Indirect Comparison of Ropinirole and Pramipexole as Levodopa Adjunctive Therapy in Advanced Parkinson’s Disease: A Systematic Review and Network Meta-Analysis

  • Hongxin Zhao
  • Yi Ning
  • James Cooper
  • Rodrigo Refoios Camejo
  • Xiajun Ni
  • Bingming Yi
  • Daniel ParksEmail author



To evaluate the comparative efficacy and safety of ropinirole and pramipexole as adjunctive therapies to levodopa (l-dopa) for the management of advanced Parkinson’s disease (PD), via a systematic review and network meta-analysis.


Twenty-one double-blind randomised controlled trials of patients with advanced PD with motor fluctuations receiving l-dopa comparing ropinirole or pramipexole with comparators were identified from 2550 publications. Bayesian indirect comparison methods were applied to independently review efficacy outcomes including off-time reduction, Unified Parkinson's Disease Rating Scale-Activity of Daily Living (UPDRS-ADL) and UPDRS-motor scores, and safety outcomes including adverse events (AE) and patient withdrawals, to determine indirect treatment comparison mean differences (MD) or hazard ratios (HR) with 95% confidence intervals (CI).


The indirect efficacy comparison resulted in a statistically nonsignificant off-time reduction difference (hours) of ropinirole-sustained release (SR) versus pramipexole-immediate release (MD − 0.25; 95% CI − 0.71, 0.21) and ropinirole-SR versus pramipexole-extended release (ER) (MD 0.18; 95% CI − 0.40, 0.76). Ropinirole-SR adjunctive treatment showed a tendency towards more improvement in UPDRS-ADL score (MD 1.24; 95% CI 0.23, 2.24) than adjunctive treatment of pramipexole-ER. Pramipexole-ER may be less likely to induce somnolence as an AE compared with ropinirole-SR (HR 0.46; 95% CI 0.23, 0.89). However, there were no statistically significant differences in UPDRS-motor score reduction, incidence of dyskinesia, hallucination, hypotension, insomnia and nausea, or withdrawals due to AE, for any reason.


Adjunctive therapy with ropinirole-SR or pramipexole appears to offer similar efficacy and tolerability in patients with advanced PD on the basis of this indirect comparison.




Indirect treatment comparison Network meta-analysis Parkinson’s disease Pramipexole Ropinirole 




Funding for this study (internal study number 206707/HO-16-17237) and the journal’s article processing charges was provided by GSK.

Medical Writing and/or Editorial Assistance

Editorial support in the form of formatting text, tables and figures and grammatical editing was provided by Jennie McLean, PhD, Fishawack Indicia Ltd, UK, and funded by GSK.


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.


James Cooper is an employee of, and holds stocks/shares in GSK. Daniel Parks is an employee of, and holds stocks/shares in GSK. Rodrigo Refoios Camejo is an employee of, and holds stocks/shares in GSK. Hongxin Zhao was an employee of GSK at the time of the study and is now employed by Synyi AI, Shanghai, China. Yi Ning was an employee of GSK at the time of the study and is now employed by Meinian Institute of Health, Beijing, China and Peking University School of Public Health, Beijing, China. Xiajun Ni was an employee of GSK at the time of the study and is now employed by Eisai China Inc. Jiangsu Province, China. Bingming Yi was an employee of GSK at the time of the study and is now employed by Vertex Pharmaceuticals, Boston MA, USA

Compliance with Ethics Guidelines

This article does not contain any studies with human participants or animals performed by any of the authors.

Data Availability

Anonymised individual participant data and study documents can be requested for further research from

Supplementary material

12325_2019_938_MOESM1_ESM.docx (24 kb)
Supplementary file1 (DOCX 24 kb)


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Copyright information

© Springer Healthcare Ltd., part of Springer Nature 2019

Authors and Affiliations

  1. 1.GlaxoSmithKlineShanghaiChina
  2. 2.GlaxoSmithKlineBrentfordChina
  3. 3.GlaxoSmithKlineCollegevilleUSA

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