抗CD20单克隆抗体治疗寻常型天疱疮研究进展

寻常型天疱疮是一种累及皮肤、黏膜,以泛发性水疱为特征的自身免疫性皮肤病,药物治疗寻常型天疱疮主要是通过抑制免疫系统,减少相关特异性抗体的产生,从而控制疾病的发展.目前糖皮质激素仍作为常规治疗的首选,而利妥昔单抗作为辅助治疗的一种抗CD20单克隆抗体,近年来已在寻常型天疱疮治疗中获得满意疗效.由于利妥昔单抗治疗可出现严重输液相关反应,增加感染风险,且价格昂贵、治疗累积时间长、易复发及耐药等缺点,临床上已减少了利妥昔单抗在寻常型天疱疮中的应用.新一代抗CD20单克隆抗体,克服了利妥昔单抗治疗的不良反应,有改善用药方式、减少治疗时间等优点,逐渐用于寻常型天疱疮治疗,新的研究成果给患者提供更多治疗选择.     

利妥昔单抗治疗自身免疫性大疱病的研究进展

自身免疫性大疱病是以患者体内B淋巴细胞产生自身抗体,破坏皮肤黏附结构为特征的一组皮肤病。利妥昔单抗作为一种新型的生物制剂,以B淋巴细胞表面的CD20抗原为靶点,导致B淋巴细胞清除,减少自身抗体的生成,从而达到治疗疾病的目的。在自身免疫性大疱病的治疗中,利妥昔单抗应用越来越多。该文对利妥昔单抗在天疱疮、大疱性类天疱疮、疱疹样皮炎、获得性大疱性表皮松解症等自身免疫性大疱病治疗中的应用进行综述。     

The application of rituximab in dermatology

利妥昔单抗作为一种抗CD20的单克隆抗体,在皮肤科的应用日益广泛.如重症天疱疮、重症系统性红斑狼疮、皮肤淋巴瘤等,它通过清除体内B细胞、改变诸多细胞因子和影响凋亡等多种途径发挥作用.但是对于它在使用过程中的不良反应也不容忽视.     

低剂量利妥昔单抗治疗51例天疱疮患者的护理

近年来,糖皮质激素联合使用利妥昔单抗(Rituximab,RTX)已成为天疱疮患者一线治疗方案,且利妥昔单抗治疗天疱疮的效果得到了充分认可[1] .联合使用利妥昔单抗既可有效缩短糖皮质激素减量时间,减少糖皮质激素或免疫抑制剂的用量,又可有效避免长期大剂量糖皮质激素和免疫抑制带来的严重并发症(如严重感染、股骨头坏死、白内...     

利妥昔单抗对顽固SLE和血管炎的长期治疗比较：缓解、复发和复治

SLE和血管炎的传统治疗方法缓解率低，而且其毒性作用、疾病的复发和活动性还可以导致患者死亡和残疾。B细胞耗竭疗法可以控制某些自身免疫性疾病。利妥昔单抗是一种抗CD20单克隆抗体，可以使B细胞耗竭。英国剑桥大学临床医学院Smith博士对利妥昔单抗治疗SLE和血管炎的长期有效性和安全性进行研究。     

生物制剂治疗天疱疮与大疱性类天疱疮

研究显示,生物制剂治疗难治性天疱疮、类天疱疮疗效显著,其中利妥昔是一种源自基因工程的人鼠嵌合型抗B淋巴细胞CD20的单克隆抗体,最早应用于天疱疮和类天疱疮的治疗。除利妥昔外,p38丝裂原活化蛋白激酶抑制剂KC706、PI-0824疫苗、肿瘤坏死因子拮抗剂或单克隆抗体如英夫利西等均取得满意疗效。但应用生物制剂治疗天疱疮和类天疱疮存在严重不良反应的可能性,且价格昂贵、缺乏一定量的可靠临床疗效的数据,影响了生物制剂在临床中的广泛应用。     

天疱疮治疗的研究进展

糖皮质激素是治疗天疱疮的首选药物,免疫抑制剂、静脉注射免疫球蛋白、利妥昔单抗、血浆置换、免疫吸附等辅助治疗逐渐用于天疱疮的治疗,特别是难治性天疱疮。这些辅助治疗不仅有助于改善病情,减少疾病的复发,而且可以帮助减少糖皮质激素的用量。此外一些新的免疫疗法未来可能成为天疱疮的替代治疗手段,如修饰的嵌合性抗原受体,T细胞免疫疗法,B细胞激活因子等。本文对以上治疗方法进行了综述。     

利妥昔单抗在天疱疮的应用

天疱疮是一种严重的自身免疫性大疱病,部分病例对传统治疗的疗效不佳.近几年临床研究发现,利妥昔单抗可明显提高天疱疮患者的临床治愈率,且可获得长期缓解,复发后再次治疗的安全性与临床缓解率仍较理想.利妥昔单抗不仅适用于重症难治性天疱疮,也有治疗轻至中度甚至儿童天疱疮的相关报道.目前已有较多关于利妥昔单抗不同单次治疗剂量或总剂量使天疱疮病情缓解的报道.利妥昔单抗可联合用药提高临床缓解率,其在安全剂量内仍会出现相关不良反应.     

利妥昔单抗治疗天疱疮六例并文献复习

目的：评价利妥昔单抗治疗天疱疮的疗效和安全性并对相关文献进行复习。方法：对采用利妥昔单抗治疗并随访至少1年的天疱疮患者的临床资料和国内外相关文献进行分析。结果：2013-2019年我院共应用利妥昔单抗治疗天疱疮6例，其中1例为初治患者，5例为病情复发的患者。剂量方案：1例采用淋巴瘤方案，5例采用类风湿关节炎方案。经过2~71个月随访，6例患者中停止治疗后完全缓解2例，治疗中完全缓解3例，出院后因肺部感染死亡1例。最新国内外指南和专家共识已经将利妥昔单抗列为天疱疮的一线治疗药物。结论：利妥昔单抗治疗顽固性天疱疮有效，可达到病情长期缓解的目的，但是需要警惕感染风险。     

利妥昔单抗治疗和自身免疫性疾病:抗B细胞治疗的展望

CD2 0是B淋巴细胞的特异性标记,在前B淋巴细胞和静止及活化的成熟B淋巴细胞表面高度表达,而在干细胞、原B细胞或其他正常组织中不表达。抗CD2 0抗体能导致B淋巴细胞的死亡。利妥昔单抗(rituximab)是针对人类B淋巴细胞表面标志CD2 0的特异性嵌合单克隆抗体,能直接触发B细胞的凋亡,为该药治疗B细胞相关性疾病提供了理论依据。1 997年,利妥昔单抗成为第1个被美国食品与药品管理局批准治疗肿瘤的单克隆抗体,治疗低分化非霍奇金淋巴瘤,推荐剂量为375mg/m2 ,每周1次,连续4周。治疗后,70 %以上的患者血液和骨髓中成熟及恶性B淋巴细胞明显减少…     

Treatment of severe pemphigus with rituximab: report of 12 cases and a review of the literature

BACKGROUND: Treatment of pemphigus vulgaris can be challenging. Systemic steroids associated with other immunosuppressant agents are the mainstay of therapy and have dramatically reduced morbidity and mortality from pemphigus vulgaris. In some patients, however, these agents are not able to control the disease or have severe adverse effects. Rituximab (MabThera; Roche, Basel, Switzerland), a chimeric monoclonal anti-CD20 antibody, induces depletion of B cells in vivo and has shown efficacy in patients with refractory antibody-mediated autoimmune disorders. We report 10 cases of pemphigus vulgaris and 2 cases of pemphigus foliaceous treated with rituximab--to our knowledge the largest series of patients so far--and review the existing literature on the topic. OBSERVATION: The 12 patients were selected for treatment with the anti-CD20 antibody. Rituximab was administered intravenously at a dosage of 375 mg/m(2) once weekly for 4 weeks. The treatment was well tolerated, and all 12 patients showed a good clinical response during an 18-month follow-up period, along with a consensual decline of the serum antidesmoglein titers. No infectious complications were observed. CONCLUSIONS: Rituximab is able to induce a prolonged clinical remission in patients with both pemphigus vulgaris and pemphigus foliaceous after a single course of 4 treatments. The preliminary experiences worldwide make rituximab a promising therapeutic option for patients with autoimmune diseases. The high costs and the limited knowledge of long-term adverse effects, however, limit its use to selected patients with treatment-resistant or life-threatening disease.     

A review of rituximab in cutaneous medicine

The rituximab antibody is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. Rituximab is indicated for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin lymphoma. Rituximab is also commonly used to treat chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia, and immune or idiopathic thrombocytopenic purpura (ITP). Rituximab is an effective treatment for primary cutaneous B-cell lymphoma and other cutaneous lymphomas. Rituximab is an effective treatment for mixed cryoglobulinemia. Rituximab is a promising treatment for systemic lupus erythematosus, dermatomyositis, pemphigus, vasculitis, and a variety of hematologic diseases. Black-box warnings on rituximab include fatal infusion reactions, tumor lysis syndrome, and severe mucocutaneous reactions. A variety of cardiac, pulmonary, renal, and hematologic side effects can occur. It commonly causes mild cutaneous side effect and rarely has caused paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis.     

Successful treatment of refractory childhood pemphgus vulgaris with anti-CD20 monoclonal antibody (rituximab)

Abstract:  Pemphigus vulgaris is an uncommon autoimmune blistering skin disorder that is particularly rare in children. Immunosuppressive treatment can be challenging. Rituximab (anti-CD20 monoclonal antibody) has been used to treat autoimmune disorders by depletion of CD20 B cells. Successful rituximab therapy has been reported in adults with refractory pemphigus vulgaris. We present a girl with childhood pemphigus vulgaris unresponsive to treatment with azathioprine, mycophenolate mofetil, plasmapheresis, and intravenous immunoglobulin with systemic prednisone who responded to treatment with rituximab. She had a corresponding decline in circulating antibodies against desmoglein 1 and 3 and a decline in diphtheria and tetanus-specific antibody titers.     

Rituximab in refractory pemphigus vulgaris

ABSTRACT:  Pemphigus vulgaris (PV) is a severe chronic autoimmune blistering disease of skin and mucous membranes. The use of systemic corticosteroids in pemphigus has dramatically reduced its mortality rate, but the long-term use of steroids leads to severe side effects, many of which are serious. For this reason it is often necessary to add immunosuppressive agents to the regimen. However, there are occasional refractory cases in which therapy with conventionally accepted modalities is either not efficacious or not possible on account of side effects. Rituximab is a therapeutic monoclonal antibody targeting CD20, an integral membrane protein highly expressed on the surface of pre-B lymphocytes and activated mature B lymphocytes. We present an instance of refractory PV successfully treated with rituximab. The successful treatment of pemphigus described here demonstrates that rituximab is a viable therapeutic option for patients with refractory PV.     

Rituximab immunotherapy in pemphigus: therapeutic effects beyond B-cell depletion

The anti-CD20 mAb rituximab, first approved for use in B-cell malignancies, is increasingly used to treat a variety of autoimmune diseases. Two studies in this issue investigate the effects of rituximab in pemphigus. Rituximab induces not only a depletion of all B cells and a decline of antidesmoglein autoantibodies but also a decrease in desmoglein-specific T cells. Furthermore, B-cell populations recovered after treatment were modified. These novel aspects may contribute to the clinical responses observed in patients.     

Treatment of severe refractory pemphigus vulgaris with rituximab

Pemphigus vulgaris is a potentially fatal autoimmune bullous disease. High doses of immunosuppressive drugs are used in managing severe cases of pemphigus. Rituximab, an anti-CD20 monoclonal antibody, has proven to be effective in patients with refractory pemphigus vulgaris and pemphigus foliaceus. We review cases of pemphigus vulgaris and pemphigus foliaceus not associated with lymphoma that were treated with rituximab, and we report a new case of severe refractory pemphigus vulgaris successfully treated with rituximab.     

Rituximab: applications in dermatology

Rituximab is a chimeric anti-CD20 monoclonal antibody which has been used extensively for B-lymphocytic malignancies. In addition, applications for autoimmune diseases have emerged in recent years. Case reports support the use of rituximab in certain dermatologic conditions, including paraneoplastic pemphigus, pemphigus vulgaris, graft versus host disease, and cutaneous B-cell malignancies. Clinical trials are lacking and would be an appropriate next step.     

Anti-B- cell-directed immunotherapy (rituximab) in the treatment of refractory pemphigus--an update

Rituximab is a monoclonal antibody directed against the CD20 surface antigen present on B lymphocytes. Following its application, B cells are rapidly and specifically depleted. Rituximab has been approved for the treatment of relapsed and therapy-refractory non-Hodgkin lymphoma and has been incorporated into numerous chemotherapy regimes with promising results. Eradication of auto-reactive B cell clones is the rationale for its application in a variety of autoimmune disorders including the pemphigus group where B cells are thought to play a critical role in the pathogenesis. Preliminary reports in autoimmune disorders are encouraging. Adverse effects are generally well controlled and although severe infections have been reported following rituximab, the overall risk does not seem to be significantly increased. In the pemphigus group, rituximab has been successfully employed in refractory cases and a recent study suggests that a single course induces long-term remission in this patient group.     

Treatment of resistant pemphigus vulgaris with an anti-CD20 monoclonal antibody (Rituximab)

We describe a 54-year-old man with resistant pemphigus vulgaris. Standard therapies had afforded inadequate control and have been associated with considerable side-effects. The anti-CD20 monoclonal antibody, Rituximab (MabThera, Roche), was trialled with significant benefit. We discuss its potential mechanism of action.