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ID PMID Title PublicationDate abstract
31301116 P2Y11 receptor antagonist NF340 ameliorates inflammation in human fibroblast-like synovioc 2019 Oct Rheumatoid arthritis is a common chronic inflammatory joint disease. Fibroblast-like synoviocytes-mediated inflammation is closely associated with the development of rheumatoid arthritis. In this study, we report that P2Y11 receptor activity is required for cytokine-induced inflammation in primary fibroblast-like synoviocytes (FLS). P2Y11R is fairly expressed in primary FLS isolated from healthy subjects and is elevated to around three- to four-fold in rheumatoid arthritis-derived FLS. The expression of P2Y11R is inducible upon IL-1β treatment. Blockage of P2Y11R by its antagonist suppresses IL-1β-induced TNF-α and IL-6 induction and ameliorates oxidative stress as determined by levels of cellular ROS and the oxidative byproduct 4-HNE. Moreover, blockage of P2Y11R by NF340 inhibits IL-1β-induced matrix metalloproteinase protein expression as indicated by the levels of MMP-1, MMP-3, and MMP-13. Mechanistically, blockage of P2Y11R mitigates IL-1β-activated NFκB signaling, which was revealed by reduced IκBα phosphorylation, nuclear p65 accumulation, and NFκB promoter activity. Our study provides evidence of a protective mechanism of P2Y11R antagonist NF340 against cytokine-induced inflammation. Therefore, targeting P2Y11R could have potential therapeutic implication in the treatment of RA.
31168760 Autoimmunity in 2018. 2019 Jun In the vast database of peer-reviewed articles, the number of 2018 papers published retrieved using the "autoimmunity" keyword remained unchanged compared with the brilliant results of 2017 while returning above a 5% share within the immunology field, after the brisk decrease of this ratio in 2017. As in the past 12 years, we have now searched PubMed for publications related to autoimmunity in the major immunology and autoimmunity peer-reviewed journals and provide here an arbitrary discussion of the major themes encountered. Once again, we are happy to notice that similarities between autoimmune diseases and the common mechanisms significantly outnumber differences. Some examples include data on Th17 cells, cytokines, or other mediators variably involved in the autoimmunity mechanisms such as BLIMP-1, IL-10, IFN, or NF-kB. The study of the microbiome remains central to autoimmunity development and data are being gathered in a growing number of conditions, similar to epigenetics and long non-coding RNA. In the cases of specific diseases, such as systemic lupus erythematosus, rheumatoid arthritis, or psoriatic arthritis, multiple encouraging findings underline the importance of a strict relationship between basic and clinical science to define new pathogenetic and therapeutic developments. Cumulatively, the present scenario of autoimmunity appears bright and should be regarded as one of the fastest growing in the scientific field of immunology, despite the enormous attention paid to cancer immune mechanisms. The parallel observation that the rheumatology therapeutic pipeline is second only to oncology increases the hopes that more and more patients will be satisfactorily treated in the near future.
31353421 The longitudinal effect of biologic use on patient outcomes (disease activity, function, a 2019 Nov INTRODUCTION: Biologics effectively manage symptoms and disease activity in rheumatoid arthritis (RA), but their long-term effects remain unclear. METHOD: Longitudinal data were examined from the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) registry. Linear regression modeled the effect of biologic exposure on changes in disease activity (Disease Activity Score-28 with C-reactive protein [DAS28-CRP]), functional status (modified Health Assessment Questionnaire [mHAQ]), and RA severity (Routine Assessment of Patient Index Data [RAPID3]). Biologic exposure was the ratio of time on a biologic relative to time participating in the BRASS cohort. RESULTS: The analysis included 1395 RA patients, 82.3% female, with 6783 unique study visits from 2003 to 2015. At the patient's first visit, mean (SD) age was 56.3 (14.2) years and mean (SD) duration of RA was 12.7 (11.9) years. Average follow-up duration was 5.59 years (range, 1-13). Over time, DAS28-CRP, mHAQ, and RAPID3 scores decreased as the biologic exposure ratio increased. In repeated measures regression models, increased biologic exposure was significantly associated with decreased DAS28-CRP score (β = - 0.647; P < 0.001), decreased mHAQ score (β = - 0.096; P < 0.001), and decreased RAPID3 score (β = - 0.724; P < 0.001) during follow-up. Methotrexate use at baseline predicted decreased DAS28-CRP, mHAQ, and RAPID3 scores during follow-up. Biologic use at baseline predicted increased DAS28-CRP or mHAQ during follow-up. CONCLUSIONS: Increased biologic exposure is associated with decreased disease activity, function impairment, and RA severity. Future studies should examine whether earlier initiation of biologics improves patient outcomes in RA. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01793103 Key Points • Biologics effectively manage symptoms and disease activity in rheumatoid arthritis (RA), but their long-term effects remain unclear. • In this analysis of longitudinal annual population samples of 1395 RA patients in the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) registry, disease activity, function, and severity scores improved as time on biologic therapy increased. • In repeated measures regression models, time on biologic therapy was a significant predictor of improved outcomes for disease activity, function, and RA severity. • Further studies should examine whether earlier initiation of biologics limits the long-term effect of inflammation on RA outcomes.
31367943 A comprehensive review of rituximab therapy in rheumatoid arthritis patients. 2019 Nov Rituximab (RTX) is an approved treatment for rheumatoid arthritis (RA) patients that do not respond adequately to disease-modifying antirheumatic drugs. However, different new concerns, such as efficacy, optimum dose, safety issues, prediction of response to RTX, and pregnancy outcomes have attracted a lot of attention. The PubMed database was systematically reviewed for the last published articles, new findings, and controversial issues regarding RTX therapy in RA using "Rheumatoid arthritis" AND "rituximab" keywords, last updated on June 18, 2019. From 1812 initial recorders, 162 studies met the criteria. Regarding the optimum dose, low-dose RTX therapy (2 × 500 mg) seems as effective as standard dose (2 × 1000 mg), safer, and more cost-effective. The most common reported safety challenges included de novo infections, false negative serologic tests of viral infections, reactivation of chronic infections, interfering with vaccination outcome, and development of de novo psoriasis. Other less reported side effects are infusion reactions, nervous system disorders, and gastrointestinal disorders. Lower exposure to other biologics, presence of some serological markers (e.g., anti-RF, anti-CCP, IL-33, ESR), specific variations in FCGR3A, FCGR2A, TGFβ1, IL6, IRF5, BAFF genes, and also EBV-positivity could be used to predict response to RTX. Although there is no evidence of the teratogenic effect of RTX, it is recommended that women do not expose themselves to RTX at least 6 months before the conception. Only a reversible reduction of B cell-count in the offspring may be the pregnancy-related outcome. Although RTX is an effective therapeutic option for RA, more studies on optimum doses, prevention of RTX-related side effects, prediction of RTX response, and safety during the pregnancy are required.
30770760 Mass spectrometry-based analysis of cerebrospinal fluid from arthritis patients-immune-rel 2019 Feb 15 BACKGROUND: Signs of inflammation in cerebrospinal fluid (CSF) of rheumatoid arthritis patients correlate positively with fatigue, a central nervous system (CNS)-related symptom that can be partially suppressed by TNF blockade. This suggests a possible role for CNS inflammation in arthritis that may be affected by TNF blockade. We therefore investigated the effects of TNF blockade on the arthritis CSF proteome and how candidate proteins related to clinical measures of disease activity and inflammation. METHODS: Mass spectrometry-based quantitative proteomic analysis was performed on CSF from seven polyarthritis patients before and during infliximab treatment. Treatment-associated proteins were identified using univariate (Wilcoxon signed rank test) and multivariate (partial least squares discriminant analysis (PLS-DA)) strategies. Relations between selected candidate proteins and clinical measures were investigated using the Spearman correlations. Additionally, selected proteins were cross-referenced to other studies investigating human CSF in a thorough literature search to ensure feasibility of our results. RESULTS: Univariate analysis of arthritis CSF proteome revealed a decrease of 35 proteins, predominantly involved in inflammatory processes, following TNF blockade. Seven candidate proteins, Contactin-1 (CNTN1), fibrinogen gamma chain (FGG), hemopexin (HPX), cell adhesion molecule-3 (CADM3), alpha-1B-glycoprotein (A1BG), complement factor B (CFB), and beta-2-microglobulin (B2M), were selected for further studies based on identification by both univariate and multivariate analyses and reported detection in human CSF and known associations to arthritis. Decreased levels of FGG and CFB in CSF after treatment showed strong correlations with both erythrocyte sedimentation rate and disability scores, while CNTN1 and CADM3 were associated with pain. CONCLUSION: Several immune-related proteins in the CSF of arthritis patients decreased during TNF blockade, including FGG and CFB that both correlated strongly with systemic inflammation. Our findings stress that also intrathecal inflammatory pathways are related to arthritis symptoms and may be affected by TNF blockade.
31225762 No effect of delivery on total hip replacement survival: a nationwide register study in Fi 2019 Oct Background and purpose - Previous small studies have suggested that delivery does not adversely affect the survivorship of total hip replacement (THR). We investigated whether delivery after primary THR affects hip implant survivorship in a large population-based study sample Patients and methods - In this register-based nationwide cohort study, all women aged 15-45 who underwent primary THR in Finland from 1987 to 2007 were included from the Finnish Arthroplasty Register. Data on deliveries were obtained from the medical birth register. After primary THR, 111 women (133 THRs) delivered and formed the delivery group. In the reference group, 1,878 women (2,343 THRs) had no deliveries. We used Kaplan-Meier analysis with 95% confidence intervals (CI) to study implant survivorship at 6 and 13 years, and Cox multiple regression to assess survival and hazard ratios (HRs), with revision for any reason as an endpoint with adjustment for age, rheumatoid arthritis, and stem and cup fixation. Results - 51 (38%) revisions were recorded in the delivery group and 645 (28%) revisions in the reference group. The 6-year implant survivorship was 91% (CI 85-96) in the delivery group and 88% (CI 87-90) in the reference group. The 13-year survival rates were 50% (CI 39-62) and 61% (CI 59-64). The adjusted HR for revision after delivery was 0.7 (CI 0.4-1.2) in ≤ 6.8 years' follow-up and 1.1 (CI 0.8-1.6) in > 6.8 years' follow-up. Interpretation - Based on the findings in this nationwide study of hip replacement in fertile-aged women, delivery does not seem to decrease THR implant survivorship; women should not be afraid of or avoid becoming pregnant after THR.
30668531 The History, Symptoms, Causes, Risk Factors, Types, Diagnosis, Treatments, and Prevention 2019 Jan Gout, a common and complex form of inflammatory arthritis, is characterized by abnormally elevated levels of uric acid in the blood. The most current estimate from the Centers for Disease Control and Prevention shows an increase from 52.5 million to 54.4 million people in the U.S. have arthritis or one of the rheumatic diseases. There are over 100 rheumatic diseases and conditions. In the U.S., the most common types of arthritis or rheumatic diseases are osteoarthritis, gout, fibromyalgia, and rheumatoid arthritis, in that order according to prevalence. This article focuses on gout. Gout can be effectively treated and managed with a combination of medication (manufactured and/or compounded) and self-management strategies. Part 1 of this 2-part article provided the definition of gout and a brief history of gout. Part 2 continues the discussion of gout and includes examples of compounded formulations used in the treatment of gout.
31140401 Prevalence of calcium pyrophosphate deposition disease in a cohort of patients diagnosed w 2020 Jan OBJECTIVES: We aimed to characterise the clinical and radiographical phenotype of calcium pyrophosphate dihydrate deposition (CPPD) disease in patients initially diagnosed with seronegative RA, and to increase the awareness that CPPD disease can be falsely diagnosed as seronegative rheumatoid arthritis (RA). METHODS: Altogether 435 early seronegative RA patients were clinically diagnosed in a single rheumatology centre and scheduled for a 10-year follow-up. All clinical data were collected and reviewed. CPPD-related arthritis was suspected if a patient had typical radiographical findings and suitable clinical pattern of CPPD or calcium pyrophosphate crystals were found in the synovial fluid. These patients are the subjects of this study. RESULTS: Among 435 seronegative RA patients, 17 patients (3.9%) (baseline mean age 71.2 years, 82% women) with CPPD disease were identified. CPPD resembling clinical patterns in these patients were: chronic CPP crystal inflammatory arthritis (9 patients), acute CPP crystal arthritis (6 patients) and OA with CPPD (2 patients). All had typical radiographical findings of CPPD: Chondrocalcinosis (CC) of triangular fibrocartilage (17 patients [100%]), CC of knee (9 patients [53%]), CC or narrowing of metacarpophalangeal joints (7 patients [41.2%]), CC of metatarsophalangeal joints (4 patients [23.5%]), CC of symphysis pubis (1 patient [5.8%]), CC of glenohumeral joint (1 patient [5.8%]) and scapholunate advanced collapse (5 patients [29.4%]). None of these patients developed typical RA-like erosions. CONCLUSIONS: CPPD disease can mimic seronegative RA at baseline and is important in the differential diagnosis of seronegative arthritis at baseline and during follow-up. The prevalence of CPPD patients in our early seronegative RA patients was 3.9%, the percentage was 7.0% among patients ≥60 years at baseline.
30893257 Elevated matrix metalloproteinase-3 level may affect hearing function in patients with rhe 2019 Apr BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease. Sensorineural and conductive hearing loss have been reported in RA, but the results of most studies are not in agreement. The pathogenesis of the hearing loss is not clearly understood. The presence of sensorineural hearing loss was related to matrix metalloproteinase-3 (MMP-3). The aim of this study was to assess hearing loss in RA patients and to examine the correlation between plasma MMP-3 levels and hearing loss in such patients. METHODS: This is a cross-sectional and analytic research. Subjects consisted of 21 RA patients with hearing loss as a study group and 21 RA patients without hearing loss as controls. All patients were evaluated by pure tone audiometry and tympanometry. The amounts of plasma MMP-3 were determined using enzyme-linked immunosorbent assay. Pearson Chi-square test was used to determine the correlation of gender, age, disease duration, erythrocyte sedimentation rate, and platelet count of both groups. Independent t-test was used to assess equality of mean values at 250 to 8000 Hz hearing thresholds, pure tone mean values, air-bone gaps, and MMP-3 plasma levels of both groups. RESULTS: This study found sensorineural (76.2%), conductive (14.3%), and mixed (9.5%) hearing loss. The most common degree of hearing loss was mild (66.7%). There was an increased incidence of As-type tympanogram in the study group (28.6%) and control group (47.6%). There were significant differences between both groups in mean hearing thresholds (p < 0.001), mean of air conduction thresholds at 1000 to 8000 Hz (p < 0.05), and mean of bone conduction thresholds in all frequencies (p < 0.05). The significant difference of mean MMP-3 levels was also found between the groups (p < 0.001). CONCLUSION: Hearing loss is a common finding in RA. MMP-3 plasma contributed to degrade the incudomalleolar and incudostapedial joints and could damage the inner ear hair cells due to oxidative process in RA.
31768668 Assessment of adherence to disease-modifying anti-rheumatic drugs in rheumatoid arthritis. 2020 Jan OBJECTIVES: This work aimed to assess treatment adherence in rheumatoid arthritis patients with several tools and to identify factors associated with poor adherence. METHOD: Between February and December 2015, 183 patients were included in this cross-sectional study. A homemade 23-item self-questionnaire was filled by patients during an outpatient consultation or a day hospitalization stay. Morisky Medication Adherence Scale (MMAS)-4, MMAS-8 and Girerd scores were extracted from this homemade questionnaire. Medication possession ratio (MPR) was then calculated. For identification of factors associated with nonadherence, patients were divided in two groups according to MMAS-8 results differentiating patients with good or bad adherence to treatments. RESULTS: Of the 183 patients, 59% received a combination of biologic and conventional synthetic disease-modifying drugs, 22% a biological treatment alone, and 19% a conventional DMARD alone. Respectively, 3%, 10%, and 7% were considered as low adherent according to MMAS-4, MMAS-8, and Girerd scores. MPR was calculated for 84/183 patients; 23% were low adherent. The need for a help in preparing the drugs (p = 0.05; OR = 6.12; 95% CI: 0.86 to 268.90) and concomitant diabetes (p < 0.001; OR = 0.045, 95% CI: 0.001 to 0.299) was higher in patients with good adherence. Presence of a patient's relative reminding to take medications was associated with low adherence (p = 0.002; OR = 4.32, 95% CI: 1.41 to 13.11). CONCLUSIONS: This study highlighted the difficulty of assessing treatment adherence in rheumatoid arthritis patients despite four different tools. Objective measures by MPR indicated a higher proportion of poor adherent patients than self-questionnaires.Key Points• Proportion of patients considered as low adherent ranged from 3 to 27% according to the method of evaluation.• The use of a pillbox and/or the preparation of drugs by a patient's relative was associated with good adherence.• The presence of a patient's relative reminding to take medication was associated with low adherence.
31672633 Correlation between albumin to fibrinogen ratio, C-reactive protein to albumin ratio and T 2020 Jan BACKGROUND: The albumin to fibrinogen ratio (AFR) and the C-reactive protein to albumin ratio (CAR) have been served as inflammatory markers. However, their roles in RA remain unclear. We investigated the association of AFR/CAR with the concentration of autoantibodies and Th17 cells in RA. METHODS: A total of 196 RA patients, 200 patients with systemic lupus erythematosus (SLE), and 200 healthy donors (HD) who were admitted to the First Affiliated Hospital of Fujian Medical University were enrolled. The results of FIB, ALB, CRP, anti-cyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF) and erythrocyte sedimentation rate (ESR) from RA patients and SLE patients were retrospectively analyzed. The percentage of Th17 cells in peripheral blood of RA patients was detected by flow cytometry, and the relative expression of TNF-α, IL-6 and IL-17A was detected by RT-qPCR. Correlation analysis of AFR/CAR and Th17 cells, CRP, ESR, TNF-α, IL-6 and IL-17A in RA was conducted. RESULTS: Compared with SLE patients and healthy donors (HD), AFR concentration was significantly lower (P < 0.01) in RA patients, while CAR concentration was significantly increased (P < 0.01) in RA patients. AFR showed negative correlation with CRP (r = -0.7103), ESR (r = -0.6542), RF (-0.2219), Th17 cells (r = -0.5952) and IL-17A (r = -0.4681). CAR was positively correlated with CRP (r = 0.9899), ESR (r = 0.605), RF (0.1867), Th17 cells (r = 0.6818), TNF-α (r = 0.3388), and IL-17A (r = 0.2046). CONCLUSIONS: The concentration of AFR in RA patients was reduced, while CAR concentration was increased. AFR and CAR are associated with CRP, ESR, RF, and Th17 cell ratios in RA patients, which can be used as potential indicators for determining RA inflammation.
30978323 Risks and benefits of corticosteroids in arthritic diseases in the clinic. 2019 Jul Glucocorticoids (GCs) constitute a first line treatment for many autoimmune and inflammatory diseases. Due to their potent anti-inflammatory and immunosuppressive actions, GCs are added frequently to disease modifying antirheumatic drugs (DMARDs) in various arthritic diseases, such as rheumatoid arthritis. However, their prolonged administration or administration at high doses is associated with adverse effects that may be (quality of) life-threatening, including osteoporosis, metabolic, gastrointestinal and cardiovascular side effects. In this review, we summarize the clinical and pharmacological effects of GCs in different arthritic diseases, while documenting the current research efforts towards the identification of novel and more efficient GCs with reduced side effects.
31767935 A comparison of thermographic characteristics of the hands and wrists of rheumatoid arthri 2019 Nov 25 Thermal imaging has been applied to detect possible temperature variations in various rheumatic disorders. This study sought to determine whether rheumatoid arthritis (RA) patients without active synovitis in their hands exhibit different baseline thermographic patterns of the fingers and palms when compared to healthy individuals. Data from 31 RA patients were compared to that of 51 healthy controls. The RA patients were recruited upon confirmed absence of synovitis by clinical examination and musculoskeletal ultrasound. Participants underwent medical infrared imaging of the regions of interest (ROIs). Significant differences were found between the mean temperatures of the palm regions (29.37 °C (SD2.2); n = 306) and fingers (27.16 °C (SD3.2); n = 510) of the healthy participants when compared to the palm regions (31.4(SD1.84)°C; n = 186) and fingers (30.22 °C (SD2.4); n = 299) of their RA counterparts (p = 0.001), with the latter group exhibiting higher temperatures in all ROIs. Logistic regression models confirm that both palm and finger temperature increase significantly in RA without active inflammation. These innovative findings provide evidence that baseline thermal data in RA differs significantly from healthy individuals. Thermal imaging may have the potential to become an adjunct assessment method of disease activity in patients with RA.
31358859 Genetic Risk for Rheumatoid Arthritis is Associated with Increased Striatal Volume in Heal 2019 Jul 29 Rheumatoid arthritis (RA), an autoimmune disease, has recently been associated with increased striatal volume and decreased intracranial volume (ICV) in longstanding patients. As inflammation has been shown to precede the clinical diagnosis of RA and it is a known moderator of neuro- and gliogenesis, we were interested in testing whether these brain morphological changes appear before the clinical onset of disease in healthy young adult volunteers, as a function of relative genetic risk for RA. Genetic and structural MRI data were available for 516 healthy non-Hispanic Caucasian university students (275 women, mean age 19.78 ± 1.24 years). Polygenic risk scores were computed for each individual based on a genome-wide association study of RA, so that higher scores indicated higher risk. Striatal volume (sum of caudate, putamen, and nucleus accumbens volumes) and ICV were derived for each individual from high-resolution T1-weighted images. After controlling for sex, age, genetic components of ethnicity, socioeconomic status, and depressive symptoms, we found that higher RA polygenic risk scores were associated with increased striatal volume, but not decreased ICV. Our findings suggest that increased striatal volume may be linked to processes that precede disease onset, such as inflammation, while decreased ICV may relate to disease progression.
32598673 [The role of laboratory biomarkers in monitoring of rituximab biosimilar therapy (Acellbia 2019 May 15 AIM: to evaluate the role of laboratory biomarkers in monitoring effectiveness of rituximab (RTM) biosimilar therapy in a total dose of 1200 mg. MATERIALS AND METHODS: 20 patients (pts) with rheumatoid arthritis (RA) (18 woman, mean age 61.5(54-66.5) years, mean disease duration 39.5(20-84) months, mean DAS28 5.6(4.9-6.8)) received two intravenous RTM biosimilar infusions (600 mg â„–2) in combination with DMARDs and glucocorticoids. Laboratory biomarkers were assessed at baseline and weeks 12 and 24 after the first infusion of RTX. RESULTS: RTM biosimilar induced decreases in DAS28, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) at week 12 and 24, p.
30649682 Contraception methods used by women with rheumatoid arthritis and psoriatic arthritis. 2019 Apr Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are common in women of childbearing age and are often treated with teratogenic medications. In this study, we assessed contraceptive methods in young women with RA or PsA and correlated contraceptive method efficacy with use of concomitant rheumatic medications. We combined the data from several cross-sectional surveys of women under the age of 40 with RA or PsA. Two surveys recruited participants from a clinic setting (RA and PsA Clinic Surveys), and the third survey recruited participants from CreakyJoints.org , an online forum for patients with inflammatory arthritis (CreakyJoints Survey). Of the 164 women included, 138 had RA (67 in RA Clinic Survey, 71 in CreakyJoints Survey) and 26 had PsA (19 in PsA Clinic Survey, 7 in CreakyJoints Survey). Use of specific contraceptive and rheumatic medications were similar between the clinic and online surveys. In the pooled analysis of the Clinic and CreakyJoints survey data, women with RA and PsA reported similar utilization of highly effective contraception methods (31.9% RA, 34.6% PsA) and effective methods (31.2% RA, 30.8% PsA), but different utilization of ineffective methods (35.5% RA, 11.5% PsA) and no methods (1.5% RA, 23.1% PsA), p = 0.0002. These proportions remained similar across subgroups taking methotrexate, anti-TNF biologics, and novel medications. Approximately two thirds of women with RA and PsA reported using effective or highly effective methods of contraception, though women with PsA were more likely to report no methods of contraception.
31277720 The effect of deep or sustained remission on maintenance of remission after dose reduction 2019 Jul 5 BACKGROUND: Biologic disease-modifying antirheumatic drugs (bDMARDs) are important options for managing rheumatoid arthritis (RA). Once patients achieve disease control, clinicians may consider dose reduction or withdrawal of the bDMARD. Results from published studies indicate that some patients will maintain remission; however, others will flare. We analyzed data from three etanercept down-titration studies in patients with RA to determine what extent of remission provides the greatest predictability of maintaining remission following dose reduction or discontinuation. METHODS: Patients with moderate to severe RA from the PRESERVE, PRIZE, and Treat-to-Target (T2T) randomized controlled trials were included. We determined the proportion of patients achieving remission with etanercept at the last time point in the induction period, and sustained remission (last two time points), according to the Disease Activity Score 28-joints (DAS28), the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean criteria, and the clinical disease activity index (CDAI). We also calculated the proportion achieving DAS28 deep remission (DAS28 ≤ 1.98), sustained deep remission (last two time points), and low disease activity (LDA), and LDA according to the CDAI. Then, we evaluated whether they maintained remission or LDA following etanercept dose reduction or withdrawal. RESULTS: Patients achieving sustained and/or deep remission were more likely than patients achieving remission or LDA to maintain remission/LDA after etanercept dose reduction or withdrawal. In PRESERVE, the proportions of patients with DAS28 sustained deep remission, deep remission, sustained remission, remission, and LDA who maintained remission following etanercept dose reduction were 81%, 67%, 58%, 56%, and 36%, respectively, P < 0.001 for trend. In PRESERVE, this trend was significant when etanercept was discontinued and when ACR/EULAR Boolean and CDAI remission criteria were used. Although some sample sizes were small, the PRIZE and T2T studies also demonstrated response trends according to ACR/EULAR Boolean and CDAI remission criteria, and T2T demonstrated response trends according to DAS28. CONCLUSIONS: These results suggest that patients achieving disease control according to a stringent definition, such as sustained ACR/EULAR Boolean or CDAI remission, or a new definition of sustained deep remission by DAS28, have a higher probability of remaining in remission or LDA following etanercept dose reduction or withdrawal. TRIAL REGISTRATION: PRESERVE: ClinicalTrials.gov identifier: NCT00565409 , registered 30 November 2007; PRIZE: ClinicalTrials.gov identifier: NCT00913458 , registered 4 June 2009; T2T: ClinicalTrials.gov identifier: NCT01578850 , registered 17 April 2012.
31522319 Clinico-genetic model to predict methotrexate intolerance in rheumatoid arthritis. 2020 Jan INTRODUCTION: Methotrexate is the gold-standard DMARD in rheumatoid arthritis but is often associated with "mild" adverse effects like intolerance or laboratory abnormalities. Although non-life threatening, they are responsible for drug discontinuation in 17-50%. There is limited data on clinical and genetic markers that predict their occurrence. METHODS: This prospective study enrolled patients with active rheumatoid arthritis. They were started on methotrexate at a weekly dose of 15 mg, escalated gradually to reach 25 mg which was continued till the end of the study. Intolerance (symptomatic adverse effects) was ascertained by a questionnaire at 4, 8, 16, and 24 weeks. Laboratory testing for occurrence of cytopenia and/or transaminitis was done at the same study visits. Seven SNPs in four genes involved in methotrexate handling were genotyped using real-time polymerase chain reaction. RESULTS: This study included 110 patients with rheumatoid arthritis who received methotrexate for 24 weeks; the final mean weekly methotrexate dose was 22.0 ± 4.0 mg. Methotrexate intolerance occurred in 40 (37%), common being nausea (and vomiting) in 29 and anxiety (and dizziness) in 9. It was associated with lower BMI at baseline (21.5 ± 3.7, 23.8 ± 4.6 kg/m(2), p = 0.01). FPGS rs10106 was significantly associated with intolerance with an allelic odds ratio (95% CI) of 2.02 (1.14-3.57) and the recessive genetic model (AA+AG versus GG) with an odds ratio of 3.8 (95% CI 1.5-9.6, p = 0.004). A model including both BMI and FPGS rs10106 could modestly predict methotrexate intolerance with an accuracy of 66.3%. CONCLUSIONS: A clinical-genetic model including BMI and SNP FPGS 10101 was found to have a modest prediction ability for methotrexate intolerance.Key Points• Methotrexate intolerance (symptomatic adverse effects) was common and occurred in 37% patients over 6 months.• SNP FPGS rs10106 and low body mass index were associated with methotrexate intolerance.• Clinico-genetic model had a modest ability of 66% for predicting intolerance.
31764801 Oral steroid decreases the progression of joint destruction of large joints in the lower e 2019 Nov To identify the risk factors for destruction of large joints in the lower extremities in patients with rheumatoid arthritis (RA) during a 4-year follow-up period in a prospective study.We enrolled consecutive patients who participated in both 2012 and 2016. Clinical data, disease activity, and types of medication were collected in 2012. Standard anteroposterior radiographs of weight-bearing joints (hips, knees, and ankles) were taken in 2012 and 2016. Radiographic progression was defined as progression in the Larsen grade or the need for joint arthroplasty or arthrodesis. The association between baseline characteristics and the incidence of radiographic progression was statistically assessed.A total of 213 patient were enrolled, and, after exclusion, 186 patients were analyzed. Sixty 9 patients (37.1%) showed radiographic progression in 1 of the large joints in the lower extremities. Multivariate regression analysis showed that radiographic progression was associated with older age, higher disease activity, and the presence of radiographic destruction at the baseline. The lower dosage of oral prednisolone was a significant risk factor compared with higher dosage when used.Patients with the risk factors should be followed closely to limit the progression of large joint destruction in the lower extremities.
31483178 Pre-conception status, obstetric outcome and use of medications during pregnancy of system 2020 Sep Objective: To describe the pre-conception status, pregnancy outcomes, and medication prevalence in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Crohn's disease (CD), and ulcerative colitis (UC).Methods: E-mail-based questionnaire survey for the Japan Maternal Fetal Intensive Care Unit Network hospitals inquiring prevalence and clinical features of SLE, RA, CD and UC complicated pregnancies for 2 years.Results: The number of SLE, RA, CD and UC among 69,810 deliveries was 184, 139, 27 and 178, respectively. Less than half of pregnancies were planned. Assisted reproductive technology (ART) pregnancy rates were higher in SLE, RA and UC than in the general population (11.4, 23.0 and 7.4 vs 5.1%, p < .001 each). Preterm delivery, preeclampsia, and fetal growth restriction (FGR) were more frequent in SLE than in the general population (39.4 vs. 5.6% p < .001, 15.0 vs. 6.0% p < .001, 12.9 vs 4.2% p < .001). Prevalence of preterm delivery in RA and UC (27.5 vs. 5.6% p < .001, 11.3 vs. 5.6% p < .05) and FGR in CD (28.6 vs. 4.2% p < .001) was also higher than that in the general population.Conclusion: SLE, RA, CD, and UC complicated pregnancies were at high risks of obstetric adverse outcome. High ART rates necessitate pre-conception counseling in SLE, RA, and UC pregnancies.