Switching from Levodopa/Carbidopa Intestinal Gel to Continuous Subcutaneous Foslevodopa/Carbidopa Infusion in Advanced Parkinson's Disease: A Case Series

Abstract

Background

Continuous subcutaneous foslevodopa/foscarbidopa infusion (CSFLI) is a novel non‐surgical alternative to levodopa/carbidopa intestinal gel (LCIG) for advanced Parkinson's disease (aPD), but real‐world switch data remain limited.

Objectives

To describe the feasibility, safety, and clinical effects of switching from LCIG to CSFLI.

Methods

We retrospectively reviewed eight aPD patients switched from LCIG to CSFLI at a single center between November 2024 and May 2025. Motor and non‐motor symptoms, quality of life, and levodopa equivalent daily doses were assessed at baseline (M0) and six months (M6).

Results

Small but significant improvements occurred in UPDRS part I, III, and IV and PDQ‐8 scores at M6. Total LEDD remained stable. CSFLI was well tolerated with mild local skin reactions.

Conclusion

Switching from LCIG to CSFLI is feasible and safe, providing stable dopaminergic delivery with modest symptomatic benefits in selected aPD patients.

Continuous dopaminergic stimulation is a cornerstone in the management of advanced Parkinson's disease (aPD), aiming to reduce motor fluctuations and improve quality of life. ¹ , ² Levodopa/carbidopa intestinal gel (LCIG) has long been considered an effective therapy in patients with complex motor complications refractory to oral medications. ³ However, LCIG requires invasive gastrointestinal surgery, may present technical complications, and some patients continue to experience motor and non‐motor fluctuations despite optimization of infusion rates and titration of doses. ⁴ , ⁵ , ⁶

Continuous subcutaneous foslevodopa/foscarbidopa infusion (CSFLI) is a novel non‐surgical alternative ⁷ that offers stable plasma levodopa concentrations comparable to LCIG, ⁸ , ⁹ without the need for percutaneous endoscopic gastrojejunostomy. Emerging data suggest that CSFLI provides effective control of motor fluctuations and dyskinesias, ¹⁰ , ¹¹ , ¹² yet real‐world data on switching from LCIG to CSFLI remain scarce. ⁹

Although CSFLI shares comparable active substances as LCIG, practical differences in administration (eg, morning doses, night‐time infusion, different pharmacokinetics) may lead to distinct clinical profiles. Furthermore, it is unclear whether switching to CSFLI can reduce the total daily levodopa equivalent dose (LEDD), improve symptom control, or patient comfort, especially in individuals whose response to LCIG is suboptimal.

Here we present a single‐center case series of aPD patients who were switched from LCIG to CSFLI therapy, with a six month follow‐up. Our objective is to provide structured observational data to inform clinicians about the feasibility, safety, and preliminary clinical effects of this switch.

Methods

Study Design and Patients

This was a retrospective, single‐center case series conducted at the Parkinson's disease and Movement Disorders Unit of the Fondation Rothschild Hospital (Paris, France). We reviewed the medical records of eight consecutive patients with advanced Parkinson's disease who switched from stable levodopa/carbidopa intestinal gel (LCIG) therapy to continuous subcutaneous foslevodopa/foscarbidopa infusion (CSFLI) between November 2024 and May 2025. The decision to switch was made after multidisciplinary discussion, based on persistent motor fluctuations, troublesome dyskinesias, or poor tolerability despite LCIG optimization, or in response to technical and practical limitations of the device (eg, tube dislodgment, frequent disconnections, or device burden for patients and caregivers). All patients with an indication for switching during this period were included consecutively, and none were excluded due to cognitive or psychiatric contraindications.

Switch Procedure

Prior to switching, all patients had their LCIG rates and bolus doses optimized by a movement disorder specialist. Conversion to CSFLI was performed according to the manufacturer's recommended weight‐based levodopa equivalent daily dose (LEDD) guidelines. Dead‐space in LCIG tubing and morning bolus doses were carefully considered, especially in patients without night‐time LCIG. CSFLI was initiated as a continuous daytime infusion, with individualized morning bolus doses and optional night‐time infusion titrated during the first week to optimize control of wearing‐off and dyskinesias.

Clinical Assessments

Data were extracted at baseline (M0), defined as the last visit prior to CSFLI, and at six months post‐switch (M6). Motor and non‐motor status were evaluated using the MDS‐UPDRS part I to IV. Patient and clinician impressions were captured with the CGI‐Severity (CGI‐S) and CGI‐Improvement (CGI‐I) scales. Quality of life was measured with the PDQ‐8. Neuropsychiatric and other non‐motor symptoms were documented using the Neuropsychiatric Inventory (NPI) and structured history‐taking.

Dose Calculations

Total levodopa equivalent daily doses were calculated for each patient including infusions and any oral dopaminergic medications. Morning bolus doses, night‐time infusion rates, and tubing dead‐space were explicitly documented.

Statistical Analysis

Comparisons between M0 and M6 were conducted using the Wilcoxon signed‐rank test for continuous variables and McNemar's test for dichotomous outcomes. Given the retrospective, observational design and small cohort, analyses were considered exploratory.

Results

Baseline Characteristics (Table 1)

TABLE 1.

Detailed patient characteristics at baseline (M0) and 6 months (M6).

ID	Age	Gender	PD Duration (Years)	Type of Parkinsonism	Type of motor fluctuation duration	nocturnal AKINESIA	Type of dyskinesias/duration	MoCA at baseline	Fab at baseline	Oral co‐medication	Oral LEDD (mg)	LCIG duration (months)	Reason for LCIG discontinuation
1	63	M	20	Idiopathic PD	Wearing OFF/6 years	No	‐	22	13	‐	0	8	Device disconnection
2	70	M	17	Idiopathic PD	Wearing OFF/7 years	Yes	Peak‐dose dyskinesia/5 years	21	13	Controlled‐release levodopa	75	12	LCIG inefficacy
3	74	F	10	Idiopathic PD	Sudden OFF/1 year	Yes	Peak‐dose dyskinesia/5 years	21	14	Controlled‐release levodopa	150	4	Tube dislodgment
4	78	M	8	Idiopathic PD	Wearing OFF/2.5 years	Yes	Peak‐dose dyskinesia/4 years	21	11	Controlled‐release levodopa	75	8	Device disconnection
5	73	M	17	Idiopathic PD	Wearing OFF/4.5 years	Yes	Biphasic dyskinesia/3 years	19	15	Controlled‐release levodopa	150	12	Device burden for patient and caregiver
6	71	F	8	Idiopathic PD	Non motor OFF/3 years	Yes	‐	24	11	‐	0	36	Device burden for patient and caregiver
7	83	F	29	Idiopathic PD	Non motor OFF/6 years	Yes	Biphasic and peak‐dose dyskinesia/3.5 years	23	13	Controlled‐rel28ease levodopa	75	10	LCIG inefficacy
8	76	M	24	Idiopathic PD	‐	No	Peak‐dose dyskinesia/8 years	28	17	‐	0	14	Peak‐dose dyskinesia

Morning LCIG dose (mL)	LCIG daytime rate (mL/h)	LCIC duration (h/Day)	LCIG Nighttime Rate (mL/h)	Morning CSFLI dose (mL)	CSFLI daytime rate (mL/h)	CSFLI nighttime rate (mL/h)	Rationale for nighttime csfli use	LEDD at M0 (mg)	LEDD at M6 (mg)	Change LEDD (%)	LDp/CDp ADVERSE EVENT	CGI‐S at M0	CGI‐S at M6	CGI‐I at M6
7	4.0	12	0.0	0.6	0.65	‐		1830	2022	+10.5%	None	5	5	4
7	3.2	16	0.0	0.0	0.35	0.2	Nocturnal akinesia	1519	1725	+13.6%	Burning cuteanous sensation	5	5	4
6	3.4	18	0.0	0.0	0.34	0.15	Nocturnal akinesia	2011	1264,2	−37.1%	Erythema	5	5	3
8	4.2	18	0.0	0.6	0.45	0.2	Nocturnal akinesia	1747	1596	−8.6%	Erythema	5	3	3
12	4.8	14	0.0	0.6	0.6	0.2	Nocturnal akinesia	1659	2004	+20.8%	Inflammatory nodule	4	2	2
0	3.7	24	2.8	0.6	0.47	0.25	Nocturnal akinesia	1560	1618,4	+3.7%	Erythema	5	4	3
8	3.8	12	0.0	0.6	0.42	‐		1140	1147,2	+6.3%	Burning cuteanous sensation	5	5	4
10	5.5	16	0.0	0.9	0.7	‐		1705	1749	+2.6%	None	5	3	4

Abbreviations: CGI‐I = Clinical Global Impression – Improvement; CGI‐S = Clinical Global Impression – Severity; CSFLI = Foslevodopa/Foscarbidopa subcutaneous infusion; FAB = Frontal Battery Assessment; LCIG = Levodopa/Carbidopa Intestinal Gel; LEDD = Levodopa Equivalent Daily Dose; M0 = Baseline; M6 = 6‐month follow‐up; MoCA = Montreal Cognitive Assessment; PD = Parkinson's disease.

Eight patients (five men and three women) with a median age of 73.5 years (range 63–78) and a median Parkinson's disease duration of 16.5 years were included. Prior to switching to CSFLI, patients had been treated with LCIG for a median of 8.5 months (range 8–12). All patients had idiopathic PD without features of atypical parkinsonism, and cognitive screening at baseline showed normal or mildly impaired status in all cases. Individual profiles are detailed in Table 1.

All patients received structured pre‐treatment education by both a movement disorders neurologist and an advanced practice nurse. In our center, a nasoduodenal trial phase is not routinely performed prior to LCIG initiation. Despite this preparation, the reasons for discontinuing LCIG and switching to CSFLI were mainly related to device burden or insufficient symptomatic control (Table 1). These included technical issues with the LCIG system, such as device disconnection or tube dislodgement (n = 3), burden of the device for patients and caregivers (n = 2), lack of sustained efficacy despite dose optimization (n = 2) and adverse effects such as peak‐dose dyskinesias (n = 1). It is noteworthy that all LCIG leads were correctly positioned, ie, intrajejunal and not gastric.

Changes in Motor and Non‐motor Symptoms (Fig. 1)

FIG 1.

Motor, non‐motor, and quality‐of‐life outcomes, as well as levodopa equivalent daily dose, before and after switching from levodopa/carbidopa intestinal gel (LCIG) to continuous subcutaneous foslevodopa/foscarbidopa infusion (CSFLI). Panels show individual patient data at baseline (M0) and six months after switch (M6) for: (A) total levodopa equivalent daily dose (LEDD), (B) MDS‐UPDRS part I, (C) MDS‐UPDRS part II, (D) MDS‐UPDRS part III, (E) MDS‐UPDRS part IV, (F) PDQ‐8 total score, and(G) Clinical Global Impression‐Severity (CGI‐S). Each dot represents an individual patient, and lines connect the same patient at M0 and M6 to illustrate within‐subject changes.

At six months after switching to CSFLI, motor and non‐motor assessments remained relatively stable, with small within‐subject variations. Median MDS‐UPDRS part I scores decreased from 32.0 at M0 to 31.0 at M6 (V  =  21, P =  0.035). Median MDS‐UPDRS part III scores decreased slightly from 69.5 to 68.5 (V  =  26, P  =  0.050), a change that is unlikely to be clinically meaningful, and MDS‐UPDRS part IV scores decreased significantly from a median of 13.0 to 11.0 (V  =  28, P  =  0.021), reflecting improvements in both motor fluctuations and dyskinesias. Median MDS‐UPDRS part II scores showed a slight decrease from 39.5 to 38.5, which was not statistically significant (V  =  23, P  =  0.143).

Quality of life, as measured by the PDQ‐8 total score, improved from a median of 29.0 at baseline to 26.5 at six months (V  =  28, P =  0.021). CGI‐Severity scores showed a trend toward improvement, decreasing from a median of 5.0 to 4.5 at six months, although this did not reach statistical significance (V  =  10, P  =  0.095).

LEDD and CSFLI Regimens

LEDD remained stable overall at the group level (median change from 1680 mg at M0 to 1700 mg at M6; V = 11, P = 0.38), although individual changes ranged from a 37.1% decrease to a 20.8% increase, reflecting substantial variability across patients (Fig. 1A). Individual CSFLI regimens were tailored at switch to optimize control of motor fluctuations, typically including a morning bolus and, in most patients, continuous daytime infusion with optional night‐time infusion. Of note, seven patients were previously on daytime‐only LCIG infusion regimens (12–18 h/day). In these cases, the introduction of night‐time CSFLI infusion did not significantly increase total LEDD, as concurrent nighttime oral dopaminergic medications were reduced or withdrawn.

CSFLI was generally well tolerated and continued by all patients at six months. Mild cutaneous adverse effects were observed, including local burning sensations in two patients, localized erythema in three patients, and inflammatory nodules in one patient. None of these led to CSFLI discontinuation; all were managed with local skin care, which allowed symptomatic improvement.

Discussion

In this single‐center, retrospective case series of eight patients with aPD, we demonstrate that switching from established LCIG therapy to CSFLI is both feasible and well tolerated over a six‐month period. Our findings indicate that this transition was accompanied by overall stability in motor and non‐motor symptoms, as well as in patient‐reported quality of life, with stable overall dopaminergic load.

Our study has several limitations. First, the small sample size limits statistical power and precludes meaningful subgroup analyses. Second, the retrospective and open‐label design may introduce multiple sources of bias. Given the novelty and anticipated convenience of CSFLI, both patients and clinicians may have held high expectations, potentially influencing subjective outcome measures such as the CGI or MDS‐UPDRS I and II scores. In the absence of blinded assessments, rater bias cannot be excluded. Moreover, the lack of a control group limits the ability to distinguish the true effect of switching from natural disease fluctuations or placebo‐related improvement.

The decision to switch to CSFLI was driven by practical and clinical limitations of LCIG, including device burden, mechanical complications, and suboptimal symptomatic control despite optimization of intestinal infusion rates. These observations underscore the reality that even highly effective advanced therapies like LCIG may not fully address all patients’ needs in real‐world settings. In our cohort, one patient had moderate cognitive impairment (MoCA score 19), though none met criteria for Parkinson's disease dementia. Cognitive status is nonetheless a well‐known factor influencing long‐term satisfaction and adherence with device‐aided therapies such as LCIG. ¹³

CSFLI offers a promising non‐surgical alternative that bypasses the need for percutaneous endoscopic gastrojejunostomy, while preserving the continuous dopaminergic stimulation that is central to mitigating motor fluctuations. ⁸

Although our sample size was small, all patients maintained stable LEDD after switching, suggesting that CSFLI can achieve symptomatic control without necessitating substantial dose escalation. However, individual dose changes varied considerably, ranging from a 37.1% decrease to a 20.8% increase across patients. This variability likely reflects personalized titration strategies tailored to clinical response, tolerability, and prior LCIG regimens.

Interestingly, we observed significant improvements in MDS‐UPDRS part IV and PDQ‐8 scores, accompanied by trends toward better global clinical impression ratings. These findings support the hypothesis that CSFLI provides an effective means of delivering levodopa continuously and might reduce dyskinesias and motor fluctuations comparably to LCIG. ⁷ , ¹⁰ , ¹¹ Moreover, CSFLI is approved for 24‐h administration, and it allows individualized titration of both the morning bolus and night‐time infusion. This flexibility can facilitate tailored treatment strategies according to patients’ needs. Notably, in our series, four patients who were not receiving LCIG overnight benefited from the addition of nocturnal CSFLI, reporting subjectively improved sleep quality, likely related to reduced nocturnal akinesia. However, this effect was not formally assessed using sleep‐specific scales such as PDSS‐2, which represents a limitation of our study.

The safety and tolerability profile of CSFLI was also reassuring. Minor cutaneous adverse events were noted in some patients—including local erythema, inflammatory nodules, and burning sensations—which were successfully managed with topical treatments and did not necessitate discontinuation. This profile is consistent with previous reports and appears manageable in routine practice. ⁷ , ¹⁰ , ¹²

Of note, no severe neuropsychiatric adverse events occurred in our series. This is particularly reassuring given previous reports suggesting that such complications may arise in some patients due to a combination of factors, including rapid titration, pre‐existing vulnerability (ie, cognitive impairment, history of delirium or hallucinations), and pharmacokinetic mismatches during transition from other dopaminergic therapies. ¹⁴ , ¹⁵

In conclusion, this case series provides preliminary evidence that CSFLI can be a practical and effective alternative to LCIG in patients with aPD experiencing persistent motor fluctuations or device‐related complications. Beyond its favorable tolerability and safety profile, CSFLI offers a more manageable, non‐surgical system and allows individualized 24‐h delivery. Patients in our cohort maintained stable dopaminergic load, reported subjective improvement in sleep with nocturnal infusion, and experienced no neuropsychiatric complications, suggesting that switching between continuous infusion modalities may be better tolerated than initiating from oral therapy.

While our findings highlight the potential of CSFLI in selected cases, they should not be interpreted as support for systematically replacing LCIG. In our cohort, the switch was driven by persistent treatment burden despite prior optimization of LCIG therapy. Given the limited real‐world data on CSFLI, especially regarding long‐term outcomes, prospective and comparative studies are needed to establish its position relative to LCIG and ensure balanced, evidence‐based therapeutic decisions.

Author Roles

At the end of the manuscript, list the itemized contributions in number/letter format, as below. These should include but are not restricted to:

(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.

G.B.: 1A, 1B, 2A, 2B, 2C, 3B

N.P.K.: 1B, 3B

Q.S.: 1B, 3B

J.P.B.: 1B, 3B

C.D.: 1A, 1B, 1C, 2C, 3A, 3B

Disclosures

Ethical Compliance Statement: According to the French ethic and regulatory law (public health code) retrospective studies based on the exploitation of usual care data should not be submitted at an ethic committee. The authors confirm that the approval of an institutional review board was not required for this work. All patients received information about the study, and could express their opposition rights. 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: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work.

Financial Disclosures for the Previous 12 Months: GB, NP‐K, QS, J‐PB and CD report no disclosures.

Data Availability Statement

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.