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ID PMID Title PublicationDate abstract
30770765 Health-related quality of life in systemic sclerosis compared with other rheumatic disease 2019 Feb 15 BACKGROUND: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by fibrosis of the skin and the involvement of multiple internal organs. Previous studies reported poorer health-related quality of life (HRQoL) in patients with SSc compared with the general population. However, very little is known about how HRQoL in SSc patients compares with that in patients with other systemic autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjogren's syndrome (SjS). Thus, the main aim of this study was to compare HRQoL in SSc patients, patients with other rheumatic diseases, and the general population. METHODS: In this cross-sectional study, patients from the rheumatology clinics of Seoul National University Hospital with SSc, RA, SLE, and SjS were enrolled via a random sampling technique. HRQoL was captured by the Short Form (36) health survey (SF-36), the Short Form Six-Dimensional health index (SF-6D), and the EuroQol Five-Dimensional descriptive system (EQ-5D). Demographic characteristics and standardized disease activity for each disease were also obtained. Previously reported data from 600 healthy Koreans were used for the healthy controls. An ANCOVA test was used to compare the SF-36, SF-6D, and EQ-5D values between study subjects with adjustments for age, sex, disease duration, comorbidities, and disease activity status. RESULTS: One hundred twenty patients were included in each of the SSc, RA, SLE, and SjS cohorts. Patients with rheumatic diseases had significantly lower SF-36, SF-6D, and EQ-5D scores than healthy controls (all P < 0.001). After statistical adjustments, SSc patients reported significantly lower mental component summary (MCS) scores than patients with RA (P < 0.001) or SLE (P = 0.001). Specifically, the mental health and general health domains were significantly lower in SSc patients than reported in RA or SLE patients (P < 0.001 and P = 0.001, respectively, in both domains). In SSc patients, higher modified Rodnan skin scores (mRSS) correlated with lower MCS scores. CONCLUSIONS: SSc patients report poorer HRQoL than patients with RA or SLE. The extent of skin involvement is associated with poorer HRQoL in SSc patients. TRIAL REGISTRATION: NCT03257878 . Registered 22 August 2017.
30412434 Pattern of Scleritis in an Egyptian Cohort. 2019 Purpose: To report the clinical experience with scleritis at four Egyptian tertiary care eye centers. Methods: Multicenter retrospective chart review of all patients with scleritis visiting four ocular inflammation referral clinics in Egypt between January 2013 and October 2017. Results: A total of 303 scleritis patients were enrolled. These included 76 male and 227 female patients. The most frequent subtype of scleritis was nodular anterior scleritis (44.9%). Rheumatoid arthritis and Wegener granulomatosis were the 2 most common systemic associations among our cohort. Eyes with necrotizing scleritis with inflammation had the lowest mean initial and final BCVA. Conclusion: The visual prognosis of an eye with scleritis varies with the subtype of scleral inflammation. In our cohort, it was found to be poorer in eyes with necrotizing scleritis with inflammation compared to other subtypes.
30988121 Effect of Concomitant Disease-modifying Antirheumatic Drugs and Methotrexate Administratio 2019 Aug OBJECTIVE: Prior studies have suggested that concurrent conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy enhances the efficacy of biologic DMARD (bDMARD). Here, we assessed the effect of concomitant csDMARD use and methotrexate (MTX) route of administration on time to bDMARD discontinuation in a large Canadian (Ontario), observational, rheumatoid arthritis (RA) cohort. METHODS: Patients from the Ontario Best Practices Research Initiative (OBRI) who initiated bDMARD therapy and had ≥ 1 followup assessment were included. The effect of concomitant csDMARD use (primary analysis) and MTX route of administration (secondary analysis) on bDMARD discontinuation owing to (1) any reason, (2) ineffectiveness, (3) adverse events (AE), and (4) both (2) and (3), were assessed with multivariate Cox regression. RESULTS: Among the 814 patients included, 153 (18.8%) received bDMARD monotherapy and 661 (81.2%) combination csDMARD/bDMARD therapy. Over a mean followup of 1.9 years, bDMARD were discontinued in 38.7% of patients. In multivariate analysis, there was a nonsignificant trend toward lower discontinuation for the csDMARD/bDMARD group compared to bDMARD monotherapy for any reason (HR 0.76, 95% CI 0.55-1.05) and owing to ineffectiveness/AE (HR 0.73, 95% CI 0.50-1.06). Further, patients taking combination therapy had significantly lower risk of bDMARD discontinuation due to AE (HR 0.43, 95% CI 0.24-0.76). In the secondary analysis, no statistical association between MTX dose or route of administration and bDMARD durability was observed. CONCLUSION: Concomitant csDMARD use was associated with a significantly lower hazard for bDMARD discontinuation due to AE among patients with RA followed in routine clinical practice in Ontario, Canada. Neither MTX route of administration nor dose were significant predictors of bDMARD durability.
30820830 Leflunomide-induced colitis in association with enterocutaneous fistula in an immunosuppre 2019 Aug We describe the case of a 68-year-old man who has a complex medical background that included renal transplantation, rheumatoid arthritis and atrial fibrillation. Because of this, he was taking a number of immunosuppressant medications including leflunomide, prednisone and tacrolimus. He had experienced chronic diarrhoea over 18 months which had acutely worsened over the 6 weeks prior to hospital presentation. Recent colonoscopies had been performed to investigate this diarrhoea with biopsies revealing acute and chronic inflammatory changes in the terminal ileum and colon. No infectious cause could be found, with all bacterial and viral stool cultures returning negative. An enterocutaneous fistula had also spontaneously developed through his renal transplant scar in the days preceding hospital admission which complicated the clinical picture. Following dose reduction of leflunomide, there was a significant improvement in the frequency and severity of the patient's diarrhoea. He continues to be managed non-operatively for his fistula as he is at high risk of peri-operative morbidity and mortality.
30732199 The efficacy of the traditional Chinese medicine Jia Wei Niu Bang Zi granule combined with 2019 Feb BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic and autoimmune inflammatory disease ending with the destruction of joints. Current therapies can relieve RA symptoms, but some also bring severe adverse events. Therefore, an effective and safe therapeutic strategy remains to be created to benefit patients with RA by large. Jia Wei Niu Bang Zi granule (NBZG) consisting of RA-fighting Chinese herbals has been used in Longhua Hospital in the last several decades. NBZG has potential therapeutic effect on RA, which should be evaluated by larger sample clinical trial. METHODS: A multicenter, randomized, double-blind, placebo-controlled clinical trials will be conducted to determine the efficiency of NBZG in pain relief and joint protection. A total of 120 patients with active RA will be enrolled, and treated with NBZG or placebo for 12 weeks. The primary outcome measurements include rate of American College of Rheumatology (ACR) 50 at 12 weeks' treatment. The 2nd outcome measurements include rate change of ACR20, ACR70, the disease activity score (DAS) 28, 36-item Short-Form Health Survey Questionnaire, Health Assessment Questionnaire - Disability Index, score changes of Patient Assessment of Arthritis Pain, Patient Global Assessment of Arthritis, and the Athens insomnia scale at the same time points. DISCUSSION: Although NBZG has shown efficacy in treating RA in Longhua Hospital for decades, the universality of this efficacy needs evaluated. The results of this trial will provide a convincing evidence about NBZG's efficacy in treating active RA in a large population. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03173040 (registered on May 30, 2017).
30285515 Peptidyl arginine deiminase inhibition suppresses arthritis via decreased protein citrulli 2019 Nov Objective: To explore the relevance of citrullinated proteins and anti-citrullinated protein antibodies (ACPA) via protein arginine deiminase (PAD) inhibition in peptide glucose-6-phosphate isomerase-induced arthritis (pGIA).Methods: Cl-amidine, a PAD inhibitor, was injected into pGIA. Clinical scores and histopathological findings of ankle joints were assessed. Serum ACPA titers were analyzed using ELISA. Citrullinated protein expression in joints and sera were examined with immunohistochemistry and Western blot analysis, respectively. Serum levels of IL-6, TNFα, and IL-1β were measured with cytometric bead array (CBA). Gene expression levels of IL-6 and TNFα in joints, lymph nodes, and spleens were analyzed with quantitative PCR. GPI-specific productions of IFNγ and IL-17 from T cells in lymph nodes were evaluated.Results: Cl-amidine treatment significantly reduced arthritis severity while ACPA titers tended to be lower, but not significantly different compared to the control. Citrullinated proteins in joints and sera from treated mice were clearly decreased. With Cl-amidine treatment, serum IL-6 levels were significantly decreased, and IL-6 and TNFα gene expression were significantly reduced in joints. IL-17 production from GPI-specific T cells tended to be lower in Cl-amidine-treated mice, but not significantly different.Conclusion: Our results suggested that PAD-mediated citrullinated protein was involved in the pathogenesis of arthritis via IL-6.
30888761 Etanercept-induced granulomatous hepatitis as a rare cause of abnormal liver tests. 2019 Jan The authors report the case of a 76 year-old man with rheumatoid arthritis treated with prednisolone and etanercept. The patient was seen for persistent changes in liver tests lasting for six months, with a mixed pattern. The patient denied intake of new drugs or dietary/herbal supplements. Imaging studies showed mild steatosis. Additional study for chronic liver diseases only revealed positivity for anti-nuclear antibodies. Liver biopsy revealed noncaseating granulomas in some portal tracts. Consequent etiologic study for granulomatous diseases showed negative or normal results. So it was decided to suspend etanercept, with a subsequent gradual improvement on analytical parameters that normalized three months later. To date, only one case of granulomatous liver disease associated with an anti-TNF agent was described in the literature. This case also raises the question whether the development of granulomatous processes associated with anti-TNF agents has been underdiagnosed due to the presence of other concomitant immunosuppressant therapies.
31196844 Initiating tocilizumab, with or without methotrexate, compared with starting methotrexate 2019 Oct OBJECTIVES: Methotrexate (MTX), often combined with low moderately dosed prednisone, is still the cornerstone of initial treatment for early rheumatoid arthritis (RA). It is not known how this strategy compares with initial treatment with a biological. We therefore compared the effectiveness of tocilizumab (TCZ), or TCZ plus MTX (TCZ+MTX) with MTX plus 10 mg prednisone (MTX+pred), all initiated within a treat-to-target treatment strategy in early RA. METHODS: Using individual patient data of two trials, we indirectly compared tight-controlled treat-to-target strategies initiating TCZ (n=103), TCZ+MTX (n=106) or MTX+pred (n=117), using initiation of MTX (n=227) as reference. Primary outcome was Disease Activity Score assessing 28 joints (DAS28) over 24 months. To assess the influence of acute phase reactants (APRs), a disease activity composite outcome score without APR (ie, modification of the Clinical Disease Activity Index (m-CDAI)) was analysed. Secondary outcomes were remission (several definitions), physical function and radiographic progression. Multilevel models were used to account for clustering within trials and patients over time, correcting for relevant confounders. RESULTS: DAS28 over 24 months was lower for TCZ+MTX than for MTX+Pred (mean difference: -0.62 (95% CI -1.14 to -0.10)). Remission was more often achieved in TCZ+MTX and in TCZ versus MTX+pred (p=0.02/0.05, respectively). Excluding APRs from the disease activity outcome score, TCZ-based strategies showed a slightly higher m-CDAI compared with MTX+pred, but this was not statistically significant. Other outcomes were also not statistically significantly different between the strategies. CONCLUSIONS: In patients with early RA, although TCZ-based strategies resulted in better DAS28 and remission rates compared with MTX+pred, at least part of these effects may be due to a specific effect of TCZ on APRs.
29654921 Putative salivary biomarkers useful to differentiate patients with fibromyalgia. 2019 Jan 6 Fibromyalgia (FM) is a chronic pain disorder characterized by widespread pain and associated with unspecific symptoms. So far, no laboratory tests have been validated. The aim of the present study was to investigate the presence in saliva of potential diagnostic and/or prognostic biomarkers which could be useful for the management of FM patients. Specifically, the salivary profile of FM patients was compared with those of healthy subjects, subjects suffering migraine (model of non-inflammatory chronic pain), and patients affected by rheumatoid arthritis (model of inflammatory chronic pain). For proteomics analysis 2-DE and SELDI-TOF-MS were applied. From 2-DE serotransferrin and alpha-enolase were found differentially expressed in FM. Hence, their expression was validated by ELISA together with phosphoglycerate-mutase-I and transaldolase, which were found in a previous work. Moreover, ROC curve was calculated by comparing FM patients versus control subjects (healthy plus migraine) to investigate the discriminative power of biomarkers. The best performance was obtained by combining alpha-enolase, phosphoglycerate-mutase-I and serotransferrin. On the other hand, none of the candidate proteins showed a statistical correlation with clinical features. Finally, preliminary SELDI analysis highlighted two peaks whose identification need to be validated. Overall, these results could be useful in supporting the clinical diagnosis of FM. SIGNIFICANCE: FM is one of the most common chronic pain condition which is associated with significant disability. The fibromyalgic pain is a peculiar characteristic of this disease and FM patients suffer from reduced quality of life, daily functioning and productivity. Considering the deep complexity of FM, the discovery of more objective markers is crucial for supporting clinical diagnosis. Therefore, the aim of the present study was the selection of biomarkers effectively associated with fibromyalgic pain which will enable clinicians to achieve an unambiguous diagnosis, and to improve approaches to patients' management. We defined a panel of 3 salivary proteins which could be one of the criteria to be taken into account. Consequently, the identification of disease salivary biomarkers could be helpful in detecting FM clusters and targeted treatment. Actually, our future perspective foresees to develop a simple, rapid and not invasive point-of-care testing which will be of use during the diagnostic process. In addition, the present results can offer a clue for shedding light upon the complex entity of such a disease like FM.
29600354 Nutritional profile of patients with chronic inflammatory diseases in the age of biologica 2019 Jan Tumor necrosis factor alpha (TNFα) has an important role in the body composition of patients with rheumatoid arthritis (RA), Crohn's disease (CD), and spondyloarthritis (SpA). We aimed to assess the nutritional profile of patients with RA, CD, and SpA undergoing remission with multiple therapies comparing to controls and to analyze the effect of anti-TNFα medications in the nutritional parameters of these patients. One hundred thirty-one patients were included: 44 with RA, 43 with CD, and 44 with SpA. Patients receiving anti-TNFα were compared with those receiving non-biological treatment as well as to controls. Nutritional profile included body mass index (BMI), waist circumference (WC), mid-upper arm circumference, and triceps skinfold measurement. Overweight and obesity were highly prevalent on three assessed groups. In patients with RA, BMI was > 25 kg/m(2) in 74.9% patients and 49.2% controls (p < 0.0005); in CD, in 55.7% patients and 41.2% controls (p < 0.0001); and in SpA, in 68.1% patients and 43.5% controls (p < 0.0001). Central obesity was higher in all three disease groups when compared to healthy controls. There was no significant difference on nutritional parameters in patients using or not using anti-TNFα medications, except in patients with SpA, in which biologic therapy was significantly associated with lower BMI and WC, when compared to other therapies. Overweight, obesity, and elevated WC were more prevalent in patients with RA, CD, and SpA undergoing remission when compared to controls despite of used therapy. The use of biologic drugs in patients with SpA was associated with a lower BMI and lower WC.
30919904 Calprotectin discriminates septic arthritis from pseudogout and rheumatoid arthritis. 2019 Sep 1 OBJECTIVE: We aimed to determine whether calprotectin and α-defensins could discriminate septic from other inflammatory arthritides. METHODS: Synovial fluids with a predominance of neutrophils from patients with septic arthritis, pseudogout and RA were prospectively collected. Neutrophil-related proteins calprotectin and human neutrophil α-defensins levels were assessed in synovial fluids. Demographic parameters and biomarkers with P-value ⩽0.05 for differentiating septic from non-septic arthritis were included in a multivariable model. Multivariable logistic regression with stepwise selection was performed to build the final combined model. RESULTS: A total of 74 patients were included: septic arthritis (n = 26), pseudogout (n = 28) and RA (n = 20). Patients with septic arthritis were more likely to be male and young, and to display higher synovial neutrophil count. Calprotectin was significantly increased in patients with septic arthritis. The multivariable model included calprotectin, synovial fluid neutrophil count and gender. Calprotectin was the only biomarker that discriminated septic arthritis from non-septic inflammatory arthritides, with 76% sensitivity, 94% specificity and a positive likelihood ratio = 12.2 at the threshold for calprotectin of 150 mg/l. CONCLUSION: Synovial fluid calprotectin is a relevant biomarker to discriminate septic arthritis from other inflammatory arthritides. This biomarker should be tested in an independent cohort.
31446538 The important role of central sensitization in chronic musculoskeletal pain seen in differ 2020 Jan OBJECTIVE: This study explored the role of central sensitization (CS) pain in patients with various rheumatic diseases using the CS inventory (CSI). METHODS: A total of 193 patients of mean age 50.72 ± 9.65 years were included; they were divided into four different groups in terms of their rheumatic diseases. Patients with rheumatoid arthritis (RA), spondyloarthropathy (SpA), osteoarthritis (OA), and fibromyalgia syndrome (FMS) were evaluated in tertiary care rheumatology/pain medicine settings. Disease duration and activity, the Bath Ankylosing Spondylitis Disease Activity Index, the Disease Activity Score-28, and pain severity (evaluated using a visual analog scale) were assessed, and the Turkish version of the CSI administered. RESULTS: CS syndromes were present in almost half the patients (45% of SpA, 41% of RA, 62% of OA, and 94% of FMS patients). We found no significant relationship between disease activity and the CSI-A scores in SpA or RA patients (p = 0.731 and p = 0.390, respectively). As expected, the CSI-A scores were highest in the FMS group (p = 0.000), but were similar in the other groups (p < 0.05). CS-related syndromes (CSI-B conditions) were present at similar frequencies in the RA, SpA, and OA groups, but were less common in the FMS group (p = 0.000). CONCLUSIONS: The CSI usefully detects CS pain in patients with rheumatic diseases. Treatment of such pain can enhance the quality of daily life in patients with rheumatic diseases.Key Point• Central sensitization pain is common in patients with rheumatic diseases including rheumatoid arthritis, spondyloarthropathies, and osteoarthritis.
30552833 Comparative Risk of Venous Thromboembolism in Rheumatoid Arthritis Patients Receiving Tofa 2019 Jun OBJECTIVE: To evaluate the risk of venous thromboembolism (VTE) in rheumatoid arthritis (RA) patients receiving tofacitinib versus those receiving tumor necrosis factor (TNF) inhibitors. METHODS: RA patients who were initiating treatment with tofacitinib or a TNF inhibitor and had not previously received any biologic agent or tofacitinib were identified from the Truven MarketScan database (2012-2016) or Medicare claims (parts A, B, and D) database (2012-2015). Patients were followed up until treatment discontinuation, treatment switch, insurance disenrollment, or administrative censoring. The outcome of VTE was identified using inpatient claims for pulmonary embolism or deep vein thrombosis. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were determined using a Cox proportional hazards model after accounting for confounding through propensity score-based fine-stratification weighting. HRs were pooled across databases using the inverse variance meta-analytic method. RESULTS: A total of 34,074 RA patients (mean age 50 years; 5.6% tofacitinib initiators) and 17,086 RA patients (mean age 71 years; 5.8% tofacitinib initiators) were identified from the Truven and Medicare databases, respectively. The crude incidence rates of VTE per 100 person-years were 0.60 (95% CI 0.26-1.19) and 0.34 (95% CI 0.27-0.41) in Truven and 1.12 (95% CI 0.45-2.31) and 0.92 (95% CI 0.76-1.11) in Medicare for patients receiving tofacitinib and patients receiving TNF inhibitors, respectively. Propensity score-adjusted HRs showed no significant differences in the risk of VTE between tofacitinib-treated and TNF inhibitor-treated patients in either database, with a pooled HR of 1.33 (95% CI 0.78-2.24). CONCLUSION: Occurrence of VTE in a total of 50,865 RA patients initiating treatment with tofacitinib or a TNF inhibitor was infrequent (<1 per 100 person-years). We observed a numerically higher, but statistically nonsignificant, risk of VTE in RA patients receiving tofacitinib versus those receiving TNF inhibitors.
30835424 Exploiting CD22 To Selectively Tolerize Autoantibody Producing B-Cells in Rheumatoid Arthr 2019 Apr 19 Rheumatoid arthritis (RA) is an autoimmune disease that primarily affects the synovial joints and can lead to bone erosion and cartilage damage. One hallmark of RA is anticitrullinated protein autoantibodies (ACPA) and memory citrulline-specific B-cells, which have been implicated in RA pathogenesis. While depletion of B-cells with Rituximab improves clinical responses in RA patients, this treatment strategy leaves patients susceptible to infections. Here we use of Siglec-engaging Tolerance-inducing Antigenic Liposomes (STALs) to selectively target the citrulline-specific B-cells. ACPA production from purified human RA patients' B-cells in vitro was achieved through a set of stimulation conditions, which includes the following: BAFF, anti-CD40, IL-21, and LPS. In vivo generation of citrulline specific B-cells and ACPA production was accomplished by antigenic liposomes consisting of monophosphoryl lipid A (MPLA) and a cyclic citrullinated peptide (CCP) administered to SJL/J mice. We show that STALs that codisplay a high affinity CD22 glycan ligand and synthetic citrullinated antigen (CCP STALs) can prevent ACPA production from RA patients' memory B-cells in vitro. These CCP STALs were also effective in inducing tolerance to citrullinated antigens in SJL/J mice. The results demonstrate that tolerization of the B-cells responsible for ACPA can be achieved by exploiting the inhibitory receptor CD22 with high-affinity glycan ligands. Such a treatment strategy could be beneficial in the treatment of RA.
31131965 A tool for empirical equipoise assessment in multigroup comparative effectiveness research 2019 Jul PURPOSE: In observational research, equipoise concerns whether groups being compared are similar enough for valid inference. Empirical equipoise was previously proposed as a tool to assess patient similarity based on propensity scores (PS). We extended this work for multigroup observational studies. METHODS: We modified the tool to allow for multinomial exposures such that the proposed definition reduces to the original when there are only two groups. We illustrated how the tool can be used as a method to assess study design within three-group clinical examples. We then conducted three-group simulations to assess how the tool performed in a setting with residual confounding after PS weighting. RESULTS: In a clinical example based on rheumatoid arthritis, 44.5% of the sample fell within the region of empirical equipoise when considering first-line biologics, whereas 57.7% did so for second-line biologics, consistent with the expectation that a second-line design results in better equipoise. In a simulation where the unmeasured confounder had the same magnitude of association with the treatment as the measured confounders and a 25% greater association with the outcome, the tool crossed the proposed threshold for empirical equipoise at a residual confounding of 20% on the ratio scale. When the unmeasured variable had a twice larger association with treatment, the tool became less sensitive and crossed the threshold at a residual confounding of 30%. CONCLUSION: Our proposed tool may be useful in guiding cohort identification in multigroup observational studies, particularly with similar effects of unmeasured and measured covariates on treatment and outcome.
29975207 Folate Supplementation for Methotrexate Therapy in Patients With Rheumatoid Arthritis: A S 2019 Aug OBJECTIVE: To review the evidence for benefits and harms of folate (folic acid or folinic acid) supplementation on methotrexate (MTX) treatment for rheumatoid arthritis (RA), to assess whether or not folate supplementation would reduce MTX toxicity or reduce MTX benefits, and to decide whether a higher MTX dosage is essential. METHODS: We performed a sensitive search strategy and searched systematically the Medline, Embase, Web of Science and Cochrane Library databases from inception to 2 June 2016. Abstracts from major rheumatology meetings and major trial registers were also searched to retrieve all randomized controlled trials that interested us. RESULTS: Seven studies with 709 patients were included. No significant heterogeneity was found between these trials. For RA patients treated with MTX, those supplied with folate were less likely to have elevated transaminase (odds ratio [OR] 0.15; 95% confidence interval [95% CI] 0.10, 0.23 [p < 0.00001]) and gastrointestinal side-effects such as nausea and vomiting (OR 0.71; 95% CI 0.51, 0.99 [p = 0.04]). Folate appeared to promote compliance to MTX as it reduced patient withdrawal compared to placebo (OR 0.29; 95% CI 0.21, 0.42 [p < 0.00001]). There was no statistical difference for mouth sores between folate and placebo (OR 0.83; 95% CI 0.57, 1.22 [p = 0.35]). As the markers of disease activity in those trials were not consistent, it was impossible to decide whether folate supplementation reduced MTX efficacy. Besides, we compared high-dose folate (≥25 mg per week) and low-dose folate (≤10 mg per week) on MTX efficacy, finding no statistical difference (OR 2.07; 95% CI 0.81, 5.30 [p = 0.13]), nor on MTX toxicity (OR 1.56; 95% CI 0.80,3.04 [p = 0.19]). CONCLUSION: Folate supplementation can reduce the incidence of hepatotoxicity and gastrointestinal side-effects of MTX in patients with RA. It can also reduce patient withdrawal from MTX treatment. Although it tended to reduce mouth sores, it had no statistical significance. No significant difference was found between high-dose folate and low-dose folate on MTX efficacy or toxicity.
30685138 The Capitate-to-Axis-of-Radius Distance (CARD): A New Radiographic Measurement for Wrist 2019 Sep PURPOSE: To determine the reliability of a new radiographic index evaluating sagittal radiocarpal alignment, the capitate-to-axis-of-radius distance (CARD). A secondary purpose was to validate this index by comparing values between normal wrists and those with distal radial fractures (DRFs) and rheumatoid arthritis (RA). METHODS: The CARD is defined as the perpendicular distance from the center of the capitate head to the axis of the radius. Inter- and intraobserver reliability was tested. Cronbach alpha was calculated, and 2 methods of measurement were compared. The superior one (volar border of radial shaft) was used in the second part of the study. The normal CARD was then compared with unilateral DRFs with dorsal displacement DRF (n = 25) and RA (n = 25). Correlations between the CARD and other radiographic parameters (dorsal angulation, radial inclination, and ulnar variance) were calculated as well as between the CARD and the severity of disease or fracture displacement (mild/moderate/severe). RESULTS: The CARD showed excellent intra- and interobserver reliability. The volar radius measurement method was superior to the midaxis method and was, therefore, used for the second portion of the study. The mean CARD for normal, fractured, and RA wrists was significantly different (2.2 ± 2.5 mm, 15.7 ± 6.5 mm and 0.2 ± 4.4 mm, respectively). There was a strong side-to-side correlation in normal wrists (r = 0.77) and a significant correlation between the CARD (mm) and the severity of deformity (RA, r = -0.7; DRF, r = 0.8). CONCLUSION: The CARD is a reproducible, easy-to-use measurement of sagittal carpal alignment with a strong side-to-side correlation. The CARD increases with dorsal angulation of the distal radius and decreases as severity of deformity with RA increases. CLINICAL RELEVANCE: The correlation of the CARD with severity of deformity in DRFs and RA makes it a useful method of assessing deformities in the sagittal plane. The normal wrist can be used as a comparison when evaluating the CARD in the setting of unilateral wrist disease.
30825801 Nanogold-core multifunctional dendrimer for pulsatile chemo-, photothermal- and photodynam 2019 May 15 This investigation reports a novel nanoGold-core multifunctional dendrimer for pulsatile chemo-, photothermal- and photodynamic- therapy of rheumatoid arthritis (RA). Architecturally, the nanocomposites comprised of a nanoGold (Au) at the focal whose surface is functionalized by hydroxy-terminated thiolated-dendrons following Au-thiol bond formation to produce nanoGold-core multifunctional dendrimer (Au-DEN). The surface hydroxyl groups of Au-DEN were then conjugated with methotrexate (MTX; a disease-modifying first line anti-rheumatic drug; DMARD; 74.29 ± 0.48% loading) to form Au-DEN-MTX-NPs (Particle size: 100.15 ± 28.36 nm; poly dispersibility index, PDI: 0.39 ± 0.02; surface zeta potential, ζ: -22.45 ± 1.06 mV). MTX was strategically selected to serve as an anti-rheumatic DMARD as well as a targeting ligand to attain selective localization of the formulation in arthritic tissue via folate receptors upregulated on arthritic tissues. The docking study was performed to confirm the viable binding efficiency of MTX towards β-folate receptors that are overexpressed on arthritic tissues taking folic acid as a reference standard. The IR780, a NIR active bioactive was also loaded in Au-DEN-MTX NPs to offer photothermal benefit upon irradiation with NIR laser (wavelength: 808 nm). The hypothesis was tested by elucidation of in vitro drug release profile, photothermal activity, cellular uptake (Fluorescence and confocal laser scanning microscopy; CLSM), cell viability assay (MTT protocol) and Intracellular reactive oxygen species (ROS) generation in mouse macrophage RAW264.7 cells and Lipopolysaccharide (LPS) activated RAW264.7 cells. Furthermore, the hemolytic toxicity and stability studies were also investigated to determine the blood compatibility as well as ideal storage condition of NPs. The outcome of this investigations presents developed multifunctional targeted NPs to be potential therapeutics for the improved treatment of RA. The approach can also be applied to other clinical interventions involving countering inflammatory conditions.
30859373 C9orf72 Intermediate Alleles in Patients with Amyotrophic Lateral Sclerosis, Systemic Lupu 2019 Jun The commonest genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a large hexanucleotide expansion within the non-coding region of the C9orf72 gene. The pathogenic mechanisms of the mutation seem toxic gain of functions, while haploinsufficiency alone appears insufficient to cause neurodegeneration. C9orf72(-/-) mice rather develop features of autoimmunity. Immune-mediated dysfunctions are involved in the pathogenesis of ALS and FTD and high prevalence of autoimmune disease has recently been observed in C9orf72 expansion-positive patients. Since intermediate repeat expansions result in decreased transcription of the gene, we explored the hypothesis that C9orf72 intermediate alleles could be a genetic risk for autoimmune conditions. We genotyped 69 systemic lupus erythematosus (SLE) and 77 rheumatoid arthritis (RA) patients, with 68 expansion-negative ALS patients, as control. A cut-off of ≥ 9 and ≤ 30 hexanucleotide units was chosen to define intermediate-length expansions. In the SLE and SLE + RA cohorts, both the number of patients with intermediate expansions and the overall number of intermediate alleles were significantly higher than in controls (23.2% vs. 7.4%, p = 0.020; 13.8% vs. 3.7%, p = 0.006, and 19.9% vs. 7.4%, p = 0.033, 11% vs. 3.7%, p = 0.021, respectively) and discernible although non-significant differences were found for the RA only cohort. Three SLE patients had intermediate-length expansions on both alleles, two of them harboring sequence variations within the hexanucleotide downstream region. However, no peculiar clinical features associated with the intermediate expansion were identified. Our results suggest that C9orf72 intermediate alleles could be associated with systemic autoimmune diseases, indicating a role of C9orf72 in immunity regulation.
31709771 2019 American College of Rheumatology Recommended Patient-Reported Functional Status Asses 2019 Dec OBJECTIVE: To develop American College of Rheumatology (ACR) recommendations for patient-reported Functional Status Assessment Measures (FSAMs) for use in routine clinical practice in patients with rheumatoid arthritis (RA). METHODS: We convened a workgroup to conduct a systematic review of published literature through March 16, 2017 and abstract FSAM properties. Based upon initial search results and clinical input, we focused on the following FSAMs appropriate for routine clinical use: the Health Assessment Questionnaire (HAQ) and derived measures and the Patient-Reported Outcomes Measurement Information System (PROMIS) tool. We used the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) 4-point scoring method to evaluate each FSAM, allowing for overall level of evidence assessment. We identified FSAMs fulfilling a predefined minimum standard and, through a modified Delphi process, selected preferred FSAMs for regular use in most clinic settings. RESULTS: The search identified 11,835 articles, of which 56 were included in the review. Descriptions of the measures, properties, study quality, level of evidence, and feasibility were abstracted and scored. Following a modified Delphi process, 7 measures fulfilled the minimum standard for regular use in most clinic settings, and 3 measures were recommended: the PROMIS physical function 10-item short form (PROMIS PF10a), the HAQ-II, and the Multidimensional HAQ. CONCLUSION: This work establishes ACR recommendations for preferred RA FSAMs for regular use in most clinic settings. These results will inform clinical practice and can support future ACR quality measure development as well as highlight ongoing research needs.