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.     

Efficacy,immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.     

Acantholytic pityriasis rubra pilaris associated with topical use of imiquimod 5%: case report and literature review

Topical use of immune response modifiers, such as imiquimod, has increased in dermatology. Although its topical use is well tolerated, it may be associated with exacerbations of generalized cutaneous inflammatory diseases, possibly through the systemic circulation of pro-inflammatory cytokines. This report describes a case of development of pityriasis rubra pilaris, a rare erythematous-papulosquamous dermatosis, in a woman aged 60 years during treatment with imiquimod 5% cream for actinic keratosis. It evolved with erythrodermic conditions and palmoplantar keratoderma, presenting progressive clinical resolution after the introduction of methotrexate. The authors emphasize the importance of recognizing possible systemic reactions associated with the topical use of imiquimod.     

甲氨蝶呤皮下注射治疗应用与展望

【摘要】 研究表明，甲氨蝶呤皮下注射较口服途径可以获得更快、更好的吸收和更高的血药浓度以及较低的生物利用度变异度。在类风湿关节炎患者和银屑病患者，甲氨蝶呤皮下注射的疗效显著优于口服途径，并且胃肠道不良反应发生率更低。对于甲氨蝶呤口服疗效欠佳或者不耐受的患者，改为皮下注射后仍然可以获得较好的治疗反应。甲氨蝶呤皮下注射可以作为生物制剂使用前的治疗选择，可节省大量费用。总之，甲氨蝶呤皮下注射具有较好的临床应用前景。     

输卵管妊娠治疗方式及其对未来生育影响的研究进展

输卵管妊娠是一种临床常见的妇科急腹症。输卵管妊娠如能在包块尚未破裂前早期诊断，其相关的病死率大大降低。输卵管妊娠的治疗方式有很多，无论哪种治疗方式，都会导致患者生育功能的下降。临床中对于有生育要求的患者，选择哪种治疗方式更好地保护患者的生育功能并减少并发症仍是有争议的话题。近年有学者做了大量研究比较输卵管妊娠不同治疗方式的并发症及其对患者未来生育前景的影响，甚至提出更新的治疗方式以弥补传统治疗方式的不足。现就输卵管妊娠的治疗方式、并发症及对未来生育的影响的研究进展进行综述。     

Rheumatoid arthritis: Perioperative management of biologics and DMARDs

ObjectiveArthroplasty remains prevalent for patients with rheumatoid arthritis (RA), but outcomes are not equivalent to patients with osteoarthritis, and complications including infection are increased. The objective of this article is to review the current evidence supporting perioperative medication management. Challenges are discussed such as continuing potent disease-modifying therapy (DMARDs) and biologics, which may increase infection risk, versus withholding these medications, which may result in disease flares.MethodsPublished literature regarding arthroplasty in RA has been reviewed and discussed.ResultsSome DMARDs such as methotrexate and hydroxychloroquine appear safe in the perioperative period. Anti-TNFα biologics should be withheld due to increase in infection risk, while the impact of rituximab and abatacept on infection risk has not been as clearly defined.ConclusionThis article provides an overview of arthroplasty in RA, summarizes the evidence supporting perioperative medication management including corticosteroids, and identifies areas where further study is needed.     

Effectiveness and safety of tocilizumab in monotherapy in biologic-naïve and non-naïve patients with rheumatoid arthritis in a real-world setting

ObjectiveTo evaluate the effectiveness and safety of tocilizumab (TCZ) monotherapy in biologic-naïve patients with rheumatoid arthritis (RA) versus patients with previous biologic exposure in a real-world setting.Materials and methodsNon-controlled clinical-trial, 32-week prospective multicenter study including RA patients with moderate-severe disease activity starting TCZ in monotherapy who had a prior inadequate response or were intolerant to methotrexate (MTX). Effectiveness according to EULAR response evaluated at 24-week and safety at 32-weekwere assessed.ResultsOf the 93 were enrolled of whom 84 (90%) were eligible for the effectiveness analysis. Biologic-naïve patients (n = 46, 54.8%) were younger (51.5 versus 57.9) with shorter disease duration (6.4 versus 13.3) but presented similar comorbidities in comparison with non-naïve patients. DAS28 remission was achieved in a higher percentage in the group of patients with prior biological treatment. 89 adverse events (AE) were recorded in 50 patients, most of them non-serious AE (non-SAE) (86.3%).ConclusionsIn a real world setting, TCZ exhibit similar effectiveness and safety in monotherapy in patients with RA regardless previous exposure to other biologic therapies. This study provides additional and valuable real-world findings on the use of TCZ in patients with RA.     

他克莫司与甲氨蝶呤联合治疗难治性类风湿关节炎效果观察

摘 要 目的：探讨他克莫司与甲氨蝶呤联合治疗难治性类风湿关节炎的临床效果。方法：80例难治性类风湿关节炎患者随机分为观察组和对照组,每组40例。观察组给予他克莫司与甲氨蝶呤联合治疗,对照组给予环磷酰胺与甲氨蝶呤联合治疗,两组均治疗24周。观察两组患者治疗前后关节疼痛指数、关节肿胀指数及晨僵时间的变化,采用视觉模拟评分（VAS ）对患者疼痛情况进行评估;评价两组临床疗效;比较两组患者治疗前后红细胞沉降率（ESR）、C 反应蛋白（CRP）、肿瘤坏死因子α（TNF α）、血管内皮生长因子（VEGF）等指标变化。结果：观察组总缓解率为100.00%,显著高于对照组的67.50%（P<0.05）。治疗后两组关节疼痛指数、关节肿胀指数、晨僵时间及VAS 评分均较治疗前显著降低（P<0.05）,且观察组各项指标均明显低于对照组（P<0.05）。两组治疗后ESR、CRP、TNF α、VEGF均较治疗前显著降低（P<0.05）,且观察组明显低于对照组（P<0.05）。结论：他克莫司与甲氨蝶呤联合治疗难治性类风湿关节炎临床疗效好,安全性高,其作用机制可能与降低患者体内炎症反应及下调VEGF水平有关。