Efficacy and Safety of Mavoglurant (AFQ056) for Levodopa-Induced Dyskinesia in Parkinson’s Disease: A Systematic Review and Meta-analysis

Background: Glutamatergic overactivity mediated by metabotropic glutamate receptor 5 (mGluR5) is implicated in levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD). Mavoglurant (AFQ056), a selective mGluR5 antagonist, has shown inconsistent efficacy across clinical trials. We conducted a systematic review and meta-analysis to evaluate its efficacy and safety in PD patients with LID. Methods: Randomized controlled trials (RCTs) comparing mavoglurant with placebo in patients with PD and LID were systematically identified. Outcomes were pooled using random-effects models. Primary outcome was dyskinesia severity measured by the modified Abnormal Involuntary Movement Scale (mAIMS). Secondary outcomes included daily OFF-time, ON-time without troublesome dyskinesia, Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS), Unified Parkinson’s Disease Rating Scale (UPDRS) Parts III and IV, and safety outcomes. PROSPERO (CRD420261446524). Results: Four publications reporting six RCTs involving 485 participants were included. Mavoglurant significantly improved mAIMS scores compared with placebo (MD −2.43, 95% CI −3.79 to −1.07; p < 0.001). No significant benefits were observed for daily OFF-time (MD −0.27 h/day, 95% CI −0.79 to 0.24), ON-time without troublesome dyskinesia, total ON-time, LFADLDS, UPDRS Part III, or total UPDRS-IV (MD −0.33, 95% CI −0.70 to 0.04). Improvement was observed for UPDRS-IV Item 32 (duration of dyskinesia) (MD −0.35, 95% CI −0.66 to −0.04). Conclusion: Mavoglurant provides modest improvement in dyskinesia severity as measured by the mAIMS but does not consistently improve motor fluctuations, motor function, or overall dyskinesia-related disability. Its limited efficacy and increased adverse-event risk suggest restricted clinical utility for LID management in PD.