Department of Genetics and Genomic Sciences, ISMMS (Icahn School of Medicine at Mount Sinai), New York, New York.
Division of Gastroenterology, Department of Medicine, ISMMS, New York, New York.
JAMA Neurol. 2018 Aug 1;75(8):939-946. doi: 10.1001/jamaneurol.2018.0605.
Despite established genetic and pathophysiologic links between inflammatory bowel disease (IBD) and Parkinson disease (PD), clinical data supporting this association remain scarce. Although systemic inflammation is considered a potential biological mechanism shared between the 2 diseases, the role of reduced systemic inflammation through IBD-directed anti-tumor necrosis factor (anti-TNF) therapy in PD risk is largely unknown.
To compare the incidence of PD among individuals with or without IBD and to assess whether PD risk among patients with IBD is altered by anti-TNF therapy.
DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective cohort study analyzing information in the Truven Health MarketScan administrative claims database and the Medicare Supplemental Database between January 1, 2000, and March 31, 2016. Individuals were selected who had at least 2 claims for IBD diagnoses, at least 6 months of follow-up, and no prior diagnosis of PD on or before the IBD index date. Exposure to Anti-TNF therapy was measured from the anti-TNF index date to the last date of anti-TNF coverage or the end of enrollment or PD index date, whichever was earliest. Incidence rates per 1000 person-years were calculated, and crude and adjusted incidence rate ratios were estimated by Poisson regression models and presented with 95% CIs.
Incidence of PD among patients with IBD with or without exposure to anti-TNF therapy.
In total, 144 018 individuals with IBD were matched on age, sex, and year of index date with 720 090 unaffected controls. Of them, 1796 individuals had at least 2 PD diagnoses and at least 1 filled PD-related prescription. The mean (SD) age of individuals with IBD was 51 (17) years, and 44% were men. The incidence of PD among patients with IBD was 28% higher than that among unaffected matched controls (adjusted incidence rate ratio, 1.28; 95% CI, 1.14-1.44; P < .001). A 78% reduction in the incidence rate of PD was detected among patients with IBD who were exposed to anti-TNF therapy compared with those who were not exposed (adjusted incidence rate ratio, 0.22; 95% CI, 0.05-0.88; P = .03).
A higher incidence of PD was observed among patients with IBD than among individuals without IBD. Early exposure to antiinflammatory anti-TNF therapy was associated with substantially reduced PD incidence. These findings support a role of systemic inflammation in the pathogenesis of both diseases. Further studies are required to determine whether anti-TNF treatment administered to high-risk individuals may mitigate PD risk.
尽管炎症性肠病(IBD)和帕金森病(PD)之间存在已确立的遗传和病理生理学联系,但支持这种关联的临床数据仍然很少。尽管全身性炎症被认为是这两种疾病之间共同存在的潜在生物学机制,但通过 IBD 靶向抗肿瘤坏死因子(anti-TNF)治疗降低系统性炎症对 PD 风险的作用在很大程度上仍是未知的。
比较有或没有 IBD 的个体中 PD 的发生率,并评估 IBD 患者中 PD 风险是否因 anti-TNF 治疗而改变。
设计、设置和参与者:这是一项回顾性队列研究,分析了 Truven Health MarketScan 行政索赔数据库和 Medicare 补充数据库 2000 年 1 月 1 日至 2016 年 3 月 31 日之间的信息。选择了至少有 2 次 IBD 诊断、至少 6 个月随访且在 IBD 索引日期之前没有 PD 诊断的个体。抗 TNF 治疗的暴露情况从抗 TNF 索引日期到抗 TNF 覆盖的最后一天或入组或 PD 索引日期结束的时间测量,以最早的为准。每 1000 人年计算发生率,并通过泊松回归模型估计粗发病率和调整发病率比,并以 95%CI 呈现。
有或没有接受 anti-TNF 治疗的 IBD 患者中 PD 的发生率。
总共 144018 例 IBD 患者按年龄、性别和索引日期与 720090 例无影响对照进行匹配。其中,有 1796 例至少有 2 次 PD 诊断和至少 1 次 PD 相关处方。IBD 患者的平均(SD)年龄为 51(17)岁,其中 44%为男性。与无影响匹配对照相比,IBD 患者的 PD 发生率高出 28%(调整发病率比,1.28;95%CI,1.14-1.44;P<0.001)。与未暴露于抗 TNF 治疗的患者相比,接受抗 TNF 治疗的 IBD 患者的 PD 发生率降低了 78%(调整发病率比,0.22;95%CI,0.05-0.88;P=0.03)。
与无 IBD 的个体相比,IBD 患者的 PD 发生率更高。早期接受抗炎性 anti-TNF 治疗与 PD 发生率显著降低有关。这些发现支持全身性炎症在这两种疾病发病机制中的作用。需要进一步研究以确定在高危人群中给予抗 TNF 治疗是否可能降低 PD 风险。