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ID PMID Title PublicationDate abstract
30148441 Tocilizumab modulates serum levels of adiponectin and chemerin in patients with rheumatoid 2019 Mar OBJECTIVES: Adipokines play an important role in the pathophysiology of rheumatoid arthritis (RA), provide a link between the disease and overweight, contributing to explain the enhanced cardiovascular (CV) risk and influence the response to disease-modifying anti-rheumatic drugs. The aim of this study was to determine the possible effects of intravenous (IV) tocilizumab (TCZ), an interleukin-6 receptor antagonist, on serum levels of leptin, adiponectin, resistin, visfatin, and chemerin. METHODS: Forty-four RA patients with active disease (DAS28-ESR ≥3.2) were treated with IV TCZ (8 mg/kg) once every 4 weeks for six months: 20 patients received TCZ as monotherapy and 24 in association with methotrexate (MTX). At baseline and monthly, before each infusion, body mass index, DAS28-ESR and Health Assessment Questionnaire (HAQ) were recorded. The laboratory parameters, including the adipokines serum levels were collected at baseline and after six months. RESULTS: At the end of the follow-up, ESR, CRP, DAS28-ESR and HAQ resulted significantly improved in patients received TCZ as monotherapy or combined with MTX. Lipid profile showed only a significant increase of total cholesterol. A significant reduction of chemerin and an increase of adiponectin were observed in the whole population and in the subgroups of the patients analysed (TCZ mono or combined therapy) without any significant correlations with clinical and biochemical parameters. No changes in the leptin and resistin levels were detected. CONCLUSIONS: TCZ is able to regulate serum levels of chemerin and adiponectin in RA patients, independently of the disease treatment response, which contributes to explain the CV safety of TCZ.
31468683 Adjuvant-induced arthritis affects testes and ventral prostate of Wistar rats. 2020 Mar BACKGROUND: Rheumatoid arthritis (RA) may reduce the testosterone production, thereby leading to testicular dysfunction and subfertility. OBJECTIVES: This study aimed to evaluate whether adjuvant-induced arthritis (AIA) induces histopathological and morphometric-stereological alterations on testes with repercussions on the prostate, and alternatively, verifying AIA-induced direct effects on the prostate, regardless of the testicular involvement. MATERIAL AND METHODS: Adult male Wistar rats were sham-orchiectomized or orchiectomized. Twenty days after the surgery, these animals were injected with vehicle (SHAM and ORQ groups, respectively) or adjuvant (Mycobacterium tuberculosis) to induce arthritis (AIA and ORQ/AIA groups, respectively). Forty days later, testes and ventral prostate were processed for histopathological and morphometric-stereological analyses, as well as to PCNA immunohistochemistry. Collagen deposit was evaluated in prostate. Circulating testosterone levels were determined 15 days post-AIA induction in SHAM and AIA rats and 40th day in all groups. RESULTS: In the testes, AIA promoted histopathological changes characterized by an increase in the percentage of abnormal tubules and reduction in the height of the seminiferous epithelium, daily production of spermatozoa, and cellular proliferation. In the prostate, AIA decreased the luminal volume of the secretory ducts. In condition of androgenic deprivation due to the orchiectomy, AIA induced proliferation of the prostatic epithelium. DISCUSSION: The effects of arthritis on testes and prostate were observed 40 days post-AIA induction, possibly results of the hypoandrogenism were already established on 15th day post-induction, which is related to the decline of the steroidogenesis in the Leydig cells. On the other hand, the joint inflammatory process may also have direct repercussions upon the prostate, regardless of this hypoandrogenism. CONCLUSION: AIA effects on reproductive tissues may be related to both hypoandrogenism and other direct inflammatory mechanisms. Possibly, these AIA effects on the testes and prostate occur at a stage in which the inflammatory process is most active, about 15-20 days after induction, remaining evident until the 40th day.
31287230 Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Ina 2019 Nov OBJECTIVE: To evaluate the efficacy, including capacity for inhibition of radiographic progression, and safety of upadacitinib, a JAK1-selective inhibitor, as compared to placebo or adalimumab in patients with rheumatoid arthritis (RA) who have experienced an inadequate response to methotrexate (MTX). METHODS: In total, 1,629 RA patients with an inadequate response to MTX were randomized (2:2:1) to receive upadacitinib (15 mg once daily), placebo, or adalimumab (40 mg every other week) while continuing to take a stable background dose of MTX. The primary end points were achievement of an American College of Rheumatology 20% (ACR20) improvement response and a Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) of <2.6 in the upadacitinib group compared to the placebo group at week 12; inhibition of radiographic progression was evaluated at week 26. The study was also designed and powered to test for the noninferiority and superiority of upadacitinib compared to adalimumab, as measured both clinically and functionally. RESULTS: At week 12, both primary end points were met in patients receiving upadacitinib compared to those receiving placebo (P ≤ 0.001). An ACR20 improvement response was achieved by 71% of patients in the upadacitinib group compared to 36% in the placebo group, and a DAS28-CRP score of <2.6 was observed in 29% of patients receiving upadacitinib compared to 6% of patients receiving placebo. Upadacitinib was superior to adalimumab based on the ACR50 response rate, achievement of a DAS28-CRP score of ≤3.2, change in pain severity score, and change in the Health Assessment Questionnaire disability index. At week 26, more patients receiving upadacitinib than those receiving placebo or adalimumab achieved low disease activity or remission (P ≤ 0.001). Radiographic progression was significantly inhibited in patients receiving upadacitinib and was observed in fewer upadacitinib-treated patients than placebo-treated patients (P ≤ 0.001). Up to week 26, adverse events (AEs), including serious infections, were comparable between the upadacitinib and adalimumab groups. The proportions of patients with serious AEs and AEs leading to discontinuation were highest in the adalimumab group; the proportions of patients with herpes zoster and those with creatine phosphokinase (CPK) elevations were highest in the upadacitinib group. Three malignancies, 5 major adverse cardiovascular events, and 4 deaths were reported among the groups, but none occurred in patients receiving upadacitinib. Six venous thromboembolic events were reported (1 in the placebo group, 2 in the upadacitinib group, and 3 in the adalimumab group). CONCLUSION: Upadacitinib was superior to placebo and adalimumab for improving signs, symptoms, and physical function in RA patients who were receiving background MTX. In addition, radiographic progression was significantly inhibited by upadacitinib as compared to placebo. The overall safety profile of upadacitinib was generally similar to that of adalimumab, except for higher rates of herpes zoster and CPK elevations in patients receiving upadacitinib.
30666911 Lifestyle Modification in Rheumatoid Arthritis: Dietary and Physical Activity Recommendati 2019 BACKGROUND: Rheumatoid arthritis is a systemic autoimmune disease, considered the most common inflammatory articular disease among the general population. However, not only the joints are affected; rheumatoid arthritis also has an extra-articular manifestation. As for many other chronic diseases, rheumatoid arthritis may be exacerbated by poorer lifestyle choices. In fact, recent studies emphasize the role of nutrition and physical activity in this disease. AIM: In the current paper, we aim to describe lifestyle modifications based on diet and physical activity and other recommendations that seem to improve the clinical management and the disease outcome of Rheumatoid arthritis. RESULTS: A three-component lifestyle modification programme has been considered based on: (i) A low-fat low-sodium Mediterranean diet rich in fruits, vegetables, whole grains and nuts and poor in sugar-sweetened beverages, red and processed meat and trans fats, and the supplementation with omega-3 fatty acids, non-essential amino acids and probiotics, (ii) An appropriate physical activity programme based on an active daily lifestyle, aerobic exercise and resistance training and (iii) Adequate sleep hygiene and smoking reduction/cessation, that seems to have positive effects in terms of disease progression and related outcomes. CONCLUSION: Lifestyle modification programme should be considered as the basis of any treatment, (i.e., pharmacological treatment), in patients with rheumatoid arthritis.
31283012 Validity of administrative database detection of previously resolved hepatitis B virus in 2019 Nov The risk of hepatitis B virus (HBV) reactivation has increased owing to advances in the immunosuppressive therapy field. However, the HBV reactivation incidence among patients with previously resolved HBV (prHBV) infection during immunosuppressive therapy for rheumatoid arthritis (RA) remains unclear. The objective of this work is to describe the validity of detecting prHBV infection from administrative data through comparisons with chart abstraction and determine the incidence of HBV reactivation during immunosuppressive therapy for RA in Japan. In this retrospective cohort study, data on selected patients were extracted from administrative claims data. To identify patients with prHBV infection and de novo hepatitis, and HBsAg carriers, we conducted chart abstraction. The incidence rate of de novo hepatitis was 1.23 of 100 person-years. The positive predictive value (PPV) and its 95% confidence interval (CI) of administrative data for the identification of suspected prHBV infections was 85.8% (95% CI: 81.7%-89.3%). This study evaluated the PPV of the algorithm of HBV-DNA testing with immunosuppressive therapy performed four times or more per year for the detection of prHBV infection from administrative data. Additionally, we determined the incidence rate of HBV reactivation among preHBV infections during immunosuppressive therapy for RA to be 1.23 of 100 person-years.
31414225 Effect of TNF inhibitors on bone mineral density in rheumatoid arthritis patients receivin 2020 Mar We aimed to determine whether tumor necrosis factor inhibitors (TNFi) have beneficial effects on bone mineral density (BMD) in rheumatoid arthritis (RA) patients with osteoporosis receiving bisphosphonate. A total of 199 RA patients, who were newly diagnosed with osteoporosis and receiving bisphosphonate between January 2005 and March 2017, were reviewed. Changes in BMD after 1 year were compared between patients treated with and without TNFi. The inverse probability of treatment weighting (IPTW) method using the propensity score was performed to minimize confounding factors, and logistic regression analysis was applied to identify any factors associated with significant BMD improvement (≥ 3%) at the lumbar spine and femur neck. Among patients receiving bisphosphonate, 29 were exposed to TNFi, and 170 patients were not exposed. The percentage change in BMD and the proportion of significant improvements at the lumbar spine and femur neck were similar between patients treated with and without TNFi, before and after IPTW adjustment. In addition, the disease activity score 28 (DAS28) with three variables [adjusted odds ratio (OR) 0.741, 95% confidence interval (CI) 0.592-0.927, p = 0.009] and cumulative steroid dose (adjusted OR 0.639, 95% CI 0.480-0.851, p = 0.002) were inversely associated with an improvement in BMD. Conversely, TNFi use was not associated with any improvement in BMD after adjustment by IPTW using the propensity score. TNFi did not influence BMD improvement in RA patients with osteoporosis receiving bisphosphonate, suggesting that TNFi cannot be considered as a preferred therapeutic option for increasing BMD.
29276053 Inter-observer agreement of standard joint count examination and disease global assessment 2019 Sep OBJECTIVES: To assess the inter-observer agreement of standard joint count between experienced Rheumatology professor (Prof) and young Rheumatology fellow (candidate), and to compare disease global assessment between professor, young candidate and patients. METHODS: This study included one hundred rheumatoid arthritis patients. For all patients independent clinical evaluation was done by two rheumatologists (professor and candidate) for detection of tenderness in 28 joints and swelling in 26 joints. The study also involved global assessment of disease activity by the provider (Prof and candidate) (EGA) as well as by the patient (PGA). The EGA was determined without previous knowledge of the patient's laboratory test results. RESULTS: A highly significant accordance (correlation) between professor and candidate was found in both the number of tender joints (p<0.001) (r=0.946), and the number of swollen joints (p<0.001) (r=0.797). Regarding swollen joints, the highest agreement was in right knee (0.929), while poor agreement was found in the right 5th MCP (0.049). Regarding tender joints, the highest analogy was in the right elbow (0.899), in contrast to the left 3rd PIP (0.462) which showed the least congruence. Agreement study using kappa measurement for disease global assessment showed: moderate agreement (between professor and candidate) (0.405), fair agreement between (professor and patient) (0.213), fair agreement between (candidate and patient) (0.367). CONCLUSION: Inter-observer reliability was better for TJCs than SJCs. Regarding SJCs agreement was better in large joints such as the knees compared to the small joints such as the MCPs. Disease global assessment may show discrepancy between patients and physicians.
31669808 Predictive factors of tumour necrosis inhibitor treatment persistence for rheumatoid arthr 2020 Mar OBJECTIVES: To determine whether changes in ultrasonography (US) features of monosodium urate crystal deposition is associated with the number of gouty flares after stopping gout flare prophylaxis. METHODS: We performed a 1-year multicentre prospective study including patients with proven gout and US features of gout. The first phase of the study was a 6-month US follow-up after starting urate-lowering therapy (ULT) with gout flare prophylaxis. After 6 months of ULT, gout flare prophylaxis was stopped, followed by a clinical follow-up (M6 to 12) and ULT was maintained. Outcomes were the proportion of relapsing patients between M6 and M12 according to changes of US features of gout and determining a threshold decrease in tophus size according to the probability of relapse. RESULTS: We included 79 gouty patients (mean [±SD] age 61.8±14 years, 91% males, median disease duration 4 [IQR 1.5; 10] years). Among the 49 completers at M12, 23 (47%) experienced relapse. Decrease in tophus size≥50% at M6 was more frequent without than with relapse (54% vs. 26%, P=0.049). On ROC curve analysis, a threshold decrease of 50.8% in tophus size had the best sensitivity/specificity ratio to predict relapse. Probability of relapse was increased for patients with a decrease in tophus size <50% between M0 and M6 (OR 3.35 [95% confidence interval 0.98; 11.44]). CONCLUSION: A high reduction in US tophus size is associated with low probability of relapse after stopping gout prophylaxis. US follow-up may be useful for managing ULT and gout flare prophylaxis.
30813156 Top 100 cited articles on rheumatoid arthritis: A bibliometric analysis. 2019 Feb BACKGROUND: Rheumatoid arthritis (RA) is a worldwide health issue; although the prospects for most patients are favorable, many still do not respond to the current therapies. Numerous articles related to RA have been published in the past 3 decades; an analysis of the most cited articles in this field was undertaken to identify important articles regarding RA related to pathogenesis, diagnosis, and treatment. METHODS: We searched the Web of Science and collected the general information of the top 100 cited articles. The citation number, publication year, authorship, impact factor (IF) of the journal in the publication year, country origins, article types, and funding source were evaluated. RESULTS: The total citations of the top 100 articles varied from 11,922 to 556 and were published between 1985 and 2014. These articles were published in 24 journals, led by Arthritis and Rheumatism (n = 33), followed by the New England Journal of Medicine (n = 15). Most of the articles (n = 80) were produced by ≥5 authors. They were from 34 countries, and the United Stated contributed to most of the articles (n = 58), followed by the United Kingdom (n = 42). The article types were divided into clinical study (n = 55), review (n = 17), meta-analysis (n = 4), clinical guideline (n = 10), and basic science (n = 14). Eighty-seven percent of the articles were supported either by public organizations or medical companies. CONCLUSION: This study provided insights into the development of publications and their citations of RA in the past 3 decades. Clinical studies or clinical guidelines published in high-impact journals were more likely to be cited in the field of RA. The latest publications may not be included in the top 100 cited articles, as the more recent studies have not had sufficient time to accumulate the number of citations.
30365902 Use of synthetic and biologic DMARDs during pregnancy. 2019 Jan Introduction: Since most of the autoimmune diseases (AID) affect mostly women in their fertile years, and fertility is in general preserved, the use of disease-modifying antirheumatic drugs (DMARDs) during conception, pregnancy, and lactation has been a matter of concern in the treatment of women affected by AID. Areas covered: We performed a comprehensive review of the latest and most relevant research papers published in the field and discussed different aspects related to the use of synthetic and biologic DMARDs and immunosuppressants in the preconceptional period, during pregnancy and lactation in AID patients, both in males and females. Expert commentary: Active AID impose an increased risk for adverse maternal and fetal outcomes, such as preeclampsia, miscarriage, intrauterine growth restriction, prematurity, low birth weight, and stillbirth. Family planning with proper contraception and shared decision-making on the ideal time to conceive with treatment adjustment must be a rule. One of the main challenges when counseling and/or adjusting treatment of patients that are planning a pregnancy is to provide a medication that is at the same time efficacious and safe at the conceptional period and to developing the fetus.
31468712 Coronary artery calcium score in female rheumatoid arthritis patients: Associations with a 2019 Oct AIMS AND METHODS: In rheumatoid arthritis (RA), cardiovascular (CV) comorbidities are a major cause of mortality. Coronary Calcium Score (CCS) assessed by computed tomography has been associated with RA prognosis. In this work, we aimed to assess CCS in female RA patients and determine CCS association with different clinical, laboratory and imaging disease parameters. RESULTS: We evaluated 60 female patients, with a mean age of 53.6 ± 10.4 years, a mean Disease Activity Score of 28 joints (DAS28) (4v) and Health Assessment Questionnaire (HAQ) of 4.542 ± 1.317 and 1.488 ± 0.631, respectively, and a disease duration of 14.7 ± 10.3 years. Mean CCS value was 35.192 ± 117.786. CCS > 10 was significantly associated with CV risk factors (age: odds ratio [OR] = 1.120; P = .002, body mass index [BMI] ≥ 25 kg/m(2) : OR = 0.271; P = .025, high-density lipoprotein [HDL]: OR = 0.011; P = .025, low-density lipoprotein/ HDL ratio: OR = 2.084; P = .030, apolipoprotein A1 [ApoA1]: OR = 0.965; P = .014, apolipoprotein B/ApoA1 [ApoB/ApoA1] ratio: OR = 59.834; P = .011, homocysteine: OR = 1.287; P = .045, diabetes: OR = 10.400; P = .043, and anti-diabetic therapy: OR = 10.667, P = .041), disease parameters (C-reactive protein [CRP]: OR = 1.038; P = .046, DAS[4v]: OR = 1.900; P = .009, DAS28[4v; CRP]: OR = 1.700; P = .019, DAS[3v]: OR = 1.947; P = .010, DAS28[3v; CRP]: OR = 1.696; P = .022, HAQ: OR = 3.299; P = .023, erosion score: OR = 1.015; P = .012, and total modified Sharp/van der Heijde Score: OR = 1.008; P = .035), biomarkers (osteoprotegerin: OR = 1.505; P = .022), and bone mineral density (femoral: OR = 0.005; P = .018, lumbar spine: OR = 0.001; P = .002, left hand: OR = 7.9 × 10(-9) ; P = .005, and osteoporosis: OR = 6.628; P = .007). After adjustment for age and BMI, significant associations were maintained with ApoA1, ApoB/ApoA1 ratio, homocysteine, CRP, DAS(4v), DAS(4v; CRP), DAS(3v) and DAS(3v; CRP). A sensitivity analysis undertaken after excluding the 6 diabetics yielded similar results. CONCLUSIONS: Our work reinforces the hypothesis that in RA, CCS may be a useful tool in CV risk assessment, particularly valuable in poorer controlled patients with certain lipoprotein profiles.
29447492 Physiotherapists' management of challenging situations in guiding people with rheumatoid a 2019 Jan OBJECTIVES: To explore strategies used by physiotherapists (PTs) in guiding people with rheumatoid arthritis to health-enhancing physical activity (HEPA) in a group setting during a 1-year intervention study. METHODS: Exploratory design with qualitative video analysis performed in three steps. Eleven female PTs were video recorded while leading support group sessions aiming at facilitating HEPA (twice-weekly exercise sessions at public gyms and 150 weekly minutes of moderately intense aerobic physical activity). RESULTS: Three categories of challenging situations emerged. They occurred when the HEPA intervention participants reported barriers to performing physical activity, when they neglected to use the planning tool for physical activity as intended in the program, and when they received negative results from physical capacity tests. PTs used different strategies to manage these challenges, with main focus either on information-giving, corresponding to a traditional health professional approach, or utilizing group resources by organizing participation. CONCLUSIONS: This study provides detailed descriptions of PTs' clinical behavior in video-recorded sessions. The results imply that motivated PTs can, despite their biomedical and practitioner-focused training, learn to adapt their communication strategies to different situations, altering between traditional information-giving and utilizing group resources by organizing participation.
30824652 Breastfeeding among Women with Rheumatoid Arthritis Compared with the General Population: 2019 Sep OBJECTIVE: The World Health Organization recommends that infants be exclusively breastfed until the age of 6 months. The first objective was to compare breastfeeding frequencies and time of cessation between women with rheumatoid arthritis (RA) and the general population. The second objective was to identify why patients with RA discontinue breastfeeding. METHODS: This study was embedded in the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) study, a nationwide prospective cohort study. From 2002 to 2008, a total of 249 pregnancies were followed from pregnancy until 6 months postpartum. Data on lactation and medication use were collected. Proportion tests were used to compare percentages of breastfeeding between the study population and the general/reference population. RESULTS: At 4-6, 12, and 26 weeks postpartum, 43%, 26%, and 9% of the RA patients breastfed their offspring, respectively, compared with 63%, 46%, and 41% in the general population, respectively (p < 0.001). The main reason for women to discontinue breastfeeding was the restart of medication (n = 129, 57.8%). Nevertheless, more than 40% of these patients restarted medication that was considered compatible with breastfeeding. CONCLUSION: This large prospective study demonstrates that RA is associated with lower proportions of women breastfeeding their offspring and earlier cessation compared with the general population. A considerable number of patients discontinued breastfeeding so that they could start medication, even though many of the medications are considered safe to use during lactation. Using the results of this study, intervention strategies supporting RA patients who wish to breastfeed may be developed.
30886732 Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis 2019 OBJECTIVES: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). We examined response to tofacitinib 5 or 10 mg two times a day in patients with seropositive vs seronegative RA. METHODS: Data were pooled from five Phase III studies of conventional synthetic disease-modifying antirheumatic drug (csDMARD)- or biological DMARD-inadequate responders (ORAL Step [NCT00960440]; ORAL Scan [NCT00847613]; ORAL Solo [NCT00814307]; ORAL Sync [NCT00856544]; ORAL Standard [NCT00853385]). 'Serotype' subgroups were: anticyclic citrullinated peptide (CCP) and rheumatoid factor (RF) positive (anti-CCP+/RF+); anti-CCP+/RF negative (-); anti-CCP-/RF+; anti-CCP-/RF-. At month 3, ACR20/50/70 response rates, Disease Activity Score (DAS28-4[ESR])-defined remission (DAS28-4[ESR]<2.6) and low disease activity (LDA; DAS28-4[ESR]≤3.2), changes from baseline (CFB) in Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 Health Survey (SF-36) physical functioning and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated. Safety endpoints were compared. RESULTS: Baseline demographics/characteristics were similar across subgroups. Tofacitinib significantly improved ACR20/50/70 response rates, DAS28-4(ESR) LDA rates and CFB in HAQ-DI and FACIT-F vs placebo across subgroups. More anti-CCP+/RF+ than anti-CCP-/RF- patients had ACR20/50/70 responses (ACR20/50: both tofacitinib doses; ACR70: 10 mg two times a day). SF-36 physical functioning improved in anti-CCP+/RF+, anti-CCP+/RF- and anti-CCP-/RF+ patients (both tofacitinib doses) and anti-CCP-/RF- patients (10 mg two times a day) vs placebo. More anti-CCP+/RF+ and anti-CCP+/RF- than anti-CCP-/RF- patients achieved DAS28-4(ESR) remission and LDA with tofacitinib 10 mg two times a day. Frequency of adverse events (AEs), serious AEs and discontinuations due to AEs were similar across subgroups. CONCLUSION: Generally, tofacitinib efficacy (ACR20/50/70 responses) and safety were similar across subgroups. DAS28-4(ESR) remission rates and SF-36 physical functioning appeared lower in anti-CCP- patients.
31820358 Patients with rheumatoid arthritis have an increased risk of incident chronic kidney disea 2020 Jan OBJECTIVES: Patients with rheumatoid arthritis (RA) may have a higher risk of developing chronic kidney (CKD) compared with general population, but the data on this risk are still not well characterized. This systematic review and meta-analysis aimed to comprehensively investigate this association by reviewing all available studies. METHODS: A systematic review was performed using MEDLINE and EMBASE database from inception to July 2019 to identify all cohort studies that compared the risk of developing CKD after index date among patients with RA versus individuals without RA. Pooled risk ratio and 95% confidence interval (CI) were calculated using random-effect, generic inverse-variance method of DerSimonian and Laird. RESULTS: A total of four cohort studies (three retrospective cohort studies and four prospective cohort study) comprising of 1,627,833 participants met the inclusion criteria and were included in the meta-analysis. The overall quality of the included studies was good. The risk of incident CKD was significantly increased among patients with RA with the pooled risk ratio of 1.52 (95% CI 1.28-1.80). The statistical heterogeneity was high with an I(2) of 82%. CONCLUSIONS: A significantly increased risk of incident CKD among patients with RA compared with individuals without RA was demonstrated in this study.
31385219 Benefits and Safety of Tripterygium Glycosides and Total Glucosides of Paeony for Rheumato 2019 Sep OBJECTIVE: To summarize the evidence from systematic reviews (SRs) on the benefits and safety of Tripterygium glycosides (TG) and total glucosides of paeony (TGP), commonly used to treat rheumatoid arthritis (RA) in China, for patients with RA. METHODS: SRs of randomized controlled trials (RCTs) on TG or TGP in treating RA were included, by searching 8 databases from their inception until December 2017. Two authors extracted data independently. We assessed the quality of SRs using AMSTAR and graded the quality of evidence according to the GRADE approach. RESULTS: Eleven SRs containing an average of 7.6 RCTs, involving a total of 7,012 participants were included in this overview. On the basis of included SRs, TG and TGP could improve the following indexes for RA patients: American College of Rheumatology (ACR) 20 response rate, ACR50 response rate and ACR70 response rate, swollen joint count, tender joint count, erythrocyte sedimentation rate and C-reactive protein. Moreover, TGP could reduce incidence of hepatotoxicity. The most common adverse effects of TG were gastrointestinal discomfort and gonad toxicity, while for TGP was mild to moderate diarrhea. The overall quality of evidence for these findings ranged from "low" to "moderate". CONCLUSIONS: TG and TGP might be 2 potentially effective complementary and alternative drugs for patients with RA. Nevertheless, due to gonad toxicity, TG should only be considered in elderly patients or patients without reproductive needs. More evidence from high quality RCTs and SRs is warranted to support the use of TG and TGP for RA patients.
31693422 Epigenetically regulated co-expression network of genes significant for rheumatoid arthrit 2019 Nov Aim: To identify epigenetically regulated network of genes in peripheral blood mononuclear cells significant for rheumatoid arthritis (RA). Methods: Differentially expressed genes (DEGs) and their associated differentially expressed miRNAs and differentially methylated positions (DMPs) were identified. Causal inference test (CIT) identified the causal regulation chains. The analyses, for example, weighted gene co-expression network (WGCNA), protein-protein interaction and functional enrichment, evaluated interaction patterns among the DEGs and the associated epigenetic factors. Results: A total of 181 DEGs were identified. The DEGs were significantly regulated by DMPs and/or differentially expressed miRNAs. Causal inference test analyses identified 18 causal chains of DMP-DEG-RA and 16 intermediate DEGs enriched in 'protein kinase inhibitor activity'. BTN2A1 was co-expressed with other 9 intermediate genes and 11 known RA-associated genes and played a pivotal role in the co-expression network. Conclusion: Epigenetically regulated network of genes in peripheral blood mononuclear cells (PBMC) contributed to RA. The causal DMPs and key intermediate genes may serve as potential biomarkers for RA.
29496419 Rheumatoid factor testing in Spanish primary care: A population-based cohort study includi 2019 Nov OBJECTIVE: Rheumatoid factor (RF) testing is used in primary care in the diagnosis of rheumatoid arthritis (RA); however a positive RF may occur without RA. Incorrect use of RF testing may lead to increased costs and delayed diagnoses. The aim was to assess the performance of RF as a test for RA and to estimate the costs associated with its use in a primary care setting. MATERIAL AND METHODS: A retrospective cohort study using the Information System for the Development of Research in Primary Care database (contains primary care records and laboratory results of >80% of the Catalonian population, Spain). Participants were patients ≥18 years with ≥1 RF test performed between 01/01/2006 and 31/12/2011, without a pre-existing diagnosis of RA. Outcome measures were an incident diagnosis of RA within 1 year of testing, and the cost of testing per case of RA. RESULTS: 495,434/4,796,498 (10.3%) patients were tested at least once. 107,362 (21.7%) of those tested were sero-positive of which 2768 (2.6%) were diagnosed with RA within 1 year as were 1141/388,072 (0.3%) sero-negative participants. The sensitivity of RF was 70.8% (95% CI 69.4-72.2), specificity 78.7% (78.6-78.8), and positive and negative predictive values 2.6% (2.5-2.7) and 99.7% (99.6-99.7) respectively. Approximately €3,963,472 was spent, with a cost of €1432 per true positive case. CONCLUSIONS: Although 10% of patients were tested for RF, most did not have RA. Limiting testing to patients with a higher pre-test probability would significantly reduce the cost of testing.
30995344 Combined Collagen-Induced Arthritis and Organic Dust-Induced Airway Inflammation to Model 2019 Sep Rheumatoid arthritis (RA) is characterized by extra-articular involvement including lung disease, yet the mechanisms linking the two conditions are poorly understood. The collagen-induced arthritis (CIA) model was combined with the organic dust extract (ODE) airway inflammatory model to assess bone/joint-lung inflammatory outcomes. DBA/1J mice were intranasally treated with saline or ODE daily for 5 weeks. CIA was induced on days 1 and 21. Treatment groups included sham (saline injection/saline inhalation), CIA (CIA/saline), ODE (saline/ODE), and CIA +  ODE (CIA/ODE). Arthritis inflammatory scores, bones, bronchoalveolar lavage fluid, lung tissues, and serum were assessed. In DBA/1J male mice, arthritis was increased in CIA +  ODE >  CIA >  ODE versus sham. Micro-computed tomography (µCT) demonstrated that loss of BMD and volume and deterioration of bone microarchitecture was greatest in CIA +  ODE. However, ODE-induced airway neutrophil influx and inflammatory cytokine/chemokine levels in lavage fluids were increased in ODE >  CIA +  ODE versus sham. Activated lung CD11c(+) CD11b(+) macrophages were increased in ODE >  CIA +  ODE >  CIA pattern, whereas lung hyaluronan, fibronectin, and amphiregulin levels were greatest in CIA +  ODE. Serum autoantibody and inflammatory marker concentrations varied among experimental groups. Compared with male mice, female mice showed less articular and pulmonary disease. The interaction of inhalation-induced airway inflammation and arthritis induction resulted in compartmentalized responses with the greatest degree of arthritis and bone loss in male mice with combined exposures. Data also support suppression of the lung inflammatory response, but increases in extracellular matrix protein deposition/interstitial disease in the setting of arthritis. This coexposure model could be exploited to better understand and treat RA-lung disease. © 2019 American Society for Bone and Mineral Research.
31101603 T cell receptor β repertoires as novel diagnostic markers for systemic lupus erythematosu 2019 Aug OBJECTIVE: T cell receptor (TCR) diversity determines the autoimmune responses in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and is closely associated with autoimmune diseases prognosis and prevention. However, the characteristics of variations in TCR diversity and their clinical significance is still unknown. Large series of patients must be studied in order to elucidate the effects of these variations. METHODS: Peripheral blood from 877 SLE patients, 206 RA patients and 439 healthy controls (HC) were amplified for the TCR repertoire and sequenced using a high-throughput sequencer. We have developed a statistical model to identify disease-associated TCR clones and diagnose autoimmune diseases. RESULTS: Significant differences were identified in variable (V), joining (J) and V-J pairing between the SLE or RA and HC groups. These differences can be utilised to discriminate the three groups with perfect accuracy (V: area under receiver operating curve > 0.99). One hundred ninety-eight SLE-associated and 53 RA-associated TCRs were identified and used for diseases classification by cross validation with high specificity and sensitivity. Disease-associated clones showed common features and high similarity between both autoimmune diseases. SLE displayed higher TCR heterogeneity than RA with several organ specific properties. Furthermore, the association between clonal expansion and the concentration of disease-associated clones with disease severity were identified, and pathogen-related TCRs were enriched in both diseases. CONCLUSIONS: These characteristics of the TCR repertoire, particularly the disease-associated clones, can potentially serve as biomarkers and provide novel insights for disease status and therapeutical targets in autoimmune diseases.