Objective: Evaluate the comparative efficacy of treatment options for Parkinson’s disease (PD) motor complications using indirect treatment comparison.

Background: Amantadine delayed release/extended release (DR/ER) capsules [1] and Deep Brain Stimulation (DBS) are effective, FDA-approved/FDA-authorized treatments for PD motor complications, reducing both OFF time and dyskinesia. Other therapies for adjunctive use with levodopa effectively reduce OFF time in PD patients but may worsen dyskinesia. No published studies directly compare the efficacy of treatments for motor complications.

Method: We compared efficacy data from pivotal clinical trials for approved levodopa-adjunctive treatments, including the MAO-B inhibitor safinamide,[2] the A2A antagonist istradefylline,[3] the dopamine agonist rotigotine,[4] the COMT inhibitor opicapone,[5] amantadine DR/ER,[1] and DBS, as well as levodopa/carbidopa ER[6] and intestinal gel (CLIG).[7] Baseline data were extracted from treatment and placebo arms, and LS mean (or mean) treatment differences in PD diary states (OFF and ON with Troublesome Dyskinesia) were obtained either directly, or calculated from active and placebo arms, relative to baseline. The magnitude of effect for each treatment was computed as a percentage for comparison.

Results: While there are demographic differences across samples, trials generally included patients, on average, within 7 to 12 years of PD diagnosis, using 600-950 mg/day levodopa and experiencing 6 to 10 hours of daily motor complications. DBS reduced OFF time by 44% and dyskinesia by 54%. Amantadine DR/ER reduced OFF time by 36% and dyskinesia by 30%. Oral dopaminergic treatments and CLIG reduced OFF time by 15-29%, with a non-statistically significant 12-31% increase in dyskinesia for the oral treatments, and no significant impact on dyskinesia for CLIG.

Conclusion: DBS and amantadine DR/ER capsules each significantly reduced OFF time and dyskinesia by over 30%. Dopaminergic treatments (studied in trials that specifically excluded dyskinetic patients) modestly improved OFF time (15-29%) while worsening dyskinesia. These results can be applied to cost effectiveness analyses across the variable spectrum of OFF and dyskinesia time in PD patients, consistent with product labeling.

References: [1] Gocovri (amantadine) extended release capsules (prescribing information). Emeryville, CA: Adamas Pharmaceuticals, Inc.; 1/2020. [2] Xadago (safinamide) tablets (U.S. prescribing information). Louisville, KY: US Worldmeds, LLC.; 3/2017. [3] Nourianz (istradefylline) tablets (prescribing information). Bedminster, NJ: Kyowa Kirin, Inc.; 5/2020. [4] Neupro (rotigotine transdermal system) (U.S. Prescribing Information). Smyrna, GA: UCB, Inc.; 4/2020. [5] Ongentys (opicapone) capsules (prescribing information). San Diego, CA: Neurocrine Biosciences, Inc.; 4/2020. [6] Rytary (carbidopa and levodopa) extended-release capsules (prescribing information). Bridgewater, NJ: Amneal Pharmaceuticals LLC; 12/2019. [7] Duopa (carbidopa and levodopa) enteral suspension (prescribing information). North Chicago, IL: AbbVie Inc.; 5/2020.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/indirect-treatment-comparison-of-adjunctive-treatments-for-patients-with-parkinsons-disease-experiencing-motor-complications/