Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave., CHS 37-121, Los Angeles, CA 90095, USA.
Int J Infect Dis. 2011 Jan;15(1):e2-16. doi: 10.1016/j.ijid.2010.03.025. Epub 2010 Nov 11.
Rituximab has increasingly been used for the treatment of hematological malignancies and autoimmune diseases, and its efficacy and safety are well established. Although clinical trials have shown conflicting results regarding the association of rituximab with infections, an increased incidence of infections has recently been reported in patients with lymphomas being treated with rituximab. However, clinical experience regarding the association of rituximab with different types of infection is lacking and this association has not been established in patients with rheumatoid arthritis.
All previous studies included in our literature review were found using a PubMed, EMBASE, and Cochrane database search of the English-language medical literature applying the terms 'rituximab', 'monoclonal antibodies', 'infections', 'infectious complications', and combinations of these terms. In addition, the references cited in these articles were examined to identify additional reports.
We performed separate analyses of data regarding the association of rituximab with infection in (1) patients with hematological malignancies, (2) patients with autoimmune disorders, and (3) transplant patients. Recent data show that rituximab maintenance therapy significantly increases the risk of both infection and neutropenia in patients with lymphoma or other hematological malignancies. On the other hand, data available to date do not indicate an increased risk of infections when using rituximab compared with concurrent control treatments in patients with rheumatoid arthritis. However, there is a lack of sufficient long-term data to allow such a statement to be definitively made, and caution regarding infections should continue to be exercised, especially in patients who have received repeated courses of rituximab, are receiving other immunosuppressants concurrently, and in those whose immunoglobulin levels have fallen below the normal range. Few data are available concerning the risk of organ transplant recipients developing infections following rituximab therapy. Data from case reports, case series, and retrospective studies correlate rituximab use with the development of a variety of infections in transplant patients.
Further studies are needed to clarify the association of rituximab with infection. Physicians and patients should be educated about the association of rituximab with infectious complications. Monitoring of absolute neutrophil count and immunoglobulin levels and the identification of high-risk groups for the development of infectious complications, with timely vaccination of these groups, are clearly needed.
利妥昔单抗已越来越多地用于治疗血液系统恶性肿瘤和自身免疫性疾病，其疗效和安全性已得到充分证实。虽然临床试验对于利妥昔单抗与感染的相关性结果存在矛盾，但最近有报道称，接受利妥昔单抗治疗的淋巴瘤患者感染的发生率增加。然而，目前缺乏关于利妥昔单抗与不同类型感染的临床经验，且这种相关性在类风湿关节炎患者中尚未得到证实。
通过对英文医学文献的 PubMed、EMBASE 和 Cochrane 数据库进行检索，应用“rituximab”、“monoclonal antibodies”、“infections”、“infectious complications”以及这些术语的组合，对我们文献综述中包含的所有既往研究进行了查找。此外，还对这些文章中的参考文献进行了检查，以确定其他报告。
我们分别分析了利妥昔单抗与（1）血液系统恶性肿瘤患者、（2）自身免疫性疾病患者和（3）移植患者感染相关的数据。最近的数据显示，利妥昔单抗维持治疗显著增加了淋巴瘤或其他血液系统恶性肿瘤患者感染和中性粒细胞减少症的风险。另一方面，目前的数据并未表明在类风湿关节炎患者中，与同期对照治疗相比，使用利妥昔单抗会增加感染的风险。然而，由于缺乏足够的长期数据，目前还不能明确地做出这样的陈述，因此仍需谨慎对待感染，尤其是那些已经接受了多次利妥昔单抗治疗、同时接受其他免疫抑制剂治疗以及免疫球蛋白水平低于正常值的患者。关于利妥昔单抗治疗后器官移植受者发生感染的风险，仅有少量数据。来自病例报告、病例系列和回顾性研究的数据表明，利妥昔单抗的使用与移植患者发生各种感染有关。
需要进一步研究以阐明利妥昔单抗与感染的相关性。应向医生和患者宣传利妥昔单抗与感染性并发症的相关性。显然需要监测绝对中性粒细胞计数和免疫球蛋白水平，并确定发生感染性并发症的高危人群，及时对这些人群进行疫苗接种。
