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

Rajesh Pahwa; Jason Aldred; Aristide Merola; Niodita Gupta; Emi Terasawa; Viviana Garcia-Horton; David R Steffen; Prasanna L Kandukuri; Yanjun Bao; Omar Ladhani; Connie H Yan; Vivek Chaudhari; Stuart H Isaacson

doi:10.1016/j.prdoa.2022.100181

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

Clin Park Relat Disord. 2022 Dec 20:8:100181. doi: 10.1016/j.prdoa.2022.100181. eCollection 2023.

Authors

Rajesh Pahwa¹, Jason Aldred², Aristide Merola³, Niodita Gupta⁴, Emi Terasawa⁵, Viviana Garcia-Horton⁵, David R Steffen⁵, Prasanna L Kandukuri⁴, Yanjun Bao⁴, Omar Ladhani⁴, Connie H Yan^{4

6}, Vivek Chaudhari⁴, Stuart H Isaacson⁷

Affiliations

¹ University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
² Selkirk Neurology & Inland Northwest Research, PLLC, 610 S Sherman Suite 201, Spokane, WA 99202, USA.
³ Ohio State University, Wexner Medical Center, 480 Medical Center Drive, Columbus, OH 43210, USA.
⁴ AbbVie, Inc., 1 N. Waukegan Road, North Chicago, IL 60064, USA.
⁵ Analysis Group, Inc., 151 West 42nd Street, 23rd Floor, New York, NY 10036, USA.
⁶ University of Illinois at Chicago, 833 S. Wood Street, Chicago, IL 60612, USA.
⁷ Parkinson's Disease and Movement Disorders Center, 951 NW 13th St, Boca Raton, FL 33486, USA.

Abstract

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.

Keywords: ADL, Activities of daily living; APD, Advanced Parkinson's disease; CGI-S, Clinical Global Impression of disease severity; CLES, Carbidopa/levodopa enteral suspension; Carbidopa/levodopa enteral suspension; Carbidopa/levodopa intestinal gel; Duodopa; Duopa; Dyskinesia; HR, Hazard ratio; IRR, Incidence rate ratio; Long-term effectiveness; OFF, “Off” time; ON, “On” time; ON-wTD, “On” time with troublesome dyskinesia; ON-woTD, “On” time without troublesome dyskinesia; OR, Odds ratio; PD, Parkinson’s disease; PEG-J, Percutaneous endoscopic gastrojejunostomy; Parkinson’s disease; QoL, Quality of life; RCT, Randomized controlled trial; SD, Standard deviation.