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ID PMID Title PublicationDate abstract
34101706 Perioperative Management of Antirheumatic Medications in Patients with RA and SLE Undergoi 2021 Jun 8 »: Recent literature has shown that continued use rather than discontinuation of various antirheumatic agents throughout the perioperative period may present an opportunity to mitigate the risks of elective surgery. »: For patients with rheumatoid arthritis and systemic lupus erythematosus, perioperative management of medication weighs the risk of infection against the risk of disease flare when immunosuppressive medications are withheld. »: Broadly speaking, current evidence, although limited in quality, supports perioperative continuation of disease-modifying antirheumatic drugs, whereas biologic drugs should be withheld perioperatively, based on the dosing interval of the specific drug. »: For any withheld biologic drug, it is generally safe to restart these medications approximately 2 weeks after surgery, once the wound shows evidence of healing, all sutures and staples have been removed, and there is no clinical evidence of infection. The focus of this recommendation applies to the optimization of wound-healing, not bone-healing. »: In most cases, the usual daily dose of glucocorticoids is administered in the perioperative period rather than administering "stress-dose steroids" on the day of surgery.
32573409 Toenail abnormalities in rheumatoid arthritis patients are associated with radiographic da 2021 May OBJECTIVES: Cutaneous involvement is an extra-articular manifestation of rheumatoid arthritis (RA). This includes nail abnormalities, which are often overlooked. We described nail findings in RA patients currently attending an early arthritis cohort (n=145), and associated them with disease activity and/or damage, as well as patient-reported outcomes. METHODS: A standardised nail examination was performed in 122 patients (84.1% of the cohort), concomitant to the rheumatic assessment. Disability, quality of life and perceived nail-related health were also assessed. Nail findings and their location were recorded and classified according to standardised definitions. Logistic and linear regression models were used to investigate predictors of nail findings and to identify the impact of toenail findings on disability, which was evaluated with the HAQ. Patients consented to participate. RESULTS: Patients were primarily middle-aged females, with median follow-up of 9 years, and had disease under control. Most patients (62.3%) had at least one nail finding and these patients scored lower their nail-related health. The median (IQR) of findings/abnormalities per patient was 3 (2-5) and the number of nails affected per patient was 10 (2-12). Age (OR: 1.04, 95%CI: 1.007-1.074) and erosive disease (OR: 2.26, 95%CI: 1.1-5.1) were associated with nail findings. Toenail involvement was consistently associated with HAQ score out of normal range (OR=3.4, 95%CI=1.24-9.35, p=0.02). There was a linear association between the number of toenails affected and the HAQ score. CONCLUSIONS: Nail abnormalities are common and heterogeneous findings in RA patients; they are associated with erosive damage and impact disability.
33666156 Benefits of anakinra versus TNF inhibitors in rheumatoid arthritis and type 2 diabetes: lo 2021 Mar OBJECTIVES: Interleukin (IL)-1β is considered a shared pathogenic mediator between rheumatoid arthritis (RA) and type 2 diabetes (T2D). In the TRACK study, participants with both diseases were randomised to an IL-1 inhibitor, anakinra, or a TNF inhibitor (TNFi). After 6 months, anakinra induced a such of improvement on metabolic and inflammatory parameters, leading to a premature stoppage of the study. Thus, we aimed to assess how long IL-1 inhibition benefits lasted. METHODS: Since the TRACK was prematurely discontinued for "early benefit", we furtherly followed-up the enrolled participants to assess how long persisted the improvement of glycated haemoglobin (HbA1c%) and of RA disease activity. RESULTS: After a mean follow-up of 18 months (15 participants in anakinra-group and 14 in TNFi-group), RA clinical response was retained in both groups (DAS28: 2.59±1.01 vs. 2.88±0.91; p=0.109). Concomitant glucocorticoids were reduced in both groups (2.01±0.71 vs. 3.01±0.87 mg/die; p=0.124), but a larger percentage of anakinra-treated participants discontinued such drugs (53.3% vs. 28.6%; p=0.004). There was no difference between anakinra and TNFi for HbA1c% (6.60±0.52 vs. 6.79±0.43; p=0.291), but a reduction of anti-diabetic drugs was observed in anakinra-treated participants (53.3% vs. 7.1%; p=0.008) whereas an increase of anti-diabetic therapies was needed in TNFi-treated ones. Significant correlations were also observed among HbA1c% with DAS28 and with C-reactive protein. Analysing the safety profile, only minor side effects were recorded. CONCLUSIONS: Data deriving from the long-term extension of participants with RA and T2D, enrolled in the TRACK study, could suggest that the benefits of IL-1 inhibition on metabolic and inflammatory parameters could last longer than first 6 months of follow-up, but further studies are needed to confirm these findings.
33995417 Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis. 2021 Mitochondria are major energy-producing organelles that have central roles in cellular metabolism. They also act as important signalling hubs, and their dynamic regulation in response to stress signals helps to dictate the stress response of the cell. Rheumatoid arthritis is an inflammatory and autoimmune disease with high prevalence and complex aetiology. Mitochondrial activity affects differentiation, activation and survival of immune and non-immune cells that contribute to the pathogenesis of this disease. This review outlines what is known about the role of mitochondria in rheumatoid arthritis pathogenesis, and how current and future therapeutic strategies can function through modulation of mitochondrial activity. We also highlight areas of this topic that warrant further study. As producers of energy and of metabolites such as succinate and citrate, mitochondria help to shape the inflammatory phenotype of leukocytes during disease. Mitochondrial components can directly stimulate immune receptors by acting as damage-associated molecular patterns, which could represent an initiating factor for the development of sterile inflammation. Mitochondria are also an important source of intracellular reactive oxygen species, and facilitate the activation of the NLRP3 inflammasome, which produces cytokines linked to disease symptoms in rheumatoid arthritis. The fact that mitochondria contain their own genetic material renders them susceptible to mutation, which can propagate their dysfunction and immunostimulatory potential. Several drugs currently used for the treatment of rheumatoid arthritis regulate mitochondrial function either directly or indirectly. These actions contribute to their immunomodulatory functions, but can also lead to adverse effects. Metabolic and mitochondrial pathways are attractive targets for future anti-rheumatic drugs, however many questions still remain about the precise role of mitochondrial activity in different cell types in rheumatoid arthritis.
34838126 Performance of 4 methods for screening of latent tuberculosis infection in patients with c 2021 Nov 27 BACKGROUND: The reactivation rate of tuberculosis in patients with chronic inflammatory arthritis (CIA) on TNFα inhibitors (TNFi) and baseline negative screening for latent tuberculosis infection (LTBI) is higher than in the general population. AIM: To compare the performance of tuberculin skin test (TST), TST-Booster, ELISPOT (T-SPOT.TB) and QuantiFERON-TB Gold in tube (QFT-IT) to detect LTBI in patients with CIA on TNFi. PATIENTS AND METHODS: A total of 102 patients with CIA [rheumatoid arthritis (RA), n = 40; ankylosing spondylitis (AS), n = 35; psoriatic arthritis (PsA), n = 7; and juvenile idiopathic arthritis (JIA), n = 20] were prospectively followed-up for 24 months to identify incident LTBI cases. Epidemiologic data, TST, T-SPOT.TB, QFT-IT and a chest X-ray were performed at baseline and after 6 months of LTBI treatment. RESULTS: Thirty six percent (37/102) of patients had positive TST or Interferon Gamma Release Assays (IGRAs) tests. Agreement among TST and IGRAs was moderate (k = 0.475; p = 0.001), but high between T-SPOT.TB and QFT-IT (k = 0.785; p < 0.001). During the 24-Month follow-up, 15 (18.5%) incident cases of LTBI were identified. In comparison to TST, the IGRAs increased the LTBI diagnosis power in 8.5% (95% CI 3.16-17.49). TST-Booster did not add any value in patients with negative TST at baseline. After 6-Month isoniazid therapy, IGRAs results did not change significantly. CONCLUSIONS: Almost 20% of CIA patients had some evidence of LTBI, suggesting higher conversion rate after exposition to TNFi. TST was effective in identifying new cases of LTBI, but IGRAs added diagnostic power in this scenario. Our findings did not support the repetition of IGRAs after 6-Month isoniazid therapy and this approach was effective to mitigate active TB in 2 years of follow-up.
33004335 EULAR definition of difficult-to-treat rheumatoid arthritis. 2021 Jan BACKGROUND: Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis (RA) remain symptomatic. These patients can be considered to have 'difficult-to-treat RA'. However, uniform terminology and an appropriate definition are lacking. OBJECTIVE: The Task Force in charge of the "Development of EULAR recommendations for the comprehensive management of difficult-to-treat rheumatoid arthritis" aims to create recommendations for this underserved patient group. Herein, we present the definition of difficult-to-treat RA, as the first step. METHODS: The Steering Committee drafted a definition with suggested terminology based on an international survey among rheumatologists. This was discussed and amended by the Task Force, including rheumatologists, nurses, health professionals and patients, at a face-to-face meeting until sufficient agreement was reached (assessed through voting). RESULTS: The following three criteria were agreed by all Task Force members as mandatory elements of the definition of difficult-to-treat RA: (1) Treatment according to European League Against Rheumatism (EULAR) recommendation and failure of ≥2 biological disease-modifying antirheumatic drugs (DMARDs)/targeted synthetic DMARDs (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated); (2) presence of at least one of the following: at least moderate disease activity; signs and/or symptoms suggestive of active disease; inability to taper glucocorticoid treatment; rapid radiographic progression; RA symptoms that are causing a reduction in quality of life; and (3) the management of signs and/or symptoms is perceived as problematic by the rheumatologist and/or the patient. CONCLUSIONS: The proposed EULAR definition for difficult-to-treat RA can be used in clinical practice, clinical trials and can form a basis for future research.
33210410 Biomarkers and immunological parameters in haemophilia and rheumatoid arthritis patients: 2021 Jan INTRODUCTION: Haemophilia (HA) and rheumatoid arthritis (RA) patients may develop joint damage caused by recurrent joint bleedings in HA or by chronic inflammation in RA. Only few data exist for biomarker studies in these patients. AIM: The objective of the present study is to assess a large array of biomarkers in peripheral blood samples obtained from HA patients without or with arthropathy and to compare pattern to RA patients and healthy controls. METHODS: A panel of biomarkers was assessed in 129 men (40 HA patients without arthropathy, 23 HA patients with arthropathy, 23 RA patients and 43 control subjects). 37 different biomarkers (cytokines, angiogenesis-related proteins) were analysed using a multiple analyte profiling technology and supplemented by acute phase proteins, coagulation and immunological parameters. RESULTS: Evidence for systemic inflammation was obtained by increased acute phase reactants in all patient groups. 13 or 14 from 42 soluble parameters demonstrated significant differences (p < .05) between HA patients without arthropathy and healthy controls, or between HA patients with arthropathy and healthy controls, respectively. Largely overlapping patterns were obtained except for interleukin-7 being increased in HA patients without arthropathy and being decreased in HA in the presence of arthropathy. CONCLUSIONS: In addition to data supporting systemic inflammation, we provide evidence for a common biomarker profile in HA patients and RA patients compared to healthy controls. A distinctive biomarker profile for HA patients with arthropathy did not appear except for interleukin-7 demonstrating specific changes depending on the absence or presence of arthropathy in HA patients.
33385862 C-reactive protein and implications in rheumatoid arthritis and associated comorbidities. 2021 Feb C-reactive protein (CRP) is routinely assessed as a marker of systemic inflammation in rheumatoid arthritis (RA). However, it is also an immune regulator that plays an important role in inflammatory pathways associated with RA and promotes atherogenic effects. Comorbidities linked to systemic inflammation are common in RA, and CRP has been associated with the risk for cardiovascular disease, diabetes, metabolic syndrome, pulmonary diseases, and depression. The relationship between systemic inflammation, CRP, and comorbidities in RA is complex, and it is challenging to determine how changing CRP levels may affect the risk or progression of these comorbidities. We review the biological role of CRP in RA and its implications for disease activity and treatment response. We also discuss the impact of treatment on CRP levels and whether reducing systemic inflammation and inhibiting CRP-mediated inflammatory pathways may have an impact on conditions commonly comorbid with RA.
33938387 Pharmacokinetics, distribution and efficacy of triptolide PLGA microspheres after intra-ar 2021 Jun The UPLC-MS/MS method was established with good precision, accuracy and stability to determine the concentrations of TPL in biological samples, such as heart, liver, spleen, lung, kidney, plasma and joint.After being made into microspheres, TPL can stay in the joint tissue for a long time, further reducing the number of times joint cavity administration, and its sustained release effect was significantly improved compared with the solution dosage form.The pharmacokinetic parameters, such as AUC((0-t)), AUC((0-∞)), T(1/2), T(max), MTR((0-t)), and MTR((0-∞)) of the TPL-PLGA-MS group were significantly increased compared with those of the solution group. The microsphere preparation could significantly slow the release rate of the drug from the joint cavity.TPL-PLGA-MS can significantly reduce the expression of inflammatory factors such as IL-1, IL-6, TNF-α and hs-CRP. TPL-PLGA-MS for articular cavity injection has potential as a new preparation for the treatment of RA.
33547917 Perceptions of patients with rheumatoid arthritis about self-assessment of disease activit 2021 Apr To evaluate the perceptions of patients with rheumatoid arthritis (RA) about self-assessment of their disease activity after watching an educational video. Consecutive patients with RA consulting their rheumatologist in six Middle Eastern Countries were invited to watch an educational video developed to teach self-assessment using Disease Activity Score (DAS-28). Then, a rheumatology nurse conducted a semi-structured interview and collected the patients' perception about the understanding of the video, feasibility, capability and confidence in performing self-assessment using Likert-type items. The degree of confidence with self-assessment was correlated to the patients' socio-demographic characteristics. Sixty-two patients were included and had an overall positive reaction to the video. It was easy to understand in 96% and helped facilitate self-assessment in 92% of cases. Self-assessment was considered totally feasible in 74%, and 66% of patients were capable of always doing it, with a confidence of 60% (always) to 34% (sometimes). Confidence was associated with a higher educational level. Nevertheless, 77% of patients felt that the self-assessment would not fully replace the physician's visit. Open-ended questions identified five themes: better understanding of the disease, easier communication with the rheumatologist, less consultation time, difficulty with the scoring part and importance of practice. Patients with RA felt that self-assessment was feasible and helpful in understanding RA, improving communication with the rheumatologist and shortening the visit time.
33413913 Change in skeletal muscle mass is associated with lipid profiles in female rheumatoid arth 2021 Jun BACKGROUND & AIMS: To examine the relationship between changes in skeletal muscle mass and lipid metabolism and glycometabolism in patients with rheumatoid arthritis (RA). METHODS: Data were analyzed from 148 female RA patients and 145 age-matched non-RA (control) female subjects from a prospective cohort study (TOMORROW; TOtal Management Of Risk factors in Rheumatoid arthritis patients to lOWer morbidity and mortality study). Appendicular skeletal muscle mass (ASM) was assessed using dual-energy x-ray absorptiometry and skeletal muscle mass index (SMI) was calculated as ASM divided by the square of height. The reference value for SMI in Asian women, 5.4 kg/m(2), was used to define low SMI. Data were assessed using cross-sectional (2010 baseline data) and longitudinal (change in value from 2010 to 2013) methods from the retrospective cohort. RESULTS: At baseline in RA patients, the low SMI group showed significantly higher low-density lipoprotein cholesterol (LDL-chol) (p = 0.015), apolipoprotein (Apo)B (p = 0.046), and ApoB-to-A1 (ApoB/A1) (p = 0.025) than the normal SMI group. In multiple regression analysis of RA patients, sequential changes from 2010 to 2013 (Δ) in SMI and ApoB and ApoC2 showed significant negative relationships (β = -0.19, -0.18, respectively) even after adjusting for age, RA duration, exercise habits, medication for RA, disease severity, activities of daily living (ADL) and body fat mass. No significant relation was evident between ΔSMI and various glycometabolism parameters in RA patients. CONCLUSIONS: Skeletal muscle mass might be related to lipid metabolism in RA patients. This relationship is independent of factors such as disease severity and body fat mass.
33682890 Characteristics of patients with difficult-to-treat rheumatoid arthritis in clinical pract 2021 Nov 3 OBJECTIVES: The aim of this study was to investigate the clinical characteristics of patients with difficult-to-treat RA (D2T RA) and the usefulness of switching to drugs with different modes of action in real-world. METHODS: We reviewed all consecutive patients with RA treated at Keio University Hospital between 2016 and 2017 with a definition of D2T RA. We analysed clinical characteristics and evaluated the usefulness of changing drugs according to mode of action. RESULTS: Among 1709 patients with RA, 173 (10.1%) were D2T RA. The reason for the D2T RA was multi-drug resistance in 59 patients (34.1%), comorbidity in 17 (9.8%), and socio-economic reasons in 97 (56.1%). The multi-drug-resistance group had significantly higher tender joint count and evaluator global assessment than the other groups, despite receiving the most intensive treatment. The comorbidity group showed a significantly older age and higher rheumatic disease comorbidity index. Although changing the drug to another with a different mode of action was useful, the proportion of patients who achieved remission or low disease activity decreased as the number of switches increased. CONCLUSION: Of the patients with RA, 10.1% were still difficult to treat in clinical practice, despite intensive treatment. Their characteristics were distinct by the reasons of D2T RA, which suggests the need for a personalized approach to D2T RA.
33076745 Intracranial and extracranial multiple arterial dissecting aneurysms in rheumatoid arthrit 2021 Apr OBJECTIVE: We describe a case of intracranial and extracranial multiple arterial dissecting aneurysms in rheumatoid arthritis (RA). CASE PRESENTATION: A 29-year-old man with a medical history of RA since 18 years of age was admitted to our hospital for vomiting, dysarthria, and conscious disturbance. At 23, he underwent ligation of the left internal carotid artery (ICA) with superficial temporal artery to middle cerebral artery anastomosis because of acute infarct of the left hemisphere caused by arterial dissection of the left ICA. During the current admission, computed tomography (CT) revealed subarachnoid hemorrhage, and digital subtraction angiography (DSA) demonstrated dissecting aneurysms of the left intracranial vertebral artery (VA) and right extracranial VA. We diagnosed him with a ruptured dissecting aneurysm of the left intracranial VA and performed endovascular parent artery occlusion on the left VA. For the right unruptured VA aneurysm, we performed coil embolization simultaneously. At 2 weeks after the endovascular treatment, follow-up DSA revealed that multiple de novo dissecting aneurysms developed on the origin of the left VA and left and right internal thoracic arteries. Those aneurysms were treated with coil embolization. Other remaining aneurysms on the left thyrocervical trunk, right transverse cervical artery, and both common iliac arteries were treated by conservative therapy. While continuing medical treatment for RA, the patient recovered and was discharged to a rehabilitation hospital. CONCLUSION: Considering that RA-induced vasculitis can be a potential risk of vascular complications including multiple arterial dissections, physicians should carefully perform endovascular interventional procedures for patients with long-term RA.
33493604 PLGA/PCADK composite microspheres containing hyaluronic acid-chitosan siRNA nanoparticles: 2021 Mar 1 Myeloid cell leukemia-1 (Mcl-1), a member of the Bcl-2 anti-apoptotic family, is overexpressed in the synovial macrophages of patients with rheumatoid arthritis (RA). Small interfering RNA (siRNA) Mcl-1 can induce macrophage apoptosis in the joints and is a potential therapeutic target of RA. Nevertheless, the application of siRNA is limited owing to its instability and susceptibility to degradation in vivo. To address these shortcomings, we developed composite microspheres (MPs) loaded with hyaluronic acid (HA)-chitosan (CS) nanoparticles (NPs). First, we synthesized HA-CS/siRNA NPs (HCNPs) using ionotropic gelation process. Then, HCNPs, as an internal aqueous phase, were loaded into poly (D, L-lactide-co-glycolide) (PLGA) and poly (cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) MPs using the double emulsion method. The NPs-in-MPs (NiMPs) composite system provided sustained release of NPs, protected siRNA against nuclease degradation in the serum, and could readily cross the cellular membrane. In addition, we evaluated the advantages of NiMPs in an adjuvant-induced arthritis rat model. Our experimental results demonstrate that NiMPs have greater pharmacodynamic effects than common MPs. Meanwhile, compared with HCNPs, NiMPs reduced the frequency of drug administration. Therefore, NiMPs are a promising and novel siRNA delivery vehicle for RA therapy.
33125809 The patient perspective of nurse-led care in early rheumatoid arthritis: A systematic revi 2021 Jan INTRODUCTION: Management of rheumatoid arthritis has changed dramatically over the last decade and is characterised by early start of intensive treatment and tight monitoring of disease activity until remission. The role of nurse-led care at early stage of disease is not well understood. AIMS: To develop an understanding of rheumatology nurse-led care from the perspective of patients with early rheumatoid arthritis. METHODS: A systematic review of qualitative studies, reported in line with PRISMA checklist. In March 2019, the following databases were searched: MEDLINE, EMBASE, CINAHL, PsycINFO and OpenGrey. Studies were included if they: included adults with rheumatoid arthritis; were qualitative studies with data on patients' perspectives of nurse-led care; and published in peer-reviewed journals, in English, between 2010-2019. Due to few studies in early rheumatoid arthritis, inclusion was extended to adults with established rheumatoid arthritis. Two reviewers screened abstracts and full texts. Joanna Briggs Institute Critical Appraisal Tool was used for quality assessment. Thematic synthesis was conducted according to the framework of Thomas and Harden (2008). RESULTS: The search identified 1034 records. After screening and assessing for eligibility, eight qualitative studies were included in the review (133 patients). Three themes were identified from the synthesis. Nurse-led care was seen to provide professional expertise in planning and delivery of care. A person-centred approach was used combined with good communication skills, thus creating a positive therapeutic environment. Nurse-led care was described as providing a sense of empowerment and psychological support. CONCLUSION: Patients with rheumatoid arthritis are supportive of nurse-led care. They value its professionalism and person-centred approach which provide a sense of security and confidence. RELEVANCE TO CLINICAL PRACTICE: The findings outline ingredients of nurse-led care that are important to patients. These can inform nurses' professional development plans, service improvement and the competence framework for rheumatology nursing.
34772990 Phenotypic and functional characterization of synovial fluid-derived fibroblast-like synov 2021 Nov 12 Fibroblast-like synoviocytes (FLS) play an important pathological role in persistent inflammatory joint diseases such as rheumatoid arthritis (RA). These cells have primarily been characterized in the RA synovial membrane. Here we aim to phenotypically and functionally characterize cultured synovial fluid-derived FLS (sfRA-FLS). Paired peripheral blood mononuclear cells (PBMC) and sfRA-FLS from patients with RA were obtained and monocultures of sfRA-FLS and autologous co-cultures of sfRA-FLS and PBMC were established. The in situ activated sfRA-FLS were CD34-, CD45-, Podoplanin+, Thymocyte differentiation antigen-1+. SfRA-FLS expressed uniform levels of NFкB-related pathway proteins and secreted several pro-inflammatory cytokines dominated by IL-6 and MCP-1. In a co-culture model with autologous PBMC, the ICAM-1 and HLA-DR expression on sfRA-FLS and secretion of IL-1β, IL-6, and MCP-1 increased. In vivo, human sfRA-FLS were cartilage invasive both at ipsilateral and contralateral implantation site. We conclude that, sfRA-FLS closely resemble the pathological sublining layer FLS subset in terms of surface protein expression, cytokine production and leukocyte cross-talk potential. Further, sfRA-FLS are comparable to tissue-derived FLS in their capabilities to invade cartilage at implantation sites but also spread tissue destruction to a distant site. Collectively, sfRA-FLS can serve as a an easy-to-obtain source of pathological sublining FLS in RA.
33078254 Methotrexate use does not increase the prevalence of hepatic steatosis: a real-world retro 2021 May OBJECTIVE: We aimed to determine whether methotrexate (MTX) treatment in patients with rheumatoid arthritis (RA) leads to the development of non-alcoholic fatty liver (NAFL). METHOD: Data were derived from records of all patients with RA who underwent abdominal ultrasonography at the Jeonbuk National University Hospital. Patients with ultrasound-proven NAFL were identified, and those without NAFL were matched by age and sex using the propensity score matching method at 1:3 ratio. We also analyzed the Health Insurance Review and Assessment Service-National Patient Samples, a nationwide cohort database, to determine the association between MTX use and NAFL in a large number of patients (n = 24,653). RESULTS: In the hospital cohort, 92 patients with NAFL did not show significant differences in the cumulative MTX dose when compared with the no-NAFL group (n = 276) (1908.5 ± 1757.5 vs. 1948.6 ± 2118.8 mg, p = 0.911). The prevalence of NAFL was not significantly different across strata of cumulative MTX dose. Multiple logistic analyses identified hypertriglyceridemia (OR, 4.88 [95% CI, 1.13-20.93]) and higher body mass index (OR, 1.22 [95% CI, 1.05-1.41]) as being associated with an increased risk of NAFL. In the nationwide cohort, the MTX exposure rate between the NAFL and no-NAFL groups was not significantly different. CONCLUSIONS: Collectively, no significant association between NAFL development and administration of MTX was detected in this study. Our results suggest that it is more efficient to adjust for individualized risk factors for NAFL prevention rather than discontinuation of MTX in patients with RA. Key Points • NAFLD has been highlighted with increasing prevalence worldwide and possible progression to end-stage liver disease. • Cumulative dose or exposure history of MTX does not show a significant association with NAFLD prevalence. • Modifying well-established risk factors is more efficient in NAFLD prevention rather than discontinuation of MTX.
33492182 Good response to methotrexate is associated with a decrease in the gene expression of ABCG 2021 Nov OBJECTIVES: Methotrexate (MTX) is used as an anchor drug in the treatment of rheumatoid arthritis (RA), although more than a half of the patients with RA require additional treatments. We designed a prospective study involving two medical centers in Japan to examine the association between the expression of MTX-related genes including a drug transporter ATP-binding cassette sub-family G member 2 (ABCG2) gene and the clinical response to MTX in MTX-naive patients with RA. METHODS: The primary endpoint of this study was good response based on the European League Against Rheumatism (EULAR) response criteria by Disease Activity Score using 28-joint count (DAS28). We evaluated the association between the baseline expression of six genes involved in the intracellular pharmacokinetics of MTX, including ABCG2, as well as their temporal changes, and the clinical response at week 12 from the initiation of MTX. RESULTS: Based on the clinical response at 12 weeks after the initiation of MTX, 24 patients were classified into good responders (n = 9) and non-good responders (n = 15; 10 moderate responders and 5 non-responders) groups. A univariate logistic regression analysis of the baseline gene expression levels to predict the EULAR good response at week 12 showed a significant association with ABCG2 expression alone. Furthermore, the rate of baseline expression of ABCG2 mRNA above the cut-off value determined using a receiver operating characteristic curve was higher in good responders than in non-good responders (p = .012). Moreover, ABCG2 expression decreased in almost all good responders, but not in non-good responders, after MTX treatment for 12 weeks (median -76% vs. +41% from baseline, respectively; p = .011). The ABCG2 expression level did not correlate with DAS28 at baseline or week 12. CONCLUSIONS: Our study revealed that good response to MTX is associated with a decrease in the expression of ABCG2 in patients with RA.
32144843 A Population-Based Approach to Reporting System-Level Performance Measures for Rheumatoid 2021 May OBJECTIVE: To operationalize and report on nationally endorsed rheumatoid arthritis (RA) performance measures (PMs) using health administrative data for British Columbia (BC), Canada. METHODS: All patients with RA in BC ages ≥18 years were identified between January 1, 1997 and December 31, 2009 using health administrative data and followed until December 2014. PMs tested include: the percentage of incident patients with ≥1 rheumatologist visit within 365 days; the percentage of prevalent patients with ≥1 rheumatologist visit per year; the percentage of prevalent patients dispensed disease-modifying antirheumatic drug (DMARD) therapy; and time from RA diagnosis to DMARD therapy. Measures were reported on patients seen by rheumatologists, and in the total population. RESULTS: The cohort included 38,673 incident and 57,922 prevalent RA cases. The percentage of patients seen by a rheumatologist within 365 days increased over time (35% in 2000 to 65% in 2009), while the percentage of RA patients under the care of a rheumatologist seen yearly declined (79% in 2001 to 39% in 2014). The decline was due to decreasing visit rates with increasing follow-up time rather than calendar effect. The percentage of RA patients dispensed a DMARD was suboptimal over follow-up (37% in 2014) in the total population but higher (87%) in those under current rheumatologist care. The median time to DMARD in those seen by a rheumatologist improved from 49 days in 2000 to 23 days in 2009, with 34% receiving treatment within the 14-day benchmark. CONCLUSION: This study describes the operationalization and reporting of national PMs using administrative data and identifies gaps in care to further examine and address.
33868292 Metabolic Control of Autoimmunity and Tissue Inflammation in Rheumatoid Arthritis. 2021 Like other autoimmune diseases, rheumatoid arthritis (RA) develops in distinct stages, with each phase of disease linked to immune cell dysfunction. HLA class II genes confer the strongest genetic risk to develop RA. They encode for molecules essential in the activation and differentiation of T cells, placing T cells upstream in the immunopathology. In Phase 1 of the RA disease process, T cells lose a fundamental function, their ability to be self-tolerant, and provide help for autoantibody-producing B cells. Phase 2 begins many years later, when mis-differentiated T cells gain tissue-invasive effector functions, enter the joint, promote non-resolving inflammation, and give rise to clinically relevant arthritis. In Phase 3 of the RA disease process, abnormal innate immune functions are added to adaptive autoimmunity, converting synovial inflammation into a tissue-destructive process that erodes cartilage and bone. Emerging data have implicated metabolic mis-regulation as a fundamental pathogenic pathway in all phases of RA. Early in their life cycle, RA T cells fail to repair mitochondrial DNA, resulting in a malfunctioning metabolic machinery. Mitochondrial insufficiency is aggravated by the mis-trafficking of the energy sensor AMPK away from the lysosomal surface. The metabolic signature of RA T cells is characterized by the shunting of glucose toward the pentose phosphate pathway and toward biosynthetic activity. During the intermediate and terminal phase of RA-imposed tissue inflammation, tissue-residing macrophages, T cells, B cells and stromal cells are chronically activated and under high metabolic stress, creating a microenvironment poor in oxygen and glucose, but rich in metabolic intermediates, such as lactate. By sensing tissue lactate, synovial T cells lose their mobility and are trapped in the tissue niche. The linkage of defective DNA repair, misbalanced metabolic pathways, autoimmunity, and tissue inflammation in RA encourages metabolic interference as a novel treatment strategy during both the early stages of tolerance breakdown and the late stages of tissue inflammation. Defining and targeting metabolic abnormalities provides a new paradigm to treat, or even prevent, the cellular defects underlying autoimmune disease.