Emery Paul, Furst Daniel E, Kirchner Petra, Melega Simone, Lacey Stuart, Lehane Patricia B
NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds University, Leeds, UK.
University of California, Los Angeles, Los Angeles, CA, USA.
Rheumatol Ther. 2020 Mar;7(1):121-131. doi: 10.1007/s40744-019-00183-6. Epub 2019 Nov 21.
Patients with rheumatoid arthritis (RA) are at an increased risk of developing malignancies, but it is unclear whether this increased risk is the result of disease pathobiology or immunosuppressant treatments for RA. This analysis evaluated the potential risk of malignancy in patients with RA treated with rituximab (MabThera/Rituxan) a CD20+ B-cell depleting agent manufactured by F. Hoffmann-La Roche Ltd.
Malignancy rates were obtained from the rituximab global company safety database for adverse event reporting and from the rituximab global clinical trial program for RA consisting of eight randomized clinical trials, two long-term open-label extensions, and one open-label prospective study. Global company safety database searches were performed using the standard Medical Dictionary for Regulatory Activities (MedDRA) queries "Malignant tumors wide" and "Skin malignant tumors wide" up to April 30, 2017. Age- and sex-specific comparator values from the general population were obtained from the US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database.
For the 409,706 patients with RA in the rituximab global company safety database since first market approval in 2006, 1739 cumulative malignant events were reported, with an overall malignancy reporting rate of approximately 4.2 events per 1000 patients. No evidence of increased risk of malignancy, of any organ-specific type, was found following rituximab treatment. The rate of malignancies from rituximab-treated patients in RA clinical trials was 7.4 per 1000 patient-years. This is within the expected range, with no evidence for increased risk over time or with additional rituximab courses.
Analyses of the global postmarketing safety database and long-term clinical trial data showed no evidence of an increased risk of malignancy of any type following rituximab treatment in patients with RA.
F. Hoffmann-La Roche Ltd.
类风湿性关节炎（RA）患者发生恶性肿瘤的风险增加，但尚不清楚这种风险增加是疾病病理生物学的结果还是RA免疫抑制治疗的结果。本分析评估了接受利妥昔单抗（美罗华/ Rituxan）治疗的RA患者发生恶性肿瘤的潜在风险，利妥昔单抗是F. Hoffmann-La Roche Ltd生产的一种CD20 + B细胞耗竭剂。
恶性肿瘤发生率来自利妥昔单抗全球公司不良事件报告安全数据库以及利妥昔单抗全球RA临床试验项目，该项目包括八项随机临床试验、两项长期开放标签扩展试验和一项开放标签前瞻性研究。使用标准的医学监管活动词典（MedDRA）查询“广泛的恶性肿瘤”和“广泛的皮肤恶性肿瘤”，对全球公司安全数据库进行检索，截止至2017年4月30日。从美国国家癌症研究所监测、流行病学和最终结果（SEER）数据库获得一般人群的年龄和性别特异性对照值。
自2006年首次上市批准以来，利妥昔单抗全球公司安全数据库中有409,706例RA患者，报告了1739例累积恶性事件，总体恶性事件报告率约为每1000例患者4.2例。未发现利妥昔单抗治疗后发生任何器官特异性类型恶性肿瘤风险增加的证据。RA临床试验中接受利妥昔单抗治疗患者的恶性肿瘤发生率为每1000患者年7.4例。这在预期范围内，没有证据表明随着时间推移或增加利妥昔单抗疗程会增加风险。
对全球上市后安全数据库和长期临床试验数据的分析表明，RA患者接受利妥昔单抗治疗后，没有证据表明任何类型恶性肿瘤的风险增加。
F. Hoffmann-La Roche Ltd。
