Switching Gears: From Intrajejunal Levodopa to Subcutaneous Foslevodopa

By providing continuous infusion through a percutaneous endoscopic gastrostomy with a jejunal tube (PEG-J), levodopa/carbidopa intestinal gel (LCIG; Duopa®/Duodopa®, Abbvie–Chicago, IL, US) was introduced to address the issue of dyskinesias and motor fluctuations in Parkinson's disease (PD). However, LCIG use is limited by surgical risks such as infections and tube complications. A more recent non-invasive option is the subcutaneous infusion of foslevodopa/foscarbidopa (SCpLD; Vyalev®/Produodopa®, Abbvie),1 which has been shown to provide stable plasma levels and good motor outcomes in clinical trials.2, 3 This study reports the first clinical experience of three consecutive PD patients undergoing the transition from LCIG to SCpLD. After receiving LCIG treatment for 1.2–4.0 years at Toronto Western Hospital, three male patients (aged 61–73 years, disease duration 11.0–14.5 years) switched to SCpLD because of its smaller pump and less invasive delivery method. PEG-J was kept in place (not used) for at least 1 month before concluding that SCpLD was tolerated (Fig. 1A). Patient-reported changes in the motor, non-motor, and quality-of-life domains were recorded at 3-months using an ad hoc structured questionnaire. The motor section (part III) of the Movement Disorders Society—Unified Parkinson Disease Rating Scale (MDS-UPDRS) was used to measure motor function in both treatments. Levodopa-equivalent daily dose (LEDD) was calculated as well.4 All patients have been on SCpLD for at least 6 months. Supplementary Material contains statistical, ethical, and dosing adjustment details. Levodopa dosing parameters and adjunctive medication use during LCIG and SCpLD treatments are summarized in Table S1. In brief, total LEDD was comparable between the two approaches (LCIG: 3524 ± 427.6 mg/day; SCpLD: 3200.7 ± 954.6 mg/day). Two patients kept consistent their oral drugs whereas one patient discontinued all oral medications during SCpLD. The mean score for motor function, as measured by the MDS-UPDRS III, decreased by 8.7 points, from 32.0 ± 3.5 on the LCIG to 23.3 ± 6.8 on the SCpLD. Although two patients had worsening tremor, most patients’ rigidity, bradykinesia, and gait remained stable. Postural stability, falls, and posture all showed modest improvements (Fig. 1B). Non-motor outcomes varied. All patients reported improvements in nocturia and sleep quality although nighttime mobility did not improve consistently across the group. Diurnal urinary frequency improved in one case while other symptoms (eg, restless legs syndrome, constipation) remained stable (Fig. 1B). This study evaluated the poorly explored transition from LCIG to SCpLD. While motor symptom changes were limited, improvements were observed in sleep quality, nocturia, and some axial motor signs, confirming the benefits of around the clock infusion, consistent with recent post-hoc findings.5 In spite of comparable LEDDs, motor symptoms improved by 27% on MDS-UPDRS III with SCpLD, likely reflecting a placebo effect. Although our study offers insights into transitioning from LCIG to SCpLD in PD patients, its small sample size and limited follow-up limit the conclusions about the long-term effects. Larger studies with extended follow-up are needed. (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. W.M.: 1B, 1C, 2B, 3A A.M.: 3C. Y.Y.: 3C. A.F.: 1A, 1B, 2A, 2C, 3B. Ethical Compliance Statement: In accordance with the University Health Network Research Ethics Board (UHN REB) guidance, studies involving three or fewer patients do not require REB review. This report meets those criteria. Informed patient consent was not necessary for this work. 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 Conflicts of Interest: YYP and AF have received financial support from Abbvie, the manufacture of LCIG and SCpLD. The authors declare that there are no funding sources or conflicts of interest relevant to this work. Financial Disclosures for the Previous 12 Months: WM has nothing to report. AM has nothing to report. YYP has nothing to report. 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. 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. Supplementary Material Details the dosing strategy and nocturnal adjustment approach for SCpLD therapy. Includes rationale for the 30% nocturnal dose reduction, ethical considerations under UHN REB guidance, and a description of the statistical methods applied for clinical and patient-reported outcomes. TABLE S1. Comparison of Levodopa Dosing and Adjunctive Medication Use During LCIG and SCpLD Treatment across three patients. Includes total LEDD, diurnal/nocturnal doses, extra doses, and oral adjuncts. Values are presented as mean ± standard deviation. *, mg/day; LCIG, Levodopa/Carbidopa Intestinal Gel; LD/CD CR, Levodopa/Carbidopa Controlled Release; LD/CD IR, Levodopa/Carbidopa Immediate Release; LEDD, Levodopa Equivalent Daily Dose; mg/day, milligrams per day; OD, once daily; PRN, as needed; QID, four times daily; SCpLD, Subcutaneous Foslevodopa/Foscarbidopa; TID, three times daily. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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