Objective: To characterize the efficacy and safety of zonisamide (ZNS) in patients with dementia with Lewy bodies (DLB) with parkinsonism, we performed subgroup analysis by severity of cognitive dysfunction or BPSD in a pooled analysis of two trials.

Background: The treatment of parkinsonism in DLB requires risk management, taking cognitive function and BPSD into account. We have conducted exploratory phase 2 [1] and confirmatory phase 3 [2] trials (multicenter, randomized, double-blind, parallel-group, placebo-controlled trials) and reported that ZNS improves parkinsonism in DLB.

Method: This analysis included 498 patients, who were stratified by severity (mild, moderate, or severe) of cognitive dysfunction based on the baseline score of MMSE, and also severity of BPSD based on the baseline score of NPI-10. In terms of each efficacy variable (UPDRS part III, MMSE and NPI-10), the change from baseline at week (W) 12 of treatment with ZNS (25 or 50 mg) was calculated by severity of cognitive dysfunction or BPSD, and compared to that with placebo.

Results: In all strata of the severity of cognitive dysfunction, ZNS reduced or tended to reduce UPDRS part III score [Figure 1a]. By severity of BPSD, ZNS reduced or tended to reduce UPDRS part III score in the mild and moderate strata, with similar score reductions also in the severe stratum [Figure 1b]. In addition, the changes in the scores of MMSE by severity of cognitive dysfunction and NPI-10 by severity of BPSD did not differ between ZNS and placebo in any stratum of severity [Figure 2a, 2b].

Conclusion: The analysis indicated that ZNS is effective for parkinsonism irrespective of the severity of cognitive dysfunction or BPSD in DLB patients, without major safety concerns.

References: [1] Murata M, Odawara T, Hasegawa K, et al. Adjunct zonisamide to levodopa for DLB parkinsonism: a randomized, double‐blind phase 2 study. Neurology. 2018; 90: e664-e672. [2] Murata M, Odawara T, Hasegawa K, et al. Zonisamide improves parkinsonism in DLB patients: A randomized phase 3 trial. Mov Disord. 2018; 33 (Suppl. 2).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/effects-of-zonisamide-on-parkinsonism-in-patients-with-dementia-with-lewy-bodies-by-severity-of-cognitive-dysfunction-and-bpsd-subgroup-analysis-of-pooled-data-from-two-trials/