Mavoglurant Shows Modest Efficacy in Reducing OFF-time but no Consistent Motor Benefit in Parkinson’s Disease: A Meta-analysis of Randomized Controlled Trials
Zain Abidin1, Jamir Pitton Rissardo2, Omar Elmandouh2, Ana Leticia Fornari Caprara2, Ian M. Walker2
1Cooper Medical School of Rowan University, 2Cooper University Hospital
Objective:

To assess the efficacy of mavoglurant, a metabotropic glutamate receptor 5 (mGluR5) antagonist, on motor fluctuations and dyskinesia in Parkinson’s disease (PD).

Background:
Glutamatergic overactivity contributes to levodopa-induced dyskinesia (LID) in PD. Mavoglurant, an mGluR5 antagonist, was developed to mitigate LID and improve motor control, but trial results have been inconsistent.
Design/Methods:

We systematically searched randomized controlled trials (RCTs) evaluating mavoglurant versus placebo in PD patients with motor fluctuations or dyskinesia. Continuous outcomes were extracted and pooled using standardized mean differences (SMD) or mean differences (MD) under a random-effects model with DerSimonian–Laird estimation. Outcomes included changes in daily OFF-time, ON-time without troublesome dyskinesia, dyskinesia severity (Lang-Fahn, mAIMS), and UPDRS motor and complications scores. Heterogeneity was quantified with I² and τ², and prediction intervals were calculated. Subgroup analyses explored dose-response effects (20–300 mg).

Results:

Four trials (PMID 21484867, 23853029, 24007304, and 27214258) were included. Mavoglurant significantly reduced OFF-time compared to placebo (SMD = –0.73, 95% CI: –1.18 to –0.27, p = 0.0019), with low heterogeneity (I² = 0.8%). However, ON-time without troublesome dyskinesia showed no significant improvement (SMD = –0.10, 95% CI: –1.01 to 0.81). Dyskinesia severity improved on mAIMS (MD = –2.17, 95% CI: –3.50 to –0.85, p = 0.0013), but Lang-Fahn and UPDRS-IV changes were not significant under random-effects. Subgroup analysis suggested greater OFF-time reduction at higher doses (≥200 mg). Publication bias was minimal.

Conclusions:
Mavoglurant modestly reduces OFF-time and improves dyskinesia severity on mAIMS but does not consistently enhance ON-time or UPDRS scores. These findings highlight the limited clinical utility of mGluR5 antagonism in PD and underscore the need for alternative strategies to manage LID.
10.1212/WNL.0000000000215017
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