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What Effects Might Exenatide have on Non-Motor Symptoms in Parkinson's Disease: A Post Hoc Analysis

Athauda, D; Maclagan, K; Budnik, N; Zampedri, L; Hibbert, S; Skene, SS; Chowdhury, K; ... Foltynie, T; + view all (2018) What Effects Might Exenatide have on Non-Motor Symptoms in Parkinson's Disease: A Post Hoc Analysis. Journal of Parkinson's Disease , 8 (2) pp. 247-258. 10.3233/JPD-181329. Green open access

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Abstract

Background: Exenatide is a GLP-1 receptor agonist that was recently studied for potential disease-modifying effects in a randomised, placebo-controlled clinical trial in patients with moderate stage Parkinson’s disease, and showed positive effects on the motor severity of the disease which were sustained 12 weeks beyond the period of exenatide exposure. Analysis of pre-defined secondary outcomes revealed no statistically significant differences between patients treated with exenatide in total non-motor symptom burden and overall quality of life measures. Objective: The response of individual non-motor symptoms to an intervention may vary and thus this post hoc analysis was conducted to explore the possible effects of exenatide compared to placebo on individual non-motor symptoms. Results: Compared to placebo, patients treated with exenatide-once weekly had greater improvements in individual domains assessing mood/depression across all observer-rated outcome measures after 48 weeks including the “mood/apathy” domain of the NMSS, – 3.3 points (95% CI – 6.2, – 0.4), p = 0.026; the “mood” score (Q1.3+Q1.4 of the MDS-UPDRS Part 1), – 0.3 points (95% CI – 0.6, – 0.1), p = 0.034; and a trend in the MADRS total score, – 1.7 points (95% CI – 3.6, 0.2), p = 0.071. In addition, there was an improvement in the “emotional well-being” domain of the PDQ-39 of 5.7 points ((95% CI – 11.3, – 0.1), p = 0.047 though these improvements were not sustained 12 weeks after exenatide withdrawal. At 48 weeks these changes were of a magnitude that would be subjectively meaningful to patients and were not associated with changes in motor severity or other factors, suggesting exenatide may exert independent effects on mood dysfunction. Conclusions: These exploratory findings will contribute to the design of future trials to confirm the extent of motor and non-motor symptom effects of exenatide in larger cohorts of patients.

Type: Article
Title: What Effects Might Exenatide have on Non-Motor Symptoms in Parkinson's Disease: A Post Hoc Analysis
Open access status: An open access version is available from UCL Discovery
DOI: 10.3233/JPD-181329
Publisher version: http://doi.org/10.3233/JPD-181329
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Parkinson’s disease, exenatide, non-motor symptoms, clinical trial, GLP-1 agonist
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst of Clinical Trials and Methodology > Comprehensive CTU at UCL
URI: http://discovery.ucl.ac.uk/id/eprint/10052627
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