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ID PMID Title PublicationDate abstract
32922407 Methotrexate Enhances Apoptosis of Transmembrane TNF-Expressing Cells Treated With Anti-TN 2020 BACKGROUND: Concomitant use of methotrexate (MTX) improves the clinical efficacy of anti-TNF agents in the treatment of rheumatoid arthritis (RA). We aimed to clarify the cytotoxic effect of MTX on transmembrane TNF (tmTNF)-expressing cells treated with anti-TNF agents. METHODS: Jurkat T cells stably expressing tmTNF were used for the following experiments. Cytotoxicity induced by an anti-TNF agent (infliximab, adalimumab, or certolizumab pegol) with concomitant MTX were compared with that by MTX alone or by an anti-TNF agent alone using flow cytometry. Apoptosis-induction mediated by reverse signal through tmTNF, complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP) were evaluated. Folic acid and Y-27632, a Rho kinase inhibitor, were used as inhibitors to study intracellular signaling pathway in apoptosis induced by MTX and anti-TNF agents. RESULTS: Apoptosis of tmTNF-expressing cells was significantly increased by the concomitant administration of MTX and an anti-TNF agent, compared with MTX alone or an anti-TNF agent alone. The apoptosis induction by concomitant MTX was most pronounced in infliximab-treatment. Reverse signal transduction, but not CDC or ADCC/ADCP, was responsible for the coordinate effect of MTX and an anti-TNF agent on tmTNF-expressing cells. Folic acid inhibited MTX-mediated apoptosis, while Y-27632 suppressed JNK activation and infliximab-induced apoptosis via revere signal through tmTNF. CONCLUSION: The apoptotic effect was enhanced by combination of MTX and an anti-TNF agent in tmTNF-expressing cells. The intracellular pathways induced by MTX and anti-TNF agents seem to be independent. These findings might explain at least in part improved the clinical response upon co-therapy of MTX and an anti-TNF agent in RA.
32982497 Risk Factors Associated with Methotrexate Intolerance in Rheumatoid Arthritis Patients. 2020 BACKGROUND: Methotrexate (MTX) Intolerance Severity Score (MISS) has been previously validated in the Arabic language and has helped to detect high levels of intolerance in rheumatoid arthritis (RA) patients. The aim of the current study was to evaluate patient and disease characteristics associated with a high risk of MTX intolerance. MATERIALS AND METHODS: A cross-sectional interview-based survey was conducted using adult RA patients as a study group, who were visiting a specialized rheumatology clinic at King Saud University Medical City. The Arabic MISS was used in this survey. Statistical analyses were performed to understand associations between MTX-intolerant and MTX-tolerant patients. RESULTS: A total of 117 patients were involved in this study. Of those, 101 (86.3%) were females with a mean (SD) disease duration of 6.6 (5.7) years. The median (interquartile range (IQR)) Disease Activity Score-28 (DAS28) was 3.6 (3.6-4.1). MTX intolerance was observed in 55 (47%) patients. The most predominant component in patients with a positive test was the behavioral component. Intolerant patients had a higher median of pain (47.3 vs. 50.0; P = 0.010) and patient global assessment (50.0 vs. 60.0; P = 0.004) scales compared to those in tolerant patients. Additionally, MTX intolerance was associated with the female gender (adjusted odds ratio (AOR) 6.724; 95% CI 1.420, 31.843, P = 0.016), marital status (AOR 2.549; 95% CI 1.037, 6.270, P = 0.042) and DAS28 (AOR 1.612; 95% CI 1.032, 2.517, P = 0.036). There was no significant difference between the two groups in the remaining disease activity parameters, background therapies, seropositivity, and smoking status (P > 0.05). CONCLUSION: Patient characteristics, rather than disease activity, significantly impact MTX intolerance. Behavioral component is the main driver of intolerance. Intolerant patients have higher patient-reported outcomes. Qualitative studies are needed to explore causes and potential solutions to MTX intolerance.
32943282 Cardiac involvement in adult-onset Still's disease: Manifestations, treatments and outcome 2021 Jan OBJECTIVE: Adult-onset Still's disease (AOSD) is a rare inflammatory disease that may be life-threatening if complicated by cardiac problems. We performed a retrospective multicenter study to describe the manifestations, treatments and outcomes of cardiac involvement in AOSD. METHODS: We reviewed the medical databases of eight centers. All AOSD patients identified as fulfilling Yamagushi's or Fautrel's criteria were included in the study. Cardiac involvement, clinical manifestations, laboratory features, the course of the disease and treatments were evaluated. RESULTS: We included 96 AOSD patients in this study: 28 (29%) had documented cardiac involvement (AOSD + C group) and 68 (71%) had no cardiac involvement (control group). Cardiac complications were observed at diagnosis in 89% of cases. It were pericarditis (n = 17), tamponade (n = 5), myocarditis (n = 5) and non-infectious endocarditis (n = 1). Levels of leukocytes, neutrophils and C-reactive protein were significantly higher (p = 0.02, p = 0.02 and p = 0.002, respectively in the AOSD + C group than in the control group. Admission to intensive care, and the use of biotherapy were more frequent during follow-up in the AOSD + C group than the control group (p = 0.0001 and p = 0.03 respectively). Cardiac involvement was associated with refractory form in multivariate analyzed (p = 0.01). Corticosteroids were effective with or without methotrexate in 71% of patients but not in severe involvement as myocarditis or tamponade. CONCLUSION: Cardiac complications are frequent, inaugural, can be life-threatening and predictive of a refractory course in patients with AOSD. Systematic cardiac screening should be proposed at diagnosis and biotherapy early use should be considered especially in myocarditis.
33107357 Xanthones from Securidaca inappendiculata antagonized the antirheumatic effects of methotr 2021 Feb BACKGROUND: This study was designed to characterize the interaction between Securidaca inappendiculata Hassk. derived xanthones and methotrexate (MTX). METHODS: Collagen-induced arthritis (CIA) was induced in rats, which were treated with MTX, a xanthone-rich fraction (XRF), or MTX+XRF by gavage for 30 days. Clinical efficacy was assessed based on arthritis scores, serological analysis, and histological examination. Protein expression was investigated by either immunohistochemical or immunoblotting methods. MTX concentrations were determined by HPLC or LC-MS methods. Obtained results were further validated by in vitro assays using 1,7-dihydroxy-3,4-dimethoxyxanthone and HEK 293 T cells. RESULTS: XRF antagonized the antirheumatic effects of MTX in vivo, suggested by higher levels of proinflammatory cytokines, and severer swelling and deformation of joints in CIA rats in the MTX+XRF group compared with MTX monotherapy. XRF reduced MTX concentration in plasma and promoted its excretion into urine. As a result, XRF attenuated MTX-induced edema of the proximal tubule. Furthermore, XRF restored the decreased expression of organic anion transporter three (OAT3), which accounts for MTX secretion in the kidney. Consistently, 1,7-dihydroxy-3,4-dimethoxyxanthone promoted the cellular intake of MTX by increasing OTA3 expression. CONCLUSION: It is suggested that the combined use of S. inappendulata with MTX should be optimized to avoid the antagonistic effects and improve the safety of the MTX regimen.
34434435 Hepatic Hodgkin Lymphoma Presenting as Solitary Hepatic Mass Following Other Iatrogenic Im 2021 Feb Lymphoproliferative disorders (LPDs) occur frequently in patients with rheumatoid arthritis (RA) under methotrexate treatment. Some LPDs spontaneously regressed after methotrexate discontinuation, but classic Hodgkin lymphoma (CHL)-type LPDs frequently relapse, and chemotherapy is usually required for the treatment. CHL usually spreads in contiguous lymph nodes and then infiltrates in organs at an advanced stage. Thus, hepatic Hodgkin lymphoma (HHL) without lymphadenopathy is extremely rare at diagnosis. We present a case of methotrexate-associated LPDs associated with systemic lymphadenopathy and hepatosplenic mass in a 71-year-old woman with RA under methotrexate treatment over 10 years. Although spontaneous remission occurred after methotrexate discontinuation, she developed HHL presenting as a solitary hepatic mass without lymphadenopathy 3 years after spontaneous regression. She received brentuximab vedotin (BV) combination chemotherapy without bleomycin to avoid pulmonary toxicity. Complete metabolic response was achieved after four courses of BV combination chemotherapy, and the activity of RA was kept to be in remission. Our case suggested that the recurrence lesions of LPDs may present at unexpected site, which is not coincide with the primary site, and BV combination chemotherapy is a promising regimen for limited-stage CHL-type LPDs in patients with RA owing to its anti-lymphoma effect on CHL-type LPDs and a possible targeted therapy for RA.
32876903 Efficacy and Safety of Baricitinib in Chinese Rheumatoid Arthritis Patients and the Subgro 2020 Dec INTRODUCTION: Baricitinib is an oral selective inhibitor of Janus kinase (JAK) 1 and JAK 2, which has demonstrated significant efficacy in patients with moderately to severely active rheumatoid arthritis (RA). This analysis aims to describe the efficacy and safety of baricitinib in Chinese RA patients with an inadequate response to methotrexate (MTX-IR), and to analyze the effects of baseline characteristics on the efficacy of baricitinib treatment. METHODS: In this 52-week, randomized, double-blind, placebo-controlled study, 231 Chinese patients with moderately to severely active RA who had MTX-IR were randomly assigned to placebo (n = 115) or baricitinib 4 mg once daily (n = 116). The primary endpoint was American College of Rheumatology 20% (ACR20) response at week 12. Other efficacy measures included ACR50, ACR70, Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, patient's assessment of pain, Disease Activity Score in 28 joints using high-sensitivity C-reactive protein, remission and low disease activity rates according to Simplified Disease Activity Index or Clinical Disease Activity Index, Health Assessment Questionnaire-Disability Index, and mean duration and severity of morning joint stiffness, worst tiredness and worst joint pain were analyzed. Additionally, subgroup analyses were performed across baseline characteristics. RESULTS: Statistically significant improvement in ACR20 response was achieved with baricitinib at week 12 (53.4 vs. 22.6%, p = 0.001) in Chinese patients, compared to placebo. Most of the secondary objectives were met with statistically significant improvements. Efficacy of baricitinib was irrespective of patient demographics and baseline characteristics. Safety events were similar between the baricitinib and placebo groups. CONCLUSIONS: The efficacy of baricitinib 4 mg in Chinese patients with moderately to severely active RA and prior MTX-IR was clinically significant compared to placebo regardless of baseline characteristics. Baricitinib was well tolerated with an acceptable safety profile during the full study period. TRIAL REGISTRATION: NCT02265705.
33115760 Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELEC 2020 Oct 28 OBJECTIVES: This integrated analysis presents the safety profile of upadacitinib, a Janus kinase inhibitor, at 15 mg and 30 mg once daily in patients with moderately to severely active rheumatoid arthritis (RA). METHODS: Treatment-emergent adverse events (TEAEs) and laboratory data from five randomised, placebo- or active-controlled phase III trials of upadacitinib for patients with RA were analysed and summarised. Exposure-adjusted event rates are shown for placebo (three trials; 12/14 weeks), methotrexate (two trials; mean exposure: 36 weeks), adalimumab (one trial; mean exposure: 42 weeks), upadacitinib 15 mg (five trials; mean exposure: 53 weeks) and upadacitinib 30 mg (four trials; mean exposure: 59 weeks). RESULTS: 3834 patients received one or more doses of upadacitinib 15 mg (n=2630) or 30 mg (n=1204), for a total of 4020.1 patient-years of exposure. Upper respiratory tract infection, nasopharyngitis and urinary tract infection were the most commonly reported TEAEs with upadacitinib. Rates of serious infection were similar between upadacitinib 15 mg and adalimumab but higher compared with methotrexate. Rates of herpes zoster and creatine phosphokinase (CPK) elevations were higher in both upadacitinib groups versus methotrexate and adalimumab, and rates of gastrointestinal perforations were higher with upadacitinib 30 mg. Rates of deaths, malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs) were similar across treatment groups. CONCLUSION: In the phase III clinical programme for RA, patients receiving upadacitinib had an increased risk of herpes zoster and CPK elevation versus adalimumab. Rates of malignancies, MACEs and VTEs were similar among patients receiving upadacitinib, methotrexate or adalimumab. TRIAL REGISTRATION NUMBERS: SELECT-EARLY: NCT02706873; SELECT-NEXT: NCT02675426; SELECT-COMPARE: NCT02629159; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847.
33396851 Efficacy of Oral Vitamin Supplementation in Inflammatory Rheumatic Disorders: A Systematic 2020 Dec 30 BACKGROUND: We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of oral vitamin supplementation on symptoms and disease activity in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA). METHODS: A systematic literature review and meta-analysis of randomized controlled trials including patients with inflammatory rheumatic diseases were performed using MEDLINE, EMBASE and abstracts from recent international rheumatology congresses. Studies were reviewed in accordance with PRISMA guidelines. We analysed clinical outcomes according to each type of vitamin supplementation. RESULTS: The initial search yielded 606 articles. Of these, 13 studies were included in the qualitative synthesis: eight studied vitamin D supplementation, two assessed vitamin E supplementation, two folic acid, and one vitamin K, all of them on RA patients. No studies on SpA or PsA were selected. Oral vitamin supplementations were not associated with a reduction in RA activity (DAS-28 or pain) or RA flares. CONCLUSIONS: Despite their beneficial effects, the effects of vitamin supplementation on RA activity, if any, seem to be limited. Evidence on their efficacy on SpA or PsA activity is lacking. However, folic acid supplementation should be suggested to prevent methotrexate-related side effects, and vitamin D should be given to patients with vitamin D deficiency to prevent musculo-skeletal complications.
33396629 New Horizons in Hydrogels for Methotrexate Delivery. 2020 Dec 30 Since its first clinical application, methotrexate (MTX) has been widely used for the treatment of human diseases. Despite great advantages, some properties such as poor absorption, short plasma half-life and unpredictable bioavailability have led researchers to seek novel delivery systems to improve its characteristics for parenteral and oral administration. Recently, great attention has been directed to hydrogels for the preparation of MTX formulations. This review describes the potential of hydrogels for the formulation of MTX to treat cancer, rheumatoid arthritis, psoriasis and central nervous system diseases. We will delineate the state-of-the-art and promising potential of hydrogels for systemic MTX delivery as well as transdermal delivery of the drug-using hydrogel-based formulations.
31644053 Psoriasis Agents. 2012 Psoriasis is a chronic inflammatory skin disease that affects up to 2.5% of the United States population. Psoriasis varies greatly in severity, from an intermittent condition with a few localized patches of skin involvement, to a widespread serious skin disease with severe pruritus, extensive skin involvement, complications and disability. Psoriasis is associated with an inflammatory arthritis in at least 5% of cases. The typical psoriatic skin lesion is a raised, erythematous and sharply demarcated papule or plaque, often with a silvery crust. They are often pruritic. Histology shows acanthosis and inflammation with neutrophils and lymphocytes, which are rich in activated T cells. The etiology of psoriasis is not well defined, but it appears to be an autoimmune condition or a disease of immune dysregulation. The therapy of psoriasis ranges from topical ointments and oral therapies to intravenously or subcutaneously administered biologics. Milder cases can be managed by topical ointments, corticosteroids and vitamin D and retinoid derivatives. Systemic therapy is used for more severe disease or extensive skin involvement. Agents used include psoralen with ultraviolet light, methotrexate, acitretin, phosphodiesterase type 4 inhibitors (apremilast), cyclosporine or other immunomodulatory agents and, most recently, antitumor necrosis factor agents and monoclonal antibodies directed at activated T cells or their proinflammatory cytokines (secukinumab, ustekinumab). Psoriatic arthritis is typically treated similarly as rheumatoid arthritis. Most of the agents used to treat severe psoriasis have other major uses, such as in cancer chemotherapy (methotrexate), organ transplantation (cyclosporine), and autoimmune diseases (antitumor necrosis factor agents, secukinumab, ustekinumab). Antipsoriatic medications that have been linked to cases of hepatotoxicity include methotrexate, acitretin and the tumor necrosis factor antagonists.
31922473 Effects of biologic drugs on the prognosis of rheumatoid arthritis among patients with poo 2020 Apr OBJECTIVE: To investigate the effects of biological disease-modifying antirheumatic drugs (bDMARDs) on diabetes control among patients with rheumatoid arthritis (RA). METHODS: A total of 296 patients with RA were included in the study. The following background factors were investigated: age, gender, bDMARD type, methotrexate and prednisolone (PSL) dosages, glycated hemoglobin (HbA1c), C-reactive protein, and matrix metalloproteinase-3. We used the simplified disease activity index (SDAI) to evaluate the RA disease activity. Poor diabetes mellitus (DM) control was defined as a HbA1c of 6.0; accordingly, the patients were divided into good and poor DM control groups. SDAI and PSL dosage were the primary endpoints, respectively, 1 year later. RESULTS: HbA1c ranged from 6.6±0.68 to 6.5±0.82 and 5.1±0.29 to 5.4±0.34 in the poor and good DM control groups, respectively. Although the intergroup difference was significant (p=0.000), there was no significant intergroup difference during the treatment period (p=0.084). The SDAI ranged from 27.7±15.6 to 7.1±8.0 in the group with a poor DM control (n=83) and from 22.9±14.0 to 6.3±7.6 in the group with a good DM control (n=213). CONCLUSION: The bDMARD therapy reduced the RA disease activity regardless of a good or poor DM control.
32695560 Primary Central Nervous System Methotrexate-associated Lymphoproliferative Disorder in a P 2020 Jul Methotrexate (MTX) is an immunosuppressor that is widely used to treat autoimmune diseases, including rheumatoid arthritis (RA). However, it can have serious adverse effects including a lymphoma: MTX-associated lymphoproliferative disorder (MTX-LPD). Extranodal lesions are common in MTX-LPD patients. However, MTX-LPD in the central nervous system (CNS) is extremely rare with few reported cases. Here, we describe a case of primary CNS MTX-LPD in a patient with RA, with a review of the literature. A 68-year-old woman who had received MTX for her RA for more than 10 years was referred to our hospital. Head magnetic resonance imaging (MRI) showed multiple lesions with heterogeneous contrast enhancement scattered throughout both hemispheres. As immunosuppression caused by MTX was suspected, MTX was discontinued, based on a working diagnosis of MTX-LPD. We performed an open biopsy of her right temporal lesion. Histopathologic examination showed atypical CD20+ lymphoid cells, leading to a definitive diagnosis of diffuse large B-cell lymphoma (DLBCL). In situ hybridization of an Epstein-Barr virus-encoded small RNA (EBER) was positive. Sanger sequencing confirmed that both MYD88 L265 and CD79B Y196 mutations were absent. The LPD regressed after stopping MTX. Follow-up head MRI at 8 months after surgery showed no evidence of recurrence. Although primary CNS MTX-LPD is extremely rare, it should be included in the differential diagnosis when a patient receiving MTX develops CNS lesions. Diagnosis by biopsy and MTX discontinuation are required as soon as possible.
32170838 Modified Disease Activity Score at 3 Months Is a Significant Predictor for Rapid Radiograp 2020 Mar OBJECTIVE: Progressive rheumatoid arthritis (RA) is responsible for joint damage causing disabilities, but there is no agreement on which disease measures best predict radiographic progression. We aimed to determine which disease activity measures, including the disease activity score, the modified disease activity score in 28 joints with C-reactive protein testing (M-DAS28-CRP), the Clinical Disease Activity Index, and the Health Assessment Questionnaire Disability Index, at baseline and 3 months best predicted rapid radiographic progression (RRP) in patients with early RA. METHODS: Data were used from PREMIER, a 2-year, multicenter, double-blind, active comparator controlled study with methotrexate (MTX)-naïve patients with RA and active disease for less than 3 years. Treatments included adalimumab plus oral MTX, adalimumab, or oral MTX. Only patients in the MTX arm were analyzed in this study. RRP was defined as a change in the modified total Sharp score of less than 3.5 at month 12. The logistic regression analysis assessed the impact of measures at baseline and 3 months on RRP at 12 months. Best cutoff points of the M-DAS28-CRP were also estimated by using area under the receiver operating characteristic curve. RESULTS: A total of 149 patients were included (female patients: n = 113 [75.8%]; positive rheumatoid factor: n = 127 [85.2%]; mean [SD] age: 52.9 [13.3] years; mean [SD] disease duration: 0.8 [0.9] year; mean [SD] M-DAS28-CRP: 6.3 [0.9]). After adjusting for potential confounders, only the M-DAS28-CRP at baseline (adjusted odds ratio [AOR] = 3.29; 95% confidence interval [CI]: 1.70-6.36) and 3 months (AOR = 2.56; 95% CI: 1.43-4.56) strongly predicted RRP at 12 months. M-DAS28-CRP of 4.5 and 2.6 at baseline and 3 months, respectively, maximized positive and negative predictive values for prediction of RRP. CONCLUSION: The M-DAS28-CRP was a stronger predictor at baseline and 3 months for RRP compared with other disease activity measures. Removing tender joint count and patient global assessment from the DAS28-CRP improves prediction of RRP.
32851364 Factors Predicting Early Failure of Etanercept in Rheumatoid Arthritis: An Analysis From t 2020 Jun OBJECTIVES: This study aims to investigate the factors associated with early discontinuation (within one year) of etanercept (ETA) in rheumatoid arthritis (RA) patients who began ETA as first biologic disease-modifying antirheumatic drug (bDMARD) and who were entered into the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis; GISEA) registry. PATIENTS AND METHODS: This registry-based cohort study included 477 RA patients (95 males, 382 females; median age 53 years; range 18 to 83 years) who began ETA as first bDMARD. Patient demographics, disease features and drugs were re-evaluated after 12 months. Baseline predictors of ETA discontinuation were estimated by univariate and multivariate analyses using Cox regression model. RESULTS: Seventy patients (14.7%) discontinued ETA during the first year (for inefficacy in 55.8%, adverse events in 28.6%, and other reasons in 6.5%). Concurrent conventional synthetic DMARDs (csDMARDs) were reported in 54.3% of patients, mainly methotrexate (MTX), while 52.4% of subjects took low doses of glucocorticoids. Patients stopping ETA more frequently showed one or more comorbidities, mainly cardiovascular diseases (28.6% vs. 15.7% in patients stopping and continuing ETA, respectively, p=0.009). The presence of comorbidities and a combination therapy with csDMARDs other than MTX were independent factors associated with early discontinuation of ETA at multivariate Cox analysis. CONCLUSION: Although ETA demonstrated a high persistence in biologic-naïve RA patients, about 15% of patients discontinued the treatment within 12 months. The presence of comorbidities and a combination therapy with csDMARDs other than MTX were the main factors for an early withdrawal of the drug.
32637868 First-year drug therapy of new-onset rheumatoid and undifferentiated arthritis: a nationwi 2020 BACKGROUND: In this retrospective cohort study, we evaluated the drug therapies used for early rheumatoid (RA) and undifferentiated (UA) arthritis patients. METHODS: From a nationwide register maintained by the Social Insurance Institution, information on sex, date of birth, and date of special medicine reimbursement decision for all new Finnish RA and UA patients between 2011 and 14 were collected, and their DMARD (Disease Modifying Antirheumatic Drug) purchases during the first year after the diagnosis were analyzed. RESULTS: A total of 7338 patients with early RA (67.3% female, 68.1% seropositive) and 2433 with early UA (67.8% female) were identified. DMARDs were initiated during the first month after the diagnosis to 92.0% of the patients with seropositive RA, 90.3% with seronegative RA and to 87.7% with UA (p < 0.001). Respectively, 72.1, 63.4, and 42.9% of the patients (p < 0.001) purchased methotrexate; 49.8, 35.9, and 16.0% (p < 0.001) as part of a DMARD combination during the first month. By the end of the first year after the diagnosis, self-injected biologics were purchased by 2.6, 5.3 and 3.1% (p < 0.001) of them. Only 1.4, 2.6 and 3.0% (p < 0.001) of the patients were not receiving any DMARDs. During the first year, 83.4% of the seropositive RA patients had purchased methotrexate, 50.4% sulfasalazine, 72.1% hydroxychloroquine, and 72.6% prednisolone. CONCLUSIONS: Currently, combination therapy including methotrexate is a common treatment strategy for early seropositive RA in Finland. Despite an easy access to biologics, these drugs are seldom needed during the first year after diagnosis.
32631598 Autoimmunity, Clonal Hematopoiesis, and Myeloid Neoplasms. 2020 Aug Clonal hematopoiesis has been linked with the development of hematologic malignancy and atherosclerotic cardiovascular disease; however, the association with autoimmune diseases remains to be defined. The link between autoimmune diseases and myeloid neoplasms (MNs) is complex, often multifactorial, and seems bidirectional. The limited data suggest an increased risk of MNs in rheumatoid arthritis and systemic lupus erythematosus. Paraneoplastic manifestations of MN include arthritis, vasculitis, and connective tissue disease. Treatment options for autoimmune disease such as cyclophosphamide and azathioprine have been associated with MNs, whereas the data for methotrexate and tumor necrosis factor inhibitors are equivocal.
32066940 Methotrexate and its mechanisms of action in inflammatory arthritis. 2020 Mar Despite the introduction of numerous biologic agents for the treatment of rheumatoid arthritis (RA) and other forms of inflammatory arthritis, low-dose methotrexate therapy remains the gold standard in RA therapy. Methotrexate is generally the first-line drug for the treatment of RA, psoriatic arthritis and other forms of inflammatory arthritis, and it enhances the effect of most biologic agents in RA. Understanding the mechanism of action of methotrexate could be instructive in the appropriate use of the drug and in the design of new regimens for the treatment of RA. Although methotrexate is one of the first examples of intelligent drug design, multiple mechanisms potentially contribute to the anti-inflammatory actions of methotrexate, including the inhibition of purine and pyrimidine synthesis, transmethylation reactions, translocation of nuclear factor-κB (NF-κB) to the nucleus, signalling via the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway and nitric oxide production, as well as the promotion of adenosine release and expression of certain long non-coding RNAs.
31890833 The Masquelet technique for septic arthritis of the small joint in the hands: Case reports 2020 Feb Septic arthritis in distal interphalangeal (DIP) joints sometimes occurs in association with mucous cysts or after the surgical treatment of mallet fingers. Recently, several studies have demonstrated the effectiveness of the Masquelet technique in the treatment of bone defects caused by trauma or infection. However, only few studies have reported the use of this technique for septic arthritis in small joints of the hand, and its effectiveness in treating septic arthritis in DIP joints remains unclear. We report the clinical and radiological outcomes of three patients who were treated with the Masquelet technique for septic arthritis in DIP joints. One patient had uncontrolled diabetes and another had rheumatoid arthritis treated with methotrexate and prednisolone. The first surgical stage involved thorough debridement of the infection site, including the middle and distal phalanx. We placed an external fixator from the middle to the distal phalanx and then packed the cavity of the DIP joint with antibiotic cement bead of polymethylmethacrylate (40 g) including 2 g of vancomycin and 200 mg of minocycline. At 4-6 weeks after the first surgical stage, the infection had cleared, and the second surgical stage was performed. The external fixator and cement bead were carefully removed while carefully preserving the surrounding osteo-induced membrane. The membrane was smooth and nonadherent to the cement block. In the second surgical stage, an autogenous bone graft was harvested from the iliac bone and inserted into the joint space, within the membrane. The bone graft, distal phalanx, and middle phalanx were fixed with Kirschner wires and/or a soft wire. Despite the high risk of infection, bone union was achieved in all patients without recurrence of infection. Although the Masquelet technique requires two surgeries, it can lead to favorable clinical and radiological outcomes for infected small joints of the hand.
32097698 Effect of phenolic compounds from Oenothera rosea on the kaolin-carrageenan induced arthri 2020 May 10 ETHNOPHARMACOLOGICAL RELEVANCE: Oenothera rosea (Onagraceae), commonly known as "hierba del golpe" in Mexico, is an herbaceous plant widely used in Mexican traditional medicine for the treatment of pain and inflammation. AIM OF THE STUDY: The aim of this study was to assess the effect of extracts and compounds isolated from O. rosea in kaolin-carrageenan induced arthritis. MATERIALS AND METHODS: Hydroalcoholic extract from aerial parts of O. rosea was obtained and chemically separated in order to obtain OrEA and isolated compounds using column chromatography, HPLC, UPLC and NMR analysis. O. rosea extract and derivatives were tested on the kaolin/carrageenan (K/C) induced arthritis model on ICR mice. Knee inflammation and paw withdrawal threshold were assessed following intraarticular administration of kaolin and carrageenan (4% and 2%, respectively) and subsequent oral administration of O. rosea. TNF-α, IL-1β, IL-6 and IL-10 levels from synovial capsule were measured using ELISA kits. NF-κB activity was also measured using the RAWBlue™ cell line. Finally, spleen and lungs were dissected to investigate body index. RESULTS: Oral administration of the O. rosea ethyl acetate fraction (25, 50 and 100 mg/kg) and isolated compounds (2 mg/kg) reduced the edema induced by kaolin/carrageenan, similar to the effect of methotrexate (1 mg/kg). Hyperalgesia but not allodynia was observed during this experiment. O. rosea derivatives reduced this behavior. The quantification of cytokines showed a reduction in TNF-α, IL-1β and IL-6, as well as an increase of IL-10. NF-κB production was also reduced by administering O. rosea derivatives. Chemical analysis of O. rosea derivatives showed that the major compounds present in the ethyl acetate fraction were phenolic compounds. Gallic acid, quercetin glucoside and quercetin rhamnoside were separated and identified by UPLC-UV-MS, and myricetin glycoside and tamarixetin glucoside using (1)H and (13)C NMR. CONCLUSIONS: O. rosea produces different phenolic compounds capable of reducing the inflammation and secondary mechanical hyperalgesia produced by K/C administration. They also reduced proinflammatory cytokines and increased anti-inflammatory cytokines. Finally, NF-κB modulation was reduced by the administration of O. rosea. Therefore, O. rosea could be considered of interest in inflammatory and painful diseases.
32684761 Juvenile idiopathic arthritis in a center in the Western Anatolia region in Turkey. 2020 AIM: To demonstrate the demographic data, subgroup distributions, responses to treatment and outcomes of long-term follow-up in patients who were followed up and treated in our clinics with a diagnosis of juvenile idiopathic arthritis, and to compare these data with national and international data. MATERIAL AND METHODS: The files of 116 patients who had been diagnosed as having juvenile idiopathic arthritis, were initiated on treatment and presented for regular follow-up visits between January 2012 and January 2018, were examined. Their demographic findings, treatments, active/inactive disease states (on-medication and off-medication) and treatment response states were evaluated. RESULTS: According to the International League of Associations for Rheumatology criteria, the subtypes were specified as enthesitis-related arthritis (n=38), oligoarticular (n=37), rheumatoid factor (-) polyarticular (n=17), systemic (n=15), rheumatoid factor (+) polyarticular (n=5), and psoriatic juvenile idiopathic arthritis (n=4). In total, the female/male ratio was found to be 1.5. The mean delay time between the first complaint and the diagnosis was found to be 5.7±5.2 months. The patients with systemic type were diagnosed at the earliest, while the patients with polyarticular and enthesitis-related subtypes were diagnosed at the latest. Thirty-two percent of the patients were treated with methotrexate alone, and 38% were given additional biologic drugs. In both treatment groups, the time to achieve inactive disease was the shortest in the oligoarticular group and the longest in the enthesitis-related arthritis group. In the study period, 38 patients were in remission off-medication (the highest rate (53.3%) was observed in the systemic group) and 71 patients were in remission on-medication (the highest rate (70.2%) was observed in the oligoarticular group). Remission was obtained in 94% of the patients. CONCLUSION: Enthesitis which is the remarkable finding of enthesitis-related arthritis, should not be overlooked in routine physical examination. Awareness of enthesitis can contribute to the prevention of diagnostic delay in children with enthesitis-related arthritis.