Impact of Infusion Therapies on Quality of Life in Advanced Parkinson’s Disease

Figures & data

Figure 1 A schematic representation of the onset and progression of motor and non-motor symptoms in Parkinson disease (PD). (A) Potential timeline for manifestation of non-motor features of PD. Non-motor symptoms may develop insidiously in the prodromal phase several years before onset of motor features. The duration of this prodromal phase is variable, as is the sequence of the appearance of the non-motor symptoms. Non-motor problems continue to develop throughout the course of the disease, but timing and manifestation may vary between patients. (B) Rates of development and progression of the motor and non-motor features of PD, and the decline in dopaminergic neuronal function. The rate of decline in dopaminergic function in PD may vary between patients (blue shaded section). It is estimated that motor features appear when approximately 50–60% of dopaminergic neurons have been lost (dark blue area). Non-motor features may begin with an earlier pre-motor prodrome, progress more slowly but accumulate greater disability.

Notes: Reproduced with permission from Schapira AHV, Chaudhuri KR, Jenner P. Non-motor features of Parkinson's disease. Nat Rev Neurosci. 2017;18(7):435–450; Springer Nature.¹³

Abbreviation: RBD, REM sleep behaviour disorder.

Table 1 Published Clinical Trials of Infusion Therapies in Advanced PD That Include QoL Outcomes

Author, Year	Study Type	Patients (n)	QoL Measures & Outcomes
CSAI
Drapier et al, 2016^Citation42 (OPTIPUMP)	Prospective, open-label, observational cohort, 6-month study	142 patients enrolled; 100 completed the study	QoL assessed using PDQ-39. Significant improvement in QoL observed after 6 months of CSAI treatment versus baseline.
Kimber et al, 2017^Citation43	Observational study; single center; 10-year follow-up between 2004 and 2014	36 consecutive patients	Neurologist assessment of Clinical Global Impression: benefit of CSAI on motor function and QoL rated as ‘much improved’ or better in 83% of patients.
Houvenaghel et al, 2018^Citation44	Retrospective analysis; single center; 6 month study	22 patients without cognitive impairment	QoL assessed using the 36-item Short-Form Survey (SF-36), PDQ-39 and the Clinical Global Impression Improvement (CGI-I) scale. Trend to improved overall QoL with particular improvement in physical and psychological domains.
Katzenschlager et al, 2018^Citation33 (TOLEDO double-blind phase)	Prospective, double-blind, randomized, 12-week study versus placebo	106 included in the full analysis set (n=53 per group)	QoL assessed using PDQ-8. Change in QoL between baseline and week 12 was not significantly different between treatment groups.
Katzenschlager et al, 2021^Citation45 (TOLEDO open-label phase)	Open-label, 52-week study	84 patients entered (40 previously on CSAI, 44 on placebo); 59 completed the study	No substantial changes observed in either group at any time point from the DBP baseline to the end of the OLP in PDQ-8 scores.
Fernández-Pajarín et al, 2021^Citation46	Prospective, open-label, 6-month study versus optimized medical treatment (baseline)	20 patients with advanced PD	QoL assessed using PDQ-39. PDQ-39 scores with CSAI infusion treatment reduced by 39.6% versus optimized medical treatment.
Meira et al, 2021^Citation47	Retrospective analysis over a 6-year period; single center; 2-year follow-up	110 consecutive patients	QoL assessed using PDQ-39. QoL remained stable over the 2-year follow-up period. PDQ-39 was the only baseline predictor of QoL improvement after 2 years of treatment.
Fernández-Pajarín et al, 2022^Citation48	Prospective, open-label, 6-month study	22 patients with early stage advanced PD (<3 years since advanced PD diagnosis)	QoL assessed using PDQ-39. Mean PDQ-39 score significantly reduced versus baseline.
De Cock et al, 2022^Citation29	Randomized, multicenter, double-blind, placebo-controlled, crossover trial undertaken in 11 expert centers in France	46 patients with fluctuating PD and moderate-to-severe insomnia	Mean change in PDSS score was significantly greater with night- time CSAI compared with placebo.
LCIG infusion
Antonini et al, 2008^Citation49	Prospective, open-label study with a 2-year follow-up	22 patients with advanced PD	QoL assessed using PDQ-39. LCIG treatment led to significant improvement from baseline at 2 years.
Foltynie et al, 2013^Citation50	Case series at a single UK center; 12-month follow-up	12 patients with advanced PD	QoL assessed using PDQ-39. Improvements observed in the PDQ-39 Summary Index versus baseline.
Olanow et al, 2014^Citation32 (HORIZON study)	Double-blind, randomized, controlled trial over 12 weeks	71 patients with advanced PD randomized to LCIG infusion plus placebo oral immediate-release levodopa–carbidopa (LC-IR) capsules (n=37) or to LC-IR capsules plus placebo LCIG infusion (n=34).	QoL assessed using PDQ-39 and EQ-5D. Significantly greater improvement in QoL with LCIG versus LC-IR.
Fernandez et al, 2015^Citation51	International, prospective e, open-label study over 54-weeks	272 advanced PD patients completed the study	QoL assessed using PDQ-39, EQ-5D and EQ-5D VAS. Health-related QoL measures significantly improved by week 4 and were sustained to the end of the study.
Slevin et al, 2015^Citation52 (HORIZON study)	Open-label long-term efficacy and safety study over 52 weeks	62 patients entered (33 previously on LCIG, 29 LCIG-naïve); 55 completed the study	QoL assessed using PDQ-39, EQ-5D and EQ-5D VAS. Patients already established on LCIG treatment showed sustained improvement in QoL measures.
Chang et al, 2016^Citation53	Prospective, open-label, single-center study over 12 months	15 patients with advanced PD	QoL assessed using PDQ-39. PDQ-39 Summary Index score improved by a mean of 32.5% versus baseline.
Palhagen et al, 2016^Citation54	Prospective, open-label, observational study over 3 years	77 patients (including 37 LCIG-naïve)	QoL assessed using PDQ-39. LCIG treatment led to significant improvements in motor function and QoL over 18 months in LCIG-naïve patients with no worsening in LCIG-experienced patients.
De Fabregues et al, 2017^Citation55	Observational study over 10 years	37 patients with advanced PD	QoL assessed using PDQ-39. A significant sustained improvement of 37% in PDQ-39 was observed after 3 months and up to 1 year.
Antonini et al, 2017^Citation56 (GLORIA registry)	Registry study: Global Long-term Registry: Duodopa^® in patients with Advanced PD	258 patients with advanced PD from 75 movement disorder centers in 18 countries	QoL assessed using PDQ-8. LCIG treatment led to significant improvement from baseline at 24 months.
Kruger et al, 2017^Citation57	Prospective, international, multicenter, observational study over 12 months	64 patients with advanced PD	QoL assessed using PDQ-8. LCIG treatment led to significant improvement from baseline up to 12 months.
Fernandez et al 2018^Citation58	Phase 3, open-label multinational extension study over 52 weeks	262 patients from 11 countries	Previous improvements in activities of daily living and QoL were not maintained over the course of the study.
Antonini et al, 2020^Citation59 (TANDEM study)	Observational study over 12 months	159 advanced PD patients in routine medical care	QoL assessed using PDQ-8 or PDQ-39. LCIG treatment achieved sustained improvements in QoL.
Ehlers et al, 2020^Citation60	Prospective, observational study over 6 months	12 patients with advanced PD	QoL assessed using the SEIQoL index. Significant improvements in individual QoL was observed for LCIG-treated patients.
Simu et al, 2021^Citation61 (COSMOS study)	Sub-analysis of COSMOS study data from Romania at 12 months	95 Romanian PD patients from the COSMOS cohort	QoL assessed using PDQ-8. Patients treated with LCIG monotherapy showed PDQ-8 scores comparable to those of patients on LCIG plus add-on medication.
Standaert et al, 2021^Citation62 (DUOGLOBE study)	Prospective, multinational, observational study; 1-year interim follow-up (3 years planned)	195 LCIG-naïve patients treated with LCIG as part of routine clinical practice	QoL assessed using PDQ-8. Significant improvements observed versus baseline at the interim 12-month follow-up.
LECIG infusion
Öthman et al 2021^Citation63	Observational study; single center	24 patients with advanced PD treated for a median of 305 days; followed-up every 6 months	Self-rated QoL scale of ‘improved’, ‘unchanged’, ‘worsened’, or ‘I do not know’: 62% (13/21) improved

Abbreviations: CSAI, continuous subcutaneous apomorphine infusion; DBP, Double-blind phase; LCIG, levodopa–carbidopa intestinal gel; LECIG, levodopa–carbidopa–entacapone intestinal gel; QoL, Quality of life; OLP, open-label phase; PDQ-39, Parkinson’s Disease Questionnaire 39 items; PDQ-8, Parkinson’s Disease Questionnaire short-form 8 items.

Table 2 Ongoing Studies of Infusion Therapies in Advanced PD That Include QoL Outcomes

Study	Study Type and Objectives	QoL Measures
CSAI
AGAPO: NCT03693872	An open, non-randomized, parallel group study of CSAI versus CSAI plus dopamine agonist. Objective: To at identify differences in patients’ evolution (non-motor symptoms and QoL) over the course of 6 months.	Change in PDQ-39 scores between baseline and 6 months
EARLY-PUMP: NCT02864004	Phase 3, randomized, parallel group study of CSAI versus best medical treatment for a duration of 12 months. Objective: To determine if CSAI is superior to oral medical therapy alone in terms of its impact on QoL at a relatively early stage of PD, before the appearance of severe disabling motor complications.	Change in PDQ-39 scores between baseline and 12 months
INFUS-ON: NCT02339064	Phase 3, multicenter, open-label, safety and tolerability study over 52 weeks. Objective: To assess the long-term safety and tolerability of CSAI.	Change in PDQ-39 scores between baseline and 12 months
LCIG infusion
INSIGHTS: NCT02549092	Phase 3, open-label, randomized, parallel group study of LCIG versus OMT with NMS scores as the primary outcome. Objective: To examine the effect of LCIG relative to that of OMT on NMS associated with advanced PD; QoL is a secondary outcome measure.	Change in PDQ-8 scores between baseline and 26 weeks
LECIG infusion
Global Long-Term Registry on Efficacy and Safety of LEciGon in Patients with Advanced ParkinsoN’s Disease in Routine CarE (ELEGANCE): NCT05043103	A non-interventional, observational study of LECIG infusion. Objective: To collect data on the efficacy and safety of LECIG in daily clinical practice over 24 month; QoL is a secondary outcome measure.	Change in PDQ-39 or PDQ-8 scores between baseline and 24 months
Comparative studies
INfusion VErsus STimulation in Parkinson’s Disease (INVEST): NCT02480803	Phase 4, open-label, randomized, controlled trial of LCIG versus DBS with cost-effectiveness as the primary outcome; 26 treatment period plus an extension period for completers. Objective: To compare the efficacy and cost effectiveness of LCIG versus DBS; QoL is a secondary outcome measure.	Change in PDQ-39 scores between baseline and 36 months

Abbreviations: CSAI, continuous subcutaneous apomorphine infusion; DBS, deep brain stimulation; LCIG, levodopa–carbidopa intestinal gel; LECIG, levodopa–carbidopa–entacapone intestinal gel; OMT, optimized medical therapy; QoL, Quality of life; NMS, non-motor symptoms; PDQ-39, Parkinson’s Disease Questionnaire 39 items; PDQ-8, Parkinson’s Disease Questionnaire short-form 8 items.

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