Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.
Department of Infectious Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Mult Scler Relat Disord. 2021 Jul;52:102988. doi: 10.1016/j.msard.2021.102988. Epub 2021 May 1.
Anti-CD20 antibody therapy may be associated with an increased risk of infections. We therefore investigated risk factors for infection in patients with demyelinating diseases treated with anti-CD20 antibody therapy.
In this retrospective uncontrolled study, patients ever treated with anti-CD20 antibodies at an academic clinic were identified through the Danish Multiple Sclerosis Registry (DMSR). Data were collected from medical charts and the DMSR. We assessed occurrence of severe infections (requiring hospitalization), varicella zoster virus (VZV), major comorbidities and routine laboratory values for lymphocytes, IgG and IgM.
A total of 447 patients ever treated with anti-CD20 antibody therapy were identified; of these 416 with 649 patient years of follow-up were still under therapy. In this group, seven patients had VZV infections, and 16 patients had been hospitalized with infections during up to three years of follow-up on anti-CD20 therapy. Comorbidity was recorded in 80 patients. The risk of severe infection was associated with comorbidities, higher age, longer duration of treatment, and higher Expanded Disability Status Scale (EDSS) scores. In multivariable analyses treatment duration, EDSS scores and presence of comorbidity were independently associated with risk of severe infections. Serum concentrations of IgG and IgM decreased with increasing duration of therapy but were not associated with risk of severe infections. Patients with VZV infection had lower lymphocyte counts and lower serum concentrations of IgM. In multivariable analyses only lymphocyte counts were independently associated with risk of VZV infection.
In this retrospective study of patients treated with anti-CD20 antibodies, the risk of infections requiring hospitalization was independently associated with comorbidities, duration of treatment, and higher EDSS scores. Risk of VZV infection was independently associated with lymphopenia. Future studies investigating strategies for mitigating risk of infection in patients treated with anti-CD20 antibodies are warranted, especially for older patients, patients with higher levels of disability and for patients with a longer duration of treatment.
抗 CD20 抗体治疗可能与感染风险增加相关。因此，我们研究了接受抗 CD20 抗体治疗的脱髓鞘疾病患者感染的危险因素。
在这项回顾性非对照研究中，通过丹麦多发性硬化症登记处（DMSR）确定了在学术诊所接受过抗 CD20 抗体治疗的患者。从病历和 DMSR 中收集数据。我们评估了严重感染（需要住院治疗）、水痘带状疱疹病毒（VZV）、主要合并症和淋巴细胞、IgG 和 IgM 的常规实验室值的发生情况。
共确定了 447 例曾接受抗 CD20 抗体治疗的患者；其中 416 例患者接受了 649 患者年的随访，仍在接受抗 CD20 治疗。在该组中，7 例患者发生 VZV 感染，16 例患者在接受抗 CD20 治疗期间因感染住院，随访时间长达 3 年。80 例患者记录了合并症。严重感染的风险与合并症、年龄较大、治疗时间较长和扩展残疾状况量表（EDSS）评分较高有关。多变量分析表明，治疗持续时间、EDSS 评分和合并症的存在与严重感染的风险独立相关。随着治疗时间的延长，血清 IgG 和 IgM 浓度降低，但与严重感染的风险无关。VZV 感染患者的淋巴细胞计数和血清 IgM 浓度较低。多变量分析表明，只有淋巴细胞计数与 VZV 感染的风险独立相关。
在这项接受抗 CD20 抗体治疗的患者回顾性研究中，需要住院治疗的感染风险与合并症、治疗持续时间和较高的 EDSS 评分独立相关。VZV 感染的风险与淋巴细胞减少独立相关。需要进一步研究，以制定减轻接受抗 CD20 抗体治疗患者感染风险的策略，特别是针对老年患者、残疾程度较高的患者和治疗持续时间较长的患者。
