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ID PMID Title PublicationDate abstract
29908986 Hydroquinone exposure worsens the symptomatology of rheumatoid arthritis. 2018 Aug 1 The genesis of rheumatoid arthritis (RA) is complex and dependent on genetic background and exposure to environmental xenobiotic. Indeed, smoking is associated to developing and worsening pre-existing RA. Nevertheless, the mechanisms and cigarette compounds involved in the harmful processes have not been elucidated. Here, we investigated if the exposure to hydroquinone (HQ), an abundant pro-oxidative compound of cigarette and benzene metabolite, could worsen the ongoing RA. Hence, collagen-induced arthritis (CIA) was induced in male Wistar rats by s.c. injection of 400 μg (200 μL) of bovine collagen type II emulsified in complete Freund's adjuvant on day 1, and a booster injection was performed on day 7. Exposures to nebulized HQ (25 ppm), saline solution or HQ vehicle solution (5% ethanol in saline) were carried out for 1 h, once a day, on days 21-27 after CIA induction. On day 27, animals were euthanized and samples were collected for further analyses. Exposure to HQ caused loss of weight, intensified paw edema, enhanced levels of tumor necrosis factor-α (TNF-α) and anti-citrullinated protein antibody (ACPA) in the serum; augmented synoviocyte proliferation and influx of aril hydrocarbon receptor (AhR) positive cells into the synovial membrane, altered collagen fibre rearrangement in the synovia, and synoviocytes isolated from HQ exposed rats secreted higher levels of pro-inflammatory cytokines, TNF-α and interleukin-1β. Associated, we point out HQ as an environmental pollutant that aggravates RA, suggesting its participation on worsening RA in smoking patients.
30219772 Safety Profile of Baricitinib in Patients with Active Rheumatoid Arthritis with over 2 Yea 2019 Jan OBJECTIVE: Baricitinib is an oral, once-daily selective Janus kinase (JAK1/JAK2) inhibitor for adults with moderately to severely active rheumatoid arthritis (RA). We evaluated baricitinib's safety profile through 288 weeks (up to September 1, 2016) with an integrated database [8 phase III/II/Ib trials, 1 longterm extension (LTE)]. METHODS: The "all-bari-RA" group included patients who received any baricitinib dose. Placebo comparison was based on the 6 studies with 4 mg and placebo up to Week 24 ("placebo-4 mg" dataset). Dose response assessment was based on 4 studies with 2 mg and 4 mg including LTE data ("2 mg-4 mg-extended"). The uncommon events description used the non-controlled all-bari-RA. RESULTS: There were 3492 patients who received baricitinib for 6637 total patient-years (PY) of exposure (median 2.1 yrs, maximum 5.5 yrs). No differences in rates of death, adverse events leading to drug discontinuation, malignancies, major adverse cardiovascular event (MACE), or serious infections were seen for 4 mg versus placebo or for 4 mg versus 2 mg. Infections including herpes zoster were significantly more frequent for 4 mg versus placebo. Deep vein thrombosis/pulmonary embolism were reported with 4 mg but not placebo [all-bari-RA incidence rate (IR) 0.5/100 PY]; the IR did not differ between doses (0.5 vs 0.6/100 PY, 2 mg vs 4 mg, respectively) or compared to published RA rates. All-bari-RA had 6 cases of lymphoma (IR 0.09/100 PY), 3 gastrointestinal perforations (0.05/100 PY), 10 cases of tuberculosis (all in endemic areas; 0.15/100 PY), and 22 all-cause deaths (0.33/100 PY). IR for malignancies (0.8/100 PY) and MACE (0.5/100 PY) were low and did not increase with prolonged exposure. CONCLUSION: In this integrated analysis of patients with moderate to severe active RA with exposure up to 5.5 years, baricitinib has an acceptable safety profile in the context of demonstrated efficacy. Trial registration numbers: NCT01185353, NCT00902486, NCT01469013, NCT01710358, NCT01721044, NCT01721057, NCT01711359, and NCT01885078 at clinicaltrials.gov.
30423415 Transdermal drug delivery of triptolide-loaded nanostructured lipid carriers: Preparation, 2019 Jan 10 The objective of this present study was to develop and evaluate the triptolide-loaded nanostructured lipid carriers (TPL-NLCs) for transdermal drug delivery system (TDDS). TPL-NLCs was prepared with emulsification technique and optimized by central composite design of a response surface methodology (CCD-RSM). The optimized TPL-NLCs were spherical and physically stable with the average size of 139.6.0 ± 2.53 nm and Zeta potential of -36.03 ± 2.41 mV. The encapsulation efficiency and drug loading were 97.15% ± 9.46 and 10.35% ± 1.12, respectively. Moreover, the in vitro release study showed that TPL-NLCs had a sustained release profiles and the in vitro penetration study indicated that TPL-NLCs could effectively penetrate into skin. Besides, the methodology of skin-blood synchronous microdialysis was established to evaluate the pharmacokinetics of TPL-NLCs in vivo and the results displayed that the TPL concentration in skin was higher than that in blood. And TPL-NLCs presented a remarkable effect of decreasing knee edema, inhibiting inflammation by regulating the levels of TNF-α, IL-1β and IL-6, which indicated that TPL-NLCs was a promising topical administration in treatment of edema and inflammation associated with rheumatoid arthritis (RA).
30183602 Rheum4U: Development and testing of a web-based tool for improving the quality of care for 2019 May OBJECTIVES: To develop a web-based tool (Rheum4U) to capture clinically meaningful data to direct treatment. Rheum4U integrates longitudinal clinical data capture of rheumatoid arthritis (RA) disease activity measures and patient-reported outcomes measures (PROMs). This study tests the feasibility, acceptability and efficiency of Rheum4U among patients and healthcare providers. METHODS: Rheum4U was developed in two phases: P1 design and development; and P2 pilot testing. P1: A working group of rheumatologists and researchers (n=13) performed a prioritisation exercise to determine data elements to be included in the platform. The specifications were finalised and supplied to the platform developer. Alpha testing was performed to correct initial software bugs. 18 testers (physicians, nurses and recruited non-patient lay-testers) beta tested Rheum4U for usability. P2: Rheum4U was piloted in 2 rheumatology clinics and evaluated for feasibility, efficiency and acceptability using interviews, observation and questionnaires with patients and healthcare providers. RESULTS: 110 RA patients, 9 rheumatologists and 9 allied health providers participated in the pilot. Mean patient age was 53 years and 74% were female. The majority (86%) were satisfied or very satisfied with online data entry and 79% preferred it to paper entry. Healthcare providers found Rheum4U easy and clear to use (90%), and they perceived that it improved their job performance (91%). Completeness and easy availability of the patient information improved clinic efficiency. CONCLUSIONS: Rheum4U highlights the benefits of a web-based tool for clinical care, quality improvement and research in the clinic and this study provides valuable information to inform full platform implementation.
29266862 Orthopedic Surgery Among Patients With Rheumatoid Arthritis: A Population-Based Study to I 2018 Oct OBJECTIVE: To identify risk factors for large-joint surgery (LJS) versus small-joint surgery (SJS) in rheumatoid arthritis (RA) and evaluate trends in surgery rates over time. METHODS: A retrospective medical record review of all orthopedic surgeries following first fulfillment of the 1987 American College of Rheumatology criteria for adult-onset RA among residents of Olmsted County, Minnesota between 1980 and 2013 was performed. Risk factors were examined using Cox models adjusted for age, sex, and calendar year of RA incidence. Trends in incidence of joint surgeries were examined using Poisson regression models. RESULTS: A total of 1,077 patients with RA (mean age 56 years, 69% female, 66% seropositive for rheumatoid factor [RF] and anti-cyclic citrullinated peptide [anti-CCP] antibodies) were followed for a median of 10.7 years, during which 112 patients (90 women) underwent at least 1 SJS and 204 (141 women) underwent at least 1 LJS. Risk factors included advanced age, and RF and anti-CCP antibody positivity for both SJS and LJS, and body mass index ≥30 kg/m(2) for LJS. Risk factors for SJS and LJS at any time during followup included the presence of radiographic erosions, large-joint swelling, and methotrexate use. SJS rates decreased by calendar year of incidence (hazard ratio 0.53, P = 0.001), with significant decline in the rates of SJS after 1995. The cumulative incidence of SJS was higher in women than men (P = 0.008). CONCLUSION: In recent years, there has been a significant decline in the rates of SJS but not LJS in patients with RA. The incidence of SJS is higher among women. Traditional RA risk factors are strong predictors for SJS and LJS. Increasing age and obesity are predictive of LJS.
30076153 Ectopic RASGRP2 (CalDAG-GEFI) expression in rheumatoid synovium contributes to the develop 2018 Dec OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune polyarthritis, in which fibroblast-like synoviocytes (FLS) play a key role in cartilage and bone destruction through tumour-like proliferation and invasiveness. Considering still unsatisfactory remission rate in RA even under treatment with biological disease-modifying antirheumatic drugs, novel therapeutic strategy for treatment-resistant RA is still awaited. In this study, we analysed the expression and function of Ras guanine nucleotide-releasing proteins (RASGRPs), guanine exchange factors for small GTPase Ras, in FLS as a potential therapeutic target for RA. METHODS: The expression of RASGRPs mRNA was quantified by a real-time PCR assay in FLS isolated from synovial tissue samples. RASGRP2 protein was also evaluated immunohistochemically. Then, we transiently transfected FLS with RASGRP2 expression vector and assessed their proliferation, adhesion, migration and invasion by cellular functional assays and downstream signalling activation using immunoblot. Finally, the therapeutic effect of RASGRP2 silencing was evaluated in type-II collagen-induced arthritis rats. RESULTS: RASGRP2 was abundantly expressed in FLS from RA synovium, whereas scarcely found in those from osteoarthritis. Expression of RASGRP2 in RA-FLS was enhanced by transforming growth factor-beta. RASGRP2 activated RAP-1, subsequently affecting nuclear factor kappa-light-chain-enhancer of activated B cells pathway and actin dynamics in FLS. RASGRP2-overexpressed FLS had increased abilities of adhesion, migration and interleukin (IL)-6 production. Silencing of RASGRP2 using the intra-articular injection of Rasgrp2-specific siRNAs dampened experimental arthritis in rats by inhibiting pannus formation. CONCLUSIONS: RASGRP2 was identified to be involved in the pathogenesis of RA by promoting adhesion, migration and IL-6 production from FLS, proposed as a potential novel non-immunosuppressive therapeutic target for RA.
29548542 Predictors of hypogammaglobulinemia during rituximab maintenance therapy in rheumatoid art 2018 Oct OBJECTIVE: Rituximab (RTX) is an anti-CD20 monoclonal antibody that selectively depletes B-cell population. Thus, it presents a potential risk for the development of hypogammaglobulinemia and related infectious events. Our aim was to identify predictors of hypogammaglobulinemia in RA patients long-term treated with RTX. METHODS: Multicenter observational usual care study of patients with RA on RTX maintenance therapy (minimal exposition of 30 months). Serum protein electrophoresis was performed before each RTX infusion. Hypogammaglobulinemia and severe hypogammaglobulinemia were defined as total gammaglobulin <6g/L and <4g/L, respectively. The primary outcome was the occurrence within the follow-up period of hypogammaglobulinemia. RESULTS: 134 patients met inclusion criteria and were followed-up for 79.5 ± 24.6 months. Hypogammaglobulinemia occurred during the follow-up period in 23 patients (2.7 events per 100 pt-yrs). The mean time to development of hypogammaglobulinemia was 64 ± 23 months. Patients who developed hypogammaglobulinemia were more likely to experience severe infections (26.1% vs. 6.3%, P = 0.033). Multivariate Cox analysis identified gammaglobulin levels <8g/L at baseline as an independent predictor of hypogammaglobulinemia (HR 7.34 [95% CI: 2.00-26.90], P = 0.003). Concomitant methotrexate (MTX) intake was also predictive of a reduced risk of hypogammaglobulinemia occurrence (HR 0.26 [95% CI: 0.08-0.87], P = 0.03). CONCLUSION: Our results show that gammaglobulin levels of less than 8g/L at baseline is a strong independent risk factor for developing subsequent hypogammaglobulinemia, whereas concomitant MTX therapy seems to be a protective factor in RA patients treated long-term with RTX.
29578852 Economic Burden of Patients with Inadequate Response to Targeted Immunomodulators for Rheu 2018 Apr BACKGROUND: Targeted immunomodulators (TIMs), including biologic disease-modifying antirheumatic drugs (DMARDs) and JAK/STAT inhibitors, are effective therapies for rheumatoid arthritis (RA), but some patients fail to respond or lose response over time. This study estimated the real-world prevalence of RA patients with inadequate responses to an initial TIM (nonresponders) in the United States and assessed their direct and indirect economic burden compared with treatment responders. METHODS: Administrative claims data (January 1999-March 2014) from a large private-insurer database were used, which included work-loss data from a subset of reporting companies. Eligible patients (classified as responders and nonresponders) had ≥ 1 claim for a TIM approved for the treatment of RA and ≥ 2 RA diagnoses in the claims history, with continuous pharmaceutical and medical benefit eligibility for 6 months before (baseline) and 12 months after (study period) the date of the first TIM claim (index date). All-cause and RA-related health care resource use (HCRU) and costs, work loss, and indirect costs during the study period were compared for responders versus nonresponders. Multivariable regression was used to adjust for baseline covariates. Sensitivity analyses of HCRU and direct costs were conducted for patients with index dates before and after 2008 to account for different approval dates of TIMs. RESULTS: Of 7,540 eligible patients with RA, 2,527 (34%) were classified as responders, and 5,013 (66%) were classified as nonresponders; 407 and 723 had work-loss data, respectively. After adjusting for baseline covariates, nonresponders had significantly higher HCRU, including inpatient admissions (incidence rate ratio [IRR] = 1.94), outpatient visits (IRR = 1.19), emergency department visits (IRR = 1.53), and number of prescription fills (IRR = 1.09; all, P < 0.001). Nonresponders also had significantly higher adjusted all-cause ($12,868 vs. $9,621, respectively) and RA-related ($5,740 vs. $4,495; both, P < 0.001) medical costs compared with responders. In addition, nonresponders reported significantly more days of work lost compared with responders (22.1 vs. 16.7 days, respectively; IRR = 1.21; P = 0.007) and higher indirect costs ($3,548 vs. $2,890; P = 0.002). Sensitivity analyses of HCRU and direct costs by index date (before and after 2008) were consistent with the full sample. CONCLUSIONS: A large portion of patients with RA had inadequate responses to their initial TIM therapy with significantly higher economic burden, including higher HCRU, medical costs, and indirect costs due to work loss, compared with TIM therapy responders. DISCLOSURES: Funding for this research was provided by AbbVie, which was involved in all stages of the study research and manuscript preparation. Tundia and Fuldeore are employed by AbbVie. Song and Macaulay are employed by Analysis Group, which received grants from AbbVie to conduct this study. Strand reports grants and personal fees from AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Celltrion, Corrona, Crescendo, Genentech/Roche, GSK, Janssen, Lilly, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, and UCB outside the submitted work. Study concept and design were contributed by Tundia, Song, and Macaulay, along with other authors. Data analyses were designed and conducted by Song and Macaulay. All authors contributed to data interpretation. Writing of the manuscript was led by Tundia, Song, and Macaulay, with revisions by all authors. A synopsis of the current research was presented at the American College of Rheumatology/Association of Rheumatology Health Professionals meeting, which took place in Washington, DC, during November 11-16, 2016.
28719435 Leukocytoclastic Vasculitis and Dermal Perivascular Hemophagocytosis Associated With Adali 2018 Jan Tumor necrosis factor (TNF)-α inhibitors target TNF-α to effectively treat autoimmune inflammatory conditions, such as rheumatoid arthritis. However, many cases of cutaneous and systemic vasculitis related to TNF-α inhibitors have been reported in the literature. Here, the authors report the first case of a 61-year-old Japanese woman who developed leukocytoclastic vasculitis with cutaneous perivascular hemophagocytosis, which was related to elevated cytokines and immune complexes after initiating adalimumab for rheumatoid arthritis without evidence of hemophagocytic syndrome and rarely encountered in the skin. The patient was successfully treated by discontinuing adalimumab and initiating corticosteroid therapy, which should be considered as the treatment of choice. We believe that our case confirms and adds to the evidence pertaining to the involvement of TNF-α in dermal perivascular hemophagocytosis, a histologic finding rarely observed in the skin.
29490707 A pyoderma gangrenous-like cutaneous leishmaniasis in a Libyan woman with rheumatoid arthr 2018 Mar 1 BACKGROUND: Several case reports describe diseases presenting with skin ulcerations, which resemble pyoderma gangrenosum especially in immune-compromised patients, often proven on further workup, to have an infective or malignant etiology. However, treatment of pyoderma gangrenosum by systemic steroids or other immunosuppressive agents may worsen the condition. CASE PRESENTATION: We report here, a 45 year-old Libyan woman with rheumatoid arthritis on low dose steroids with pyoderma gangrenosum-like skin lesions and positive pathergy. Slit-smear was positive for Leishmania amastigotes and histopathological examination confirmed the diagnosis of cutaneous leishmaniasis. The lesions healed completely by parenteral sodium stibogluconate (Pentostam) 600 mg daily. CONCLUSION: We report for the first time, a rare and unusual presentation of pyoderma gangrenosum like-cutaneous leishmaniasis in a patient with rheumatoid arthritis. Atypical cutaneous leishmaniasis should not be ruled out in the differential diagnosis of unresponsive skin diseases, with slit/smear and a skin biopsy is required.
29439591 Assessment of effectiveness and safety of biosimilar infliximab (CT-P13) in a real-life se 2018 Oct OBJECTIVE: To assess the effectiveness and safety of infliximab biosimilar, CT-P13, administered in a real-life setting to adult patients with active rheumatoid arthritis (RA) or ankylosing spondylitis (AS). METHODS: This multi-center, non-interventional, observational study was conducted in Bulgaria, the Czech Republic, and Romania. A total of 151 patients with severe active RA (n = 81) or AS (n = 70) were enrolled and treated with CT-P13 for 24 weeks, according to current medical recommendations. Effectiveness was assessed using the 4-item Disease Activity Score 28 with C-reactive protein (DAS28-CRP) for RA patients, and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS patients. Safety was assessed by withdrawals and adverse events (AEs). RESULTS: A total of 129 patients (RA: 67; AS: 62) were included in the effectiveness analysis. CT-P13 treatment significantly improved DAS28-CRP scores at 12 and 24 weeks (p = .0001 vs baseline for both timepoints) in patients with RA and BASDAI scores at 12 and 24 weeks (p = .0001 vs baseline for both timepoints) in patients with AS. CRP levels were significantly reduced at 12 and 24 weeks (p = .0001 vs baseline for both timepoints). Among 713 infusions, 34 AEs were reported (4.8% of infusions), of which 11 were considered related to CT-P13 treatment. Two of seven serious AEs were considered possibly (hepatocellular injury) or definitely (dyspnoea due to allergic infusion reaction) treatment-related. Eight patients discontinued CT-P13 due to AEs and four patients were withdrawn due to therapeutic failure. CONCLUSIONS: CT-P13 was effective and safe in a real-life setting in patients with active RA or AS.
30657069 Hand strength in patients with RA correlates strongly with function but not with activity 2018 Aug 3 BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints, especially of the hands. The evaluation of handgrip strength (HS) and pinch strength can be useful to detect reduction in hand function in RA patients. The aim of the study was to compare HS and pinch strength between RA patients (RA Group - RAG) and a non-RA control group (CG) and to relate HS and pinch strength to functional capacity, duration and disease activity in the RAG. METHODS: A cross-sectional case control study. The RAG was assessed for disease activity by the Disease Activity Score (DAS-28); for functional capacity by the Health Assessment Questionnaire (HAQ), the Cochin Hand Functional Scale (CHFS) questionnaire, and the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire; and for HS and pinch strength (2-point tip-to-tip, lateral or key, and 3-point) using Jamar® and pinch gauge dynamometers, respectively. Associations were analyzed by Pearson and Spearman tests, and groups were compared by the independent samples t test, with a significance level of P <  0.05. RESULTS: The convenience sample included 121 rheumatoid patients and a control group matched by age, sex, and body mass index. The RAG showed lower strength values compared with the CG in all measurements (P <  0.01, 95% CI) and these values were associated with worse performance in the functional questionnaires and greater disease activity and duration. There was a strong correlation among the functional assessment instruments. CONCLUSIONS: The decrease in grip and pinch strength, easily measured by portable dynamometers, is a strong indicator of functional disability in RA patients.
29324347 Design, synthesis and biological evaluation of 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivati 2018 Feb 10 Bruton's tyrosine kinase (Btk) is a Tec family kinase with a well-defined role in the B cell receptor (BCR) and Fcγ receptor (FcR) signaling pathways, which makes it a uniquely attractive target for the treatment of autoimmune diseases, such as rheumatoid arthritis (RA). We reported a series of compounds bearing 7H-pyrrolo [2,3-d]pyrimidin-4-amine scaffold that potently inhibited Btk in vitro. Analysis of the structure-activity relationships (SAR) and drug-like profiles led to the discovery of the optimal compound B16. B16 preferentially inhibited Btk (IC(50) = 21.70 ± 0.82 nM) over closely related kinases with moderate selectivity. Cell-based tests also confirmed that B16 significantly inhibited Btk Y223 auto-phosphorylation and PLCγ2 Y1217 phosphorylation. MTT revealed that B16 displayed weak suppression against normal LO2, HEK293 and THP-1 cell lines with IC(50) values over 30 μM. Moreover, B16 showed very weak potential to block the hERG channel (IC(50) = 11.10 μM) in comparison to ibrutinib (IC(50) = 0.97 μM). Owing to its favorable physicochemical properties (ClogP = 2.53, aqueous solubility ≈ 0.1 mg/mL), pharmacokinetic profiles (F = 49.15%, t(1/2) = 7.02 h) and reasonable CYP450 profile, B16 exhibited potent anti-arthritis activity and similar efficacy to ibrutinib in reducing paw thickness in CIA mice. In conclusion, B16 is a potent, selective and durable inhibitor of Btk and has the potential to a safe and efficacious treatment for arthritis.
29605999 Synthesis and Evaluation of Hydrogen Peroxide Sensitive Prodrugs of Methotrexate and Amino 2018 Apr 26 A series of novel hydrogen peroxide sensitive prodrugs of methotrexate (MTX) and aminopterin (AMT) were synthesized and evaluated for therapeutic efficacy in mice with collagen induced arthritis (CIA) as a model of chronic rheumatoid arthritis (RA). The prodrug strategy selected is based on ROS-labile 4-methylphenylboronic acid promoieties linked to the drugs via a carbamate linkage or a direct C-N bond. Activation under pathophysiological concentrations of H(2)O(2) proved to be effective, and prodrug candidates were selected in agreement with relevant in vitro physicochemical and pharmacokinetic assays. Selected candidates showed moderate to good solubility, high chemical and enzymatic stability, and therapeutic efficacy comparable to the parent drugs in the CIA model. Importantly, the prodrugs displayed the expected safer toxicity profile and increased therapeutic window compared to MTX and AMT while maintaining a comparable therapeutic efficacy, which is highly encouraging for future use in RA patients.
29799517 The ABP Dendrimer, a Drug-Candidate against Inflammatory Diseases That Triggers the Activa 2018 May 25 The ABP dendrimer, which is built on a phosphorus-based scaffold and bears twelve azabisphosphonate groups at its surface, is one of the dendrimers that has been shown to display immuno-modulatory and anti-inflammatory effects towards the human immune system. Its anti-inflammatory properties have been successfully challenged in animal models of inflammatory disorders. In this review, we trace the discovery and the evaluation of the therapeutic effects of the ABP dendrimer in three different animal models of both acute and chronic inflammatory diseases. We emphasize that its therapeutic effects rely on the enhancement of the production of Interleukin-10, the paradigm of anti-inflammatory cytokines, by different subsets of immune cells, such as monocytes/macrophages and CD4+ T lymphocytes.
29516170 Can cardiovascular magnetic resonance prompt early cardiovascular/rheumatic treatment in a 2018 Jun Life expectancy in autoimmune rheumatic diseases (ARDs) remains lower compared to the general population, due to various comoborbidities. Cardiovascular disease (CVD) represents the main contributor to premature mortality. Conventional and biologic disease-modifying antirheumatic drugs (DMARDs) have considerably improved long-term outcomes in ARDs not only by suppressing systemic inflammation but also by lowering CVD burden. Regarding atherosclerotic disease prevention, EULAR has recommended tight disease control accompanied by regular assessment of traditional CVD risk factors and lifestyle changes. However, this approach, although rational and evidence-based, does not account for important issues such as myocardial inflammation and the long asymptomatic period that usually proceeds clinical manifestations of CVD disease in ARDs before or after the diagnosis of systemic disease. Cardiovascular magnetic resonance (CMR) can offer reliable, reproducible and operator independent information regarding myocardial inflammation, ischemia and fibrosis. Some studies suggest a role for CMR in the risk stratification of ARDs and demonstrate that oedema/fibrosis visualisation with CMR may have the potential to inform cardiac and rheumatic treatment modification in ARDs with or without abnormal routine cardiac evaluation. In this review, we discuss how CMR findings could influence anti-rheumatic treatment decisions targeting optimal control of both systemic and myocardial inflammation irrespective of clinical manifestations of cardiac disease. CMR can provide a different approach that is very promising for risk stratification and treatment modification; however, further studies are needed before the inclusion of CMR in the routine evaluation and treatment of patients with ARDs.
30008127 Foot function in rheumatoid arthritis patients: a cross-sectional study. 2018 Dec Rheumatoid arthritis (RA) is a chronic disease that affects mainly small joints from hands and feet. The aims of this study were to analyze the prevalence of foot involvement in a sample of Brazilian RA patients and to explore the influence of disease variables such as inflammatory activity, serological, and epidemiological profile in this type of involvement. One hundred RA patients and 100 healthy controls paired for gender, age, and body mass index answered the FFI-BR (Foot Functional Index-Brazilian version) that evaluates foot function. RA patients had epidemiological and clinical data collection upon direct questioning and chart review. C-reactive protein (CRP), ESR (erythrocyte sedimentation rate), and DAS28-ESR were used to measure disease activity. In the RA sample, 98% had foot pain versus 76% in the controls (p < 0.0001; OR = 15.4; 95% CI = 3.4-67.5); 96% had some difficulty in function versus 66% of controls (p < 0.0001; OR = 12.3; 95% CI = 4.1-36.5); and 73% had some incapacity versus 20% of controls (p < 0.0001; OR = 10.8; 95% CI = 5.5-20.9). Values of FFI-BR showed correlation with ESR (p = 0.006), CRP (p = 0.01), and DAS28-ESR (p < 0.0001). No association between FFI-BR total score and gender, ethnic background, positive rheumatoid factor, tobacco exposure, and any of used medications was found (all p = ns). The majority of RA patients suffers from foot problems and was associated with inflammatory biomarkers. The control of inflammatory activity may help in the treatment of this problem.
29538083 Risk Factors for Transfusions Following Total Joint Arthroplasty in Patients With Rheumato 2018 Dec BACKGROUND/OBJECTIVE: Despite effective therapies, rheumatoid arthritis (RA) can result in joint destruction requiring total joint arthroplasty to maintain patient function. An estimated 16% to 70% of those undergoing total joint arthroplasty of the hip or knee will receive a blood transfusion. Few studies have described risk factors for blood transfusion following total joint arthroplasty in patients with RA. The aim of this study was to identify demographic and clinical risk factors associated with receiving a blood transfusion following total joint arthroplasty among patients with RA. METHODS: A retrospective study (n = 3270) was conducted using deidentified patient health claims information from a commercially insured, US data set (2007-2009). Data analysis included descriptive statistics and multivariate logistic regression. RESULTS: Females were more likely to receive a blood transfusion (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.16-1.87; p = 0.001). When compared with those in the South, patients residing the Midwest were less likely to receive a blood transfusion following total joint arthroplasty (OR, 0.56; 95% CI, 0.44-0.71). Relative to those receiving total knee arthroplasty, patients who underwent total hip arthroplasty were more likely to receive a blood transfusion (OR, 1.39; 95% CI, 1.14-1.70), and patients who underwent a total shoulder arthroplasty were less likely to receive a blood transfusion (OR, 0.14; 95% CI, 0.05-0.38; p < 0.001). Patients with a history of anemia were more likely to receive a blood transfusion compared with those who did not have this diagnosis (OR, 3.30; 95% CI, 2.62-4.14; p < 0.001). CONCLUSIONS: Risk factors for the receipt of blood transfusions among RA patients who have undergone total joint arthroplasty were identified.
30327652 PD-L1(+) Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients a 2018 Background: B cells play an important role in the development and maintenance of rheumatoid arthritis (RA). Although IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) able to suppress autoimmune and inflammatory responses, recent reports showed that B cell-mediated immune suppression may also occur independent of IL-10. For instance, B cells can modulate T cell immune responses through the expression of regulatory molecules such as PD-L1. So far, PD-L1-expressing B cells have not been analyzed in RA patients. Objective: To analyze the frequency of PD-L1-expressing B cells in the peripheral blood of RA patients compared to healthy controls (HC) matched for sex and age, their function on T cell response and their changes in response to therapy. Methods: Fresh peripheral blood B cells from RA patients and HC were characterized by flow cytometry and their functionality assessed in a co-culture system with autologous T cells. Results: The frequencies of CD19(+)PD-L1(+) B cells, CD24(hi)CD38(-)PD-L1(+) and CD24(hi)CD38(hi)PD-L1(+) B cells were significantly lower in untreated RA patients than in HC. In a follow-up study, the frequencies of PD-L1(+) B cells (CD19(+)PD-L1(+) B cells, CD24(hi)CD38(-)PD-L1(+) and CD24(hi)CD38(hi)PD-L1(+) B cells) increased significantly after treatment in good responder patients, although the frequency of total CD24(hi)CD38(hi) B cells decreased. CD19(+) B cells from untreated RA patients and HC upregulated PD-L1 expression similarly upon stimulation with CpG plus IL-2 and were able to suppress, in vitro, CD8(+) T cell proliferation and cytokine production in a PD-L1-dependent manner. Conclusions: Our results show that PD-L1(+) B cells exhibiting T cell suppressive capacity are significantly decreased in untreated RA patients but increase in response to successful treatment. PD-L1 expression on B cells from RA patients can be modulated in vitro and PD-L1(+) B cells could thus provide new perspectives for future treatment strategies.
29595274 [Chronic pain therapy in inflammatory rheumatic diseases]. 2018 Spring Chronic pain is a common health problem related to most of inflammatory rheumatic disorders. It is pain that has persisted for at least 3 month and cannot be fully relieved by standard pain medication. 40-60 % of patients do not have adequate relief of their pain. Paramount in the management of chronic pain patients is assessment of the pain and its impact on physical and psychosocial functioning. Multidisciplinary and multimodal approach is of vital importance. Non-steroidal anti-rheumatic drugs (NSA) have been used mainly due to their strong analgesic effect, especially in the treatment of acute pain as well as their anti-inflammatory effect in the treatment of chronic i pain. Long-term systemic administration of NSA may be associated with a number of serious side effects, which significantly limit NSA use in long term therapy. Due to opiophobia, opioids are insufficiently used treatment modality. Knowledge about pain and its management, as well as an awareness of barriers to effective pain therapy, are important not only for pain specialists but also primary care physicians.Key words: chronic pain - non-steroidal antirheumatic drugs - opiophobia - opioids - pain assessment - paracetamol - rheumatoid arthritis.