Precautions before starting tofacitinib in persons with rheumatoid arthritis

Tofacitinib is an immunosuppressive and disease-modifying therapy in rheumatoid arthritis. It may result in many infections flaring up. It is important to take precautions of all kinds (cardiovascular, malignancy, infections etc.) before starting tofacitinib. In this article, we have highlighted important steps where we need to take precautions before starting tofacitinib.     

IL-37b作用于树突状细胞CD39/ATP轴抑制类风湿性关节炎大鼠炎症反应的作用及机制

目的探讨白细胞介素37b重组蛋白(rmIL-37b)通过调节CD39/ATP轴抑制树突状细胞(DC)诱导类风湿性关节炎(RA)大鼠炎症反应的机制。方法将SD大鼠随机分为空白对照组(CTL)、CIA模型组、rmIL-37b 5μg/kg组、rmIL-37b 10μg/kg组,每组各10只。除了空白对照组外,其余大鼠采用含有卡介苗的完全弗氏佐剂和牛Ⅱ型胶原混合乳液免疫刺激,建立CIA模型。确定建模成功当天(D0),rmIL-37b组分别尾静脉注射5μg/kg、10μg/kg rmIL-37b;CTL组和CIA模型组注射相同体积的(1 ml/kg)生理盐水,连续给药15 d。免疫组化法检测滑膜组织Nod样受体蛋白3(NRPL3)炎症小体的表达,流式细胞术检测DC表型,另外试剂盒检测血清三磷酸腺苷(ATP)和免疫学指标。结果与CIA模型组相比,rmIL-37b 10μg/kg组大鼠足容积、AI值、NLRP3炎症小体表达量、血清ATP、IL-1β、IL-18、肿瘤坏死因子α(TNF-α)、抗Ⅱ型胶原抗体亚型(anti-ColⅡ-IgG、anti-ColⅡ-IgG2a)水平均降低,同时DC表面CD...     

Rheumatoid arthritis occurring after coronavirus disease 2019 (COVID-19) infection: Case based review

IntroductionRheumatoid arthritis (RA) is a multifactorial disease. Genetic predisposition and environmental triggers including infections are the major players of autoimmunity. We present a case of rheumatoid arthritis occurring after the coronavirus disease 2019(COVID-19) infection.Case presentationA 72-year-old woman with a medical history of hypertension and atrial fibrillation presented for a 2-month history of bilateral symmetric polyarthritis starting 2 weeks after asymptomatic COVID-19 infection. Physical examination showed swelling and tenderness of the metacarpophalangeal and proximal interphalangeal joints, wrists, and knees. She had increased inflammatory biomarkers (C-reactive protein:108 mg/L, erythrocyte sedimentation rate: 95 mm, alpha-2 and gamma-globulins, interleukin 6: 16.5 pg/mL). Immunological tests revealed positive rheumatoid factor (128 UI/mL), anti-cyclic citrullinated peptide antibodies (200UI/mL), anti-nuclear antibodies (1:320), and anti-SARS-CoV-2 IgG (12.24U/mL). She had the genotype: HLA-DRB1*04:11, HLA-DQB1*03:01, and HLA-DQB1* 03:02. Hands and feet radiographs did not show any erosion. Ultrasonography showed active synovitis and erosion of the 5th right metatarsal head. The diagnosis of RA was made. The patient received intravenous pulses of methylprednisolone (250 mg/day for 3 consecutive days) then oral corticosteroids (15 mg daily) and methotrexate (10 mg/week) were associated, leading to clinical and biological improvement.ConclusionDespite its rarity, physicians should be aware of the possibility of the occurrence of RA after COVID-19 infection. This finding highlights the autoimmune property of this emerging virus and raises further questions about the pathogenesis of immunological alterations.     

Diagnostic potential of interleukin-40 (IL-40) in rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) is the most common type of inflammatory arthritis. Newly emerging evidence has highlighted the role of B-cell produced cytokines in the development and progression of RA. Specifically, the expression of IL-40 has been shown to be significantly increased in affected patients.Patients and methodsThe study included 66 patients attending Rheumatology Unit, Baghdad Teaching Hospital and 66 matched controls. C-reactive protein (CRP), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were measured. Disease activity score (DAS28) was assessed. Serum IL-40 levels were assessed using an enzyme-linked immunosorbent assay (ELISA).ResultsThe mean ages of patients were 46.5 ± 10.2 years (23–68 years) and were 55 females and 11 males (F:M 5:1). 4 were smokers. Positivity of CRP, RF and anti-CCP were 75.8 %, 65.2 % and 62.2 % respectively. Steroids were received by 21.2 %, methotrexate by 56.1 %, biologics in the form of etanercept and adalimumab by 86.4 %. IL-40 was significantly higher in patients (9.1 ± 1.3 ng/ml) than in controls (7.5 ± 2.2 ng/ml; p < 0.001). The IL-40 level was comparable between females and males and was not related to smoking, CRP, RF or anti-CCP positivity or to receiving medications. Serum IL-40 showed good validity in diagnosing RA at a cut-off value (≥8.2 ng/ml) and area under curve (AUC) (0.74), the sensitivity was 73.2 %, specificity (66.7 %), and the accuracy (70.5 %)(p < 0.001).ConclusionThe increased level of serum IL-40 and its potential diagnostic role have been revealed in RA. Further studies are needed to be implement and elucidate the complete role of IL-40 in RA.     

Targeted drug delivery of Methotrexate in situ gels for the treatment of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is considered a debilitating disease that increases the risk of significant morbidity and premature mortality. To circumvent drug-related toxicity and ineffectiveness of anti-inflammatory drugs, there is a significant need for an advanced delivery system that increases bioavailability. The feasibility of in situ gel of methotrexate sodium (MTS) as an effective management for Rheumatoid arthritis was investigated. It was formulated with pluronic F-127 (PLF-127) as primary polymer, hydroxypropyl methylcellulose K4M (HK4M), and polycarbophil (PCL) as a copolymer and characterized by various parameters. The efficacy evaluation by Freund's complete adjuvant (FCA) model, biocompatibility assessment by histopathological studies conducted. The optimized in situ gel (M4) was thermoresponsive, released 93.26 ± 2.39% MTS at 96 hours. In addition, distribution of MTS was even in the optimized sterile and syringeable in situ gel. In vivo studies on wistar rats demonstrated a substantial reduction in paw oedema during the 28-day study period and were biocompatible with the tissues at the injection site. The study was successful in formulating, optimizing MTS in situ gel for effective management of RA.     

温阳补肾法对高原类风湿关节炎患者血清25羟维生素D3水平的影响

目的:观察温阳补肾法对高原类风湿关节炎患者血清25羟维生素D3水平的影响。方法:选取2015年7月至2017年8月青海省中医院收治的高原类风湿关节炎患者132例作为研究对象,随机分为对照组和观察组,每组66例。对照组应用常规西医治疗,观察组在对照组治疗基础上应用温阳补肾法治疗,2组均连续治疗3个月。比较2组治疗后临床疗效,统计2组治疗前后主要临床症状与体征、健康状况评定量表(HAQ)评分和DAS28评分,检测2组治疗前后实验室检查指标、血清25羟维生素D3以及血液流变学指标水平。结果:治疗后,观察组临床治疗总有效率显著高于对照组(P 0. 05); 2组关节肿胀指数、关节疼痛指数、关节压痛指数、晨僵时间、关节功能分级和20 m步行时间均较治疗前显著降低(P 0. 05),且观察组均显著低于对照组(P 0. 05); 2组HAQ评分、DAS28评分、类风湿因子(RF)、C反应蛋白(CRP)和红细胞沉降率(ESR)水平均较治疗前显著降低(P 0. 05),且观察组均显著低于对照组(P 0. 05); 2组血清25羟维生素D3水平均较治疗前显著升高(P 0. 05),且观察组显著高于对照组(P 0. 05); 2组红细胞电泳指数、红细胞压积、血浆黏度、全血低切黏度、全血高切黏度水平均较治疗前显著降低(P 0. 05),且观察组均显著低于对照组(P 0. 05)。结论:温阳补肾法治疗高原类风湿关节炎,疗效满意,同时能明显增加血清25羟维生素D3水平。     

Cinnamaldehyde suppresses NLRP3 derived IL-1β via activating succinate/HIF-1 in rheumatoid arthritis rats

Cinnamaldehyde (CA) is an essential component of cinnamon (Cinnamomum cassia Presland), which is often used as a flavoring condiment in beverages, pastries, perfumes, etc. Cinnamon is also used as herbal medicine in China and Southeast Asia to treat rheumatoid arthritis. However, the molecular mechanism is unclear. In this study, we aim to investigate its anti-inflammatory effects against Rheumatoid arthritis (RA) using activated macrophages (Raw246.7) in vitro and adjuvant arthritis rats (AA) in vivo. The results demonstrated that CA significantly reduced synovial inflammation in AA rats, possibly due to suppression of the expressions of pro-inflammatory cytokines, especially the IL-1β. Further investigation found that CA also suppressed the activity of HIF-1α by inhibiting the accumulation of succinate in cytoplasm. As we know, the reduction of HIF-1α nucleation slows down IL-1β production, because HIF-1α activates the expression of NLRP3, which is involved in the assembly of inflammasome and processing of IL-1β. In addition, CA also inhibited the expression of the succinate receptor GPR91, which in turn inhibited the activation of HIF-1α. In conclusions, our results suggested that CA might be a potential therapeutic compound to relieve rheumatoid arthritis progress by suppressing IL-1β through modulating succinate/HIF-1α axis and inhibition of NLRP3.     

Formulation and characterization of lornoxicam-loaded cellulosic-microsponge gel for possible applications in arthritis

Rheumatoid arthritis (RA) is an autoimmune disease associated with severe joint pain. Herein, we report lornoxicam loaded cellulosic microsponge gel formulation with sustained anti-inflammatory effects that are required to manage arthritic pain. The microsponges were formulated using quasi emulsion-solvent diffusion method employing four different surfactant systems, namely polyvinyl alcohol (PVA), Tween80, Gelucire 48/16 and Gelucire 50/13. All the lornoxicam loaded microsponge formulations were extensively characterized with a variety of analytical tools. The optimized microsponge formulation was then converted into gel formulation. The lornoxicam loaded microsponge gel formulation had adequate viscosity and sufficient pharmaceutical properties as confirmed by the texture analysis and the drug release followed Super case II transport. It is noteworthy that we described the preparation of a new cellulosic polymers based microsponge system for delivery of lornoxicam to provide quick as well as lasting (sustained) anti-inflammatory effects in rats using carrageenan induced rat paw edema model. We were able to demonstrate a 72% reduction in inflammation within 4 h using the optimize transdermal gel formulation utilizing Transcutol P as permeation enhancer and with the aid of skin micro-piercing by microneedles, hence, demonstrating the potential of this microsponge gel formulation in arthritis management.