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接受奥瑞珠单抗或利妥昔单抗治疗多发性硬化症和视神经脊髓炎谱系疾病患者低丙种球蛋白血症和严重感染的预测因素。

Predictors of hypogammaglobulinemia and serious infections among patients receiving ocrelizumab or rituximab for treatment of MS and NMOSD.

作者信息

Mears Veronica, Jakubecz Collin, Seeco Catherine, Woodson Sophia, Serra Alessandro, Abboud Hesham

机构信息

Department of Pharmacy Services, University Hospitals Cleveland Medical Center, United States of America.

Neurology/MS, Department of Specialty Pharmacy, University Hospitals Home Care Services, United States of America.

出版信息

J Neuroimmunol. 2023 Apr 15;377:578066. doi: 10.1016/j.jneuroim.2023.578066. Epub 2023 Mar 8.

Abstract

BACKGROUND AND OBJECTIVES

Ocrelizumab and rituximab are monoclonal antibodies targeting the CD20 marker on B lymphocytes. The enhanced efficacy of B lymphocyte depleting therapies poses a greater risk of decreased immunoglobulin (Ig) levels. The rate and risk factors of hypogammaglobulinemia in MS and NMOSD patients treated with anti-CD20 therapies are unknown.

METHODS

A retrospective study was conducted among patients who received anti-CD20 therapy for the treatment of MS, NMOSD, and other related neurological disorders. The goal was to determine the incidence and risk factors of hypogammaglobulinemia and serious infections in patients receiving ocrelizumab versus rituximab. The secondary goals were to determine the rates of lymphopenia, neutropenia, and early B cell repopulation among patients on anti-CD20 therapy.

RESULTS

Overall, 184 patients (mean age 48.4 ± 13.7, 66.8% female) met inclusion criteria; 152 patients received ocrelizumab and 32 patients received rituximab. A total of 22 patients (12%) developed hypogammaglobulinemia. Patients who developed hypogammaglobulinemia were more likely to have been ≥50 years of age (p = .0275) with lower baseline IgG (p = .001) and IgA (p = .0038) levels. Serious infections were observed in 21 patients (11%) and seen more commonly in those that developed total lymphopenia (<1.0 × 109/L) and had longer duration of B-cell therapy. Multivariate analysis identified age ≥ 50 years, white race, and rituximab as independent predictors of hypogammaglobulinemia, and absolute lymphopenia as an independent risk factor for serious infections.

DISCUSSION

Among patients receiving anti-CD20 therapy, 12% of patients experienced hypogammaglobulinemia which was seen more commonly in white patients, at least 50 years old, with lower baseline IgG and IgA levels and in those treated with rituximab. Serious infections were seen more commonly in patients with total lymphopenia and longer exposure to anti-CD20 therapy.

摘要

背景与目的

奥瑞珠单抗和利妥昔单抗是靶向B淋巴细胞上CD20标志物的单克隆抗体。B淋巴细胞清除疗法疗效增强,导致免疫球蛋白(Ig)水平降低的风险更高。接受抗CD20疗法治疗的多发性硬化症(MS)和视神经脊髓炎谱系疾病(NMOSD)患者中低丙种球蛋白血症的发生率及危险因素尚不清楚。

方法

对接受抗CD20疗法治疗MS、NMOSD及其他相关神经系统疾病的患者进行了一项回顾性研究。目的是确定接受奥瑞珠单抗与利妥昔单抗治疗的患者中低丙种球蛋白血症和严重感染的发生率及危险因素。次要目的是确定接受抗CD20疗法治疗的患者中淋巴细胞减少、中性粒细胞减少和早期B细胞再增殖的发生率。

结果

总体而言,184例患者(平均年龄48.4±13.7岁,66.8%为女性)符合纳入标准;152例患者接受奥瑞珠单抗治疗,32例患者接受利妥昔单抗治疗。共有22例患者(12%)发生低丙种球蛋白血症。发生低丙种球蛋白血症的患者更可能年龄≥50岁(p = 0.0275),基线IgG(p = 0.001)和IgA(p = 0.0038)水平较低。21例患者(11%)发生严重感染,在发生全淋巴细胞减少(<1.0×10⁹/L)且B细胞治疗持续时间较长的患者中更常见。多变量分析确定年龄≥50岁、白种人和利妥昔单抗是低丙种球蛋白血症的独立预测因素,绝对淋巴细胞减少是严重感染的独立危险因素。

讨论

在接受抗CD20疗法治疗的患者中,12%的患者发生低丙种球蛋白血症,在年龄至少50岁、基线IgG和IgA水平较低的白种患者以及接受利妥昔单抗治疗的患者中更常见。严重感染在全淋巴细胞减少且接受抗CD20疗法治疗时间较长的患者中更常见。

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