Disease-modifying drugs for multiple sclerosis and infection risk: a cohort study
Disease-modifying drugs for multiple sclerosis and infection risk: a cohort study
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DOI：
10.1136/jnnp-2017-317493
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发表时间：
2018-10-01
影响因子：
11
通讯作者：
Tremlett, Helen
中科院分区：
文献类型：
--
作者：
Wijnands, Jose Maria Andreas;Zhu, Feng;Tremlett, Helen
目的多发性硬化（MS）的疾病修饰治疗（DMT）与感染风险的关系尚不清楚。我们研究了DMTs和感染相关的medical encounters.Methods之间的关联使用人口为基础的行政数据从加拿大不列颠哥伦比亚省，我们确定了MS的情况下，并遵循他们的第一次脱髓鞘事件（1996-2013年），直到移民，死亡或研究结束（2013年12月）。使用复发性事件发生时间模型评估DMT暴露（按DMT世代或类别）与感染相关的医生或医院索赔之间的关联，并对年龄、性别、社会经济状况、指数年和合并症计数进行调整。结果在6793例MS病例中，平均随访8.5年，1716例（25.3%）暴露于DMT。相对于无DMT，暴露于任何第一代DMT（β-干扰素或醋酸格拉替雷）与感染相关的医生声明无关（aHR：0.96; 95% CI 0.89 - 1.02），单独评估时也不暴露于这些药物类别。暴露于任何第二代DMT（口服DMT或那他珠单抗）与感染相关医生索赔的风险增加相关（aHR：1.47; 95% CI 1.16 - 1.85）;单独评估时，与那他珠单抗的相关性显著（aHR：1.59; 95% CI 1.19 - 2.11），但口服DMT（aHR：1.17; 95% CI 0.88 - 1.56）未发生。虽然没有DMT与感染相关的医院索赔，这些住院治疗也是uncomment.Conclusion暴露于第一代DMT是不相关的感染风险改变。然而，暴露于第二代DMT，与那他珠单抗相关的感染相关的医生索赔的风险增加了59%。继续药物警戒是必要的，包括对患者结局的DMT相关感染负担的调查。
Objective Little is known about disease-modifying treatments (DMTs) for multiple sclerosis (MS) and infection risk in clinical practice. We examined the association between DMTs and infection-related medical encounters.Methods Using population-based administrative data from British Columbia, Canada, we identified MS cases and followed them from their first demyelinating event (1996-2013) until emigration, death or study end (December 2013). Associations between DMT exposure (by DMT generation or class) and infection-related physician or hospital claims were assessed using recurrent time-to-events models, adjusted for age, sex, socioeconomic status, index year and comorbidity count. Results were reported as adjusted HRs (aHRs).Results Of 6793 MS cases, followed for 8.5 years (mean), 1716 (25.3%) were DMT exposed. Relative to no DMT, exposure to any first-generation DMT (beta-interferon or glatiramer acetate) was not associated with infection-related physician claims (aHR: 0.96; 95% CI 0.89 to 1.02), nor was exposure to these drug classes when assessed separately. Exposure to any second-generation DMT (oral DMT or natalizumab) was associated with an increased hazard of an infection-related physician claim (aHR: 1.47; 95% CI 1.16 to 1.85); when assessed individually, the association was significant for natalizumab (aHR: 1.59; 95% CI 1.19 to 2.11) but not the oral DMTs (aHR: 1.17; 95% CI 0.88 to 1.56). While no DMTs were associated with infection-related hospital claims, these hospitalisations were also uncommon.Conclusion Exposure to first-generation DMTs was not associated with an altered infection risk. However, exposure to the second-generation DMTs was, with natalizumab associated with a 59% increased risk of an infection-related physician claim. Continued pharmacovigilance is warranted, including an investigation of the DMT-associated infection burden on patient outcomes.