Long-term results of carbidopa/levodopa enteral suspension across the day in advanced Parkinson's disease: Post-hoc analyses from a large 54-week trial.

Introduction: Carbidopa/levodopa enteral suspension (CLES) previously demonstrated reduction in total daily OFF from baseline by over 4 hours in advanced Parkinson's disease patients across 54 weeks. Evidence on CLES's long-term effectiveness on patterns of motor-symptom control throughout the day remains limited.
Methods: We present post-hoc analyses of a large, open-label study of CLES monotherapy (N = 289). Diary data recorded patients' motor states at 30-minute intervals over 3 days at baseline and weeks 4, 12, 24, 36, and 54. Adjusted generalized linear mixed models assessed changes from baseline at each timepoint for four outcome measures: time to ON without troublesome dyskinesia (ON-woTD) after waking, motor-symptom control as measured by motor states' durations throughout the day, number of motor-state transitions, and presence of extreme fluctuations (OFF to ON with TD).
Results: Patients demonstrated short-term (wk4) and sustained (wk54) improvement in all outcomes compared to baseline. At weeks 4 and 54, patients were more likely to reach ON-woTD over the course of their day (HR: 1.86 and 2.51, both P < 0.0001). Across 4-hour intervals throughout the day, patients also experienced increases in ON-woTD (wk4: 58-65 min; wk54: 60-78 min; all P < 0.0001) and reductions in OFF (wk4: 50-61 min; wk54: 56-68 min; all P < 0.0001). At weeks 4 and 54, patients' motor-state transitions were reduced by about half (IRR: 0.53 and 0.49, both P < 0.0001), and fewer patients experienced extreme fluctuations (OR: 0.22 and 0.15, both P < 0.0001).
Conclusion: CLES monotherapy was associated with significant long-term reductions in motor-state fluctuations, faster time to ON-woTD upon awakening, and increased symptom control throughout the day.
Competing Interests: The authors declare the following relationships, which may be considered as potential competing interests: 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, and 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. Aristide Merola has received support from the NIH (KL2 TR001426) and speaker or consultancy honoraria from CSL Behring, AbbVie, Abbott, and Cynapsus Therapeutics. He has received grant support from Lundbeck and AbbVie. Prasanna L. Kandukuri, Yanjun Bao, Omar Ladhani, and Connie H. Yan are employees of AbbVie and may own stocks/shares in the company. Niodita R. Gupta is a former employee of AbbVie, currently employed by Johnson and Johnson, and may hold AbbVie stock. Vivek S. Chaudhari is a former employee of AbbVie, currently employed by EMD Serono, Inc. and may hold AbbVie stock. Emi Terasawa, Viviana Garcia-Horton, and David R. Steffen are employees of Analysis Group, Inc., which has received consultancy fees from AbbVie. Stuart H. Isaacson has received honoraria for CME, consultant, research grants, and/or promotional speaker on behalf of: AbbVie, Acadia, Acorda, Adamas, Addex, Allergan, Amarantus, Axovant, Benevolent, Biogen, Britannia, Cerecor, Eli Lilly, Enterin, GE Healthcare, Global Kinetics, Impax, Intec Pharma, Ipsen, Jazz, Kyowa, Lundbeck, Michael J. Fox Foundation, Neurocrine, Neuroderm, Parkinson’s Study Group, Pharma2B, Roche, Sanofi, Sunovion, Teva, Theravance, UCB, US World Meds, and Zambon.
(© 2022 The Author(s).)