Dyskinesia and Pain in Advanced Parkinson's Disease: Post Hoc Analysis from the Phase 3b, Open-Label, Randomized DYSCOVER Study

Overview

Journal Neurol Ther

Publisher Springer

Specialty Neurology

Date 2024 Feb 12

PMID 38345741

Authors

Eric Freire-Alvarez

Paola Vanni

Egon Kurca

Lydia Lopez-Manzanares

Norbert Kovacs

Cleanthe Spanaki

TianMing Gao

Lars Bergmann

Olga Sanchez-Solino

Affiliations

Soon will be listed here.

Abstract

Introduction: The DYSCOVER study was a phase 3b, open-label, randomized trial (NCT02799381) that evaluated levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) in patients with Parkinson's disease (PD) and a high burden of dyskinesia at baseline (defined as Unified Dyskinesia Rating Scale [UDysRS] total score ≥ 30). At week 12, patients receiving LCIG versus OMT experienced significant improvements in dyskinesia, pain, and health-related outcomes. The objective of this analysis was to examine correlations between dyskinesia, pain, and health-related outcomes in PD.

Methods: This post hoc analysis assessed correlations between UDysRS, King's Parkinson's Disease Pain Scale (KPPS), 8-item Parkinson's Disease Questionnaire (PDQ-8), Unified Parkinson's Disease Rating Scale part II, Clinical Global Impression of Severity (CGI-S) or Change (CGI-C), and "On" time without troublesome dyskinesia at baseline and after 12 weeks of LCIG or OMT. Correlations were assessed by Pearson correlation coefficients (categorization: weak, r = 0.20-0.39; moderate, r = 0.40-0.59; strong, r ≥ 0.60).

Results: Among 61 patients, moderate-to-strong positive and significant correlations were observed between UDysRS and KPPS scores (baseline, r = 0.47; week 12 change from baseline [CFB], r = 0.63; all p < 0.001). UDysRS and KPPS scores had moderate-to-strong positive and highly significant correlations with PDQ-8 scores (baseline, r = 0.45 and 0.46, respectively; CFB, r = 0.54 and 0.64, respectively; all p < 0.001). Moderate positive and significant correlations were observed between UDysRS and CGI-S/CGI-C scores (baseline, r = 0.41; CFB, r = 0.47; all p < 0.001).

Conclusions: In patients with high dyskinesia burden, positive correlations were observed between dyskinesia, pain, and health-related quality of life (HRQoL) at baseline. Improvements in dyskinesia and pain were associated with improvements in HRQoL, demonstrating the clinical burden of troublesome dyskinesia.

Trial Registration Number: Clinicaltrials.gov identifier NCT02799381.

References

Candel-Parra E, Corcoles-Jimenez M, Delicado-Useros V, Hernandez-Martinez A, Molina-Alarcon M . Relationship between Motor and Nonmotor Symptoms and Quality of Life in Patients with Parkinson's Disease. Nurs Rep. 2022; 12(1):1-12. PMC: 8788427. DOI: 10.3390/nursrep12010001. View

Lopiano L, Modugno N, Marano P, Sensi M, Meco G, Solla P . Motor and non-motor outcomes in patients with advanced Parkinson's disease treated with levodopa/carbidopa intestinal gel: final results of the GREENFIELD observational study. J Neurol. 2019; 266(9):2164-2176. PMC: 6687881. DOI: 10.1007/s00415-019-09337-6. View

Freire-Alvarez E, Kurca E, Lopez Manzanares L, Pekkonen E, Spanaki C, Vanni P . Levodopa-Carbidopa Intestinal Gel Reduces Dyskinesia in Parkinson's Disease in a Randomized Trial. Mov Disord. 2021; 36(11):2615-2623. PMC: 9292774. DOI: 10.1002/mds.28703. View

Chaudhuri K, Antonini A, Robieson W, Sanchez-Solino O, Bergmann L, Poewe W . Burden of non-motor symptoms in Parkinson's disease patients predicts improvement in quality of life during treatment with levodopa-carbidopa intestinal gel. Eur J Neurol. 2018; 26(4):581-e43. PMC: 6590168. DOI: 10.1111/ene.13847. View

Standaert D, Rodriguez R, Slevin J, Lobatz M, Eaton S, Chatamra K . Effect of Levodopa-carbidopa Intestinal Gel on Non-motor Symptoms in Patients with Advanced Parkinson's Disease. Mov Disord Clin Pract. 2017; 4(6):829-837. PMC: 5724683. DOI: 10.1002/mdc3.12526. View

Olanow C, Kieburtz K, Odin P, Espay A, Standaert D, Fernandez H . Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol. 2013; 13(2):141-9. PMC: 4643396. DOI: 10.1016/S1474-4422(13)70293-X. View

Fernandez H, Standaert D, Hauser R, Lang A, Fung V, Klostermann F . Levodopa-carbidopa intestinal gel in advanced Parkinson's disease: final 12-month, open-label results. Mov Disord. 2014; 30(4):500-9. PMC: 4674978. DOI: 10.1002/mds.26123. View

Kovacs N, Bergmann L, Anca-Herschkovitsch M, Cubo E, Davis T, Iansek R . Outcomes Impacting Quality of Life in Advanced Parkinson's Disease Patients Treated with Levodopa-Carbidopa Intestinal Gel. J Parkinsons Dis. 2022; 12(3):917-926. PMC: 9108584. DOI: 10.3233/JPD-212979. View

Thanvi B, Lo N, Robinson T . Levodopa-induced dyskinesia in Parkinson's disease: clinical features, pathogenesis, prevention and treatment. Postgrad Med J. 2007; 83(980):384-8. PMC: 2600052. DOI: 10.1136/pgmj.2006.054759. View

10.

Ahlskog J, Muenter M . Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord. 2001; 16(3):448-58. DOI: 10.1002/mds.1090. View

11.

Antonini A, Odin P, Pahwa R, Aldred J, Alobaidi A, Jalundhwala Y . The Long-Term Impact of Levodopa/Carbidopa Intestinal Gel on 'Off'-time in Patients with Advanced Parkinson's Disease: A Systematic Review. Adv Ther. 2021; 38(6):2854-2890. PMC: 8189983. DOI: 10.1007/s12325-021-01747-1. View

12.

Othman A, Rosebraugh M, Chatamra K, Locke C, Dutta S . Levodopa-Carbidopa Intestinal Gel Pharmacokinetics: Lower Variability than Oral Levodopa-Carbidopa. J Parkinsons Dis. 2017; 7(2):275-278. PMC: 5438475. DOI: 10.3233/JPD-161042. View

13.

Goetz C, Stebbins G, Chung K, Hauser R, Miyasaki J, Nicholas A . Which dyskinesia scale best detects treatment response?. Mov Disord. 2013; 28(3):341-6. DOI: 10.1002/mds.25321. View

14.

Pechevis M, Clarke C, Vieregge P, Khoshnood B, Deschaseaux-Voinet C, Berdeaux G . Effects of dyskinesias in Parkinson's disease on quality of life and health-related costs: a prospective European study. Eur J Neurol. 2005; 12(12):956-63. DOI: 10.1111/j.1468-1331.2005.01096.x. View

15.

Slevin J, Fernandez H, Zadikoff C, Hall C, Eaton S, Dubow J . Long-term safety and maintenance of efficacy of levodopa-carbidopa intestinal gel: an open-label extension of the double-blind pivotal study in advanced Parkinson's disease patients. J Parkinsons Dis. 2015; 5(1):165-74. DOI: 10.3233/JPD-140456. View

16.

Nyholm D, Odin P, Johansson A, Chatamra K, Locke C, Dutta S . Pharmacokinetics of levodopa, carbidopa, and 3-O-methyldopa following 16-hour jejunal infusion of levodopa-carbidopa intestinal gel in advanced Parkinson's disease patients. AAPS J. 2012; 15(2):316-23. PMC: 3675750. DOI: 10.1208/s12248-012-9439-1. View

17.

Chaudhuri K, Kovacs N, Pontieri F, Aldred J, Bourgeois P, Davis T . Levodopa Carbidopa Intestinal Gel in Advanced Parkinson's Disease: DUOGLOBE Final 3-Year Results. J Parkinsons Dis. 2023; 13(5):769-783. PMC: 10473130. DOI: 10.3233/JPD-225105. View

18.

Goetz C, Nutt J, Stebbins G . The Unified Dyskinesia Rating Scale: presentation and clinimetric profile. Mov Disord. 2008; 23(16):2398-403. DOI: 10.1002/mds.22341. View

19.

Nyholm D . The rationale for continuous dopaminergic stimulation in advanced Parkinson's disease. Parkinsonism Relat Disord. 2007; 13 Suppl:S13-7. DOI: 10.1016/j.parkreldis.2007.06.005. View

20.

Chaudhuri K, Rizos A, Trenkwalder C, Rascol O, Pal S, Martino D . King's Parkinson's disease pain scale, the first scale for pain in PD: An international validation. Mov Disord. 2015; 30(12):1623-31. DOI: 10.1002/mds.26270. View