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. 2022 Dec;36(12):1269-1283.
doi: 10.1007/s40263-022-00963-9. Epub 2022 Nov 21.

Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis

Angelo Antonini  1 , Rajesh Pahwa  2 , Per Odin  3 , Stuart H Isaacson  4 , Aristide Merola  5 , Lin Wang  6   7 , Prasanna L Kandukuri  6 , Ali Alobaidi  6   8 , Connie H Yan  6   8 , Yanjun Bao  6 , Cindy Zadikoff  6 , Juan Carlos Parra  6 , Lars Bergmann  6 , K Ray Chaudhuri  9
Affiliations

Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis

Angelo Antonini et al. CNS Drugs. 2022 Dec.

Abstract

Introduction: Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson's disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD.

Methods: A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson's Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson's Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness.

Results: A total of 22 studies fulfilled the inclusion criteria (n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5-70.9 years, duration of PD was 9.1-15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT (p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL.

Conclusions: This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy.

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Conflict of interest statement

Angelo Antonini has received compensation for consultancy and speaker-related activities from UCB, Boehringer Ingelheim, Britannia, AbbVie, Kyowa Kirin, Zambon, Bial, Neuroderm, Theravance Biopharma, Roche. He receives research support from Chiesi Pharmaceuticals, Lundbeck, Bial, Horizon2020 Grant 825785, Horizon2020 Grant 101016902, Ministry of Education University and Research (MIUR) Grant ARS01_01081, Cariparo Foundation. He serves as consultant for Boehringer–Ingelheim for legal cases on pathological gambling. Rajesh Pahwa has received consulting fees from AbbVie, ACADIA, Acorda, Adamas, Cynapsus, Global Kinetics, Lundbeck, Neurocrine, Pfizer, Sage, Sunovion, Teva Neuroscience and US World Meds. He has received research grants from AbbVie, Adamas, Avid, Biotie, Boston Scientific, Civitas, Cynapsus, Kyowa, National Parkinson Foundation, NIH/NINDS, Parkinson Study Group. Per Odin has received compensations for consultancy and speaker-related activities from AbbVie, Bial, Britannia, Ever Pharma, Lobsor, Nordic Infucare, Stada, and Zambon. He has received royalties from Uni-Med Verlag. Stuart Isaacson has received honoraria for CME, consultant, research grants, and/or promotional speaker on behalf of AbbVie, Acadia, Acorda, Adamas, Addex, Affiris, Alexva, Allergan, Amarantus, Amneal, Aptinyx, Axial, Axovant, Benevolent, Biogen, Britannia, Cadent, Cala, Cerecor, Cerevel, Cipla, Eli Lilly, Enterin, GE Healthcare, Global Kinetics, Impax, Impel, Intec Pharma, Ipsen, Jazz, Kyowa, Lundbeck, Merz, Michael J. Fox Foundation, Mitsubishi Tanabe, Neuralys, Neurocrine, Neuroderm, Parkinson Study Group, Pharma2B, Prilenia, Promentis, Revance, Roche, Sanofi, Sunovion, Sun Pharma, Supernus, Teva, Theravance, UCB. Aristide Merola has received grant support from the NIH (KL2 TR001426). He has received speaker honoraria or advisory board honoraria from CSL Behring, AbbVie, Abbott, Medtronic, Theravance, and Cynapsus Therapeutics. He has received grant support from Lundbeck and AbbVie. Lin Wang, Lakshmi P. Kandukuri, Ali Alobaidi, Yanjun Bao, Cindy Zadikoff, Juan Carlos Parra, Lars Bergmann, and Connie H. Yan are employees of AbbVie and may own stocks/shares in the company. K. Ray Chaudhuri has received educational funding from UCB, and honoraria for sponsored symposia from UCB, AbbVie, Britannia, US Worldmeds, Otsuka, Medtronic, Zambon and acted as a consultant for AbbVie, UCB, Britannia, Medtronic, and Mundipharma.

Figures

Fig. 1
Fig. 1
PRISMA flow chart showing identification and selection of studies
Fig. 2
Fig. 2
Mean (95% CI) off-time reduction (h/day) with the three device-aided therapies versus best medical treatment. The analysis adjusted for baseline age, sex, disease duration, levodopa daily dose, and off-time. BMT best medical therapy, CSAI continuous subcutaneous apomorphine infusion, DBS deep brain stimulation, LCIG levodopa/carbidopa intestinal gel
Fig. 3
Fig. 3
Ranking of device-aided therapy and best medical therapy based on improvements in off-time at 6 months
Fig. 4
Fig. 4
Mean (95% CI) Parkinson’s disease-specific quality of life improvement (according to PDQ-39/PDQ-8 score) with the three device-aided therapies versus best medical treatment. The analysis adjusted for baseline age, sex, disease duration, levodopa daily dose, and off-time. BMT best medical therapy, CSAI continuous subcutaneous apomorphine infusion, DBS deep brain stimulation, LCIG levodopa/carbidopa intestinal gel, PDQ Parkinson’s Disease Questionnaire
Fig. 5
Fig. 5
Ranking of device-aided therapy and best medical therapy based on improvement in Parkinson’s disease-related quality of life at 6 months
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