title: Levodopa-carbidopa intestinal gel in advanced Parkinson's disease: final 12-month, open-label results.
abstract: Motor complications in Parkinson's disease (PD) are associated with long-term oral levodopa treatment and linked to pulsatile dopaminergic stimulation. L-dopa-carbidopa intestinal gel (LCIG) is delivered continuously by percutaneous endoscopic gastrojejunostomy tube (PEG-J), which reduces L-dopa-plasma-level fluctuations and can translate to reduced motor complications. We present final results of the largest international, prospective, 54-week, open-label LCIG study. PD patients with severe motor fluctuations (>3 h/day "off" time) despite optimized therapy received LCIG monotherapy. Additional PD medications were allowed >28 days post-LCIG initiation. Safety was the primary endpoint measured through adverse events (AEs), device complications, and number of completers. Secondary endpoints included diary-assessed off time, "on" time with/without troublesome dyskinesia, UPDRS, and health-related quality-of-life (HRQoL) outcomes. Of 354 enrolled patients, 324 (91.5%) received PEG-J and 272 (76.8%) completed the study. Most AEs were mild/moderate and transient; complication of device insertion (34.9%) was the most common. Twenty-seven (7.6%) patients withdrew because of AEs. Serious AEs occurred in 105 (32.4%), most commonly complication of device insertion (6.5%). Mean daily off time decreased by 4.4 h/65.6% (P < 0.001). On time without troublesome dyskinesia increased by 4.8 h/62.9% (P < 0.001); on time with troublesome dyskinesia decreased by 0.4 h/22.5% (P = 0.023). Improvements persisted from week 4 through study completion. UPDRS and HRQoL outcomes were also improved throughout. In the advanced PD population, LCIG's safety profile consisted primarily of AEs associated with the device/procedure, l-dopa/carbidopa, and advanced PD. LCIG was generally well tolerated and demonstrated clinically significant improvements in motor function, daily activities, and HRQoL sustained over 54 weeks.
authors.affiliation: Center for Neurological Restoration, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Hubert H
authors.initials: HH
authors.lastname: Fernandez
authors.forename: David G
authors.initials: DG
authors.lastname: Standaert
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.forename: Victor S C
authors.initials: VS
authors.lastname: Fung
authors.forename: Fabian
authors.initials: F
authors.lastname: Klostermann
authors.forename: Mark F
authors.initials: MF
authors.lastname: Lew
authors.forename: Per
authors.initials: P
authors.lastname: Odin
authors.forename: Malcolm
authors.initials: M
authors.lastname: Steiger
authors.forename: Eduard Z
authors.initials: EZ
authors.lastname: Yakupov
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chouinard
authors.forename: Oksana
authors.initials: O
authors.lastname: Suchowersky
authors.forename: Jordan
authors.initials: J
authors.lastname: Dubow
authors.forename: Coleen M
authors.initials: CM
authors.lastname: Hall
authors.forename: Krai
authors.initials: K
authors.lastname: Chatamra
authors.forename: Weining Z
authors.initials: WZ
authors.lastname: Robieson
authors.forename: Janet A
authors.initials: JA
authors.lastname: Benesh
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Espay
mesh_terms: D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D002230:Carbidopa / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D005782:Gels / Q000627:therapeutic use; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000502:physiology*; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D004338:Drug Combinations; D005782:Gels; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D002230:Carbidopa
keywords: dyskinesia; infusion; levodopa-carbidopa intestinal gel; percutaneous endoscopic gastrojejunostomy; “off” time