Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Convention Avenue, Room 765, Philadelphia, PA, 19104, USA.
F. Hoffmann-La Roche, Ltd., Basel, Switzerland.
J Neurovirol. 2018 Jun;24(3):323-331. doi: 10.1007/s13365-018-0615-7. Epub 2018 Mar 5.
This report assesses the observed risk of PML in patients treated with the anti-CD20 monoclonal antibody rituximab in the regulatory authority-approved autoimmune indications rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). This was a cumulative analysis of confirmed PML cases in patients receiving rituximab for RA or GPA/MPA from both spontaneous reports and clinical trial sources, as captured in the manufacturer global company safety and clinical databases. Overall reporting rates were calculated and patient case details were summarized. As of 17 November 2015, there were nine confirmed PML cases among patients who had received rituximab for RA and two for GPA. Corresponding estimated reporting rates were 2.56 per 100,000 patients with RA (estimated exposure ≈ 351,396 patients) and < 1 per 10,000 patients with GPA/MPA (estimated exposure 40,000-50,000 patients). In all cases, patients had ≥ 1 potential risk factor for PML independent of rituximab treatment. In the RA population, the estimated reporting rate of PML generally remained stable and low since 2009 despite increasing rituximab exposure. There was no pattern of latency from time of rituximab initiation to PML development and no association of PML with the number of rituximab courses. Global post-marketing safety and clinical trial data demonstrated that the occurrence of PML is very rare among rituximab-treated patients with RA or GPA/MPA and has remained stable over time.
本报告评估了接受抗 CD20 单克隆抗体利妥昔单抗治疗的患者发生 PML 的风险，这些患者的适应证为监管机构批准的自身免疫性疾病，包括类风湿关节炎（RA）、肉芽肿性多血管炎（GPA）和显微镜下多血管炎（MPA）。这是对来自自发报告和临床试验来源的接受利妥昔单抗治疗 RA 或 GPA/MPA 的患者中确诊 PML 病例的累积分析，这些数据均来自制造商的全球公司安全性和临床数据库。计算了总体报告率，并总结了患者病例的详细信息。截至 2015 年 11 月 17 日，有 9 例确诊的 PML 病例发生在接受利妥昔单抗治疗 RA 的患者中，2 例发生在接受利妥昔单抗治疗 GPA 的患者中。相应的估计报告率为每 100,000 例 RA 患者 2.56 例（估计暴露量约为 351,396 例），以及每 10,000 例 GPA/MPA 患者 <1 例（估计暴露量为 40,000-50,000 例）。在所有病例中，患者均有 PML 的≥1 个潜在风险因素，与利妥昔单抗治疗无关。在 RA 人群中，尽管利妥昔单抗暴露量增加，但自 2009 年以来，PML 的估计报告率总体保持稳定且较低。从利妥昔单抗开始到 PML 发病的潜伏期没有模式，并且 PML 与利妥昔单抗疗程数无关。全球上市后安全性和临床试验数据表明，接受利妥昔单抗治疗的 RA 或 GPA/MPA 患者中 PML 的发生非常罕见，并且随着时间的推移保持稳定。
