Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
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| 32965257 | ; LIVER LESION IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS WITH DIFFERENT DURATION OF M | 2020 Jul | The aim of the research was to determine liver lesion in patients with Oligoarticular and RF-negative Polyarticular forms of JIA by noninvasive methods depending on duration of Methotrexate treatment. The study included 42 patients with Rheumatoid factor (RF) negative oligo- and polyarticular joints forms of JIA from 3 to 18 years old. They were investigated by measurement of alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), haptoglobin, triglycerides, gamma glutamine transferase (GGT), apolipoprotein-A (Apo-A), a2-macroglobulin, cholesterine levels. The equation for calculating the FibroTest score regression coefficient had been done according U.S. patent 6.631.330. Student -Fisher Test, Mann - Whitney U-test were used for the statistical processing. In spite of MTX treatment progression of JIA was determined according assessment of joints functional class and radiological stage (p<0.05). Increased level of ALAT was prominent (40%) in children taken MTX for 1-5 years in comparison with other studied patients (p<0.05). 17 % of children who took MTX longer than 5 years had increased GGT content. Metabolic liver function was not changed because levels of Apo-A, haptoglobin, total bilirubin, cholesterine were within normal limits due to all stages of MTX taking. The increased level of a2-macroglobulin as a predictor of liver fibrosis was determined in all studying groups with the average frequency 36 % and it did not correspond to the duration of MTX treatment. According FibroTest score regression 14% of patients had liver fibrosis F1, which did not depend on duration of MTX treatment. According to our findings, patients using MTX for JIA management had joint damage progresses despite usage of MTX. Hepatic cytolysis is most frequently appeared within 15 years of MTX taking. Risk of liver fibrosis does not depend on duration of MTX treatment. | |
| 32823416 | Clinical profile of patients with anterior nodular scleritis in India. | 2020 Sep | PURPOSE: To report the clinical profile of a series of anterior nodular scleritis in Indian population. METHODS: We conducted a retrospective review of medical records of 140 eyes of 123 consecutive patients with nodular scleritis who presented to a tertiary eye care institute between 2007 and 2018. RESULTS: The mean age at presentation was 46.8 ± 13.1 years and 70.7% of the patients were female. Bilateral involvement was observed in 14% patients. The most common presenting symptom was redness (92.6%) and ocular pain (69.1%). Twenty-seven patients (22%) had some systemic association and rheumatoid arthritis (5%) was the most common autoimmune disease. Presumed ocular tuberculosis was diagnosed in 13% patients. Methotrexate was the most common immunosuppressive used in these patients and an additional immunosuppressive was required in 6.5% patients. Recurrence of inflammation was observed in 74.8% patients. Deterioration of vision noted in 2.8% eyes. CONCLUSION: Tuberculosis remains an important cause of nodular scleritis in India. Recurrence of scleritis is common in nodular scleritis and cases with non infectious nodular scleritis often require treatment with immune suppressives. | |
| 32166429 | Effectiveness of maintenance therapy with methotrexate compared with leflunomide for patie | 2020 Sep | INTRODUCTION/OBJECTIVES: Evidence regarding the effectiveness of step-down strategies for patients with well-controlled early rheumatoid arthritis (RA) on a combination of methotrexate (MTX) and leflunomide (LEF) is currently lacking. METHOD: The Care in early RA (CareRA) trial is a 2-year randomized pragmatic trial comparing different remission induction strategies in treatment-naïve patients with early RA. For this study, we included participants who achieved low disease activity (LDA) (DAS28-CRP ≤ 3.2) between 40 to 52 weeks after starting a combination of MTX, LEF, and a prednisone bridging scheme followed by a treat-to-target approach. Patients were re-randomized to a maintenance monotherapy of either MTX 15 mg weekly or LEF 20 mg daily. Remission rates (DAS28-CRP < 2.6) at week 65 counted from re-randomization, as well as drug retention rates and safety during the 65 weeks of follow-up, were compared. RESULTS: Remission rates at week 65 after re-randomization were numerically higher in patients assigned to MTX (29/32; 90.6%) compared with patients on LEF (20/27; 74.1%) (p = 0.091). Of patients assigned to MTX, 60% (19/32) maintained LDA while continuing their assigned monotherapy until week 65 after re-randomization versus 44% (12/27) in the LEF group (p = 0.25). Patients re-randomized to MTX were more frequently in LDA measured by Clinical Disease Activity Index (32/32; 100%) compared with patients on LEF (23/27; 85.2%) (p = 0.024) 65 weeks after re-randomization. According to survival analyses, the probability of maintaining MTX monotherapy was higher (81%) than maintaining LEF monotherapy (55%) for 65 weeks (p = 0.025) after re-randomization. Safety analysis after re-randomization showed a good safety profile in both groups. CONCLUSION: MTX monotherapy seems not significantly more efficacious as maintenance treatment compared with LEF monotherapy but has a better retention rate and is well tolerated in early RA patients in LDA after combination therapy with both. TRIAL REGISTRATION: Clinical trials NCT01172639 Key points • Methotrexate should be preferred over leflunomide as maintenance therapy after an initial intensive combination of these two drugs. • Methotrexate shows a better retention rate to leflunomide as maintenance therapy in this context. | |
| 33083414 | Rapid remission of refractory synovitis, acne, pustulosis, hyperostosis, and osteitis synd | 2020 Oct 6 | BACKGROUND: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoinflammatory disease for which clinical treatment has not been standardized. Janus kinase (JAK) inhibitors represent a novel therapeutic option for rheumatoid arthritis, psoriatic arthritis, and some other autoinflammatory diseases. However, the clinical utility of JAK inhibitors in treating SAPHO syndrome has not been thoroughly investigated. In this study, we describe a patient with SAPHO syndrome who failed to respond to conventional treatment but demonstrated a remarkable and rapid response to the JAK inhibitor tofacitinib. CASE SUMMARY: A 62-year-old female patient presented with swelling and pain at the sternoclavicular joints, back pain that limited her activities, arthralgia in the right knee, and cutaneous lesions. Her symptoms were unresponsive to nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, Tripterygium wilfordii hook f, and bisphosphonates. SAPHO syndrome was diagnosed in accordance with dermatological and osteoarticular manifestations and abnormal inflammatory factors. Multiple image studies have illustrated bone lesions and pathological fractures of vertebral bodies. Oral treatment with tofacitinib at 5 mg twice daily with methotrexate and bisphosphonates was initiated. The patient reported that her pain symptoms were relieved after 3 d and her cutaneous lesions were reduced after 4 wk of treatment. Vertebral lesions were improved after 6 mo on tofacitinib. No serious adverse effects were noted. CONCLUSION: JAK inhibitor therapy may be a promising strategy to treat SAPHO syndrome. | |
| 32910753 | Disease-modifying antirheumatic drug prescription patterns in adult rheumatoid arthritis p | 2020 Sep 3 | OBJECTIVE: To describe disease-modifying antirheumatic drug (DMARD) patterns in routine clinical practice in adult rheumatoid arthritis (RA) patients and to ascertain the reasons for methotrexate (MTX) discontinuation. METHODS: A cross-sectional observational study was conducted from March to October 2014 at the Rheumatology Units of seven hospitals in Spain. In a single visit, the treating rheumatologist completed an online case report form. This report contained sociodemographic and RA variables. This study was conducted in accordance with Good Clinical Practice and local and national research legislations. RESULTS: A total of 301 patients (71% women) with a mean age of 56.7±14.0 years and disease duration of 3.6±1.5 years were examined. The patients had RA with moderate disease activity, at least one poor prognostic factor, and comorbidities. The mean time between RA diagnosis and prescription of the first conventional synthetic DMARD (csDMARD) was 2.4±6.0 months. A total of 295 patients (98%) started the first csDMARD on monotherapy. MTX was the most-prescribed first-line drug (n=233, 79%). The mean treatment time of the first-line csDMARD was 27.0±19.4 months. Of these patients, 98% progressed to a second-line csDMARD; 118 patients were changed to another DMARD, mainly due to inefficacy (51, 37%), adverse events (AEs, 37, 27%), or intolerance (18, 13%). The use of MTX as second-line therapy reduced from 79% to 51%. At the time of the study, 200 patients (66%) received a csDMARD as monotherapy and 45 (15%) a combination of ≥2 csDMARDs. Fifty-five (18%) patients were being treated with a biological drug in monotherapy (16, 29%) or in a combination with a csDMARD (39, 71%), mainly MTX, 147 patients (57%) received steroids. Biological DMARD were prescribed as the second line for 42% of patients and 51% of patients received the third-line therapy or beyond. The rate of AEs that motivated a change in the csDMARD was 34%. CONCLUSION: MTX was the most-used csDMARD as first and second-line therapy together with corticosteroids. The combination of two or more csDMARDs as first-line treatment was very infrequent. MTX toxicity and intolerance were higher and more significant than inefficacy but progressively decreased with use. | |
| 32293465 | Importance of pediatric rheumatologists and transitional care for juvenile idiopathic arth | 2020 Mar 23 | BACKGROUND: Juvenile idiopathic arthritis-associated uveitis (JIA-U) is a serious condition associated with the risk of blindness. However, pediatric rheumatologists rarely encounter cases of blindness, because most patients reach adulthood during the course of follow-up before blindness occurs. Here, we report the progress of 9 patients with JIA-U, including 2 patients who became blind after the transition period. We aimed to highlight the importance of the role of pediatric rheumatologists and transitional care in preventing blindness associated with JIA-U. CASE PRESENTATION: We conducted a retrospective analysis of the case records of 9 JIA-U patients (1 male, 8 female; median age 16.8 years, range 5.5-19.8 years). All patients presented with oligo-juvenile idiopathic arthritis (oligo-JIA) (one presented with extended oligo-JIA); the median age of uveitis onset was 5.0 years (range 3.0-13.0 years), and the onset of uveitis preceded the onset of arthritis in 2 patients. The median disease duration was 12.5 years (range 3.5-24.7 years); 4 patients had anti-nuclear antibody (ANA) positivity (≧1:160) (all with a homogeneous and speckled-pattern subtype). All patients were negative for rheumatoid factor. Eight patients received methotrexate, 7 patients received one or more biologic drugs (etanercept, infliximab, adalimumab, and golimumab), and 6 patients required ophthalmic surgery at an early age (≦ 18 years). Two patients developed blindness after the transition period. Medical examination by pediatric rheumatologists and use of biologics had been delayed in both patients. One patient developed depression after transition and interrupted her own treatment. CONCLUSIONS: The reason for blindness in the 2 patients was thought to be the delay in the commencement of treatment and failure to provide transitional care. Inflammation is difficult to control in JIA-U even with appropriate treatment. Pediatric rheumatologists must be informed about the risk of JIA-U blindness, especially after transition. To ensure a good prognosis, the specialized treatment with the involvement of pediatric rheumatologists is necessary early on, and consideration for transitional medicine is essential. Therefore, this report reaffirms the importance of planned transitional care that has been advocated for globally. | |
| 32802941 | Nephrotoxicity Associated with Low-dose Methotrexate and Outpatient Parenteral Microbial T | 2020 | Methotrexate (MTX) toxicity can affect multiple organ systems, manifesting as nephrotoxicity, myelosuppression, hepatotoxicity, mucositis, and gastrointestinal upset. Serious adverse events are rare in patients prescribed low-dose methotrexate. We present a case of an 86-year-old female on a weekly dose of oral MTX 12.5 mg for rheumatoid arthritis presenting with painful gingiva and oral bleeding during outpatient antimicrobial therapy (OPAT) for osteomyelitis with vancomycin and piperacillin-tazobactam. She had acute kidney injury (AKI), elevated serum MTX levels, thrombocytopenia, neutropenia, and a vancomycin level three times therapeutic concentration. MTX toxicity was suspected to have been triggered by vancomycin and piperacillin-tazobactam causing AKI and impaired renal clearance of MTX which itself is nephrotoxic. The patient was managed with leucovorin, alkalinized intravenous fluids, and filgrastim injections over a 2-week period. Her renal function continued to be reduced at 5-week outpatient follow-up, far after other markers of toxicity normalized. This case demonstrates the importance of considering potential drug-drug interactions and the need for robust monitoring for OPAT in select groups. | |
| 31389299 | Probing the structural interactions between methotrexate and dexamethasone with muscle cys | 2020 Jul | Drug protein interactions have gained considerable attention over the past many years. In the current communication the association of muscle cystatin (MC) with anti-rheumatic drugs methotrexate and dexamethasone was studied by thiol proteinase inhibitor assay, ultra violet (UV) absorption, fluorescence spectroscopy, and fluorescence transform infra-red spectroscopy (FTIR). A static pattern of quenching was noticed between muscle cystatin and methotrexate (MTX). Binding constant (K(a)) of methotrexate to muscle cystatin was found to be 1 × 10(-7) M(-1) and the stoichiometry of binding was calculated to be one. Fluorescence measurement of the emission quenching reveals that the quenching process of cystatin by dexamethasone (DXN) was also static. The stoichiometry of binding and binding constant was also obtained. Additional evidence regarding MTX-MC and DXN-MC was obtained from UV spectroscopy and FTIR spectroscopic results. Such spectroscopic studies would help in modelling new candidate drugs for rheumatoid arthritis based on their cystatin binding profile.Communicated by Ramaswamy H. Sarma. | |
| 33437613 | A case of resected pulmonary lymphomatoid granulomatosis. | 2021 | Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus-associated B-cell lymphoproliferative disorder and was incorporated into the WHO classification of Tumours of the Lung, Pleura, Thymus and Heart in 2015. LYG is known to be associated with the host's immune function, and can be caused by some immunosuppressive agents, including methotrexate. A woman in her sixties with an 18-year history of methotrexate treatment for rheumatoid arthritis visited our hospital after detection of an abnormal chest shadow on her radiograph. She had been having anemia and a slight fever. Computed tomography (CT) revealed a 2.9-cm sized nodule in her left lung and hilar adenopathy, which suggested a primary lung carcinoma or an inflammatory lesion. We performed a left upper lobectomy with lymph node dissection for the purpose of diagnosis and treatment. Pathologic findings revealed that the tumor was a grade 3 LYG based on the number of EBV-positive B cells. The patient was treated with two chemotherapy regimens including R-CHOP at another hospital, and survived for four years after resection without recurrence in the lung. It is rare to find a case resected LYG, and the clinical or pathological findings of our case are expected to be extremely helpful in studying this disease and improving the understanding of this disease. | |
| 32256969 | Methotrexate Polyglutamation in a Myasthenia Gravis Clinical Trial. | 2020 | INTRODUCTION: Methotrexate (MTX) is an immunosuppressive and anti-inflammatory drug used to treat rheumatoid arthritis (RA) and other autoimmune conditions. MTX is transported into cells, where glutamate moieties are added and is retained as methotrexate polyglutamates (MTXPGs). In the RA literature, it has been reported that the degree of polyglutamation correlates with the anti-inflammatory effect of MTX in RA. There are no prior studies evaluating the relationship between MTXPGs and myasthenia gravis (MG) outcome measures. The objective of this study was to assess the correlation between methotrexate (MTX) polyglutamates (MTXPGs) with Myasthenia Gravis (MG) outcome measures. METHODS: An analysis was done of blood drawn from patients enrolled in the 12-month randomized, placebo-controlled study of MTX in MG study. Red blood cell MTXPGs were measured via ultra-performance liquid chromatography and tandem mass spectrometry. MTXPG was correlated to MG outcome measures using Spearman Correlation Coefficient. A two-group t-test was used to determine the difference in MTXPG based on clinical outcome responder definitions. RESULTS: Twenty-one polyglutamate samples were analyzed of subjects on MTX while eight samples were analyzed from subjects on placebo. Pentaglutamate had the strongest correlation with the MG-ADL (0.99), while tetraglutamate had the strongest correlation with the QMG (0.54). Triglutamate had the strongest correlation with MGC (0.76). CONCLUSION: There were variable correlations between MTXPG(1-5) and MG outcomes (rho range: 0.08 to 0.99). There are strong correlations between MTXPG and the MG-ADL, QMG, and MGC. Long chain methotrexate polyglutamates correlate better with MG outcomes. | |
| 30907188 | Treat to target approach for asthma. | 2020 Jun | Recognition that about half of asthma deaths might be preventable if recommended guidelines are followed suggests that better implementation of established management strategies is needed. However, to achieve a further substantive reduction in asthma mortality, novel strategies will also be required. It is well established that asthma is a disease of chronic inflammation, with episodes of worsening inflammation associated with increased symptoms and/or exacerbations; however, current guidelines paradoxically recommend that initial treatment is only symptomatic, rather than directed at the underlying inflammatory mechanism. The "Treat to target" (TTT) approach has become a popular concept in the medical management of several common chronic conditions, including rheumatoid arthritis (RA), diabetes, hypertension and hyperlipidemia. For example, as part of a TTT approach, rheumatologists recommend methotrexate for RA with onset within 6 months. Applying the TTT approach to asthma, the primary target could be clinical remission and the primary goals as follows: eliminate symptoms and exacerbation risk; prevent airway remodeling; and normalize lung function. To construct a TTT algorithm for chronic asthma, the proposal is to eradicate short-acting β2-agonists (SABA) at all asthma severity levels and replace SABA with "Anti-Inflammatory Reliever Therapy" (AIR), using inhaled corticosteroids (ICS)/SABA or ICS/formoterol. For individuals with equal to or less than 12 months' history of symptoms, fewer than two symptoms per month, no exacerbations in the last 12 months and normal lung function, the recommendation is early initiation of ICS/SABA or ICS/formoterol as AIR. | |
| 32497929 | Biologic therapy in severe and refractory peripheral ulcerative keratitis (PUK). Multicent | 2020 Aug | PURPOSE: We assessed the efficacy and safety of biologic therapy in severe and refractory Peripheral Ulcerative Keratitis (PUK). DESIGN: Open-label multicenter study of biologic-treated patients with severe PUK refractory to conventional immunosuppressive drugs. SUBJECTS: We studied 34 patients (44 affected eyes) (24 women/10 men; mean age, 55.26±17.4 years). PUK was associated with a well-defined condition in 29 of them (rheumatoid arthritis [n = 20], psoriatic arthritis [n = 2], inflammatory bowel disease [n = 2], Behçet disease [n = 1], granulomatosis with polyangiitis [n = 1], microscopic polyangiitis [n = 1], systemic lupus erythematosus [n = 1] and axial spondyloarthritis [n = 1]). Besides topical and oral systemic glucocorticoids, patients had received: methylprednisolone pulses [n = 9], and conventional immunosuppressive drugs, mainly methotrexate [n = 18], and leflunomide [n = 7]. Eleven patients had required ocular surgery prior to biologic therapy. METHODS: Following biologic therapy, baseline main outcomes were compared with those found at 1st week, 1st and 6th months and 1st year. MAIN OUTCOME MEASURES: Efficacy and safety of biologic therapy. Efficacy was analyzed by the assessment of corneal inflammation (corneal thinning, central keratolysis and ocular perforation); other causes of ocular surface inflammation (scleritis, episcleritis); intraocular inflammation (uveitis); visual acuity and glucocorticoid sparing effect. RESULTS: The first biologic agents used were anti-TNFα drugs (n = 25); adalimumab (n = 16), infliximab (n = 8), etanercept (n = 1), and non-TNFα agents (n = 9); rituximab (n = 7), tocilizumab (n = 1) belimumab (n = 1) and abatacept (n = 1). During the follow-up, switching to a second biologic agent was required in 12 of the 25 (48%) patients treated with anti-TNFα drugs. However, no switching was required in those undergoing biologic therapy different from anti-TNFα agents. The main outcome variables showed a rapid and maintained improvement after a mean follow-up of 23.7 ± 20 months. Major adverse effects were tachyphylaxis, relapsing respiratory infections, supraventricular tachycardia, pulmonary tuberculosis and death, one each. CONCLUSIONS: Biologic therapy is effective and relatively safe in patients with severe and refractory PUK. Non-anti-TNFα agents appear to be effective in these patients. | |
| 32647028 | Clinical characteristics and treatment of 50 cases of Blau syndrome in Japan confirmed by | 2020 Nov | OBJECTIVES: To collect clinical information and NOD2 mutation data on patients with Blau syndrome and to evaluate their prognosis. METHODS: Fifty patients with NOD2 mutations were analysed. The activity of each NOD2 mutant was evaluated in HEK293 cells by reporter assay. Clinical information was collected from medical records through the attending physicians. RESULTS: The study population comprised 26 males and 24 females aged 0-61 years. Thirty-two cases were sporadic, and 18 were familial from 9 unrelated families. Fifteen different mutations in NOD2 were identified, including 2 novel mutations (p.W490S and D512V); all showed spontaneous nuclear factor kappa B activation, and the most common mutation was p.R334W. Twenty-six patients had fever at relatively early timepoints in the disease course. Forty-three of 47 patients had a skin rash. The onset of disease in 9 patients was recognised after BCG vaccination. Forty-five of 49 patients had joint lesions. Thirty-eight of 50 patients had ocular symptoms, 7 of which resulted in blindness. After the diagnosis of Blau syndrome, 26 patients were treated with biologics; all were antitumour necrosis factor agents. Only 3 patients were treated with biologics alone; the others received a biologic in combination with methotrexate and/or prednisolone. None of the patients who became blind received biologic treatment. CONCLUSIONS: In patients with Blau syndrome, severe joint contractures and blindness may occur if diagnosis and appropriate treatment are delayed. Early treatment with a biologic agent may improve the prognosis. | |
| 33015085 | Chinese Herbal Formula Huayu-Qiangshen-Tongbi Decoction Compared With Leflunomide in Combi | 2020 | Background: Traditional Chinese Medicine is complementary and an alternative to modern medicine. The combination therapies of herbal products with disease-modifying anti-rheumatic drugs are gradually and widely adopted in the management of rheumatoid arthritis (RA) in China. Purpose: To evaluate the efficacy and safety of Huayu-Qiangshen-Tongbi (HQT) decoction, a Chinese medicine formula, combined with methotrexate (MTX) in the treatment of patients with active RA, in comparison with the combination therapy of MTX with leflunomide (LEF). Methods: This pilot study was a monocenter, open-label, randomized controlled trial with two parallel arms. Ninety patients with active RA were randomly allocated to receive either HQT at a dose of 250 ml twice daily or LEF at a dose of 20 mg once daily, and all participants received MTX at a dose of 10-15 mg once weekly. The primary efficacy endpoint was the proportion of patients who achieved a 20% improvement in the American College of Rheumatology criteria (ACR20) after a 24-week treatment. Results: 84.4% (76/90) patients completed the 24-week observation. In the intention-to-treat analysis, the percentage values of patients achieving the ACR20 response criteria were 72.1% (31/43) in MTX + HQT group and 74.4% (32/43) in MTX + LEF group (p = 0.808). No significant difference was observed in other parameters, including ACR50, ACR70, clinical disease activity index good responses, European League Against Rheumatism good response, remission rate, and low disease activity rate. The results of the per-protocol analysis showed consistency with those of the intention-to-treat analysis. The mean change from baseline at week 24 for the van der Heijde modified total sharp score had no significant difference between two groups (3.59 ± 4.75 and 1.34 ± 8.67 in the MTX + HQT group and MTX + LEF group, respectively, p = 0.613). The frequency of adverse events was similar in both groups (11 cases in the MTX + HQT and 17 cases in the MTX + LEF, p > 0.05). Conclusions: In patients with active RA, treatment with the combination of HQT and MTX was associated with improvement in signs, symptoms, and physical function. With a beneficial clinical response and acceptable tolerability, HQT or other Chinese medicine formula may be a good therapeutic option in combination with MTX for RA treatment. Trial registration: Chinese Clinical Trails Registry, ChiCTR-INR-16009031, Registered on 15th August 2016, http://www.chictr.org.cn/enindex.aspx. | |
| 32884075 | CP-25, a compound derived from paeoniflorin: research advance on its pharmacological actio | 2020 Nov | Total glycoside of paeony (TGP) has been widely used to treat inflammation and immune diseases in China. Paeoniflorin (Pae) is the major active component of TGP. Although TGP has few adverse drug reactions, the slow onset and low bioavailability of Pae limit its clinical use. Enhanced efficacy without increased toxicity is pursued in developing new agents for inflammation and immune diseases. As a result, paeoniflorin-6'-O-benzene sulfonate (CP-25) derived from Pae, is developed in our group, and exhibits superior bioavailability and efficacy than Pae. Here we describe the development process and research advance on CP-25. The pharmacokinetic parameters of CP-25 and Pae were compared in vivo and in vitro. CP-25 was also compared with the first-line drugs methotrexate, leflunomide, and hydroxychloroquine in their efficacy and adverse effects in arthritis animal models and experimental Sjögren's syndrome. We summarize the regulatory effects of CP-25 on inflammation and immune-related cells, elucidate the possible mechanisms, and analyze the therapeutic prospects of CP-25 in inflammation and immune diseases, as well as the diseases related to its potential target G-protein-coupled receptor kinases 2 (GRK2). This review suggests that CP-25 is a promising agent in the treatment of inflammation and immune diseases, which requires extensive investigation in the future. Meanwhile, this review provides new ideas about the development of anti-inflammatory immune drugs. | |
| 32101812 | Cardiac Arrhythmias in Autoimmune Diseases. | 2020 Apr 24 | Autoimmune diseases (ADs) affect approximately 10% of the world's population. Because ADs are frequently systemic disorders, cardiac involvement is common. In this review we focus on typical arrhythmias and their pathogenesis, arrhythmia-associated mortality, and possible treatment options among selected ADs (sarcoidosis, systemic lupus erythematosus, scleroderma, type 1 diabetes, Graves' disease, rheumatoid arthritis, ankylosing spondylitis [AS], psoriasis, celiac disease [CD], and inflammatory bowel disease [IBD]). Rhythm disorders have different underlying pathophysiologies; myocardial inflammation and fibrosis seem to be the most important factors. Inflammatory processes and oxidative stress lead to cardiomyocyte necrosis, with subsequent electrical and structural remodeling. Furthermore, chronic inflammation is the pathophysiological basis linking AD to autonomic dysfunction, including sympathetic overactivation and a decline in parasympathetic function. Autoantibody-mediated inhibitory effects of cellular events (i.e., potassium or L-type calcium currents, M(2)muscarinic cholinergic or β(1)-adrenergic receptor signaling) can also lead to cardiac arrhythmia. Drug-induced arrhythmias, caused, for example, by corticosteroids, methotrexate, chloroquine, are also observed among AD patients. The most common arrhythmia in most AD presentations is atrial arrhythmia (primarily atrial fibrillation), expect for sarcoidosis and scleroderma, which are characterized by a higher burden of ventricular arrhythmia. Arrhythmia-associated mortality is highest among patients with sarcoidosis and lowest among those with AS; there are scant data related to mortality in patients with psoriasis, CD, and IBD. | |
| 33425968 | Case Report: Composite Angioimmunoblastic T-Cell Lymphoma and Epstein-Barr Virus-Positive | 2020 | Immunosuppressants are widely used to treat patients with rheumatoid arthritis (RA), and their adverse effects have been known to cause other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs). We report a patient with RA who had been treated with methotrexate (MTX) and tacrolimus (TAC) and who developed whole body lymphadenopathy. We simultaneously confirmed angioimmunoblastic T-cell lymphoma (AITL) through a right cervical lymph node biopsy and Epstein-Barr virus-positive B-cell lymphoproliferative disorder (EBV-positive B-LPD) through a bone marrow examination. After cessation of immunosuppressant therapy, both LPDs completely disappeared. Patients with AITL are occasionally reported to develop B-cell lymphoma through reactivation of the EBV, which leads to clonal expansion in the microenvironment. Immunohistochemistry results revealed that both LPD components were positive for EBV-encoded RNA. Moreover, in this patient, the plasma EBV DNA level was found to be high; therefore, EBV infection was a probable etiology. Synchronous coexistence of AITL and B-LPD as an OIIA-LPD has rarely been reported. This case report is the first to discuss the disappearance of both LPDs on withdrawal of immunosuppressants only. AITL occasionally accompany B-LPD; however, this composite lymphoma comprised AITL and B-LPD, and OIIA-LPDs should not be overlooked. | |
| 32188617 | HHV-6: an unusual cause of cerebellar ataxia. | 2020 Mar 17 | Human herpesvirus 6 (HHV-6) infection is the cause of roseola infantum in children. The reactivation of HHV-6 is associated with multiple clinical syndromes including encephalitis and myelitis, especially in haematopoietic stem cell transplant recipients. However, the virus can cause encephalitis in other immunosuppressed as well as immunocompetent individuals. We report a case of a 70-year-old woman who was immunocompromised secondary to treatment of rheumatoid arthritis with leflunomide and methotrexate. The patient presented with acute ataxia, diplopia and dysarthria. MRI brain showed an enhancing lesion in the midbrain. The diagnosis of HHV-6 encephalitis was made after HHV-6 A DNA was detected in both serum and cerebrospinal fluid. Treatment consisted of a 3-week course of intravenous ganciclovir along with physiotherapy. At a 3-month follow-up, repeat MRI brain showed a decrease in size and oedema of the lesion and the patient's neurological function was improved. | |
| 31986916 | Naringenin: a potential natural remedy against methotrexate-induced hepatotoxicity in rats | 2022 Mar | Hepatotoxicity is an adverse side effect of methotrexate (MTX) administration for the treatment of different malignancies, psoriasis, and rheumatoid arthritis (RA). Naringenin (NAR) is a citrus flavone with multiple pharmacological characteristics. In this study, we aimed to investigate the protective effects of NAR on MTX-induced hepatotoxicity in rats. For this purpose, 32 Wistar rats were randomly divided into four experimental groups as group 1 Control, group 2 NAR (50 mg/kg/d, o.p.), group 3 MTX (20 mg/kg/d, i.p.), group 4 NAR + MTX. NAR was administrated for 10 consecutive days and MTX was injected on the ninth day. The results indicated that MTX significantly increased malondialdehyde (MDA), NO, TNF-α, and IL-6 levels in the liver. On the other hand, administration of MTX reduced the GSH content, as well as CAT, SOD, and GPx levels. NAR administration remarkably improved MTX-induced alteration of biochemical biomarkers. Our findings were confirmed by the histopathological examination of the liver. Based on our findings, NAR may inhibit MTX-induced hepatotoxicity through scavenging reactive free radicals and inducing anti-inflammatory effects. | |
| 32984368 | Neoplasm Risk in Rheumatic Diseases Has No Correlation With Conventional Synthetic Disease | 2020 | Objectives: To investigate whether there is an elevated neoplasm risk in patients with rheumatic diseases treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Methods: A population-based nested case-control study was performed by retrieving all patients newly diagnosed with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriatic arthritis (PsA) or psoriasis vulgaris (PsO) from the 2000 Longitudinal Health Insurance Database (LHID 2000) in Taiwan. Two hundred and sixty-one patients with neoplasm from 1997 to 2013 were enrolled in this study, and controls were matched in a 1:1 ratio with age, sex, and year of enrollment. Composition of demographic indices, comorbidities, medication usage, and differences in days of prescription of different medications between neoplasm and neoplasm-free (control) groups were compared. Results: Between the control and neoplasm groups, no differences in ratio were observed in the usage of hydroxychloroquine (50.96 vs. 49.04%, p = 0.6616), methotrexate (26.82 vs. 27.59%, p = 0.8441), azathioprine (3.45 vs. 3.07%, p = 0.8052), and cyclophosphamide (1.15 vs. 2.30%, p = 0.3131) from enrollment to index date. Medications within 3 years before the index date in patients that had ≥3 months of comparable duration also showed no difference (hydroxychloroquine: 33.06 vs. 30.25%, p = 0.6404; methotrexate: 20.66 vs. 25.21%, p = 0.4018; azathioprine: 2.48 vs. 2.52%, p = 0.9835; cyclophosphamide: 0.83 vs. 0.84%, p = 0.9906). We also made a subgroup analysis focusing on RA and SLE patients; no difference between control and neoplasm group in both the ratio of usage and days of prescription of hydroxychloroquine, methotrexate, azathioprine, and cyclophosphamide was observed. Conclusion: Neoplasm risk in patients with rheumatic diseases has no correlation with csDMARD usage. |