Rescate con rituximab en paciente con liquen plano esofágico refractario

Esophageal lichen planus (ELP) is a rare condition with unknown prevalence that can sometimes be underestimated due to the subtle and nonspecific findings of diagnostic workup. Oral lesions rarely extend to the esophageal mucosa, but when they do, the most frequent symptoms are dysphagia and odynophagia. There is often a significant delay in diagnosis and inadequate treatment. We report the case of a 59-year-old woman diagnosed with ELP, successfully treated with rituximab, a chimeric monoclonal antibody that depletes CD20+B cells. To our knowledge, this is only the second report of this treatment in ELP.     

Rituximabe para o tratamento da artrite reumatoide: Revisão sistemática

IntroductionRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation that often leads to significant disability. Several effective anti–TNF agents have been used, but some patients have shown an inadequate response. Rituximab is a therapeutic monoclonal antibody indicated in such cases.MethodsWe conducted a systematic review to access efficacy and safety of rituximab in patients with active RA which have or have not been treated with anti–TNF agents before, and to relate outcome with RF and anti–CCP serology. We searched major electronics databases, grey literature and searched for references manually. We used Review Manager®5.1 for meta–analysis.ResultsWe included six RCTs comparing rituximab 1000 mg with placebo. Methotrexate was used by both groups. Treatment with rituximab was more effective in naïve and in anti–TNF treatment failure patients ACR20/50/70 and EULAR response. We observed lower changes in Total Genant–modified Sharp score, erosion score and joint narrowing scores in the rituximab group, and SF–36, FACIT–T and HAQ–DI scores were also better in this group. There were no differences between groups regarding safety outcomes, with exception of acute injection reactions, which were more common on rituximab group. More RF/anti–CCP seropositive patients achieved ACR20 than RF/anti–CP negative patients in rituximab group.ConclusionAvailable data support the use of rituximab for the treatment of RA, as it is an effective and safe option for naïve and anti–TNF treatment failure patients. RF and anti–CCP seam to influence treatment results, but this inference needs further research.     

Preparation of clinical‐scale 177Lu‐Rituximab: Optimization of protocols for conjugation,radiolabeling, and freeze‐dried kit formulation

Rituximab is a monoclonal chimeric antibody, which has been approved by the US Food and Drug Administration for immunotherapy of non–Hodgkin lymphoma. Bexxar and Zevalin are the two other approved radiolabeled antibodies for radioimmunotherapy of non–Hodgkin lymphoma; however, they are of murine origin that reduces their treatment efficacy. So as to circumvent this, efforts have been made to radiolabel Rituximab with various therapeutic radioisotopes. In the present study, an effort has been made to optimize the conjugation (bifunctional chelating agent and antibody) and radiolabeling procedures for the preparation of clinical‐scale ¹⁷⁷Lu‐labeled Rituximab. An attempt was also made to prepare the freeze‐dried Rituximab kit for the easy and convenient clinical translation of the agent. Clinical‐scale ¹⁷⁷Lu‐Rituximab (40 mCi, 1.48 GBq) was prepared with >95% radiochemical purity using the kit. Biological evaluation of ¹⁷⁷Lu‐Rituximab was performed by in vitro cell binding studies in Raji cell lines, which showed satisfactory binding at 4°C and 37°C. Pharmacokinetic behavior of the agent, evaluated by biodistribution studies in normal Swiss mice, revealed high blood and liver uptake at the initial time points, although it exhibited slow and gradual clearance with time. The study indicates that clinical‐scale ¹⁷⁷Lu‐Rituximab could be conveniently formulated using the methodology described in the present article.     

长疗程利妥昔单抗治疗难治性幼年型特发性炎症性肌病3例

特发性炎症性肌病是一组具有临床表现异质性的自身免疫性疾病,以骨骼肌无力和肌肉炎症病变为特征.临床分型包括皮肌炎、多发性肌炎、散发的包涵体肌炎、免疫介导的坏死性肌病和抗合成酶抗体综合征等[1-3].在儿童期,皮肌炎为最常见的临床类型,约占80％[4].特发性炎症性肌病为临床罕见病,年发病率约为每年每百万人1 ～ 19例[5].美国儿童皮肌炎的发病率约为每年每百万人2.5～4.1例[6],国内尚未见流行病学资料.特发性炎症性肌病的治疗一直非常具有临床挑战性,尤其是一线治疗药物失败的病例[7].近年来,对难治性病例的精准治疗成为特发性炎症性肌病领域的研究重点[8].自20世纪初期开始,利妥昔单抗在国外就被尝试用于难治性特发性炎症性肌病的治疗,但关于利妥昔单抗的应用剂量和疗程,目前尚无统一认识[9],国内也尚未见相关临床研究报道.本文分享了3例传统药物治疗反应欠佳、经长疗程(2年7个月至3年2个月)利妥昔单抗联合治疗后获得临床缓解的特发性炎症性肌病患者的治疗过程,以期为该疾病的治疗提供参考.本观察研究开始前获北京大学第一医院生物医学研究伦理委员会审查批准(批准号:2021科研263).     

Rituximab‐mediated Raf kinase inhibitor protein induction modulates NF‐κB in Sjögren syndrome

Primary Sjögren syndrome (pSS) is an autoimmune disorder characterized by an epithelial injury surrounded by dense lymphocytic infiltrates. The conditions for the long‐term maintenance of human salivary gland epithelial cells from pSS patients and a co‐culture system with pSS lymphocytes were used to assess the effect of Rituximab (RTX) on the inflammatory condition and progression in pSS. Quantitative real‐time PCR, genes and protein array analysis, Western blot, flow cytometry, small interfering RNA transfection and nuclear factor‐κB (NF‐κB) DNA binding assays were used as methods. Supporting the benefits of RTX, this study demonstrates that RTX decreases NF‐κB activity and interrupts the NF‐κB signalling pathway through the up‐regulation of the Raf‐1 kinase inhibitor protein (RKIP). Over‐expression of RKIP down‐regulates interleukins, their receptors and the expression of genes encodes proteins that attracted lymphocytes. Silencing of the RKIP gene leads to significantly increased expression and release of pro‐inflammatory mediators supporting that RKIP expression could be involved in the suppression of NF‐κB activation in pSS salivary gland epithelial cells.