Fabbri Margherita, Zibetti Maurizio, Calandra-Buonaura Giovanna, Contin Manuela, Sambati Luisa, Mohamed Susan, Romagnolo Alberto, Berchialla Paola, Imbalzano Gabriele, Giannini Giulia, Rizzone Mario G, Artusi Carlo Alberto, Cortelli Pietro, Lopiano Leonardo
Department of Neuroscience "Rita Levi Montalcini" University of Torino Turin Italy.
Department of Neurosciences, Clinical Investigation Center CIC 1436, Parkinson Toulouse Expert Centre, NS-Park/FCRIN Network and Neuro Toul COEN Centre; Toulouse University Hospital; INSERM University of Toulouse 3 Toulouse France.
Mov Disord Clin Pract. 2020 Sep 18;7(8):930-939. doi: 10.1002/mdc3.13068. eCollection 2020 Nov.
Levodopa-carbidopa intestinal gel (LCIG) treatment has shown variable effect on dyskinesia in Parkinson's disease (PD).
To identify PD patients who are likely to have troublesome dyskinesia under LCIG treatment and describe the pharmacokinetic-dynamic profile and dyskinesia phenomenology of those patients.
PD patients were assessed for clinical and therapeutic variables, before LCIG treatment () and at last outpatient visit (). Sub-groups of patients with and without "troublesome dyskinesia" (UPDRS IV, item 33 ≥2), matched for disease and LCIG treatment duration, underwent a pharmacokinetic-dynamic assessment.
We included 53 PD patients. After a mean of 51.7 ± 34.1 months of LCIG treatment, "off-time" was significantly reduced, whereas, dyskinesia duration/disability did not change. The multivariate regression model, adjusted for LCIG treatment duration, showed that being female increases the risk of presenting troublesome dyskinesia at (odds ratio [OR] = 9.2; 95% confidence interval [CI] = 2.4-37.4) that was also significantly associated to longer off periods at (OR= 4.4; 95% CI = 1.1-14.3). Female patients showed a higher risk for a higher dyskinesia score at (sum of the items 32 and 33: = 0.001). Patients with troublesome dyskinesia showed a tendency for a lower motor benefit and the appearance of more severe dyskinesia despite similar levodopa plasma concentration.
Dyskinesia should be carefully monitored in patients undergoing LCIG, with particular caution for female patients. Whether combined clinical and pharmacodynamic assessments could be helpful to manage patients with troublesome dyskinesia under LCIG treatment needs further evaluation in a larger group of patients.
左旋多巴-卡比多巴肠凝胶(LCIG)治疗对帕金森病(PD)的异动症疗效不一。
识别在LCIG治疗下可能出现严重异动症的PD患者,并描述这些患者的药代动力学-药效学特征及异动症表现。
对PD患者在LCIG治疗前()和最后一次门诊就诊时()进行临床和治疗变量评估。将疾病和LCIG治疗时长相匹配的有和没有“严重异动症”(统一帕金森病评定量表IV部分,第33项≥2)的患者亚组进行药代动力学-药效学评估。
我们纳入了53例PD患者。在平均51.7±34.1个月的LCIG治疗后,“关期”显著缩短,而异动症持续时间/功能障碍未改变。经LCIG治疗时长校正的多因素回归模型显示,女性在时出现严重异动症的风险增加(优势比[OR]=9.2;95%置信区间[CI]=2.4 - 37.4),这也与时更长的“关期”显著相关(OR = 4.4;95% CI = 1.1 - 14.3)。女性患者在时异动症评分更高的风险也更高(第32项和第33项之和:=0.001)。有严重异动症的患者尽管左旋多巴血药浓度相似,但运动获益倾向较低且出现更严重的异动症。
接受LCIG治疗的患者应密切监测异动症,女性患者尤其要谨慎。联合临床和药效学评估对管理接受LCIG治疗的严重异动症患者是否有帮助,需要在更大规模的患者群体中进一步评估。