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ID PMID Title PublicationDate abstract
27447696 Associations between eNOS polymorphisms and susceptibility to systemic lupus erythematosus 2017 Oct OBJECTIVE: The aim of this study was to determine whether endothelial nitric oxide synthase (eNOS) polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: A meta-analysis was conducted on associations between the 4b/a, T786C, and G894T polymorphisms of eNOS and SLE or RA using the following methods: (1) allele contrast, (2) recessive model, (3) dominant model, and (4) homozygous contrast. RESULTS: Nineteen studies were included in this meta-analysis, comprising eleven studies on SLE (1561 patients and 1565 controls) and eight on RA (1624 patients and 2118 controls). Meta-analysis showed a significant association between SLE and the 4b/a polymorphism using the recessive model and the homozygous contrast (odds ratio [OR] = 1.836, 95 % confidence interval [CI] = 1.171-2.878, p = 0.008; OR = 2.055, 95 % CI = 1.302-3.243, p = 0.002). Ethnicity-specific meta-analysis showed a significant association between the aa vs. bb of the 4b/a polymorphism and SLE in European populations (OR = 2.096, 95 % CI = 1.288-4.0, p = 0.027), but not in Arab populations. Stratification by presence of lupus nephritis (LN) indicated a significant association between the a allele and the aa + ab genotype of the 4b/a polymorphism and LN in SLE patients (OR = 2.125, 95 % CI = 1.289-3.054, p = 0.003; OR = 2.655, 95 % CI = 1.509-4.671, p = 0.001). Meta-analysis indicated no association between SLE and the T786C and G894T polymorphisms. No association was found between the eNOS 4b/a, T786C, and G894T polymorphisms and RA CONCLUSIONS: This meta-analysis of published studies shows that the eNOS 4b/a polymorphism may be associated with the development of SLE, but the 4b/a, T786C, and G894T polymorphisms may be not associated with RA susceptibility.
28356243 Efficacy of glucocorticoids, conventional and targeted synthetic disease-modifying antirhe 2017 Jun OBJECTIVES: To perform a systematic literature review (SLR) informing the 2016 update of the recommendations for the management of rheumatoid arthritis (RA). METHODS: An SLR for the period between 2013 and 2016 was undertaken to assess the efficacy of glucocorticoids (GCs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and targeted synthetic DMARDs (tsDMARDs) (tofacitinib and baricitinib) in randomised clinical trials. RESULTS: For GCs, four studies were included in the SLR. Patients without poor prognostic factors experienced benefit when GCs were added to methotrexate (MTX). Lower doses of GCs were similar to higher doses. For csDMARDs, two new studies comparing MTX monotherapy with combination csDMARD were included in the SLR. In the tREACH trial at the end of 12 months no difference between the groups in disease activity, functional ability and radiographic progression was seen, using principles of tight control (treat-to-target). In the CareRA trial, combination therapy with csDMARDs was not superior to MTX monotherapy and monotherapy was better tolerated.For tsDMARDs, tofacitinib and baricitinib were shown to be more effective than placebo (MTX) in different patient populations. CONCLUSIONS: Addition of GCs to csDMARD therapy may be beneficial but the benefits should be balanced against the risk of toxicity. Under tight control conditions MTX monotherapy is not less effective than combination csDMARDs, but better tolerated. Tofacitinib and baricitinib are efficacious in patients with RA, including those with refractory disease.
27323772 Antimodified protein antibody response pattern influences the risk for disease relapse in 2017 Feb OBJECTIVE: To perform a detailed analysis of the autoantibody response against post-translationally modified proteins in patients with rheumatoid arthritis (RA) in sustained remission and to explore whether its composition influences the risk for disease relapse when tapering disease modifying antirheumatic drug (DMARD) therapy. METHODS: Immune responses against 10 citrullinated, homocitrullinated/carbamylated and acetylated peptides, as well as unmodified vimentin (control) and cyclic citrullinated peptide 2 (CCP2) were tested in baseline serum samples from 94 patients of the RETRO study. Patients were classified according to the number of autoantibody reactivities (0-1/10, 2-5/10 and >5/10) or specificity groups (citrullination, carbamylation and acetylation; 0-3) and tested for their risk to develop relapses after DMARD tapering. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining the role of autoantibodies in predicting relapse. RESULTS: Patients varied in their antimodified protein antibody response with the extremes from recognition of no (0/10) to all antigens (10/10). Antibodies against citrullinated vimentin (51%), acetylated ornithine (46%) and acetylated lysine (37%) were the most frequently observed subspecificities. Relapse risk significantly (p=0.011) increased from 18% (0-1/10 reactivities) to 34% (2-5/10) and 55% (>5/10). With respect to specificity groups (0-3), relapse risk significantly (p=0.021) increased from 18% (no reactivity) to 28%, 36% and finally to 52% with one, two or three antibody specificity groups, respectively. CONCLUSIONS: The data suggest that the pattern of antimodified protein antibody response determines the risk of disease relapse in patients with RA tapering DMARD therapy. TRIAL REGISTRATION NUMBER: 2009-015740-42; Results.
27993828 Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monothera 2017 Jun OBJECTIVES: To evaluate the efficacy and safety of different doses of filgotinib, an oral Janus kinase 1 inhibitor, as monotherapy in patients with active rheumatoid arthritis (RA) and previous inadequate response to methotrexate (MTX). METHODS: In this 24-week phase IIb study, patients with moderately to severely active RA were randomised (1:1:1:1) to receive 50, 100 or 200 mg filgotinib once daily, or placebo, after a ≥4-week washout from MTX. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR)20 response at week 12. RESULTS: Overall, 283 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib at any dose achieved ACR20 responses versus placebo (≥65% vs 29%, p<0.001). For other key end points at week 12 (ACR50, ACR70, ACR-N, Disease Activity Score based on 28 joints and C reactive protein, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index) significant differences from baseline in favour of filgotinib 100 and 200 mg versus placebo were seen; responses were maintained or improved through week 24. Rapid onset of action was observed for most efficacy end points. Dose-dependent increases in haemoglobin were observed. The percentage of patients with treatment-emergent adverse events (TEAE) was similar in the placebo and filgotinib groups (∼40%). Eight patients on filgotinib and one on placebo had a serious TEAE, and four patients, all of whom received filgotinib, experienced a serious infection. No tuberculosis or opportunistic infections were reported. CONCLUSIONS: Over 24 weeks, filgotinib as monotherapy was efficacious in treating the signs and symptoms of active RA, with a rapid onset of action. Filgotinib was generally well tolerated. TRIAL REGISTRATION NUMBER: NCT01894516.
28167169 Adaptation, reliability and validity testing of a Persian version of the Health Assessment 2017 Jan OBJECTIVE: The aim of the present study was to culturally adapt and evaluate reliability and validity of Health Assessment Questionnaire-Disability Index (HAQ-DI) in Iranian patients with rheumatoid arthritis (RA). SUBJECTS: 234 patients with RA for validation study, Eighty-six participants for reliability study. METHODS: Test-retest relative reliability and internal consistency of Persian version of HAQ-DI were examined by intraclass correlation coefficient (ICC) and Cronbach's alpha, respectively. Additionally, HAQ-DI construct validity (Spearman's correlation) was examined using Persian version of Short-Form 36 Health survey (SF-36), activity and severity parameters. RESULTS: Persian version of HAQ-DI total score showed excellent test-retest reliability (ICC = 0.98) and internal consistency (Cronbach's alpha = 0.95). Spearman's correlations between the total PHAQ-DI score and activity and severity parameters were above 0.55. Correlation between PHAQ-DI and SF-36 Physical Health were higher as compared with SF-36 Mental Health. CONCLUSION: Persian version of HAQ-DI is a reliable and valid culturally-adapted instrument in order to measure functional limitations in Iranian people with RA.
28118833 An empirical evaluation of the SF-12, SF-6D, EQ-5D and Michigan Hand Outcome Questionnaire 2017 Jan 24 BACKGROUND: The aim of this study was to assess the psychometric properties, namely acceptability, validity, reliability, interpretability and responsiveness of the EuroQol EQ-5D (EQ-5D visual analogue (VAS) and EQ-5D (utility)), Short Form 12 Dimensions (SF-12), SF-6D and Michigan Hand Outcome Questionnaire (MHQ) in patients with rheumatoid arthritis (RA) of the hand. METHODS: The empirical investigation was based upon data from a randomised controlled trial of 488 adults with rheumatoid arthritis who had pain and dysfunction of the hands and/or wrists. Participants completed the EQ-5D, SF-12 and MHQ at baseline and at 4 and 12 months follow up. Acceptability was measured using completion rates over time; construct validity using the "known groups" approach, based on pain troublesomeness; convergent validity using spearman's rho correlation (ρ); reliability using internal consistency (Cronbach's alpha); interpretability using minimal important differences (MID); and responsiveness using effect sizes and standardised response means (SRM) stratified by level of self-rated improvement in hand and wrist function or level of self-rated benefit and satisfaction from trial treatments. RESULTS: At baseline, the study population had a mean age of 62.4 years, a mean MHQ score of 52.1 and included 76% women. The EQ-5D (utility) had the highest completion rates across time points. All instruments discriminated between pre-specified groups based on pain troublesomeness. Convergent validity analysis indicated that the MHQ score correlated strongly with the EQ-5D (ρ = 0.65) and SF-6D (ρ = 0.63) utility scores. The MHQ was most responsive at detecting change in indicators of RA pain severity between baseline and 4 months, whilst minimal important differences varied considerably across PROMs. CONCLUSIONS: The instruments evaluated in this study displayed varying psychometric properties in the context of RA of the hand. The selection of a preferred instrument in evaluative studies should ultimately depend on the relative importance placed on individual psychometric properties and the importance placed on generation of health utilities for economic evaluation purposes.
28064207 Rheumatoid arthritis is getting less frequent-results of a nationwide population-based coh 2017 May 1 OBJECTIVES: The objectives of this study were to examine changes in the incidence and prevalence of RA between 1990 and 2014 and to explore if there is any geographic variation in the incidence and prevalence of RA in the UK. METHODS: This was a primary care-based prospective cohort study. People contributing acceptable data to Clinical Practice Research Datalink between 1 January 1990 and 31 December 2014 were included. Read codes were used to identify RA cases ⩾18 years of age. The prevalence and incidence rates for each year were standardized to the 2014 population and the regional incidence and prevalence of RA for the year 2014 were standardized to the overall population. RESULTS: The incidence and prevalence of RA was 3.81/10 000 person-years and 0.67%, respectively, in 2014. The annual incidence of RA decreased by 1.6% (95% CI 0.8, 2.5) between 1990 and 2014, with significant joinpoints at 1994 and 2002. The prevalence of RA increased by 3.7%/year (95% CI 3.2, 4.1) from 1990 to 2005 and decreased by 1.1%/year (95% CI 2.0, 0.2) between 2005 and 2014. There were significant differences in the occurrence of RA throughout different regions of the UK, with the highest incidence in East Midlands, Yorkshire and Humber and the highest prevalence in North East, Yorkshire and Humber. CONCLUSION: The incidence of RA is decreasing, with a reduction in prevalence in recent years. There is significant geographic variation in the occurrence of RA in the UK. Further research is required to identify the reasons underlying this phenomenon so that public health interventions can be designed to further reduce the incidence of RA.
27181115 The efficacy and safety of additional administration of tacrolimus in patients with rheuma 2017 Jan OBJECTIVES: Tocilizumab (TCZ) shows good retention in patients with rheumatoid arthritis (RA), but no previous reports demonstrated hopeful treatment options against inadequate response to TCZ. Tacrolimus (TAC) has proved to show efficacy against inadequate response to tumor necrosis factor alpha inhibitors, yet its add-on effects on TCZ remain unknown. METHODS: Twenty patients with RA (17 women, age 58.6 years, disease duration 12.1 years, prior TCZ duration 2.6 years, 18 intravenous [8 mg/kg/month] and 2 subcutaneous [324 mg/month] TCZ treatments, methotrexate 6.1 mg/week [70.0%]) who showed an inadequate response to TCZ (clinical disease activity index [CDAI] ≥ 5.8, 18 secondary non-responders) were additionally treated with TAC (1.1 mg/day), and enrolled in this 24-week, prospective study. RESULTS: Seventeen patients (85.0%) continued the treatment for 24 weeks. Statistically significant decreases in outcome measures were as follows: disease activity score based on 28 joints with C-reactive protein (DAS28-CRP) from 3.3 at baseline to 2.1 at week 24 (p < 0.001), CDAI from 17.7 to 7.6 (p < 0.001), and serum matrix metalloproteinase-3 levels from 232.8 to 66.2 ng/ml (p < 0.001). About 15 patients (75%) achieved low disease activity or remission (DAS28-CRP ≤2.7 or CDAI ≤10) at week 24. CONCLUSIONS: Adding low-dose TAC to inadequate responders to TCZ may be a promising complementary treatment option.
29136759 Novel function of hydroxychloroquine: Down regulation of T follicular helper cells in coll 2018 Jan Hydroxychloroquine (HCQ) is an immunosuppressive agent widely used in rheumatoid arthritis (RA). T follicular helper (Tfh) cells play a vital role in the pathogenesis of RA. However, whether HCQ suppresses arthritis development through interfering with Tfh cells have never been reported. To address this issue, we investigated the percent of Tfh cells in newly diagnosed RA patients and found that they were up-regulated in peripheral blood. Importantly, in ex vivo experiments of peripheral blood mononuclear cells (PBMCs) from healthy volunteers, we proved that the percentage of Tfh cells in PBMCs and purified CD4(+) T cells were decreased after HCQ treatment. In in vivo experiments of collagen-induced arthritis (CIA) model, we discovered that HCQ suppressed the incidence and score of arthritis, reduced the secretion of proinflammatory cytokines in serum. Similar to ex vivo study, the ratio of Tfh cells in HCQ treated CIA mice declined to the level of vehicle-treated group. Further research demonstrated that HCQ inhibited the generation of Tfh cells stimulated by IL-12 and IL-21. In conclusion, our study indicates a previously unrecognized mechanism of HCQ in RA, that HCQ directly suppresses the generation of Tfh cells by blocking IL-12 and IL-21 signaling pathways probably.
28848352 Suppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbo 2017 Dexamethasone (DEX), a non-particulate glucocorticoid (GC) to inhibit anti-inflammatory response, has been widely used for the treatment of various diseases such as arthritis, cancer, asthma, chronic obstructive pulmonary disease, cerebral edema, and multiple sclerosis. However, prolonged and/or high-dose GC therapy can cause various serious adverse effects (adrenal insufficiency, hyperglycemia, Cushing's syndrome, osteoporosis, Charcot arthropathy, etc). In this study, developed DEX-carbon nanotube (CNT) conjugates improved intracellular drug delivery via increased caveolin-dependent endocytosis and ultimately suppressed the expression of major pro-inflammatory cytokines in tumor necrosis factor-α (TNF-α)-stimulated human fibroblast-like synoviocytes (FLS) at low drug concentrations. Specifically, DEX on polyethylene-glycol (PEG)-coated CNTs induced caveolin uptake, recovered mitochondrial disruption, and inhibited reactive oxygen species production by targeting mitochondria that was released from the early endosome in TNF-α-stimulated FLS. The obtained results clearly demonstrated that DEX-PEG-coated CNTs significantly inhibited the inflammation by FLS in rheumatoid arthritis (RA) by achieving greater drug uptake and efficient intracellular drug release from the endosome, thus suggesting a mechanism of effective low-dose GC therapy to treat inflammatory diseases, including RA and osteoarthritis.
28882929 RhoB blockade selectively inhibits autoantibody production in autoimmune models of rheumat 2017 Nov 1 During the development of autoimmune disease, a switch occurs in the antibody repertoire of B cells so that the production of pathogenic rather than non-pathogenic autoantibodies is enabled. However, there is limited knowledge concerning how this pivotal step occurs. Here, we present genetic and pharmacological evidence of a positive modifier function for the vesicular small GTPase RhoB in specifically mediating the generation of pathogenic autoantibodies and disease progression in the K/BxN preclinical mouse model of inflammatory arthritis. Genetic deletion of RhoB abolished the production of pathogenic autoantibodies and ablated joint inflammation in the model. Similarly, administration of a novel RhoB-targeted monoclonal antibody was sufficient to ablate autoantibody production and joint inflammation. In the MRL/lpr mouse model of systemic lupus erythematosus (SLE), another established preclinical model of autoimmune disease associated with autoantibody production, administration of the anti-RhoB antibody also reduced serum levels of anti-dsDNA antibodies. Notably, the therapeutic effects of RhoB blockade reflected a selective deficiency in response to self-antigens, insofar as RhoB-deficient mice and mice treated with anti-RhoB immunoglobulin (Ig) both mounted comparable productive antibody responses after immunization with a model foreign antigen. Overall, our results highlight a newly identified function for RhoB in supporting the specific production of pathogenic autoantibodies, and offer a preclinical proof of concept for use of anti-RhoB Ig as a disease-selective therapy to treat autoimmune disorders driven by pathogenic autoantibodies.
28797877 Annual trends in knee arthroplasty and tibial osteotomy: Analysis of a national database i 2017 Oct BACKGROUND: Various nationwide studies have reported differing annual trends in utilization of knee arthroplasty and tibial osteotomy. Using the Diagnosis Procedure Combination database in Japan, the present series examined annual trends and demographics in total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA) and tibial osteotomy. METHODS: All patients were identified who underwent TKA, UKA or tibial osteotomy for osteoarthritis, osteonecrosis or rheumatoid arthritis of the knee between July 2007 and March 2015. RESULTS: A total of 170,433 cases of TKA, 13,209 cases of UKA and 8760 cases of tibial osteotomy were identified. The proportion of patients undergoing UKA rose from 4.0% in 2007 to 8.1% in 2014 (P<0.001), and that of tibial osteotomy from 2.6% in 2007 to 5.5% in 2014 (P<0.001); the proportion undergoing TKA fell from 93.4% in 2007 to 86.3% in 2014 (P<0.001). Between 2007 and 2014 the proportions of patients with osteonecrosis who underwent UKA and tibial osteotomy increased from 34.7% and 11.6% to 38.6% and 16.2%, respectively (P=0.001 for UKA and P=0.004 for tibial osteotomy). The proportions of patients with osteonecrosis undergoing UKA or tibial osteotomy were significantly greater than those with other diagnoses (P<0.001 for both). CONCLUSIONS: The popularity of UKA and tibial osteotomy in Japan increased during the period 2007-2014 at the expense of TKA. The proportions of UKA and tibial osteotomy in patients with osteonecrosis also increased, and were larger than those in patients with other causative diseases.
28656478 Autoantibodies against myelin sheath and S100β are associated with cognitive dysfunction 2017 Sep Rheumatoid arthritis (RA) has been associated with cognitive impairment and peripheral production of autoantibodies. Autoantibodies against central nervous system (CNS) proteins and S100 calcium-binding β (S100β) were found increased in diseases characterized by cognitive impairment like Alzheimer disease and Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). The aim of this study was to investigate the plasma levels of autoantibodies against myelin basic protein (anti-MBP), myelin oligodendrocyte glycoprotein (anti-MOG) and S100β, and their relationships with cognitive performance in RA patients. Twenty patients with active rheumatoid arthritis and 19 age-, sex-, and schooling-matched healthy controls were recruited. Multiple dimensions of cognitive function were evaluated by structured clinical questionnaires. Autoantibodies and S100β levels were assessed by ELISAs. Patients had significantly higher levels of anti-MBP IgG (17.51 ± 1.36 vs. 5.24 ± 0.53 ng/mL), anti-MOG IgG (5.68 ± 1.34 vs. 0.51 ± 0.49 ng/mL), and S100β protein (2.24 ± 0.50 vs. 0.47 ± 0.06) than controls (all p < 0.0001). After adjusting for potential confounders, RA group presented worse cognitive performance involving the working memory and executive functions such as inhibition, flexibility, and mental control in parallel to higher autoantibodies and S100β levels than healthy controls (all p < 0.001). Levels of anti-MBP were negatively associated with delayed verbal recall (DVR; r = -0.42, p = 0.005), Stroop Color-Word (r = -0.48, p = 0.004), and N-Back Total scores (r = -0.59, p < 0.0001) and positively with Trail Making Test B (TMB, r = 0.53, p = 0.001). Negative correlation was found between levels of anti-MOG and DVR (r = -0.64, p < 0.0001), N-Back Total scores (r = -0.35, p = 0.03), Stroop Color-Word (r = -0.51, p = 0.001), and positively with TMB (r = 0.50, p = 0.003). S100β levels were associated with DVR (r = -0.51, p = 0.002), TMB (r = 0.46, p = 0.008), Stroop Color-Word (r = -0.67, p < 0.0001), and N-Back Total (r = -0.52, p = 0.003). RA is associated with impaired cognitive performance associated with higher levels of CNS-related autoantibodies and S100β levels. Given the importance of myelin integrity to cognition, our data indicate that these autoantibodies may be harmful to proper cognitive function.
29037904 Rheumatic diseases and autoimmune vascular dementia. 2017 Dec Vascular dementia (VD) comes second after Alzheimer's disease (AD) as a cause of impaired cognition. VD is not a specific nosological entity, but rather a syndrome encompassing a number of diseases caused by impaired supply of blood to the brain. Systemic autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis and antiphospholipid syndrome (APS) can be associated with dementia. VD is often related to the presence of traditional cardiovascular risk factors, but it may also be associated with a host of disorders affecting the brain blood vessels, neuronal cells, or both. It is important to entertain in the differential diagnosis of VD, to recognize and to cure them accurately in order to preserve life's quality of our patients.
29261674 Mitochondrial haplogroups in patients with rheumatoid arthritis: No association with disea 2017 OBJECTIVE: To describe the distribution of specific mitochondrial DNA (mtDNA) haplogroups (hgs) in a cohort of patients with rheumatoid arthritis (RA). METHODS: Two-hundred nineteen consecutive patients with RA had mtDNA isolated from their blood, sequenced and haplotyped. Patients were diagnosed according to the American College of Rheumatology (ACR)/European league against Rheumatism (EULAR) criteria. Demographic and clinical data were retrieved from the Danish nationwide database (DANBIO). Logistic regression analyses were performed to test for associations. RESULTS: One-hundred eighty-four patients were eligible for analysis. Haplogroup frequencies were: H (n = 88; 47.8%), U (n = 37; 20.1%), T (n = 22; 12.0%), J (n = 16; 8.7%), K (n = 11; 5.9%), HV (n = 6; 3.3%) and V (n = 4; 2.2%). The distribution of individual hgs was identical to the background population. Radiographic erosions were significantly associated with hg clusters JT (OR = 2.37, 95% confidence interval (CI): 1.07-5.53, p = 0.038). Significantly fewer patients from hg cluster JT received biological treatment (OR = 0.17, 95% CI: 0.03-0.87, p = 0.038). Albeit, none of these associations were significant when corrected for multiple tests. CONCLUSION: There was no significant association between mtDNA hgs and presence of RA or disease manifestations. There was an, albeit insignificant, overrepresentation of patients with hg JT among patients with erosive disease; however, slightly fewer patients in the JT group were treated with biological drugs.
27722854 Disease-Drug Interaction of Sarilumab and Simvastatin in Patients with Rheumatoid Arthriti 2017 Jun INTRODUCTION: Elevated interleukin (IL)-6 occurs in patients with active rheumatoid arthritis (RA), which has been shown to lead to a decrease in cytochrome P450 (CYP) enzyme activity and alterations in drug concentrations metabolized by CYP. IL-6 signaling blockade by IL-6 receptor (IL-6R) antagonists may reverse this effect of IL-6 and restore CYP activity. This study evaluated the pharmacokinetic profile of simvastatin (a CYP3A4 substrate) before and 1 week after a single dose of sarilumab (a human monoclonal antibody [mAb] blocking the IL-6Rα) in patients with RA, to assess potential interaction. METHODS: Nineteen patients with active RA received oral simvastatin 40 mg 1 day before and 7 days after subcutaneous injection of sarilumab 200 mg. The pharmacokinetic parameters of simvastatin and its primary metabolite, β-hydroxy-simvastatin acid, were calculated using noncompartmental analysis. RESULTS: Compared with simvastatin alone, single-dose simvastatin administration 7 days after single-dose sarilumab administration in patients with RA resulted in reduced simvastatin and β-hydroxy-simvastatin acid exposure in plasma. Mean effect ratios (90 % confidence interval) for simvastatin peak plasma concentration (C (max)) and area under the concentration-time curve extrapolated to infinity (AUC(∞)) were 54.1 % (42.2-69.4 %) and 54.7 % (47.2-63.3 %), respectively. No changes occurred in time to C (max) or half-life for either simvastatin or β-hydroxy-simvastatin acid after sarilumab administration. CONCLUSIONS: Sarilumab treatment resulted in a reduction in exposure of simvastatin, consistent with reversal of IL-6-mediated CYP3A4 suppression in patients with active RA, as was reported for tocilizumab with simvastatin and for sirukumab with midazolam. CLINICAL TRIAL REGISTRATION NUMBER: NCT02017639.
28476652 Lipoprotein(a) concentrations in rheumatoid arthritis on biologic therapy: Results from th 2017 May BACKGROUND: Plasma concentrations of lipoprotein (a) (Lp(a)), a lipoprotein with atherogenic and thrombogenic properties, have a strong genetic basis, although high concentrations of Lp(a) have also been reported in the context of inflammation, as in rheumatoid arthritis (RA). Few studies evaluate the impact of biologic therapies (BT) on Lp(a) in RA, taking into account that with these new therapies a better control of inflammation is achieved. OBJECTIVE: The aim of the study was to evaluate the plasma concentrations of Lp(a) in Spanish RA patients on BT attending rheumatology outpatient clinics. METHODS: Baseline analysis of the CARdiovascular in rheuMAtology project, a 10-year prospective study, evaluating the risk of cardiovascular events in RA and other forms of inflammatory arthritis. RA patients were classified according to treatment: no biologic, anti-tumor necrosis factor, anti-interleukin-6 receptor tocilizumab (TCZ), and other biologic (rituximab or abatacept). A model of linear multivariate regression was built in which the dependent variable was Lp(a) concentration and the explanatory variable was BT. The model was adjusted for confounding factors. RESULTS: Seven hundred and seventy-five RA patients were analyzed. Plasma concentrations of total cholesterol and triglyceride were significantly higher in TCZ-treated patients. Nevertheless, no significant difference in the atherogenic index between TCZ-treated patients and patients without BT was found. After adjusting for confounding factors, patients with BT had lower concentrations of Lp(a) than those without BT; however, only TCZ-treated patients achieved statistically significant differences (β: -0.303, 95% confidence interval: -0.558 to -0.047; P = .02). CONCLUSIONS: RA patients treated with TCZ show lower plasma concentrations of Lp(a) compared with patients without BT.
29201904 Correlation in the Coronal Angle between Knee and Hindfoot Was Observed in Patients with R 2017 The purpose of this study is to investigate the compensatory correlation between knee and hindfoot in patients with rheumatoid arthritis (RA). This cross-sectional study included 218 patients (407 lower extremities). Radiographs of the hindfoot and full-length posteroanterior hip-to-calcaneus standing radiographs were evaluated. The destruction of the hindfoot was evaluated using the Larsen grading system. The coronal angular deformity of the knee and hindfoot was evaluated by the femorotibial angle (FTA) and the angle between the tibial shaft and the entire hindfoot (tibiohindfoot angle, THFA). The correlation between FTA and THFA was determined by Pearson's coefficient. For all patients, FTA correlated to THFA (R = 0.28, p < 0.001). The correlation was observed as long as the talocrural joint was preserved (Larsen grade ≤ 2), even if the subtalar joint had been destroyed (Larsen grade ≥ 3). However, the correlation was not observed when the talocrural joint was destroyed (Larsen grade ≥ 3, R = -0.02, p = 0.94). The pain in the hindfoot did not correlate with FTA or THFA. In conclusion, a compensatory deformity of the hindfoot against the deformity of the knee was observed in RA, and the correlation was lost when talocrural joint was destroyed.
28052711 'Like the worst toothache you've had' - How people with rheumatoid arthritis describe and 2017 Nov BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease often associated with disability. Despite new treatments, pain and activity limitations are still present. OBJECTIVES: To describe how persons with RA experience and manage pain in their daily life. METHODS: Seven semi-structured focus groups (FGs) were conducted and analyzed using content analysis. RESULTS: The analysis revealed four categories: 1) Pain expresses itself in different ways referred to pain as overwhelming, aching or as a feeling of stiffness. 2) Mitigating pain referred to the use of heat, cold, medications and activities as distractions from the pain. 3) Adapting to pain referred to strategies employed as coping mechanisms for the pain, e.g. planning and adjustment of daily activities, and use of assistive devices. 4) Pain in a social context referred to the participants' social environment as being both supportive and uncomprehending, the latter causing patients to hide their pain. CONCLUSIONS: Pain in RA is experienced in different ways. This emphasizes the multi-professional team to address this spectrum of experiences and to find pain management directed to the individual experience that also include the person's social environment.
28515234 A methodological approach for assessing the uptake of core outcome sets using ClinicalTria 2017 May 17 Objective To assess the uptake of the rheumatoid arthritis core outcome set using a new assessment method of calculating uptake from data in clinical trial registry entries.Design Review of randomised trials.Setting ClinicalTrials.gov.Subjects 273 randomised trials of drug interventions for the treatment of rheumatoid arthritis and registered in ClinicalTrials.gov between 2002 and 2016. Full publications were identified for completed studies from information in the trial registry or from an internet search using Google and the citation database Web of Science.Main outcome measure The percentage of trials reporting or planning to measure the rheumatoid arthritis core outcome set calculated from the information presented in the trial registry and compared with the percentage reporting the rheumatoid arthritis core outcome set in the resulting trial publications.Results The full rheumatoid arthritis core outcome set was reported in 81% (116/143) of trials identified on the registry as completed (or terminated) for which results were found in either the published literature or the registry. For trials identified on the registry as completed (or terminated), using information only available in the registry gives an estimate for uptake of 77% (145/189).Conclusions The uptake of the rheumatoid arthritis core outcome set in clinical trials has continued to increase over time. Using the information on outcomes listed for completed or terminated studies in a trial registry provides a reasonable estimate of the uptake of a core outcome set and is a more efficient and up-to-date approach than examining the outcomes in published trial reports. The method proposed may provide an efficient approach for an up-to-date assessment of the uptake of the 300 core outcome sets already published.