A (r(s) = 0.66), but not in Group B (r(s) = 0.33). The sensitivity and specificity of assessment of the most symptomatic joint for routine assessment positivity were high (84.0% and 100%, respectively) in Group A, but low (50.0% and 61.8%, respectively) in Group B. Additional examination detected synovitis in 38% of Group B with negative results in the routine. CONCLUSIONS: On-demand US assessment in the most symptomatic joint, combined with the routine assessment, is useful for detecting RA synovitis.
26916043 An effective medical partnership in Nagasaki, Japan for patients with rheumatoid arthritis 2016 Nov OBJECTIVES: A clear division of the roles of inpatient facilities and outpatient clinics treating patients with rheumatoid arthritis (RA) is needed. To address this, we created a medical partnership between a university hospital and 43 community clinics in Nagasaki, Japan. METHODS: We recruited the clinic physicians and compiled a list of the RA medications used (i.e. methotrexate [MTX], other disease-modifying antirheumatic drugs [DMARDs], and biologics). When a patient's low disease activity or remission was confirmed at the university hospital, the hospital/clinic partnership provided double follow-up/medical care with semiannual meetings between the hospital and clinic physicians. RESULTS: We enrolled 149 patients who maintained clinical remission at 43 clinics over a 54-month period, without rare serious events. Among the nine patients who returned to the university hospital due to relapse, 66.7% had exacerbated RA within 18 months. An average 8.8-9.6 mg/week (max. 14 mg/week) MTX dose was prescribed at the clinics. The biologic usage rate was 22.1%, with a yearly increase. Among the patients treated with biologics, the DAS28ESR at enrollment was 2.65, with 58% treated with an MTX/biologic combination. A significant reduced number of patients with RA per rheumatologist were observed. CONCLUSIONS: Maintenance of DAS remission without major adverse events was attained in the medical partnership.