OhioHealth Multiple Sclerosis Center, Columbus, OH, United States.
South Shore Neurologic Associates, Islip, NY, United States.
Mult Scler Relat Disord. 2022 Jul;63:103921. doi: 10.1016/j.msard.2022.103921. Epub 2022 Jun 2.
Infections in people with multiple sclerosis (PwMS) may have a detrimental effect on disease progression, risk of hospitalization, and healthcare resource utilization (HRU). The infection risk and HRU costs may vary between disease-modifying therapies (DMTs); however, the individual risks and differences associated with DMTs are not well characterized. Some DMTs may increase the risk for infections in PwMS; however, previous studies have reported an intact humoral immune response in dimethyl fumarate (DMF)-treated patients. The objective was to compare infection-related HRU and healthcare costs (HCCs) between PwMS treated with DMF or ocrelizumab (OCR).
Eligible patients were identified from the Optum US claims database between April 2017 and September 2020 (DMF n = 1429; OCR n = 3170). Patients were followed from index date to first occurrence of: (1) end of study, (2) end of insurance eligibility, (3) discontinuation of index DMT, or (4) switch from index DMT to another DMT. Outcomes were annualized rate of infection encounters (defined as infection encounters [n] during follow-up window / days followed [n] × 365); annualized infection-related HCCs (defined as aggregated costs of infection encounters during follow-up window / days followed [n] × 365); location-specific infections, and overall infection-related events. Propensity score matching (PSM) 1:1 method was used; PS was calculated via logistic regression for probability of DMF treatment conditional on demographics and comorbidities. Mean differences (MD) were reported for infection encounter measures.
After PSM, DMF and OCR cohorts (n = 1094 in each cohort) were balanced based on baseline characteristics (standardized MD of adjusted baseline characteristics <0.1). Mean (standard deviation) follow-up was 296 (244) days for DMF patients and 297 (243) for OCR patients. DMF patients experienced lower annualized rates of overall infection encounters vs OCR patients (MD -0.51 [95% confidence interval (CI): -0.92 to -0.11], p = 0.01). When stratified by type of infection encounter, DMF patients experienced significantly lower annualized rates of outpatient (MD [95% CI]: -0.44 [-0.80 to -0.08], p = 0.02) and inpatient/hospitalization infection encounters (-0.08 [-0.14 to -0.02], p<0.01) vs OCR patients. A trend towards a shorter duration of infection-related hospitalization in the DMF vs the OCR group was observed (MD [95% CI]: -2.20 [-4.73 to 0.26] days, p = 0.08). The most common infection types in both DMT groups were urinary tract infections, sepsis, and pneumonia. DMF patients experienced lower annualized infection-related HCCs (MD [95% CI]: -$3642 [-$6380 to -$904], p < 0.01) vs OCR patients, which were driven largely by infection-related hospitalization costs (-$3639 [-$6019 to -$1259], p < 0.01).
DMF-treated patients PS-matched with OCR patients experienced lower annualized rates of infection encounters and lower infection-related HCCs.
多发性硬化症（MS）患者的感染可能对疾病进展、住院风险和医疗资源利用（HRU）产生不利影响。疾病修正治疗（DMT）之间的感染风险和 HRU 成本可能有所不同；然而，与 DMT 相关的个体风险和差异尚未得到很好的描述。一些 DMT 可能会增加 MS 患者感染的风险；然而，之前的研究报告称，在用二甲基富马酸（DMF）治疗的患者中存在完整的体液免疫反应。目的是比较 DMF 或奥瑞珠单抗（OCR）治疗的 MS 患者与感染相关的 HRU 和医疗保健费用（HCC）。
从 2017 年 4 月至 2020 年 9 月期间，从 Optum US 索赔数据库中确定符合条件的患者（DMF 组 n=1429；OCR 组 n=3170）。从索引日期到以下任何事件的首次发生进行随访：（1）研究结束，（2）保险资格结束，（3）索引 DMT 停药，或（4）索引 DMT 转换为另一种 DMT。结果是感染发生率（定义为随访期间的感染发生率[n] / 随访天数[n]×365）；感染相关 HCC 年度发生率（定义为随访期间感染发生率的累计成本 / 随访天数[n]×365）；特定部位感染和总体感染相关事件。采用倾向评分匹配（PSM）1:1 方法；通过逻辑回归计算 DMF 治疗的概率作为条件，使用协变量和合并症作为 PS。对于感染发生率的测量，报告了平均值差异（MD）。
在 PSM 后，DMF 和 OCR 队列（每个队列 n=1094）基于基线特征平衡（调整基线特征的标准化 MD <0.1）。DMF 患者的平均（标准偏差）随访时间为 296（244）天，OCR 患者为 297（243）天。与 OCR 患者相比，DMF 患者的总感染发生率年度率较低（MD-0.51 [95%置信区间（CI）：-0.92 至 -0.11]，p=0.01）。按感染发生率类型分层时，DMF 患者的门诊（MD [95% CI]：-0.44 [-0.80 至 -0.08]，p=0.02）和住院/住院感染发生率显著较低，与 OCR 患者相比。与 OCR 组相比，DMF 组观察到感染相关住院时间缩短（MD [95% CI]：-2.20 [-4.73 至 0.26]天，p=0.08）。在这两种 DMT 组中，最常见的感染类型是尿路感染、败血症和肺炎。与 OCR 患者相比，DMF 治疗的患者感染相关 HCC 年度发生率较低（MD [95% CI]：-3642 [美元] [-6380 至 -904]，p < 0.01），这主要是由于感染相关的住院费用较低（-3639 [美元] [-6019 至 -1259]，p < 0.01）。
与 OCR 患者匹配的 DMF 治疗患者的感染发生率和感染相关 HCC 年度发生率较低。
