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ID PMID Title PublicationDate abstract
31373751 Biomimetic hydroxyapatite as potential polymeric nanocarrier for the treatment of rheumato 2019 Dec Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology with much higher prevalence in world's population. RA is initially associated with inflammation of joints and cartilages that ultimately leads to their destruction thus requiring a therapeutic intervention. The available conventional therapeutic strategies for RA are not satisfactory because of the associated side effects such as toxicity, delayed action, and dependence. Therefore, a carrier system is required that should deliver the drug to the target site with minimal side effects. In this connection, nanocarrier systems are of prime importance because of the associated benefits such as their nano-scaled size, targeted drug delivery, and reduced toxicity that can improve the patient's compliance. Moreover, in the past few decades, nano-particulate-based drug delivery approaches that have been investigated for the treatment of RA include ceramics, polymers, and hydrogels. Among these nanocarrier systems, ceramics like hydroxyapatite have gathered striking attention due to their bioactive, biocompatible, and bio-conductive characteristics. Nano-sized hydroxyapatite (HA) permeates the bone tissues and serves as a source of calcium phosphates required for bone repairing that are damaged during disease process. The aim of this review article is to highlight the potential use of HA as nanocarrier for anti-rheumatic drugs as well its possible effect on bone remodeling.
30902094 Use of daily electronic patient-reported outcome (PRO) diaries in randomized controlled tr 2019 Mar 22 BACKGROUND: Rheumatoid arthritis (RA) is associated with significantly diminished health-related quality of life. Patient-reported outcomes (PROs) are considered important in RA; however, some symptoms such as morning joint stiffness (MJS) and fatigue that are considered important by patients are not captured by the American College of Rheumatology "core set" measures for RA trials. The US Food and Drug Administration has endorsed electronic capture of clinical trial data including PROs, and electronic PRO (ePRO) systems may lead to more accurate and complete data capture, improved compliance, and patient acceptance compared with paper-based methods. Our objective was to assess the implementation of ePRO measures of Duration and Severity of MJS, Severity of Worst Tiredness, and Severity of Worst Joint Pain in baricitinib RA-BEAM and RA-BUILD phase 3 randomized clinical trials (RCTs). METHODS: A daily electronic diary (handheld device; Invivodata®, Inc.) was utilized to capture PRO data in the RCTs. Three "reporting window" options were incorporated to accommodate differences in patients' routine daily schedules, and alarms were programmed for each reporting window. Duration of MJS was recorded in "hours and minutes," and Severity of MJS, Worst Tiredness, and Worst Joint Pain were captured on a 0 to 10 rating scale, with a higher score indicating more severe symptoms. The patients and site staff were trained to use the daily electronic diary. RESULTS: Patients with moderately to severely active RA used the daily electronic diary in the RA-BEAM study (N = 1305) and RA-BUILD study (N = 684). The average compliance, calculated as total days completed by patients compared with total days expected to complete the diary, through Week 12 was high (RA-BEAM 94% patients; RA-BUILD 93% patients), potentially attributable to appropriate training, clarity of instructions, simple user interface, and electronic device design. Identified process challenges included non-timely issuance of the device, low battery, inadequate training of patients before data collection, inappropriate diary set-up, and first response entry 1 day after the baseline visit. CONCLUSIONS: High compliance rates support the use of the daily electronic PRO diary in large RCTs. Despite the anticipated issues, the daily electronic diary is expected to reduce recall bias and improve the quality of PRO data collection. TRIAL REGISTRATION: RA-BEAM ( NCT01710358 ) and RA-BUILD ( NCT01721057 ).
30713533 Polarization of Rheumatoid Macrophages by TNF Targeting Through an IL-10/STAT3 Mechanism. 2019 Macrophages contribute to the pathogenesis of rheumatoid arthritis (RA). They can display different states of activation or "polarization," notably the so-called inflammatory "M1" and the various alternative "M2" polarizations, characterized by distinct functions. Data regarding the effects of RA anti-cytokine biological disease-modifying anti-rheumatic drugs (bDMARDs) on macrophage polarization are scarce. We aimed to assess in vitro modulation of macrophage polarization by bDMARDs targeting pro-inflammatory cytokines in RA. We generated monocyte derived macrophages using blood samples from 20 RA patients with active RA and 30 healthy controls. We evaluated in vitro the impact on M1 inflammatory macrophages of: etanercept (ETA), adalimumab (ADA), certolizumab (CZP), tocilizumab (TCZ), and rituximab (RTX). We assessed the impact on macrophage polarization using flow cytometry and RTqPCR to study the expression of surface markers and perform functional studies of cytokine production, phagocytosis, and negative feedback control of inflammation. Among evaluated bDMARDs, anti-TNF agents modulated the polarization of inflammatory macrophages by decreasing inflammatory surface markers (CD40, CD80) and favoring alternative markers (CD16, CD163, MerTK). Anti-TNF agents also induced alternative functions in macrophages activated in inflammatory condition with (i) the inhibition of inflammatory cytokines (TNF, IL-6, IL-12), (ii) an increase in phagocytosis. These findings were mechanistically related to an increase in early IL-10 production, responsible for higher negative feedback control of inflammation involving SOCS3 and Gas6. This IL-10 effect was STAT3-dependent. Anti-TNF agents not only inhibit in vitro inflammatory functions of macrophages, but also favor resolution of inflammation through polarization toward alternative features specifically involving the IL-10/STAT3 axis.
31030360 The superb microvascular imaging is more sensitive than conventional power Doppler imaging 2019 Sep OBJECTIVES: This study evaluated Superb Microvascular Imaging (SMI) technology for detection of active synovitis in patients with rheumatoid arthritis (RA). METHODS: Between June 2015 and October 2016, 56 patients with RA (42 females; mean age, 53.2 years) underwent gray-scale ultrasound (US) imaging, power Doppler imaging (PDI), and SMI for synovitis of both wrists and hands (total 22 joints), scored for each joint from grades 0 to 3. The sum of grades for 22 joints was determined for gray-scale (SYN-sum), PDI (PDI-sum), and SMI (SMI-sum) according to clinical parameters. Follow-up US was performed in 17 patients (mean interval, 251.6 days). RESULTS: The SMI-sum (7.27 ± 4.56) was significantly higher than the PDI-sum (4.38 ± 3.09, p < 0.001) and the SYN-sum (4.55 ± 3.72, p < 0.001), and was significantly correlated with the erythrocyte sedimentation rate, C-reactive protein (CRP), and Disease Activity Score-28 (DAS28)-CRP (γ = 0.409, p = 0.002; γ = 0.695, p < 0.001; γ = 0.726, p < 0.001, respectively). Moreover, in 28 patients with clinical remission, the SMI-sum (4.32 ± 2.01) was greater than the PDI-sum (2.61 ± 1.60, p < 0.001). In 17 patients with follow-up US, the SMI-sum (2.35 ± 1.73) was significantly greater than the PDI-sum (1.24 ± 1.20; p < 0.001) and was also significantly correlated with DAS28 (γ = 0.880). CONCLUSION: SMI may detect active synovitis with greater sensitivity than PDI in RA patients, even with clinical remission, and is well-correlated with inflammatory parameters during follow-up. KEY POINTS: • SMI correlated well with PDI and was more sensitive for detection of active synovitis in RA. • The SMI-sum was not only of greater value but also more strongly correlated than the PDI-sum with clinical inflammatory indicators including ESR, CRP, and DAS28 on initial and follow-up US examinations. • The SMI-sum was even significantly increased in patients with clinical remission.
31612736 Association among anti-citrullinated protein antibody status, erosive disease and healthca 2020 Feb Objective: To characterize the rate of healthcare resource utilization (HCRU) between anti-cyclic citrullinated peptide (CCP; a surrogate for anti-citrullinated protein antibodies [ACPAs]) positive (+) patients with rheumatoid arthritis (RA), either with or without erosions, who initiated biologic disease-modifying antirheumatic drug (bDMARD) treatment.Methods: Data from the Corrona RA registry, a prospective registry of adult patients with RA from 177 sites across 42 states in the US, were analyzed. Annual rates of HCRU (measured based on rates of all-cause hospitalization, joint surgery, imaging procedures and use of assistive devices) were estimated in anti-CCP + patients with and without erosions following bDMARD initiation using a Poisson regression model.Results: Among the 3333 patients with known anti-CCP and erosion status and 12-month post-bDMARD follow-up information in the Corrona registry, 2047 were anti-CCP + and included in this analysis; 868 with and 1179 without erosions. Baseline characteristics were generally well balanced between patients with and without erosions; however, those with erosions had a longer mean RA duration and a higher prior DMARD use. Over 12 months, among anti-CCP + patients, those with erosions had significantly higher rates of all HCRU, except joint surgery, than those without erosions. Age-adjusted risk ratios (95% confidence interval) were as follows: all-cause hospitalization, 1.47 (1.14, 1.90); all-cause imaging, 1.25 (1.03, 1.53); and assistive device use 1.12 (1.00, 1.25). The rate of joint surgery visits was also numerically higher in patients with versus without erosion.Conclusions: ACPA seropositivity with erosive disease was associated with higher rates of HCRU compared with seropositivity without erosions. These findings suggest that providers may want to manage anti-CCP + patients aggressively to achieve better disease control to prevent the development of erosions and the associated increase in HCRU.
31089921 CD147 participates in the activation function of circulating angiogenic T cells in patient 2019 Sep OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory and angiogenic disease. This study aimed to explore the profiles of circulating angiogenic T cells (Tang cells) and the role of CD147 in Tang cell activation function in RA. METHODS: Samples were obtained from patients with RA and health controls (HC). Then, Tang cells were quantified by flow cytometry (FCM) in the samples from 87 patients with RA and 29 HC. Tang cells were purified by magnetic cell sorting in cell culture-conditioned media, and the phosphorylation signals were determined by FCM. In addition, cytokine levels were assessed by enzyme-linked immunosorbent assay. RESULTS: The percentage of circulating Tang cells increased and positively correlated with the number of endothelial progenitor cells in the RA group. Further, the percentage of Tang cells was closely related to disease activity, autoantibody positivity, and proangiogenic cytokine levels. Meanwhile, the expression of CD147 on Tang cells increased in patients with RA. CD147 participated in the Akt phosphorylation and VEGF level of the activated Tang cells. CONCLUSIONS: CD147 may play a critical role in regulating VEGF production of activated Tang cells by affecting Akt signaling, which in turn may serve an essential function in angiogenesis and RA pathogenesis.
30499364 Disease activity, treatment and long-term prognosis of adult juvenile idiopathic arthritis 2020 Jan Objective: To evaluate the difference between adult juvenile idiopathic arthritis (JIA, starting at <16 years) and rheumatoid arthritis (RA).Methods: Data on 128 adult JIA patients were from the National Database of Rheumatic Diseases in Japan (NinJa), 2014, divided into 4 groups by period of disease onset (Group 1: 2000-2013, n = 32; Group 2: 1981-1999, n = 32; Group 3: 1966-1980, n = 31; Group 4: ∼1965, n = 33). Disease activity, treatment and long-term prognosis of adult JIA patients were compared with RA patients matched for sex- and disease duration in each era.Results: In Groups 1 and 2, adult JIA patients had significantly lower clinical disease activity indices (CDAI) (Group 1: adult JIA 1.5 [0.4-6.9]-vs-RA 5.3 [2.5-10.3], p = .001, Group 2: 2.6 [0.6-9.0]-vs-6.9 [3.5-11.0], p = .001, shown as median [quartile range], p-value, respectively), and had higher CDAI remission rates than RA patients (Group 1: 54.8%-vs-28.2%, p = .002, Group 2: 51.7%-vs-17.0%, p < .001). More adult JIA than RA patients in Group 1 used biologics (62.5%-vs-24.7%, p < .001). However, there were no adult JIA-vs-RA differences in joint destruction and physical function in any group.Conclusions: Adult rheumatologists must recognize that adult JIA patients are different from RA patients even when disease duration is the same.
31699188 [High Expression of Multidrug Resistance Gene-1 Can Aggravate Resistance to Methotrexate i 2019 Oct 30 Objective To explore the role of multidrug resistance gene-1(MDR1)gene in methotrexate(MTX)resistance in patients with rheumatoid arthritis(RA).Methods Fibroblast-like synoviocytes(FLS)from RA patients were infected with recombinant adenovirus Ad-EGFP-MDR1 in vitro to obtain MDR1 over-expressed RA FLS.The transcription level of MDR1 gene and the expression level of its coding product P-glycoprotein(P-gp) rotein were detected by real-time PCR and Western blot analysis.The efflux function was verified by rhodamine 123 efflux assay.The resistance to MTX was detected by MTT assay.Results RA FLS were infected with recombinant adenovirus Ad-EGFP-MDR1;72 hours later,the particles size in MDR1 over-expressed RA FLS increased,the cell volume became larger,and the growth rate decreased.The transcription level of MDR1(1.4325±0.3924 vs.0.0650±0.0070;t=6.035,P=0.004),the expression level of P-gp protein(1.8667±0.2857 vs. 0.9367±0.0551;t=5.536,P=0.005),and the ability of extracellular rhodamine 123(979.43±196.81 vs.1680.06±147.04;t=-4.940,P=0.008) in MDR1 over-expressed RA FLS were significantly higher than those of negative virus control RA-FLS,and the survival rate of MDR1 over-expressed RA FLS was significantly increased at each concentration of MTX(P<0.05).Conclusion The high expression of MDR1 can affect the efflux ability to MTX by up-regulating the expression of P-gp,thus enhancing the drug resistance to MTX in RA FLS.
31300634 The very early inflammatory triquetral lesion by MRI - is this the first sign in Rheumatoi 2019 Dec 15 INTRODUCTION/AIM: Rheumatoid Arthritis (RA) an autoimmune, chronic, and disabling disease if untreated, affects wrist joints, with a diagnostic delay of up to 2 years. Triquetral bone allows rotational movement that pivots over the rest wrist bones, and maintains physiological loads during mobility. Magnetic Resonance Imaging (MRI) is the most sensitive (96%) method for diagnosis, evidencing lesions as early as in the initial RA stages. Our aim was to determine the most frequently affected structures in the hand-wrist joint by MRI using the OMERACT-RAMRIS Score (2003) in three different RA stages, including clinically suspicious arthralgia (CSA) that haven't reported before. METHODS: We performed an exploratory, transverse, observational, descriptive study in 60 patients enrolled and classified by rheumatologists as: CSA, early rheumatoid arthritis (ERA), and established RA, prior to performing a dominant hand-wrist MRI for evaluation and descriptive analysis by an expert radiologist. RESULTS: Female predominance 83% (50), with a mean age 42+13.5 years; A total of 1,731 hand-wrist bone and joint sites were evaluated using EULAR-OMERACT Atlas (2005), identifying 56% (964 sites) with typical RA lesions: synovitis, erosions, and bone marrow edema (BME or osteitis); synovitis was the most frequent with 46% (445 site-lesion), and triquetral synovitis the most frequent each clinical group: CSA 87% (20/23), ERA 91% (20/22), and RA 93% (14/15). CONCLUSION: Synovitis and triquetral synovitis were the most prevalent lesion in three-studied phases. This could suggest the triquetrum as the first morphological site to be affected by RA; so it's assessment should be considered in the RA evaluation when it´s clinically suspected.
31119369 Conventional radiography of the hands and wrists in rheumatoid arthritis. What a rheumatol 2019 Aug Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane, leading to joint damage and bone destruction. Conventional radiography (CR) of the hands and wrists has been, for many years, the primary imaging modality used to diagnose and monitor RA. On the other hand, many investigators in clinical trials and observational studies used CR of the hands and wrists to demonstrate drug effectiveness and structural damage progression. The purpose of this review is to discuss the evaluation and interpretation of the hands and wrists by CR in RA patients and the radiographic changes occurring in a specific joint. Thus, the literature was reviewed until January 2019 for studies regarding RA radiological evaluation of the hands and wrists, as well as radiological progression using CR. The assessment of joint pathology in RA patients should begin with CR which is the best imaging modality to evaluate any subtle changes occurring at the bone level. Once high-quality radiographs are obtained in appropriate views/projections, then an accurate evaluation can often be made without any further imaging studies. Therefore, CR is a valuable tool for RA screening. It is an easy-to-perform technique and gives important information assisting in differentiating between RA from other arthritides. In contrary CR does not provide good information when early RA changes start to appear, such as synovial inflammation or other soft-tissue structural changes. Nevertheless, it still remains the most commonly used imaging tool in rheumatology and has a number of advantages: it is easily available in most rheumatologists and readily accessible in most patients. It is inexpensive and relatively safe. It provides immediate information and can be interpreted easily by the requested rheumatologist. Finally, the data are reproducible and can be used for serial evaluation and follow-up.
30899988 The impact of physical activity on serum levels of inflammatory markers in rheumatoid arth 2019 May This review aims to determine the specific effects of PA on systemic levels of interleukins and inflammatory markers. A systematic literature search was conducted in three computerized bibliographic databases (Medline, Embase, CENTRAL) to identify randomized controlled trials and matched case studies. Applied key words were: RA and PA including the terms exercise, exercise therapy, gymnastics and exercise movement techniques. Inclusion criteria were data on all types of proinflammatory interleukins (IL), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). For data synthesis, the populations, interventions and outcomes were described according to the PRISMA statement. A total of 1289 publications were found. Fifteen papers, related to 14 different study populations, met the inclusion criteria. No study revealed a significant change regarding IL or CRP levels in response to the intervention (PA). In three study populations, a significant reduction of the ESR was identified, but the effect from PA was not discernible from effects of changes of the anti-rheumatic medication in these studies. The strong variability in study designs, cohort size and types of physical training programs remains an obstacle in the assessment of the measurable effects of PA on inflammatory markers in patients with RA. At present, there is no sufficient evidence to conclude that PA has a significant impact on systemic levels of inflammatory markers in RA.
30589626 Assessing the Value of Sarilumab Monotherapy for Adults with Moderately to Severely Active 2019 Jan BACKGROUND: Rheumatoid arthritis is associated with a societal burden greater than $39 billion annually. Novel treatments, known as targeted immune modulators (TIMs), are expensive but effective, producing improvements in response rates compared with conventional disease-modifying antirheumatic drugs (cDMARDs). Sarilumab, a TIM approved in 2017, shows superior improvements compared with cDMARDs and produced significantly greater likelihood of achieving response and improvement in the Health Assessment Questionnaire Disability Index than adalimumab monotherapy. Although sarilumab monotherapy has shown improvements over cDMARDs and the TIM market leader adalimumab, treatment with sarilumab is costly, with an annual wholesale acquisition cost of $39,000. OBJECTIVE: To estimate the lifetime cost-effectiveness of starting treatment with sarilumab monotherapy for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to cDMARDs. METHODS: A sequential treatment cohort model followed a hypothetical cohort from initiation of sarilumab monotherapy until death. The model allowed patients to switch therapies up to 3 times due to effectiveness or adverse events. The first switch was to a TIM within the same treatment category; the second switch was to a TIM within a different treatment category; and the third switch was to a cDMARD. Sarilumab monotherapy was compared with a cDMARD (methotrexate) and the TIM market leader (adalimumab monotherapy). Key risk and benefit evidence came from clinical studies and network meta-analyses of data on radiographic progression and response. We used a lifetime time horizon and the U.S. health sector payer perspective assuming therapy net pricing. We also incorporated loss of productivity to reflect a restricted societal perspective. RESULTS: Over a lifetime time horizon, a treatment pathway starting with sarilumab resulted in 17.16 life-years and 13.66 quality-adjusted life-years (QALYs). Treatment pathways starting with the cDMARD resulted in 16.54 life-years and 11.77 QALYs; treatment pathways starting with adalimumab resulted in 17.05 life-years and 13.35 QALYs. Total costs for sarilumab ($492,000 for payer perspective, $634,000 for societal perspective) were less than total costs for adalimumab ($536,000 for payer perspective, $689,000 for societal perspective) but higher than total costs for the cDMARD ($63,000 for payer perspective, $272,000 for societal perspective). When compared with cDMARD therapy, sarilumab resulted in a cost-effectiveness estimate of $227,000 per QALY gained from the payer perspective and $191,000 per QALYs gained from the societal perspective. When compared with adalimumab, sarilumab was dominant from both perspectives. CONCLUSIONS: Sarilumab resulted in better health outcomes than conventional therapy alone. However, its additional cost with assumed class-level net prices led to cost-effectiveness estimates above commonly cited thresholds. When compared with the market leader, sarilumab achieved favorable value. This evaluation informs stakeholders of the value of sarilumab and its alternatives to promote high value practices in health care. DISCLOSURES: Funding for this research was contributed by the Institute for Clinical and Economic Review (ICER). Ollendorf, Chapman, Kumar, Synnott, and Agboola are employees of ICER, an independent organization that evaluates the evidence on the value of health care interventions, which is funded by grants from the Laura and John Arnold Foundation, Blue Shield of California Foundation, and the California HealthCare Foundation. The organization's annual policy summit is supported by dues from Aetna, AHIP, Anthem, Blue Shield of California, CVS Caremark, Express Scripts, Harvard Pilgrim Health Care, Omeda Rx, United Healthcare, Kaiser Permanente, Premera Blue Cross, AstraZeneca, Genentech, GlaxoSmithKline, Johnson & Johnson, Merck, National Pharmaceutical Council, Takeda, Pfizer, Novartis, Lilly, and Humana. This work is an extension of an analysis presented at the New England Comparative Effectiveness Public Advisory Council on March 24, 2017, where the authors received public feedback on the analysis, results, and effect of a value assessment for targeted immune modulators. At the time of presentation, sarilumab was still an investigational product; therefore, a price was not known, so cost-effectiveness estimates were not generated. Since the presentation of that material, additional evidence for sarilumab has become available. The additional evidence has been incorporated into this analysis to present cost-effectiveness estimates for sarilumab.
30539352 Diastolic dysfunction in rheumatoid arthritis patients with low disease activity. 2019 Apr INTRODUCTION/OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk for congestive heart failure (CHF) and left ventricular diastolic dysfunction (LVDD), as compared to the general population. High disease activity is to be associated with higher incidence of cardiovascular disease (CVD), CHF, and mortality in RA patients. LVDD is not anticipated in RA patients without CVD symptoms and may be underdiagnosed especially in those with low disease activity. METHOD: The study group consisted of 70 RA patients (54 women, 16 men) with no CVD and 33 healthy controls, of comparable age. All RA patients had low disease activity (DAS28 ≤ 3.2) from 2 to 7 years. Laboratory and imaging assessments included metabolic, RA-related, and cardiovascular parameters. Echocardiographic and Doppler studies were conducted in patients and controls with assessment of ejection fraction (EF) and diastolic dysfunction (assessed as E/A ratio). RESULTS: The mean E/A ratio did not differ significantly between RA patients and healthy controls (1.08 (0.28) vs 0.99 (0.21), NS); comparable numbers of patients and controls had abnormal E/A (< 1.0) (26 (37.1%) vs 10 (30.3%), NS). Patients with decreased E/A were significantly older and had higher disease duration, activity, and presence of bone erosions than their RA counterparts with normal E/A. The mean EF was not significantly different in patients and controls. CONCLUSIONS: The prevalence of DD as expressed by E/A ratio in RA patients with continued low disease activity was not different from that of controls. Higher disease duration and severity may predispose to DD occurrence in patients with preserved EF.
31285112 Changes to Body Composition in Women With Long-Standing Established Rheumatoid Arthritis: 2020 Oct INTRODUCTION: Few studies on rheumatoid arthritis have investigated disease activity and body composition by dual-energy X-ray absorptiometry including evaluation of visceral adipose tissue. Thus, we sought to verify the association between body composition by dual-energy X-ray absorptiometry, including visceral adipose tissue, and inflammatory activity in long-standing established rheumatoid arthritis. METHODS: Seventy-eight postmenopausal women with rheumatoid arthritis (American College of Rheumatology 2010) were studied. Disease activity was assessed by composite indexes (DAS28, CDAI, SDAI) and C-reactive protein. Potential association between body composition and disease activity was analysed by Pearson correlation and Tukey´s test (p < 0.05). RESULTS: There was significant negative correlation between C-reactive protein and appendicular lean mass index (r = -0.234, p = 0.039). After adjusting for confounding variables, women with C-reactive protein >10 mg/L had a lower appendicular lean mass index than those with C-reactive protein 5-10 mg/L and <5 mg/L (6.3 ± 0.8 kg/m(2) vs 7.2 ± 1.2 kg/m(2) vs 6.8 ± 1.0 kg/m(2), respectively; p = 0.013). Women with moderate inflammation (C-reactive protein 5-10 mg/L) had more fat than those with C-reactive protein >10 mg/L and C-reactive protein <5 mg/L (12.4 ± 3.5 kg/m(2) vs 9.9 ± 3.6 kg/m(2) vs 10.5 ± 2.8 kg/m(2), respectively; p = 0.040), as well as more visceral adipose tissue than women with higher and lower C-reactive protein (812.5 ± 266.4 cm(3) vs 604.3 ± 236.3cm(3) vs 658.9 ± 255.6 cm(3); p = 0.009). CONCLUSIONS: High inflammatory activity that persists after a long disease duration was associated with both lower muscle and fat mass (including visceral adipose tissue), which is suggestive of more exuberant rheumatoid cachexia. Conversely, moderate activity was associated with greater visceral adipose tissue, which is associated with increased cardiovascular risk. These results point to the existence of different body composition profiles according to inflammatory status and the importance of individualized approaches to muscle mass and adiposity according to disease activity level in long-standing rheumatoid arthritis.
30642376 The value of the simplified RAMRIS-5 in early RA patients under methotrexate therapy using 2019 Jan 14 BACKGROUND: The aim of the study was to evaluate a simplified version of the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) for five joints of the hand (RAMRIS-5) in patients with early rheumatoid arthritis (RA) before and after the initiation of methotrexate (MTX) therapy using high-resolution, 3-T magnetic resonance imaging (MRI). METHODS: Twenty-eight patients with a seropositive, early RA (disease duration of less than 6 months (range 2-23 weeks)) according to 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria (mean age 56.8 years, range 39-74) were prospectively assessed with a baseline investigation including clinical assessment (disease activity score of 28 joints (DAS-28) and C-reactive protein (CRP)) and 3-T MRI of the clinically dominant hand. Follow-up visits were performed 3 and 6 months after initiation of a MTX therapy at baseline. MRI scans were analyzed in accordance with RAMRIS and the simplified RAMRIS-5. RESULTS: DAS-28 and CRP decreased significantly after initiation of MTX therapy. Even though erosion scores increased over time, RAMRIS and RAMRIS-5 also decreased significantly after the start of therapy. There was a strong correlation between the total RAMRIS-5 and RAMRIS at baseline (r = 0.838; P <0.001) and follow-up (3 months: r = 0.876; P <0.001; 6 months: r = 0.897; P <0.001). In the short term (3-month follow-up), RAMRIS and RAMRIS-5 demonstrated similar ability to detect changes for all subgroups (bone edema, erosion, and synovitis). In the long-term comparison (6-month follow-up), RAMRIS-5 also showed similar effectiveness when detecting changes in bone edema and erosion compared with RAMRIS. Deviations occurred regarding only synovitis, where change was slightly higher in RAMRIS-5: SRM (RAMRIS) = 0.07 ± 0.14; SRM (RAMRIS-5) = 0.34 ± 0.06. CONCLUSIONS: Three-Tesla MRI-based RAMRIS-5 is a simplified and resource-saving RAMRIS score which compares favorably with the RAMRIS when detecting changes in early RA. Even though there is a slight abbreviation between RAMRIS-5 and the original score regarding the change of synovitis, it may be used for diagnosis and therapy monitoring in follow-up evaluations.
30358109 Pharmacodynamic biomarkers and differential effects of TNF- and GM-CSF-targeting biologics 2019 Apr AIM: The aim of our study was to identify pharmacodynamic biomarkers and assess differential effects of tumor necrosis factor (TNF)- and non-TNF-targeting agents on rheumatoid arthritis (RA) patients with an inadequate response to anti-TNF agents (anti-TNF-IR) in comparison with biologic-naïve patients. METHODS: EARTH EXPLORER 2, a phase IIb trial, evaluated golimumab, an anti-TNF antibody, and mavrilimumab, an granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor antibody, in disease-modifying antirheumatic drug (DMARD)-IR and anti-TNF-IR patients. Our current study assessed peripheral protein markers and gene expression levels in association with clinical response post-treatment in two disease strata. RESULTS: Serum proteomics results indicated the existence of specific pharmacodynamic markers for golimumab and mavrilimumab, regardless of prior anti-TNF treatment. In contrast, both antibodies induced early and sustained suppression of RA disease markers, including interleukin (IL)-6, C-reactive protein, IL2RA, and matrix metalloproteinase 1, in DMARD-IR patients. Golimumab-induced early changes rapidly returned toward baseline concentrations in anti-TNF-IR patients, whereas mavrilimumab-induced changes were maintained through to day 169. RNA sequencing demonstrated gene expression changes at day 169 after administration of mavrilimumab but not golimumab in anti-TNF-IR patients. Additionally, receiver operating characteristic curve and regression analysis showed the association of early IL-6 change and subsequent clinical responses to golimumab in anti-TNF-IR patients. CONCLUSION: Our results revealed golimumab- and mavrilimumab-specific pharmacodynamic biomarkers, and demonstrated differential biomarker-treatment relationships in anti-TNF-IR and DMARD-IR patients, respectively. Early IL-6 change after anti-TNF antibody treatment may be a potential predictive biomarker for selection of different treatment regimens in anti-TNF-IR patients.
30630365 Tuberculosis, hepatitis B and herpes zoster in tofacitinib-treated patients with rheumatoi 2019 Mar There is currently interest in the risk of infections during treatment with new targeted synthetic disease-modifying antirheumatic drugs (DMARDs), specifically the Janus kinase inhibitor tofacitinib. Tofacitinib has been studied extensively in patients with rheumatoid arthritis and has been shown to be effective and generally safe. East Asian countries have a high background rate of tuberculosis (TB) and hepatitis B virus (HBV) infection and the risk of recurrence or reactivation of infections such as TB, HBV and herpes zoster during DMARD therapy is of particular interest in the region. This paper reviews available data on the risk of TB, HBV and herpes zoster infections, including recurrence/reactivation of infections, during treatment with tofacitinib, with a focus on east Asia.
31987685 The epidemiology of established rheumatoid arthritis. 2019 Oct No published epidemiological study has specifically focused on the prevalence of established rheumatoid arthritis (RA), as epidemiologists do not study established RA separated from RA as a whole; especially no incidence studies can be found, as incidence refers to new cases (early RA). Such a study, if it existed, would find a prevalence much larger than that of recent-onset RA, and should be planned based on clear definitions that currently do not exist in epidemiology. As a result, any study addressing RA as a whole, leaving aside early arthritis, would be actually studying established RA. This work reviews the epidemiology of RA, in contraposition of early RA, and tried to highlight epidemiological characteristics of established RA in published studies as well as methodological issues, including differences between recent-onset and established RA regarding the prevalence of comorbidities and other characteristics, and differences across countries. The global epidemiology of established RA teaches us that long-term outcomes could largely depend on health care models and are modifiable.
30217121 Involvement of midkine in autoimmune and autoinflammatory diseases. 2019 Jul Midkine (MK) is a heparin-binding growth factor that markedly expressed during embryogenesis but downregulated to inconsiderable levels in healthy adults. However, MK is upregulated during tissue repair and in many pathologic conditions, mostly malignancies and inflammatory diseases. MK promotes a number of functions in target cells such as migration, proliferation, survival, growth, reproduction and repair, angiogenesis, and gene expression. It acts as a pro-inflammatory cytokine and contributes to chronic inflammation via promoting chemotaxis and tissue infiltration of neutrophils and macrophages. Furthermore, MK upregulated the production of various inflammatory mediators (i.e. interleukin (IL) 6 and IL8). Recent studies have demonstrated strong evidence that MK is involved in the onset and progression of autoimmune rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS) and other autoimmune conditions such as multiple sclerosis (MS). Additionally, it has been shown that MK is overexpressed in two major clinically defined forms of inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), which are classified as autoinflammatory diseases. Taken together, MK is involved in the pathogenesis of autoimmune and autoinflammatory diseases and may serve as an indicator and biomarker in these conditions. Furthermore, MK inhibitors are expected to contribute in the management of these diseases.
32598671 [Chronic pain and depression in patients with rheumatoid arthritis: results of five - year 2019 May 15 The aim of the study was to analyze the factors affecting chronic pain in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: 128 patients with reliable diagnosis of RA [111 (86.7%) women and 17 (13.3%) men] were examined. The mean age of patients was 47.4±11.3 years, the median duration of the disease was 96 [48; 228] months. When included in the study in most patients, the activity of RA in DAS28 was moderate (n=56; 43.7%) or high (n=48; 37.5%). BPI (Brief Pain Inventory) scale was used to determine the severity of pain and its impact on various aspects of life. The anxiety - depressive spectrum disorders (ADDs) were diagnosed by psychiatrist during a semistructured interview according to ICD-10 criteria in 123 (96.1%) patients. The severity of depression was determined by the Montgomery-Asberg depression rating scale, anxiety - by Hamilton anxiety scale. For the diagnosis of cognitive impairment used clinical and psychological techniques. Psychopharmacotherapy (PPhT) by antidepressants or anxiolytics is offered to all patients with ADDs, 52 of them agreed to treatment, 71 patients refused. The next groups selected depending on the therapy: 1st - with conventional disease - modifying antirheumatic drugs (cDMARDs; n=39), 2nd - with cDMARDs+PPhT (n=43), 3d - with cDMARDs + biologic (b) DMARDs (n=32), 4th - with cDMARD+bDMARDs+PPhT (n=9). The dynamics of ADDs and outcomes of RA in 5 years were evaluated in 83 (67.5%) patients. RESULTS: When included in the study, 94 (75.2%) patients with RA had moderate and severe pain. According to the regression analysis, the maximum intensity pain in BPImax after 5 years of follow - up associated not the only factors connected with RA - high DAS28, the serum level of C-reactive protein, the degree of radiological stage and functional insufficiency, duration of RA and a lesser duration of glucocorticoids intake, but also with continuing depressive episodes in the framework of recurrent depression and the initial presence of cognitive impairment. The severity of pain after 5 years of follow - up was higher in RA patients receiving only сDMARDs, without the use of bDMARDs and in the absence of PPhT associated with ADDs. CONCLUSION: Depressive episode within recurrent major depression is a significant factor in the chronicity of pain in patients with RA. Timely effective PPhT of depression, selected taking into account depression structure and personal characteristics of the patient, leads to a steady decrease in the severity of pain in patients with RA.