Diurnal‐Only Foslevodopa/Foscarbidopa

Foslevodopa/Foscarbidopa (LDp/CDp) is a continuous subcutaneous infusion approved for 24-h use, supported by clinical trials demonstrating a significant reduction in motor complications associated with Parkinson's disease (PD).1, 2 Real-world data demonstrates that a sizeable proportion of patients discontinue treatment due to skin-related complications or behavioral effects of high-dose levodopa, emphasizing the need for customized infusion regimens.3 Of 61 LDp/CDp patients initiated, we report the clinical experience of four men and one woman (aged 55–86 years, PD duration 12–19 years) whose motor, psychiatric, and/or skin complications associated with 24-h LDp/CDp resolved with diurnal-only delivery. Patients initiated LDp/CDp at their levodopa equivalent daily dose (LEDD), calculated according to the product monograph (Table 1). Nocturnal rates were 29–63% lower than diurnal rates. Optimization of LDp/CDp ranged from 2 to 9 weeks. Patient 1 developed severe morning OFF, troublesome dyskinesia, insomnia, infusion-site nodules, and worsening anxiety. Patient 2 developed profound OFF with freezing of gait, new-onset paranoia and hallucinations, and one case of infusion-site cellulitis (ISC) requiring intravenous antibiotics. Patient 3 experienced troublesome dyskinesia and four episodes of ISC requiring oral antibiotics. Patient 4 experienced persistent motor fluctuations and four episodes of ISC requiring oral antibiotics. Patient 5 reported poor motor benefit, re-emerging hallucinations, and worsening RBD and vivid nightmares. Re-education about skin hygiene and daily cannula repositioning provided minimal improvement. Given the association between adverse effects and overnight infusion, a trial of diurnal-only delivery was undertaken as opposed to discontinuation. While offered, patients preferred not to pursue alternative device-aided therapies. To mitigate morning akinesia after overnight cessation, oral levodopa was taken upon awakening. LDp/CDp was then infused for 11.5–14 h daily, with 200–983 mg of oral levodopa. Patient 1 achieved full-day ON without troublesome dyskinesia, normalized sleep, resolution of nodules, and improved anxiety. For Patient 2, diurnal-only infusion eliminated psychosis and resulted in more consistent ON time, with no recurrence of ISC. Patient 3's troublesome dyskinesia resolved and there was no recurrence of ISC. Patient 4 experienced enhanced motor benefit with no recurrence of ISC. Patient 5 also reported improved motor benefit, and resolution of hallucinations and troublesome overnight symptoms. Our experience suggests that diurnal-only LDp/CDp—analogous to the infusion typically used for levodopa intestinal gel—may reduce complications associated with 24-h delivery, while maintaining motor benefit. Infusion-site reactions and neuropsychiatric complications are leading causes of LDp/CDp cessation in real-world use.3, 4 Previously proposed strategies to manage neuropsychiatric effects include reducing nocturnal rates or infusion duration.5 Our experience adds practical insight by describing a rescue strategy of diurnal-only LDp/CDp in patients who developed significant complications with overnight infusion and otherwise would have discontinued therapy. Our approach ultimately resulted in retaining LDp/CDp and is still working 4–14 months after its implementation. Diurnal-only LDp/CDp with oral levodopa may provide a favorable balance between benefit and safety in high-risk patients. Limitations include small sample size, absent MDS-UPDRS assessments, and above-average LDp/CDp dosing. Although neuropsychiatric complications resolved after stopping LDp/CDp overnight, the possible contribution of concomitant agents cannot be overlooked. Clinicians may consider flexible infusion schedules to balance efficacy and tolerability. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique. A.M.: 1B, 1C, 3A. Y.Y.P.: 1B, 3B. G.K.: 1A, 1C, 3B. A.F.: 1A, 1B, 3B. Ethical Compliance Statement: This retrospective chart review study has been approved by the University Health Network Ethical Review Board (UHN #25–6064). Informed consent was obtained. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflict of Interest: AM has nothing to report. YYP has nothing to report. GK has nothing to disclose. AF has received financial support from Abbvie, the manufacturer of LDp/CDp. Financial Disclosures for the Previous 12 Months: AM has nothing to report. YYP has nothing to report. GK has received honoraria from Ipsen pharmaceuticals. AF has stock ownership in Inbrain Pharma and has received payments as consultant and/or speaker from Abbvie, Abbott, Boston Scientific, Ceregate, Dompé Farmaceutici, Inbrain Neuroelectronics, Ipsen, Medtronic, Iota, Syneos Health, Merz, Sunovion, Paladin Labs, UCB, Sunovion. He has received research support from Abbvie, Boston Scientific, Medtronic, Praxis, ES and receives royalties from Springer. Author disclosures are available in the Supporting Information. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Data S1.COI_disclosure. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. 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