The Long-Term Impact of Levodopa/Carbidopa Intestinal Gel on ‘Off’-time in Patients with Advanced Parkinson’s Disease: A Systematic Review

TY - JOUR

T1 - The Long-Term Impact of Levodopa/Carbidopa Intestinal Gel on ‘Off’-time in Patients with Advanced Parkinson’s Disease

T2 - A Systematic Review

AU - Antonini, Angelo

AU - Odin, Per

AU - Pahwa, Rajesh

AU - Aldred, Jason

AU - Alobaidi, Ali

AU - Jalundhwala, Yash J.

AU - Kukreja, Pavnit

AU - Bergmann, Lars

AU - Inguva, Sushmitha

AU - Bao, Yanjun

AU - Chaudhuri, K. Ray

N1 - Funding Information: Financial support for the study and the journal?s Rapid Service and Open Access Fees were provided by AbbVie. AbbVie participated in study design, research, data collection, analysis and interpretation of data, writing, reviewing, and approving the publication. The authors would like to thank Niodita Gupta, who is an employee of AbbVie, for her support with data synthesis. We acknowledge editorial support in the preparation of this manuscript from Martin Gilmour, PhD, CMPP of ESP Bioscience, funded by AbbVie. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Angelo Antonini has received compensation for consultancy and speaker related activities from UCB, Bial, GE, Boehringer Ingelheim, Biogen, Theravance Biopharma, AbbVie, Zambon, Neuroderm. He also received research support from Chiesi Pharmaceuticals, Lundbeck, Horizon 2020?PD_Pal Grant 825785, Ministry of Education University and Research (MIUR) Grant ARS01_01081, Cariparo Foundation. Per Odin has received compensation 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. Rajesh Pahwa has received consulting fees from AbbVie, ACADIA, Acorda, Adamas, Cynapses, 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, Cynapses, Kyowa, National Parkinson Foundation, NIH/NINDS, Parkinson Study Group. Jason Aldred has been a consultant and received honorarium from AbbVie, Acorda, Adamas, Allergan, Boston Scientific, Teva, Medtronic, and US World Meds. He has also received research support from NINDS, Abbott, AbbVie, Acadia, Biogen, Boston Scientific, Denali, Impax/Amneal, Sunovion, Neuroderm, Novartis, and Theravance. 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. Sushmita Inguva was employed with AbbVie at the time of the study. Ali Alobaidi, Yash J Jalundhwala, Pavnit Kukreja, Yanjun Bao, Lars Bergmann are employees of AbbVie and may own stock/shares in the company. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. Data sharing is not applicable to this manuscript as no datasets were generated or analysed during the reported study. Funding Information: Angelo Antonini has received compensation for consultancy and speaker related activities from UCB, Bial, GE, Boehringer Ingelheim, Biogen, Theravance Biopharma, AbbVie, Zambon, Neuroderm. He also received research support from Chiesi Pharmaceuticals, Lundbeck, Horizon 2020—PD_Pal Grant 825785, Ministry of Education University and Research (MIUR) Grant ARS01_01081, Cariparo Foundation. Per Odin has received compensation 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. Rajesh Pahwa has received consulting fees from AbbVie, ACADIA, Acorda, Adamas, Cynapses, 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, Cynapses, Kyowa, National Parkinson Foundation, NIH/NINDS, Parkinson Study Group. Jason Aldred has been a consultant and received honorarium from AbbVie, Acorda, Adamas, Allergan, Boston Scientific, Teva, Medtronic, and US World Meds. He has also received research support from NINDS, Abbott, AbbVie, Acadia, Biogen, Boston Scientific, Denali, Impax/Amneal, Sunovion, Neuroderm, Novartis, and Theravance. 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. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/6

Y1 - 2021/6

N2 - Introduction: Levodopa/carbidopa intestinal gel (LCIG; carbidopa/levodopa enteral suspension) has been widely used and studied for the treatment of motor fluctuations in levodopa-responsive patients with advanced Parkinson’s disease (PD) when other treatments have not given satisfactory results. Reduction in ‘off’-time is a common primary endpoint in studies of LCIG, and it is important to assess the durability of this response. This systematic literature review was conducted to qualitatively summarise the data on the long-term effects of LCIG therapy on ‘off’-time. Methods: Studies were identified by searching PubMed, EMBASE and Ovid on 30 September 2019. Studies were included if they reported on patients with PD, had a sample size of ≥ 10, LCIG was an active intervention and ‘off’-time was reported for ≥ 12 months after initiation of LCIG treatment. Randomised clinical trials, retrospective and prospective observational studies, and other interventional studies were included for selection. Data were collected on: ‘off’-time (at pre-specified time periods and the end of follow-up), study characteristics, Unified Parkinson’s Disease Rating Scale (UPDRS) II, III and IV total scores, dyskinesia duration, quality of life scores, non-motor symptoms and safety outcomes. Results: Twenty-seven studies were included in this review. The improvement in ‘off’-time observed shortly after initiating LCIG was maintained and was statistically significant at the end of follow-up in 24 of 27 studies. ‘Off’-time was reduced from baseline to end of follow-up by 38–84% and was accompanied by a clinically meaningful improvement in quality of life. Stratified analysis of ‘off’-time demonstrated mean relative reductions of 47–82% at 3–6 months and up to 83% reduction at 3–5 years of follow-up. Most studies reported significant improvements in activities of daily living and motor complications. Most frequent adverse events were related to the procedure or the device. Conclusion: In one of the largest qualitative syntheses of published LCIG studies, LCIG treatment was observed to provide a durable effect in reducing ‘off’-time. Infographic: [Figure not available: see fulltext.] [MediaObject not available: see fulltext.]

AB - Introduction: Levodopa/carbidopa intestinal gel (LCIG; carbidopa/levodopa enteral suspension) has been widely used and studied for the treatment of motor fluctuations in levodopa-responsive patients with advanced Parkinson’s disease (PD) when other treatments have not given satisfactory results. Reduction in ‘off’-time is a common primary endpoint in studies of LCIG, and it is important to assess the durability of this response. This systematic literature review was conducted to qualitatively summarise the data on the long-term effects of LCIG therapy on ‘off’-time. Methods: Studies were identified by searching PubMed, EMBASE and Ovid on 30 September 2019. Studies were included if they reported on patients with PD, had a sample size of ≥ 10, LCIG was an active intervention and ‘off’-time was reported for ≥ 12 months after initiation of LCIG treatment. Randomised clinical trials, retrospective and prospective observational studies, and other interventional studies were included for selection. Data were collected on: ‘off’-time (at pre-specified time periods and the end of follow-up), study characteristics, Unified Parkinson’s Disease Rating Scale (UPDRS) II, III and IV total scores, dyskinesia duration, quality of life scores, non-motor symptoms and safety outcomes. Results: Twenty-seven studies were included in this review. The improvement in ‘off’-time observed shortly after initiating LCIG was maintained and was statistically significant at the end of follow-up in 24 of 27 studies. ‘Off’-time was reduced from baseline to end of follow-up by 38–84% and was accompanied by a clinically meaningful improvement in quality of life. Stratified analysis of ‘off’-time demonstrated mean relative reductions of 47–82% at 3–6 months and up to 83% reduction at 3–5 years of follow-up. Most studies reported significant improvements in activities of daily living and motor complications. Most frequent adverse events were related to the procedure or the device. Conclusion: In one of the largest qualitative syntheses of published LCIG studies, LCIG treatment was observed to provide a durable effect in reducing ‘off’-time. Infographic: [Figure not available: see fulltext.] [MediaObject not available: see fulltext.]

KW - Advanced Parkinson’s disease

KW - LCIG

KW - Long-term

KW - ‘Off’-time

UR - http://www.scopus.com/inward/record.url?scp=85106283817&partnerID=8YFLogxK

U2 - 10.1007/s12325-021-01747-1

DO - 10.1007/s12325-021-01747-1

M3 - Review article

C2 - 34018146

AN - SCOPUS:85106283817

SN - 0741-238X

VL - 38

SP - 2854

EP - 2890

JO - ADVANCES IN THERAPY

JF - ADVANCES IN THERAPY

IS - 6

ER -