Knapp Rachel, Hardtstock Fränce, Krieger Julia, Wilke Thomas, Maywald Ulf, Chognot Cathy, Muros-Le Rouzic Erwan, Craveiro Licinio
Cytel, Potsdamer Straße 58, 10785 Berlin, Germany.
IPAM e.V., Alter Holzhafen 19, 23966 Wismar, Germany.
Mult Scler Relat Disord. 2022 Dec;68:104245. doi: 10.1016/j.msard.2022.104245. Epub 2022 Oct 17.
People with multiple sclerosis (pwMS) have a higher risk of serious infection (i.e., infection-related hospitalizations) than people without MS. Few studies have explored the risk of serious infections by MS phenotype in a real-world setting. This retrospective study compared the incidence of serious infections among people with relapse remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS).
Adult pwMS were selected from a German claims database, based on one inpatient or two outpatient diagnoses of MS (ICD-10 G35) by a neurologist from 01/01/2016 to 12/31/2018. Three cohorts (RRMS, PPMS, SPMS) were identified based on codes for MS subtypes included in the German Modification of the ICD-10 system. A fourth cohort of unspecified MS patients combined those with conflicting MS subtype diagnoses and multiple unspecified codes for MS. Serious infections were defined as hospitalizations for which infections were selected as the primary inpatient diagnosis. Infections were identified from a basket of ICD-10 codes distributed across 11 main categories, according to possible pathogen (e.g., other bacterial diseases [A30-A49]) or anatomical location (e.g., urinary tract infection [N39.0]). Multiple infections were counted if an interval of at least 60 days was recorded between episodes. Serious infections were counted from index (i.e., first recorded MS code) until the end of the study period or death. Incidence rates (IRs) were reported per 100 patient years (PY).
A total of 4,250 pwMS (RRMS: 2,307, PPMS: 282, SPMS: 558, unspecified MS: 1,135) were included; 32 patients progressed from RRMS to SPMS during the follow-up period. Mean (SD) age at baseline was 46.6 (13.6), 61.9 (12.4), and 62.5 (11.8) years in patients with RRMS, PPMS, and SPMS, respectively. Most pwMS were female (RRMS 74.8%, PPMS 62.1%, SPMS 67.4%). Progressive pwMS were more likely to have at least 1 comorbidity (PPMS 87.2%, SPMS 87.5%) compared to those with relapsing MS (61.9%). Most RRMS patients received disease-modifying therapy during follow-up (82.1%), while less than half of progressive MS patients did (PPMS 23.8%, SPMS 31.4%). Over a mean (SD) follow-up period of 3.5 (0.8) years, the IR of serious infections per 100 PY was higher in progressive MS cohorts (PPMS 13.5 [11.3-16.1], SPMS 13.6 [12.0-15.3]) than in the RRMS group (3.4 [3.0-3.7]). Yearly IRs remained stable over time in each cohort. Where anatomical location was specified, respiratory (2.0 per 100 PY) and genitourinary (1.9 per 100 PY) infections were most common. Across all subtypes, higher rates of serious infections were observed in men and older patients.
Progressive MS, older age and male sex are associated with an increased risk of serious infections. Overall, respiratory and genitourinary infections were the most commonly reported serious infections.
与无多发性硬化症（MS）的人相比，多发性硬化症患者（pwMS）发生严重感染（即与感染相关的住院）的风险更高。很少有研究在现实环境中探讨MS表型导致严重感染的风险。这项回顾性研究比较了复发缓解型MS（RRMS）、原发进展型MS（PPMS）和继发进展型MS（SPMS）患者中严重感染的发生率。
从德国理赔数据库中选取成年pwMS，这些患者在2016年1月1日至2018年12月31日期间由神经科医生进行了一次住院或两次门诊MS诊断（ICD-10 G35）。根据ICD-10系统德国修订版中包含的MS亚型编码确定了三个队列（RRMS、PPMS、SPMS）。第四个队列是未明确MS亚型的患者，包括那些MS亚型诊断相互矛盾以及有多个未明确MS编码的患者。严重感染定义为将感染选为主要住院诊断的住院情况。根据可能的病原体（如其他细菌疾病[A30-A49]）或解剖位置（如尿路感染[N39.0]），从分布在11个主要类别的一组ICD-10编码中识别感染。如果两次发作之间记录的间隔至少为60天，则计算多次感染。从索引（即首次记录的MS编码）到研究期结束或死亡计算严重感染次数。报告每100患者年（PY）的发病率（IR）。
共纳入4250例pwMS（RRMS：2307例，PPMS：282例，SPMS：558例，未明确MS：1135例）；32例患者在随访期间从RRMS进展为SPMS。RRMS、PPMS和SPMS患者的基线平均（标准差）年龄分别为46.6（13.6）岁、61.9（12.4）岁和62.5（11.8）岁。大多数pwMS为女性（RRMS 74.8%，PPMS 62.1%，SPMS 67.4%）。与复发型MS患者（61.9%）相比，进展型pwMS更有可能至少有一种合并症（PPMS 87.2%，SPMS 87.5%）。大多数RRMS患者在随访期间接受了疾病修饰治疗（82.1%），而进展型MS患者中不到一半接受了治疗（PPMS 23.8%，SPMS 31.4%）。在平均（标准差）3.5（0.8）年的随访期内，进展型MS队列中每100 PY的严重感染IR高于RRMS组（PPMS为13.5[11.3-16.1]，SPMS为13.6[12.0-15.3]），而RRMS组为3.4[3.0-3.7]。每个队列的年度IR随时间保持稳定。在明确解剖位置的情况下，呼吸道感染（每100 PY 2.0例）和泌尿生殖道感染（每100 PY 1.9例）最为常见。在所有亚型中，男性和老年患者的严重感染发生率更高。
进展型MS、老年和男性与严重感染风险增加相关。总体而言，呼吸道和泌尿生殖道感染是最常报告的严重感染。
