Profile of People With Parkinson's Disease Treated With a Device‐Aided Therapy in Spain. A Comparative Multicenter Observational Study

Abstract

Background and objective

New device‐aided therapies (DATs) have emerged to treat people with Parkinson's disease (PwP). Our aim was to know which DATs were indicated by the neurologist and to compare the characteristics of the patients treated under real clinical practice in Spain in the year 2024.

Patients and methods

Data collected in the DATs‐PD GETM Spanish Registry were used (REDCap). This is a descriptive, observational, prospective, multicenter, clinical registry with progressive inclusion of PwP treated with a DAT in daily clinical practice conditions in more than 40 centers from Spain for 10 years. For this proposal, only data from visit V1 (indication of DAT) were analyzed, but no follow‐up data. All patients with information on DAT received until 31/DEC/2024 were included.

Results

A total of 313 PD patients (66.7 ± 9.6 years old at V2; 61.7% males) were treated with a DAT. The most frequent DAT was subcutaneous foslevodopa/foscarbidopa (fLD/fCD) (47%) followed by deep brain stimulation (DBS) (20.1%) and continuous subcutaneous apomorphine infusion (CSAI) (19.8%). Up to 23.6% had received at least one previous DAT and 47% an on‐demand therapy. Differences in age, time with fluctuations and other aspects (motor status, quality of life or activities of daily living among others) were observed between different DAT groups. Specifically, patients treated with DBS were younger and had less advanced disease, whereas those who received LECIG were the most affected.

Conclusion

Subcutaneous therapies and DBS were the most frequent DATs (86.9%) implemented in Spain in 2024. Profile differences were detected between DAT types.

Parkinson's disease (PD), the second most common neurodegenerative disease after Alzheimer's disease, it is characterized by a deficit of dopamine in the striatum and other brain areas. ¹ Dopaminergic medication administration compensates the deficit of dopaminergic stimulation at the level of the postsynaptic receptors, which causes an improvement in symptoms such as bradykinesia, tremor, or rigidity, among others. ² However, people with PD (PwP) often develop motor and non‐motor fluctuations that affect their quality of life (QoL) and autonomy. ³ First‐line medication (ie, oral medication and rotigotine patch) and on‐demand therapies (ie, inhaled levodopa, sublingual and subcutaneous apomorphine pen) may be sufficient to optimize patients’ response initially ⁴ but when symptoms control is insufficient, a device‐aided therapy (DAT) may be indicated by an expert neurologist. ⁵ Although available DATs in numerous countries for many years have been deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion (CSAI) and levodopa‐carbidopa intestinal gel infusion (LCIG), ⁶ new DATs have recently emerged, such as levodopa‐entacapone‐carbidopa intestinal gel infusion (LECIG) and subcutaneous infusion of foslevodopa‐foscarbidopa (fLD/fCD). ⁷ , ⁸ Specifically, LECIG and fLD/fCD have been used in Spain since 2022 (Q3) and 2023 (Q4), respectively. While some studies have observed that these new therapies can produce benefits in PwP, ⁹ , ¹⁰ the experience is still limited, and it is necessary to know well the profile of the treated patients as well as the clinical response in daily clinical practice conditions. Of particular interest is to understand the characteristics of PwP treated with fLD/fCD, a new treatment that is administered less invasively (subcutaneously) than enteral levodopa, allowing for easier implementation. It is also interesting to know whether there could be differences between the two available subcutaneous therapies, CSAI and fLD/fCD, in terms of the profile of the patient selected, medium‐ to long‐term response, and the percentage of short‐term dropouts. Added to previous, treatment with focused ultrasound‐guided thermal ablation (HIFU, high intensity focused ultrasounds) is already an accepted and widely used treatment for medically‐refractory PD. ¹¹

In this completely new scenario, the Movement Disorders Study Group (Grupo de Estudio de Trastornos de Movimiento [GETM]) of the Spanish Neurological Society (Sociedad Española de Neurología [SEN]) has launched a prospective registry of PwP treated with a DAT in our country (Spain). ¹² The aim of this first analysis using data from this registry was to know which DATs were indicated by the neurologist and to compare the characteristics of the PwP treated in Spain under real clinical practice in 2024 depending on the DAT they received.

Methods/Design

Data for the analysis conducted in this study were obtained from the Device‐Aided Therapies in Parkinson's Disease GETM Spanish Registry (DATs‐PD GETM Spanish Registry). This is a descriptive, observational, prospective, multicenter, open study, proposed as a clinical registry with progressive inclusion of PwP treated with a DAT in daily clinical practice conditions for 10 years. Methodology of the DATs‐PD GETM Spanish Registry has been published and can be consulted. ¹²

Eligibility Criteria and Visits

More than 40 centers from Spain with neurology teams with experience in the management of PD (Appendix A), including the use of DATs, are participating in this registry. PwP treated with a DAT are sequentially included in the registry: DBS; CSAI; LCIG; LECIG; and fLD/fCD subcutaneous infusion. In addition, PwP who are treated with HIFU are being included. Specifically, the eligibility criteria are ¹² : (1) diagnosis of PD according to the MDS criteria ¹³ ; (2) start of treatment with a DAT from January 1, 2024; (3) the patient's desire to participate on a completely voluntary basis; (4) signing of an informed consent.

The registry includes 3 types of visits: (1) baseline visit (V1), which is when the DAT is decided by the neurologist; (2) start visit (V2), which is when the DAT is initiated by the patient; (3) follow‐up visit (V3), with the patient already receiving the DAT. Specifically, the neurologist's decision on the indicated DAT is based on aspects that influence his/her clinical practice, such as knowledge, experience, opinion about the therapies, shared‐decision making with the patient's and caregiver's opinion, and so forth. The first follow‐up visit will be carried out at 6 months ± 3 months (V3_6M) and then at 1 year ± 3 months and subsequently annually ± 3 months: 1 year (V3_12M); 2 years (V3_24M); 3 years (V3_36M), and so forth. For this proposal and regarding the aim of this study, to know which DATs were indicated by the neurologist and to compare the characteristics of the PwP treated in Spain under real clinical practice in 2024, only data from the baseline visit (V1) was considered for the analysis but no follow‐up data. Specifically, all patients from the registry with information on DAT received until December 31, 2024 were included.

Assessments

Only data from the baseline visit (V1) was considered for the analysis: sociodemographic data; data about PD (age onset, disease duration, motor phenotype, etc); comorbidities; treatments; main reason for therapy indication; levodopa equivalent daily dose (LEDD) ¹⁴ ; motor symptoms; non‐motor symptoms (NMS) including cognition; Unified Parkinson's Disease Rating Scale (UPDRS‐III) ¹⁵ during the OFF state; UPDRS‐III during the ON state; Hoehn & Yahr (H&Y) ¹⁶ stage in OFF; H&Y stage in ON; Parkinson's Disease Questionnaire (PDQ‐39) ¹⁷ ; European Health Interview Survey‐Quality of Life 8‐item index (EUROHIS‐QOL 8‐item index) ¹⁸ ; Schwab and England Activities of Daily Living Scale (ADLS) ¹⁹ during the OFF and during the ON state.

All information was collected by expert neurologists in a daily clinical practice setting. Specifically, information about 16 motor symptoms was collected: percentage of the awaking day during the OFF state (0%; 1–25%; 26–50%; 51–75%; 76–100%); OFF time (hours) per day; percentage of the awaking day with dyskinesia (0%; 1–25%; 26–50%; 51–75%; 76–100%); dyskinesia severity; painful dyskinesia; nocturnal akinesia; morning akinesia; morning dystonia; freezing of gait (FOG) during the OFF state; FOG during the ON state; falls; posture; tremor during the OFF state; tremor during the ON state; hypomimia; speech problems. A score for 15 out of 16 symptom (OFF time per day was excluded) from 0 to 4 (0, no symptom; 1, slight; 2, moderate; 3, severe; 4, very severe; or according to the percentage if applicable) and a total Motor Symptoms score (MSs) from 0 (15 × 0; minimum) to 60 (15 × 4; maximum) was calculated. Regarding NMS, 20 questions were asked about different aspects: visual hallucinations; psychosis; impulse control disorder; depression; anxiety; apathy; REM behavior disorder; restless legs; falling asleep insomnia; maintenance insomnia; nicturia; other urinary symptoms; diurnal somnolence; symptomatic orthostatic hypotension; constipation; sialorrhea; dysphagia; fatigue; PD‐related pain; sweating. Similarly as with the motor symptoms, the same methodology was applied with NMS and a score for each item from 0 to 4 and a total Non‐Motor Symptoms score (NMSs) from 0 (20 × 0; minimum) to 80 (20 × 4; maximum) was calculated.

Data Collection and Statistical Analysis

Data were collected using REDCap (https://project-redcap.org/). This is a secure web application for building and managing online surveys and databases. REDCap has been used to date (19/APR/2025) in 160 countries by more than 3,673,000 users. It offers a free, easy‐to‐use, and secure method of flexible yet robust data collection. Data collected were transferred to a statistical package for subsequent analysis (SPSS 20.0 for Windows). Remote monitoring of the data was carried out (A.S.). Different variables were expressed as quantitative and/or qualitative variables. Distribution of variables was verified by one‐sample Kolmogorov–Smirnov test. For comparisons between subjects of a different DAT, the T‐Student, Mann–Whitney U, χ ² test, or ANOVA were applied. Due to the exploratory and descriptive nature of the paper, any correction method for multiple comparisons was used.

Results

A total of 313 PD patients (66.7 ± 9.6 years old at V2; 61.7% males) were treated with a DAT. The most frequent was fLD/fCD (47%) followed by DBS (20.1%) and CSAI (19.8%) (Fig. 1A). Enteral therapies (LCIG and LECIG) were only 10.9% of them. Up to 23% had received at least one previous DAT (Fig. 1B and Table 1) and 47% an on‐demand therapy (Fig. 1C). CSAI was the most frequent prior DAT received (12.8%) while inhaled levodopa was the most frequent on‐demand therapy (35.5%). By groups, PwP select to LECIG were those who had most frequently been treated with a DAT previously (41.7%; p = 0.003; Table 1).

Figure 1.

(A) Frequency of different DATs implemented in Spain in 2024, according to the DATs‐PD GETM Spanish Registry. (B) Frequency of previous DATs received in patients treated with a DAT included in the registry. (C) Frequency of previous on‐demand therapies in patients treated with a DAT included in the registry. CSAI, continuous subcutaneous apomorphine infusion; DAT, device‐aided therapy; DBS, deep brain stimulation; fLD/fCD, foslevodopa‐foscarbidopa; LCIG, levodopa‐carbidopa intestinal gel infusion; LECIG, levodopa‐entacapone‐carbidopa intestinal gel infusion; ODT, on‐demand therapy.

TABLE 1.

Previous DATs in PwP from the DATs‐PD GETM Spanish registry treated with a DAT in Spain in 2024

Characteristics	DBS	fLD/fCD	CSAI	LCIG	LECIG	HIFU	All cohort	p
	N = 62	N = 145	N = 60	N = 10	N = 24	N = 7	N = 308 a
At least 1 DAT (%)	29	25.5	6.7	30	41.7	0	23	0.003
2 or more DAT (%)	3.2	2.7	1.6	10	12.5	0	3.5	0.147
DAT type (%)
DBS	3.2	7.5	3.2	20	0	0	5.5
fLD/fCD	1.6	0	0	0	12.5	0	1.3
CSAI	20.6	14.3	0	10	20.8	0	13
LCIG	3.2	4.8	3.2	10	20.8	0	5.5
LECIG	1.6	0	0	0	0	0	0.3
Another	1.6	1.4	1.6	0	0	0	1.3

Note: The results represent percentages; p, comparison between all DATs; χ ² test was applied. P < 0.05 are shown in bold.

^a Data were collected in 308 out 313 patients (no data collected in five patients). In a small percentage of cases, it was reported that the patient had previously received the same DAT. Another indicated HIFU and/or another therapy (ie, infusion under research).

Abbreviations: CSAI, continuous subcutaneous apomorphine infusion; DAT, device‐aided therapy; DBS, deep brain stimulation; fLD/fCD, foslevodopa‐foscarbidopa; LECIG, levodopa‐entacapone‐carbidopa intestinal gel infusion.

PwP treated with DBS were younger (p < 0.0001) but no differences were observed by sex (p = 0.437) (Table 2). Up to 46.8% of PwP didn't have a principal caregiver, being the most frequent those patients treated with HIFU (100%) and DBS (71%). In those patients with a caregiver, the partner was the most frequent (72.7%) followed by the son/daughter (15.2%). Only three patients were institutionalized in a residence. No differences were found between groups (DBS vs. fLD/fCD vs. CSAI vs. LCIG vs. LECIG vs. HIFU) in terms of comorbidities or drugs received to them except anti‐aggregating/coagulants (p = 0.030), benzodiazepine (p = 0.004) and antipsychotic drugs (p = 0.032) (Table 2).

TABLE 2.

Sociodemographic and related to comorbidities aspects in PwP from the DATs‐PD GETM Spanish registry treated with a DAT in Spain in 2024

Characteristics	DBS	fLD/fCD	CSAI	LCIG	LECIG	HIFU	All cohort	p	p i
	N = 63	N = 147	N = 62	N = 10	N = 24	N = 7	N = 313
Age at initiation of DAT	60.8 ± 6.6	67.8 ± 9.2	68.7 ± 9.4	65.7 ± 14.2	70 ± 9.3	69.6 ± 9.4	66.7 ± 9.6	<0.0001	0.559
Gender (males) (%)	71.4	61.2	53.2	60	61.2	71.4	61.7	0.437	0.283
Weight (kg)	78.4 ± 15.6	71.1 ± 14.6	74.9 ± 15.8	74.6 ± 12.9	70.6 ± 8.5	N. A.	73.5 ± 14.7	0.126	0.198
BMI	26.4 ± 3.9	26.4 ± 4.2	27.1 ± 4.3	25.9 ± 3.7	24.9 ± 2.5	N. A.	26.4 ± 4.1	0.433	0.361
Principal caregiver (%)	29	61	59.7	100	47.8	0	53.2	<0.0001	0.863
Civil status (%)								0.147	0.348
Married	72.6	71.2	77.4	70	78.3	85.7	73.5
Single	16.1	14.4	9.7	10	0	14.3	12.6
Widowed	0	8.2	11.3	20	8.7	0	7.4
Other	11.3	6.2	1.6	0	13	0	6.5
Living style (%)								0.808	0.252
With the partner	77.4	73.3	79	70	82.7	85.7	76.1
Alone	11.3	13.7	8.1	0	13	14.3	11.9
With a son/daughter	6.5	4.1	9.7	10	4.3	0	5.5
Institutionalized in residency	1.6	1.4	1.6	10	0	0	1.6
Other	3.2	7.5	1.6	10	0	0	4.9
Comorbidities (%)
Arterial hypertension	25.4	38.4	49.2	30	43.5	42.9	38.1	0.150	0.150
Diabetes mellitus	9.7	11.1	18	10	17.4	0	12.4	0.549	0.180
Dyslipemia	22.2	31.5	36.1	20	29.2	28.6	29.9	0.618	0.525
Atrial fibrillation/arritmia	6.3	7.5	9.8	0	4.3	0	7.1	0.799	0.582
Ischemic cardiopathy	0	4.1	6.6	10	0	8.7	4.2	0.315	0.454
Lung disease	4.8	11.6	4.9	0	4.3	14.3	8	0.320	0.139
Polineuropathy	0	2.7	0	0	4.3	0	1.6	0.471	0.192
Treatments (%)
Antihipertensive	25.8	34.2	45	20	39.1	42.9	34.7	0.274	0.147
Antidiabetics	9.5	9.7	13.6	10	17.4	0	10.7	0.269	0.415
Hypolipidemic agents	15.9	26	31.7	10	33.3	28.6	25.2	0.750	0.411
Anti‐aggregating/coagulants	1.6	16.3	10	10	20.8	28.6	20.8	0.030	0.241
Antidepressant	30.2	34.7	25.8	20	45.8	14.3	31.9	0.362	0.209
Benzodiazepine	28.6	39.7	26.7	20	69.6	28.6	36.2	0.004	0.076
Antipsychotic	4.8	12.2	4.8	20	25	0	10.2	0.032	0.104
Anti‐dementia	0	10.2	4.8	0	12.5	0	6.7	0.068	0.207

Note: The results represent percentages, mean ± SD or median [p25, p75]; p, comparison between all DATs; p _i, comparison between both subcutaneous therapies, fLD/fCD and CSAI. Chi‐square, ANOVA, t‐Student and/or Mann–Whitney‐Wilcoxon tests were applied according to the type of analysis and distribution of the variables. P < 0.05 are shown in bold. The information was not collected for all patients. The lowest sample size was N = 196 for weight and BMI (62.6%). For the rest majority of variables the data was collected in more than 90% of the patients.

Abbreviations: BMI, body mass index; CSAI, continuous subcutaneous apomorphine infusion; DAT, device‐aided therapy; DBS, deep brain stimulation; fLD/fCD, foslevodopa‐foscarbidopa; LCIG, levodopa‐carbidopa intestinal gel infusion; LECIG, levodopa‐entacapone‐carbidopa intestinal gel infusion.

Regarding PD‐related variables, differences between groups were observed in motor phenotype (p = 0.004), previous psychosis (p = 0.006), time with fluctuations (p = 0.015), daily OFF time (p < 0.0001), H&Y‐OFF (p < 0.0001), H&Y‐ON (p = 0.030), UPDRS‐III‐OFF (p = 0.015) and UPDRS‐III‐ON (p < 0.0001) (Table 3). Specifically, PwP treated with DBS had the lowest daily OFF time (4.3 ± 2 h) and UPDRS‐III‐ON score (14.7 ± 8) whereas on the other extreme, patients treated with LECIG the highest ones, 7.8 ± 3.3 and 28.1 ± 13.3, respectively. Moreover, the group treated with LECIG had been experiencing clinical fluctuations for longer (7.1 ± 3.1 years). However, no differences were observed regarding LEDD (Table 3). With regard to the motor symptoms, the lowest MSs was for PwP treated with DBS (13.4 ± 5.3) and the highest for those who received LECIG (17.6 ± 5.8) (p = 0.025). By items and considering the five defined categories (from 0 to 4), differences were detected in percentage of the awaking day during the OFF state (p < 0.001), morning dystonia (p = 0.001), FOG during the OFF state (p = 0.004), posture (p = 0.042), tremor during the OFF state (p < 0.0001), tremor during the ON state (p < 0.0001), hypomimia (p < 0.0001) and speech problems (p < 0.0001) (Fig. S1). According specifically to the NMSs (from 0 to 80; mean 12.6 ± 7.1), PwP treated with fLD/fCD had the highest NMSs (14.9 ± 7) indicating a higher NMS burden (p < 0.0001; Table 3). By items and considering again the five defined categories (from 0 to 4), differences were detected in visual hallucinations (p = 0.049), depression (p = 0.001), apathy (p = 0.018), REM behavior disorder (p = 0.009), diurnal somnolence (p = 0.001), constipation (p = 0.004), sialorrhea (p = 0.001) and dysphagia (p = 0.001) (Fig. S2). Finally, patients treated with DBS had the best health‐related QoL (PDQ‐39) and greatest autonomy for activities of daily living during the OFF and during the ON state (Table 3 and Fig. 2). By domains, significant differences between groups were observed for mobility (p = 0.002) and communication (p = 0.035) from the PDQ‐39 and energy (p = 0.005), activities of daily living (p = 0.031) and self‐esteem (p = 0.020) from the EUROHIS‐QoL8‐item index.

TABLE 3.

PD‐related variables in PwP from the DATs‐PD GETM Spanish registry treated with a DAT in Spain in 2024

Characteristics	DBS	fLD/fCD	CSAI	LCIG	LECIG	HIFU	All cohort	p	p i
	N = 63	N = 147	N = 62	N = 10	N = 24	N = 7	N = 313
Disease duration (years)	11.9 ± 4.9	14 ± 9.3	10.9 ± 5	10.8 ± 3.9	13.6 ± 3.5	12.7 ± 4.7	12.9 ± 7.4	0.107	0.015
Motor phenotype (%)								0.004	0.033
Tremor dominant	27.7	26.1	29.6	33.3	35	100	29.8
Indeterminate	40.4	38.1	22.2	44.5	45	0	35.1
PIGD	31.9	35.8	48.2	22.2	20	0	35.1
Treatment for PD (%)
MAO‐B inhibitor	68.9	64.9	79.7	40	47.8	57.1	66.3	0.036	0.068
Dopamine agonist	66.7	47.8	69.5	50	30.4	71.4	55.3	0.003	0.015
COMT inhibitor	62.3	53	54.2	30	47.8	14.3	53.1	0.120	0.739
Amantadine	24.6	32.8	20.3	0	17.4	0	17.4	0.045	0.077
LEDD (mg)	1115.3 ± 517.4	1236.3 ± 585.2	1273.6 ± 500.3	1092.3 ± 222.9	1165.4 ± 760.1	703.7 ± 413.6	1196.8 ± 561.1	0.137	0.703
Previous psychosis (%)	1.6	15.1	3.3	10	21.7	0	10	0.006	0.008
Cognitive impairment (%)								0.341	0.580
MCI (%)	20.6	26	21.7	50	34.8	0	24.9
Dementia (%)	0	3.4	3.3	0	4.3	0	2.6
Time with fluctuations (years)	4.7 ± 2.7	5.7 ± 3.8	4.6 ± 2.6	4 ± 2.1	7.1 ± 3.1	6.3 ± 3.9	5.3 ± 3.3	0.015	0.143
Daily OFF time (h)	4.3 ± 2	4.9 ± 2.1	4.7 ± 1.9	5 ± 1.8	7.8 ± 3.3	6 ± 8.7	4.9 ± 2.4	<0.0001	0.543
H&Y – OFF	2 [2,3]	3 [2,4]	3 [2,3]	3.5 [3,4]	3 [3,4]	2 [2,3]	3 [2,4]	<0.0001	0.096
H&Y – ON	2 [1,2]	2 [2,2]	2 [2,2]	2 [2,2]	2 [2,2]	2 [1,2]	2 [2,2]	0.030	0.094
UPDRS – III – OFF	34.4 ± 9.8	37.7 ± 10.9	37.3 ± 11.2	45.9 ± 12.2	44 ± 15.7	46.3 ± 11.8	37.3 ± 11.4	0.015	0.853
UPDRS – III – ON	14.7 ± 8	19.1 ± 10.8	21.9 ± 10.6	25.7 ± 10.1	28.1 ± 13.3	26 ± 10.5	19.4 ± 10.9	<0.0001	0.142
Motor symptoms score a	13.4 ± 5.3	15.9 ± 5.7	14.2 ± 5.5	16.3 ± 4.6	17.6 ± 5.8	14.7 ± 7.6	15.2 ± 5.7	0.025	0.070
NMS score b	8.5 ± 5.4	14.9 ± 7	10.9 ± 7.4	12.7 ± 6.9	14.4 ± 4.7	N. A.	12.6 ± 7.1	<0.0001	0.001
PDQ‐39	48.3 ± 22.7	62.9 ± 21.7	59.2 ± 24.6	60.4 ± 20.7	68.4 ± 20.6	N. A.	59.7 ± 22.9	0.015	0.393
EUROHIS‐QOL8	25.6 ± 4.3	22.7 ± 5.2	23.2 ± 4.8	22 ± 4.6	21.7 ± 4.2	N. A.	23.3 ± 4.9	0.071	0.656
ADLS – OFF	72 ± 17.8	57 ± 20.4	60.4 ± 22.9	48.9 ± 19	50.6 ± 18.4	N. A.	60.2 ± 21.2	<0.0001	0.135
ADLS – ON	89 ± 12.5	80.8 ± 14.2	84.3 ± 13.8	71.1 ± 17.6	79.3 ± 12.2	N. A.	82.9 ± 14.2	0.001	0.196

Note: The results represent percentages, mean ± SD or median [p25, p75]; p, comparison between all DATs; pi, comparison between both subcutaneous therapies, fLD/fCD and CSAI. Chi‐square, ANOVA, t‐Student and/or Mann–Whitney‐Wilcoxon tests were applied according to the type of analysis and distribution of the variables. P‐values <0.05 are shown in bold. N. A., not available (not collected).

^a Information about 15 motor symptoms (percentage of the awaking day during the OFF state; percentage of the awaking day with dyskinesia; dyskinesia severity; painful dyskinesia; nocturnal akinesia; morning akinesia; morning dystonia; freezing of gait [FOG] during the OFF state; FOG during the ON state; falls; posture; tremor during the OFF state; tremor during the ON state; hypomimia; speech problems) was collected with a score for each one from 0 to 4 (0, no symptom; 1, slight; 2, moderate; 3, severe; 4, very severe; or according to the percentage if applicable) and a total score from 0 (15 × 0; minimum) to 60 (15 × 4; maximum).

^b Information about 20 NMS (visual hallucinations; psychosis; impulse control disorder; depression; anxiety; apathy; REM behavior disorder; restless legs; falling asleep insomnia; maintenance insomnia; nicturia; other urinary symptoms; diurnal somnolence; symptomatic orthostatic hypotension; constipation; dysphagia; sialorrhea; fatigue; PD‐related pain; sweating) was collected with a score for each one from 0 to 4 (0, no symptom; 1, slight; 2, moderate; 3, severe; 4, very severe) and a total score from 0 (20 × 0; minimum) to 80 (20 × 4; maximum). The information was not collected for all patients. The lowest sample size was N = 158 for the EUROHIS‐QOL8 (50.7%) and N = 187 for the PDQ‐39 (59.7%), and. For the rest majority of variables the data was collected in more than 90% of the patients. Specifically, the sample was N = 254 for the Motor symptoms score (81.2%) and N = 280 for the NMS score (89.5%).

Abbreviations: ADL, Schwab and England Activities of Daily Living Scale; BMI, body mass index; COMT, catechol‐O‐methyltransferase; CSAI, continuous subcutaneous apomorphine infusion; DAT, device‐aided therapy; DBS, deep brain stimulation; EUROHIS‐QOL8, European Health Interview Survey‐Quality of Life 8‐item index; fLD/fCD, foslevodopa‐foscarbidopa; H&Y, Hoehn & Yahr; LCIG, levodopa‐carbidopa intestinal gel infusion; LECIG, levodopa‐entacapone‐carbidopa intestinal gel infusion; LEED, levodopa equivalent daily dose; MAO‐B, type‐B monoamine oxidase; MCI, mild cognitive impairment; NMS, non‐motor symptoms; PDQ‐39SI, 39‐item Parkinson's Disease Quality of Life Questionnaire; PIGD, postural instability gait difficulty; UPDRS, Unified Parkinson's Disease Rating Scale.

Figure 2.

(A) Total score on the PDQ‐39 (left) and mean value of each domain of the PDQ‐39 (right) in PD patients from the DATs‐PD GETM Spanish Registry treated with different DATs (N = 187). ANOVA was applied. *p = 0.002; **p = 0.035; p > 0.05 for the rest of PDQ‐39 domains. On the left, data are presented as box plots, with the box representing the median and the two middle quartiles (25%–75%). In the PDQ‐39, the higher the score on the scale, the worse the quality of life. (B) Total score on the EUROHIS‐QOL8 (left) and mean value of each item of the EUROHIS‐QOL8 (right) in PD patients from the DATs‐PD GETM Spanish Registry treated with different DATs (N = 158). ANOVA was applied. *p = 0.005; **p = 0.031; ***p = 0.020; p > 0.05 for the rest of EUROHIS‐QOL8 items. On the left, data are presented as box plots, with the box representing the median and the two middle quartiles (25–75%). In the EUROHIS‐QOL8, the lower the score on the scale, the worse the quality of life. ADL, activities of daily living; CSAI, continuous subcutaneous apomorphine infusion; DAT, device‐aided therapy; DBS, deep brain stimulation; EUROHIS‐QOL8, EUROHIS‐QOL 8‐item index; fLD/fCD, foslevodopa‐foscarbidopa; LCIG, levodopa‐carbidopa intestinal gel infusion; LECIG, levodopa‐entacapone‐carbidopa intestinal gel infusion; PDQ‐39SI, 39‐item Parkinson's Disease Quality of Life Questionnaire.

When both subcutaneous therapies were compared (Table 2 and Table 3), fLD/fCD vs. CSAI, a longer disease duration (14 ± 9.3 vs. 10.9 ± 5; p = 0.015) and a higher NMSs were found in PwP group treated with fLD/fCD. Previous psychosis was more frequent in PwP who received fLD/fCD than those treated with CSAI (15.1% vs. 3.3%; p = 0.008) whereas these patients were also receiving less frequently a dopamine agonist (47.8% vs. 69.5%; p = 0.015). On the other hand, when a subcutaneous therapy was compared with enteral therapy (Table 4 and 5), despite no differences in disease duration were detected, PwP treated with an enteral therapy had more daily OFF time (6.8 ± 3.1 vs. 4.9 ± 2 h; p < 0.0001) and a worse motor status (UPDRS‐III) during the OFF (37.6 ± 10.9 vs. 37.6 ± 10.9; p = 0.005) and during the ON state (27.3 ± 12.2 vs. 19.9 ± 10.8; p = 0.003) with a less autonomy for activities of daily living (ADLS) during the OFF state (50 ± 18.3 vs. 58 ± 21.2; p = 0.044). No differences were detected between both groups in the MSs and NMs and QoL (Table 5).

TABLE 4.

Sociodemographic and related to comorbidities aspects in PwP from the DATs‐PD GETM Spanish registry treated with a DAT in Spain in 2024 comparing patients treated with subcutaneous versus enteral therapy

Characteristics	Subcutaneous	Enteral	p
	N = 209	N = 34
Age at initiation of DAT	68.1 ± 9.5	68.8 ± 10.9	0.698
Gender (males) (%)	58.9	58.8	0.998
Weight (kg)	72.4 ± 15	72.4 ± 10.5	0.996
BMI	26.6 ± 4.2	25.4 ± 3.1	0.212
Principal caregiver (%)	60.6	63.6	0.738
Civil status (%)			0.215
Married	72.7	73.5
Single	12.9	2.9
Widowed	9.1	11.8
Other	5.3	11.8
Living style (%)			0.227
With the partner	75.1	76.5
Alone	12	11.8
With a son/daughter	5.7	2.9
Institutionalized in residency	1.4	2.9
Other	3.1	5.9
Comorbidities (%)
Arterial hypertension	41.5	39.4	0.816
Diabetes mellitus	13.2	15.2	0.757
Dyslipemia	32.9	26.5	0.460
Atrial fibrillation/arritmia	8.2	3	0.294
Ischemic cardiopathy	4.8	9.1	0.315
Lung disease	9.6	3	0.213
Polineuropathy	1.9	3	0.682
Treatments (%)
Antihipertensive	37.4	33.3	0.655
Antidiabetics	10.8	15.2	0.464
Hypolipidemic agents	27.7	26.5	0.885
Anti‐aggregating/coagulants	14.5	17.6	0.633
Antidepressant	32.1	38.2	0.477
Benzodiazepine	35.9	54.5	0.041
Antipsychotic	10	23.5	0.025
Anti‐dementia	8.6	8.8	0.968

Note: The results represent percentages, mean ± SD or median [p25, p75]. Chi‐squared, T‐Student and/or Mann–Whitney U test were applied. The information was not collected for all patients. The lowest sample size was N = 164 for weight and BMI (67.5%). For the rest majority of variables the data was collected in more than 90% of the patients. p < 0.05 are shown in bold.

Abbreviations: BMI, body mass index; CSAI, continuous subcutaneous apomorphine infusion; DAT, device‐aided therapy; DBS, deep brain stimulation; fLD/fCD, foslevodopa‐foscarbidopa; LCIG, levodopa‐carbidopa intestinal gel infusion; LECIG, levodopa‐entacapone‐carbidopa intestinal gel infusion.

TABLE 5.

PD‐related variables in PwP from the DATs‐PD GETM Spanish registry treated with a DAT in Spain in 2024 comparing patients treated with subcutaneous versus enteral therapy

Characteristics	Subcutaneous	Enteral	p
	N = 209	N = 34
Disease duration (years)	13.1 ± 8.4	12.8 ± 3.7	0.820
Motor phenotype (%)			0.151
Tremor dominant	27.1	34.5
Indeterminate	33.5	44.8
PIGD	39.4	20.7
Treatment for PD (%)
MAO‐B inhibitor	69.1	45.5	0.008
Dopamine agonist	54.1	36.4	0.059
COMT inhibitor	53	54.2	0.120
Amantadine	28.9	12.1	0.043
LEDD (mg)	1246.6 ± 561.7	1139.9 ± 620.3	0.400
Previous psychosis (%)	11.6	18.2	0.288
Cognitive impairment (%)			0.211
MCI (%)	24.8	38.4
Dementia (%)	3.4	3
Time with fluctuations (years)	5.5 ± 3.5	6.2 ± 3.2	0.199
Daily OFF time (h)	4.9 ± 2	6.8 ± 3.1	<0.0001
H&Y – OFF	3 [2,4]	3 [3,4]	0.034
H&Y – ON	2 [2,2]	2 [2,2]	0.895
UPDRS – III – OFF	37.6 ± 10.9	44.7 ± 14.4	0.005
UPDRS – III – ON	19.9 ± 10.8	27.3 ± 12.2	0.003
Motor symptoms score a	15.4 ± 5.7	17.1 ± 5.4	0.118
NMS score b	13.6 ± 7.4	13.8 ± 5.5	0.904
PDQ‐39	61.8 ± 22.6	66.1 ± 20.3	0.463
EUROHIS‐QOL8	22.9 ± 5.1	21.8 ± 4.8	0.428
ADLS – OFF	58 ± 21.2	50 ± 18.3	0.044
ADLS – ON	81.9 ± 14.1	76.3 ± 134.7	0.065

Note: The results represent percentages, mean ± SD or median [p25, p75]. The results represent percentages, mean ± SD or median [p25, p75]. Chi‐squared, T‐Student and/or Mann–Whitney U test were applied. p < 0.05 are shown in bold.

^a N, Information about 15 motor symptoms (percentage of the awaking day during the OFF state; percentage of the awaking day with dyskinesia; dyskinesia severity; painful dyskinesia; nocturnal akinesia; morning akinesia; morning dystonia; freezing of gait [FOG] during the OFF state; FOG during the ON state; falls; posture; tremor during the OFF state; tremor during the ON state; hypomimia; speech problems) was collected with a score for each one from 0 to 4 (0, no symptom; 1, slight; 2, moderate; 3, severe; 4, very severe) and a total score from 0 (15 × 0; minimum) to 60 (15 × 4; maximum).

^b Information about 20 NMS (visual hallucinations; psychosis; impulse control disorder; depression; anxiety; apathy; REM behavior disorder; restless legs; falling asleep insomnia; maintenance insomnia; nicturia; other urinary symptoms; diurnal somnolence; symptomatic orthostatic hypotension; constipation; dysphagia; sialorrhea; fatigue; PD‐related pain; sweating) was collected with a score for each one from 0 to 4 (0, no symptom; 1, slight; 2, moderate; 3, severe; 4, very severe) and a total score from 0 (20 × 0; minimum) to 80 (20 × 4; maximum). The information was not collected for all patients. The lowest sample size was N = 129 for the EUROHIS‐QOL8 (53.1%) and N = 152 for the PDQ‐39 (62.6%). For the rest majority of variables the data was collected in more than 90% of the patients. Specifically, the sample was N = 222 for the Motor symptoms score (91.4%) and N = 203 for the NMS score (83.5%).

Abbreviations: ADL, Schwab and England Activities of Daily Living Scale; BMI, body mass index; COMT, catechol‐O‐methyltransferase; CSAI, continuous subcutaneous apomorphine infusion; DAT, device‐aided therapy; DBS, deep brain stimulation; EUROHIS‐QOL8, European Health Interview Survey‐Quality of Life 8‐item index; fLD/fCD, foslevodopa‐foscarbidopa; H&Y, Hoehn & Yahr; LCIG, levodopa‐carbidopa intestinal gel infusion; LECIG, levodopa‐entacapone‐carbidopa intestinal gel infusion; LEED, levodopa equivalent daily dose; MAO‐B, type‐B monoamine oxidase; MCI, mild cognitive impairment; NMS, non‐motor symptoms; PDQ‐39SI, 39‐item Parkinson's Disease Quality of Life Questionnaire; PIGD, postural instability gait difficulty; UPDRS, Unified Parkinson's Disease Rating Scale.

DISCUSSION

The present study is, to our knowledge, the first report on DATs used in daily clinical practice in PwP, which already includes the recently approved new therapies, LECIG and fLD/fCD. All DATs were initiated during the past year 2024 and the results with this sample size (N = 313) could be a reflection of the current general management of these therapies in our country. Almost half of the patients were treated with fLD/fCD and only 11% with and enteral therapy. Patients treated with DBS were younger and had less advanced disease, whereas at the other extreme, those who received LECIG were the most affected. In particular, the clinical profile of patients treated with fLD/fCD was more similar to that of other patients treated with pump‐administered therapies than to that of patients treated with DBS. In fact, the highest NMS burden was found in those patients selected for fLD/fCD.

There are some reports about the use of DATs under real clinical practice, but all of them include only DBS, CSAI and LCIG but not new recently approved DATs in some countries. ²⁰ , ²¹ , ²² , ²³ , ²⁴ , ²⁵ , ²⁶ , ²⁷ , ²⁸ , ²⁹ , ³⁰ , ³¹ , ³² , ³³ , ³⁴ , ³⁵ A first key step is the identification of the patient who can be treated with a DAT and in this sense different tools or strategies have been proposed such as NAVIGATE‐PD, ³⁶ CDEPA questionnaire, ³⁷ 5‐2‐1 criteria, ³⁸ MANAGE‐PD ³⁹ or artificial intelligence (DELIST study). ⁴⁰ One strategy before starting with a DAT may be to use an on‐demand therapy. ⁴¹ In Spain, there were only two approved in 2024, subcutaneous apomorphine pen and inhaled levodopa, and it is noteworthy that they were used before a DAT in only near half of patients. This data suggests a lower use than might be considered in patients with disabling OFF episodes ⁴² who were finally selected to receive a DAT. In contrast, one in four patients had already been previously treated with at least one DAT, with CSAI being the most frequent. It suggests the importance of being able to switch DAT or combine DATs when the patient's response is not optimal enough. ⁴³ , ⁴⁴ , ⁴⁵ , ⁴⁶ , ⁴⁷ , ⁴⁸ In particular, an infusion therapy can be implemented as a rescue therapy for DBS failure or as a complementary therapy for the management of residual motor fluctuations because of a partial response to DBS, for recurrent fluctuations because of disease progression, or for troublesome axial symptoms. ⁴⁸ In this cohort, the most frequent findings were patients previously treated with CSAI who started with fLD/fCD (N = 21) and DBS (N = 13) as well as patients with DBS who added fLD/fCD (N = 11). In fact, up to eight patients had received two previous DATs before starting the new DAT. From a practical point of view, it is important to try to optimize all treatment options that can improve the patient's clinical condition. ⁷

Many factors have to be considered before prescribing a DAT in PwP ⁴³ , ⁴⁹ : (1) physician factors (expertise and experience; PD nurse specialists; hospital facilities); (2) patient factors (age; comorbidities; motor and NMS; neuropsychiatric status; response to levodopa; genetics; patient preferences; the role of a principal caregiver; long‐term device care plan); (3) treatment‐related factors (availability; treatment invasiveness; risks and benefits; one‐time or longitudinal treatment; reimbursement methods; prognosis after each treatment). The decision must be individualized, and until the date no consensus guideline yet exists for selecting or sequencing DAT for patients with PD. However, our findings suggest that fLD/fCD may be a first option to consider as others have suggested ⁵⁰ and that subcutaneous therapies could also be positioned ahead of enteral therapies because they are less invasive, easier to implement and, in general, less expensive. Importantly, it would be necessary to have data about the response and long‐term persistence rate from this registry and from other future studies. Moreover, a bias in the selection of the DAT due to the fact that fLD/fCD was the last to be available in Spain, coinciding with the same year the registry began, cannot be excluded. As expected and consistent with other studies, ²⁰ , ²¹ PwP treated with DBS were younger and less affected overall, with a lower daily OFF time, a lower burden of motor and NMS with a better motor status during the OFF and during the ON state, and with a better perception of their QoL and a greater autonomy for daily activities. On the other extreme, patients who received an enteral infusion had more daily OFF time and a worse motor status and autonomy compared to those who received an infusion therapy. Again, this fact suggests that with the advent of fLD/fCD, subcutaneous therapies could be positioned before enteral therapies. Unfortunately, no other real world evidence data have been published about the profile of PwP treated with fLD/fCD. In this cohort, clinical characteristics were quite similar than PD patients included in both phase 3 trials. ⁸ , ⁵¹ Based on experience and current data, some authors have suggested a potential clinical pathway of care in which “early advanced PD” and “established advanced PD” were defined, being subcutaneous levodopa infusion (ie, fLD/fCD at the current moment) an earlier option compared to other DATs. ⁵⁰

An important point is that the idea that fLD/fCD can be a good option for “early advanced PD” does not mean that fLD/fCD can only be an option for less advanced patients, as more advanced patients appropriately selected can also improve with this DAT. However, based on data from clinical trials, ⁸ , ⁵¹ that doesn't mean that fLD/fCD could be only an option for early advanced PD patients, as more advanced patients appropriately selected can also improve with this DAT. More experience in clinical practice is needed, and in particular, a study comparing the effect of enteral vs. subcutaneous levodopa formulation infusion (eg, LCIG vs. fLD/fCD) could be of great interest. In this context, the DATs‐PD GETM Spanish registry ¹² will allow us to compare the effect of different DATs in clinical practice and to have more information on this point. When choosing between the two subcutaneous therapies, and despite the fact that some patients treated with fLD/fCD can develop hallucinations and psychosis, ⁸ , ⁹ , ¹⁰ , ⁵⁰ , ⁵² a profile of previous neuropsychiatric symptoms may lead us to select for fLD/fCD instead of CSAI, ⁵³ as we observed in our cohort. Similarly, a higher NMS burden may lead us to choose fLD/fCD since comparative studies between SCAI and LCIG already showed a greater benefit in patients treated with LCIG ²⁰ , ²¹ and different NMS may also improve with fLD/fCD such as sleep and urinary symptoms ⁵⁴ , ⁵⁵ and potentially others related to nocturnal and morning akinesia due to 24‐h infusion effect. On the other hand, the clinical profile of the selected patients to LCIG and LECIG is consistent with the literature. ⁷ , ²⁰ , ²¹ , ⁵⁶ , ⁵⁷ , ⁵⁸ Specifically, patients treated with LECIG were those with a more advanced established advanced PD, with characteristics similar to those recently reported in 73 patients treated in Spain ⁸ and in 167 patients from the ELEGANCE study. ⁵⁹ Differences observed in the use of some drugs such as benzodiazepines and antipsychotics corroborate the differences between the different profiles. The fact that LECIG is a treatment administered through a gastrostomy and recently introduced could explain this patient profile and secondarily the long‐term results in some series with a high percentage of drop‐outs. ⁵⁸ In our cohort, 42% of those patients treated with LECIG had received at least one previous DAT. Finally, our data show that the profile to be treated with HIFU is very specific, ¹¹ with all cases presenting a tremor phenotype and no primary caregiver. In any case, the absence of a principal caregiver was also observed in a non‐negligible percentage of patients treated with subcutaneous (39.4%) or enteral (36.4%) infusion in our cohort and some data suggest that not having care partner support may be frequent (49%) in patients treated with fLD/fCD but that it can be equally efficacious. ⁶⁰

This study has some limitations. Firstly, the limitations due to the methodology of the type of study (registry). Secondly, the sample size by subgroups in some of the therapies is small, especially in the case of LCIG (N = 10) and HIFU (N = 7). Thirdly, data were not collected in all patients for all variables. For example, in the case of NMS of Figure S1 there were only three patients treated with HIFU with data collected. Fourthly, although some of the scales used are validated, a motor and non‐motor score was also defined from the symptoms collected, which has not been validated. Fifthly, although the registry protocol indicates the inclusion of consecutive patients to avoid data biases, ¹² this requirement has not been met at all centers. Furthermore, bias in the selection of therapies cannot be ruled out, driven by factors such as resource availability or other factors that influence the neurologist. Finally, in this analysis, only data on the characteristics of PwP treated with a DAT are shown, but not on the DAT or follow‐up (effectiveness, safety and security, etc). On the other hand, the sample size of the entire cohort is large (N = 313), much information has been collected and analyzed, and this is the first cohort in which comparative data on daily clinical practice of patients selected for fLD/fCD and LECIG have been included.

In conclusion, we presented here the first real world evidence report on DATs used in daily clinical practice in PwP, which already includes the recently approved new therapies, LECIG and fLD/fCD. Subcutaneous therapies and DBS were the most frequent DATs implemented. Patients treated with DBS were younger and had less advanced disease, whereas those who received LECIG were the most affected. Data about the effectiveness and safety of each therapy in the long‐term are required.

Author Roles

(1) Research project: A. Conception, B. Organization, C. Execution (evaluation of patients, inclusion of data in the base data, review of data and queries resolution, etc); (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the first draft, B. Review and Critique.

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

Á.S.: 1C, 3B.

G.G.O.: 1B, 1C, 3B.

P.M.: 1C, 3B.

N.L.A.: 1C, 3B.

R.G.R.: 1C, 3B.

I.L.: 1C, 3B.

A.P.B.: 1C, 3B.

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

P.S.A.: 1C, 3B.

I.C.: 1C, 3B.

M.B.E.: 1C, 3B.

Á.S.F.: 1B, 1C, 3B.

DATs‐PD GETM Spanish Registry Group: 1C, 3B.

Disclosures

Ethical Compliance Statement: The project is being conducted in accordance with the ICH Good Clinical Practice version 6 Revision 2 standard, the fundamental ethical principles established in the Declaration of Helsinki and the Oviedo Convention, as well as the Spanish legal requirements for biomedical research (Biomedical Research Law 14/2007). The Project has been approved on 02/APR/2024 by the IRB “Comité de Ética de la Investigación Clínica de Galicia from Spain” with code number 2024/109. Written informed consents from all participants in this study will be 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. The protocol, statistical analysis plan and unidentified participant data will be available on request.

Funding Sources and Conflicts of Interest: The authors declare that there are no funding sources or conflicts of interest relevant to this work. We received grants from the “Fundación Professor Novoa Santos” as a result of the “CONVOCATORIA DE AYUDAS PARA LA REALIZACIÓN DE PROYECTOS DE INVESTIGACIÓN PARA GRUPOS EMERGENTES Y ASOCIADOS DEL INIBIC (2023/2024)”.

Financial Disclosures for the Previous 12 Months: DS‐G has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, Italfarmaco, Teva, Archímedes, Esteve, Stada, Merz, and grants from the “Fundación Professor Novoa Santos” as a result of the “CONVOCATORIA DE AYUDAS PARA LA REALIZACIÓN DE PROYECTOS DE INVESTIGACIÓN PARA GRUPOS EMERGENTES Y ASOCIADOS DEL INIBIC (2023/2024)”. ÁS has nothing to report. GG‐O has received honoraria for educational purposes from ABBIE, Zambon, Bial, Esteve and Italfarmaco. PM has received financial support from the Spanish Ministry of Science and Innovation (RTC2019‐007150‐1), the Instituto de Salud Carlos III‐Fondo Europeo de Desarrollo Regional (ISCIII‐FEDER) (PI16/01575, PI18/01898, PI19/01576, PI20/00613, PI21/01875, PI22/01704, PI23/00512), the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía (CVI‐02526, CTS‐7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI‐0471‐2013, PE‐0210‐2018, PI‐0459‐2018, PE‐0186‐2019), the Consejería de Transformación Económica, Industria, Conocimiento y Universidades de la Junta de Andalucía (PY20_00896), and support for attending meetings and/or travel or honorarium for lecturing from Abbott, Allergan, Abbvie, Bial, Britannia, Italfarmaco, Merz, UCB, Teva and Zambon. NL‐A has received honoraria for educational presentations and advice service or travel grants by Abbvie, Italfarmaco, Stada, Lundbeck, UCB, Esteve, Abbott, Zambon, and Bial. RG‐R has received honoraria and grants for lecturing, advisory services from Abbvie, Zambón, Bial, Merk, Stada. IL has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Zambon, Bial, and Teva. AP‐B has nothing to report. DA‐M has nothing to report. None. PS‐A has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, and Teva. IC has received honoraria for educational presentations and advice service by Abbvie, Zambon, Bial, Orion, Italfarmaco and Esteve. MB‐E has received honoraria for educational presentations by Dysport, Esteve, Bial, Italfármaco, Boston Sc. and Stada and for advice service by Esteve, Bial, Suazio. ÁS‐F has received grants or contracts from ERA‐NET Horizon 2020 program JPCOFUND2 (reference number HESOCARE‐329‐073), MDS (eDiary project) and Instituto de Salud Carlos III (reference number P122/01177), consulting fees from Abbvie, Esteve, Orion Pharma, and Prim, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Abbvie, Bayer, Esteve, MDS Society, EAN, Novartis, Monitor, Organon, Roche, SEN, Stada, Teva, and Zambon.

Supporting information

Figure S1. Frequency of patients presenting different severity of symptoms from the Motor Score (MSs; 15 items) according to the DAT (N = 280): DBS (N = 55); fLD/fCD (N = 136); CSAI (N = 57); LCIG (N = 10); LECIG (N = 19); HIFU (N = 3). 0, absence of symptoms; 1, mild; 2, moderate; 3, severe; 4, very severe. The χ ² test was applied. CSAI, continuous subcutaneous apomorphine infusion; DAT, device‐aided therapy; DBS, deep brain stimulation; Dys, dyskinesia; fLD/fCD, foslevodopa‐foscarbidopa; FOG, freezing of gait; LCIG, levodopa‐carbidopa intestinal gel infusion; LECIG, levodopa‐entacapone‐carbidopa intestinal gel infusion.

Figure S2. Frequency of patients presenting different severity of symptoms from the Non Motor Score (NMSs; 20 items) according to the DAT (N = 254): DBS (N = 51); fLD/fCD (N = 121); CSAI (N = 56); LCIG (N = 9); LECIG (N = 17). No data were collected in patients treated with HIFU. 0, absence of symptoms; 1, mild; 2, moderate; 3, severe; 4, very severe. The χ ² test was applied. CSAI, continuous subcutaneous apomorphine infusion; DAT, device‐aided therapy; DBS, deep brain stimulation; fLD/fCD, foslevodopa‐foscarbidopa; LCIG, levodopa‐carbidopa intestinal gel infusion; LECIG, levodopa‐entacapone‐carbidopa intestinal gel infusion; OH, orthostatic hypotension; RLS, restless legs syndrome.

Appendix A.

DATs‐PD GETM Spanish Registry STUDY GROUP.

Adarmes Gómez AD, Alonso Modino D, Álvarez Sauco M, Aneiros Díaz A, Ávila Rivera A, Baviera‐Muñoz R, Belmonte S, Blázquez‐Estrada M, Caballero Sánchez L, Caballol Pons N, Cabo L, Campins Romeu M, Campo Caballero D, Campolongo A, Cantarero Duque S, Carrillo García F, Casanova Mollá J, Casas Peña E, Castaño García B, Castellano Guerrero AM, Castrillo Sanz A, Cerdán Santacruz DM, Clavero Ibarra P, Cores Bartolomé C, Cots Foraster A, Cubo Delgado E, Delgado Ballestero T, Erdocia Goñi A, Escalante Arroyo S, Escamilla Sevilla F, Espinosa Rosso R, Fanjul Arbos S, Feliz Feliz C, Fernández‐Pajarín G, Fernández Revuelta A, Fernández Rodríguez B, Fernández Valle T, Freire Álvarez E, Gamo González E, García Fernández C, García Herruzo A, García‐Ramos R, García Ruíz Espiga P, Garrote Espina L, Gil Villar MP, Gómez Esteban JC, Gómez López de San Román C, Gómez Mayordomo V, Gómez Rapela C, González MV, González Ardura J, González Hernández A, González‐Ortega G, González Rojas N, Guerra Hiraldo JD, Gutiérrez García J, Hernández Vara J, Jesús Maestre S, Kulisevsky Bojarski J, Legarda L, López Ariztegui N, López Blanco R, López Dominguez D, López Manzanares L, López Veloso AC, López Valdés E, Lorenzo Barreto P, Lorenzo Brito JM, Lozano D, Macías García D, Madrid Navarro CJ, Martí Andrés G, Martí Martínez S, Martín García R, Martínez Castrillo JC, Martínez‐Torres I, Mata Álvarez Santullano M, Mauri Fabrega L, Méndez Guerrero A, Mendoza Rodríguez A, Mir Rivera P, Mondragón Rezola E, Monterde Ortega A, Morales Casado MI, Morata‐Martínez C, Muñoz Delgado L, Muñoz Ruíz T, Muro I, Novo Ponte S, Ojeda Lepe E, Olivares Romero J, Pagonabarraga J, Pardina Vilella L, Pareés Moreno, Pascual Sedano B, Paz González JM, Peral Quirós A, Pérez Calvo C, Pérez Rangel D, Perona Moratalla A, Planas‐Ballvé A, Prendes Fernández P, Quibus Requena L, Rábano Suárez P, Ramírez J, Rashid López R, Rebollo Lavado B, Rivero de Aguilar Pensado A, Rojas Pérez E, Ribacoba Díaz C, Romero Fábrega JC, Ruiz López M, Ruíz Martínez J, Samaniego Vinueza LB, San Eufrasio Martínez M, Sánchez‐Alonso P, Sánchez‐Ferro A, Sánchez Rodríguez A, Sancho Saldana A, Santos‐García D, Sastre Bataller L, Solano Vila B, Solleiro Vidal A, Suárez San Martín E, Tabar Comellas G, Tijero Merino B, Triguero Cueva L, Valero García MF, Valldeoriola Serra F, Vela L, Vinagre Aragón A, Vivas Villacampa L, Vives Pastor B, Yáñez Baña R.

First name	Last name	Centre
Diego	Santos García	Complejo Hospitalario Universitario de A Coruña
Jose Manuel	Paz González	Complejo Hospitalario Universitario de A Coruña
Carlos	Cores Bartolomé	Complejo Hospitalario Universitario de A Coruña
Lucia Belen	Samaniego Vinueza	Complejo Hospitalario Universitario de A Coruña
Ángela	Solleiro***	Complejo Hospitalario Universitario de A Coruña
María	Álvarez Sauco	Hospital General Universitario de Elche
Eric	Freire Álvarez	Hospital General Universitario de Elche
Juan Carlos	Martínez Castrillo	Hospital Universitario Ramón y Cajal
Isabel	Pareés Moreno	Hospital Universitario Ramón y Cajal
Samira	Fanjul Arbos	Hospital Universitario Ramón y Cajal
Ana Belén	Perona Moratalla	Complejo Hospitalario Universitario de Albacete
Inés	Legarda	Hospital Universitario Son Espases
Bàrbara	Vives Pastor	Hospital Universitario Son Espases
María Fuensanta	Valero García	Hospital Universitario Son Espases
Esther	Cubo Delgado	Hospital Universitario de Burgos
Nuria	López Ariztegui	Hospital Universitario de Toledo
Maria Isabel	Morales Casado	Hospital Universitario de Toledo
Guillermo	Tabar Comellas	Hospital Universitario de Toledo
Déborah	Alonso Modino	Hospital Universitario de la Candelaria
Jesús Norelis	Lorenzo Brito	Hospital Universitario de la Candelaria
Esther	Rojas Pérez	Hospital Universitario de la Candelaria
Iria	Cabo	Complejo Hospitalario Universitario de Pontevedra
Alejandro	Rivero de Aguilar Pensado	Complejo Hospitalario Universitario de Pontevedra
Jorge	Hernández Vara	Hospital Universitario Vall d'Hebron
Maria Victoria	González	Hospital Universitario Vall d'Hebron
Sara	Belmonte**	Hospital Universitario Vall d'Hebron
Juan Carlos	Romero Fábrega	Hospital Universitario Virgen de las Nieves
Francisco	Escamilla Sevilla	Hospital Universitario Virgen de las Nieves
Lucía	Triguero Cueva	Hospital Universitario Virgen de las Nieves
Carlos Javier	Madrid Navarro	Hospital Universitario Virgen de las Nieves
Rosa	Yáñez Baña	Complejo Hospitalario Universitario de Ourense
Asunción	Ávila Rivera	Complex Hospitalari Moisès Broggi
Núria	Caballol Pons	Complex Hospitalari Moisès Broggi
Anna	Planas‐Ballvé	Complex Hospitalari Moisès Broggi
Alejandro	Peral Quirós	Complex Hospitalari Moisès Broggi
Dolors	Lozano	Complex Hospitalari Moisès Broggi
Álvaro	Sánchez‐Ferro	Hospital 12 de Octubre
Pablo	Rábano Suárez	Hospital 12 de Octubre
Antonio	Méndez Guerrero	Hospital 12 de Octubre
Daniel	Pérez Rangel	Hospital 12 de Octubre
Jesús	Ramírez	Hospital 12 de Octubre
Frances	Valldeoriola Serra	Hospital Clínic
Rocío	García Ramos	Hospital Clínico Universitario San Carlos
Ana	Fernández Revuelta	Hospital Clínico Universitario San Carlos
Eva	López Valdés	Hospital Clínico Universitario San Carlos
Carmen	Ribacoba Díaz	Hospital Clínico Universitario San Carlos
Irene	Martínez‐Torres	Hospital Universitario la Fe
Carlos	Morata‐Martínez	Hospital Universitario la Fe
Raquel	Baviera‐Muñoz	Hospital Universitario la Fe
Marina	Campins Romeu	Hospital Universitario la Fe
Isabel	Sastre Bataller	Hospital Universitario la Fe
Pilar	Sánchez‐Alonso	Hospital Puerta de Hierro
Sabela	Novo Ponte	Hospital Puerta de Hierro
Elisa	Gamo González	Hospital Puerta de Hierro
Raquel	Martín García	Hospital Puerta de Hierro
Pablo	Mir Rivera	Hospital Universitario Virgen del Rocío
Laura	Muñoz Delgado	Hospital Universitario Virgen del Rocío
Astrid Daniela	Adarmes Gómez	Hospital Universitario Virgen del Rocío
Elena	Ojeda Lepe	Hospital Universitario Virgen del Rocío
Silvia	Jesús Maestre	Hospital Universitario Virgen del Rocío
Daniel	Macías García	Hospital Universitario Virgen del Rocío
Fátima	Carrillo García	Hospital Universitario Virgen del Rocío
Ana María	Castellano Guerrero***	Hospital Universitario Virgen del Rocío
Manuela	San Eufrasio Martínez***	Hospital Universitario Virgen del Rocío
Cristina	Pérez Calvo***	Hospital Universitario Virgen del Rocío
Andrés	García Herruzo	Hospital Universitario Virgen del Rocío
Cristina	Gómez Rapela*****	Hospital Universitario Virgen del Rocío
Lorena	Garrote Espina*****	Hospital Universitario Virgen del Rocío
Natalia	González Rojas*****	Hospital Universitario Virgen del Rocío
Marta	Blázquez Estrada	Hospital Universitario Central de Asturias
Esther	Suárez San Martín	Hospital Universitario Central de Asturias
Ciara	García Fernández	Hospital Universitario Central de Asturias
Patricia	Prendes Fernández****	Hospital Universitario Central de Asturias
Pedro	García Ruíz Espiga	Hospital Fundación Jiménez Díaz
Cici	Feliz Feliz	Hospital Fundación Jiménez Díaz
Raúl	Espinosa Rosso	Hospital Universitario de Jerez
Lara	Mauri Fabrega	Hospital Universitario de Jerez
Jaime	Kulisevsky Bojarski	Hospital Sant Pau de Barcelona
Berta	Pascual Sedano	Hospital Sant Pau de Barcelona
Javier	Pagonabarraga	Hospital Sant Pau de Barcelona
Antonia	Campolongo**	Hospital Sant Pau de Barcelona
Marina	Mata Álvarez‐Santullano	Hospital Universitario Infanta Sofía
Juan Carlos	Gómez Esteban	Hospital de Cruces
Tamara	Fernández Valle	Hospital de Cruces
Marta	Ruiz López	Hospital de Cruces
Beatriz	Tijero Merino	Hospital de Cruces
Lydia	López Manzanares	Hospital Universitario La Princesa
Inés	Muro	Hospital Universitario La Princesa
Elena	Casas Peña	Hospital Universitario La Princesa
Pablo	Lorenzo Barreto	Hospital Universitario La Princesa
Maria Pilar	Gil Villar	Hospital Universitari Arnau de Vilanova
Agustín	Sancho Saldana	Hospital Universitari Arnau de Vilanova
Laura	Quibus Requena	Hospital Universitari Arnau de Vilanova
Jesús	Olivares Romero	Hospital Universitario de Torrecárdenas
Belén	Rebollo Lavado	Hospital Universitario de Torrecárdenas
Lucía	Triguero Cueva*	Hospital Universitario de Torrecárdenas
Víctor	Gómez Mayordomo	Hospitales Vithas
Berta	Solano Vila	Hospital Josep Trueta de Girona y Hospital Santa Caterina de Salt
Anna	Cots Foraster	Hospital Josep Trueta de Girona y Hospital Santa Caterina de Salt
Daniel	López Dominguez	Hospital Josep Trueta de Girona y Hospital Santa Caterina de Salt
Lilian	Vivas Villacampa	Hospital Josep Trueta de Girona y Hospital Santa Caterina de Salt
Jessica	González Ardura	Hospital de Cabueñes
Belén	Castaño García	Hospital de Cabueñes
Antonio	Sánchez Rodríguez	Hospital de Cabueñes
Sonia	Escalante Arroyo	Hospital Virgen de la Cinta
Tania	Delgado Ballestero	Parc Taulí
Débora María	Cerdán Santacruz	Hospital General de Segovia
Amelia	Mendoza Rodríguez	Hospital General de Segovia
Ana	Castrillo Sanz	Hospital General de Segovia
Lorena	Caballero Sánchez	Hospital General de Segovia
Claudia	Gómez López de San Román	Hospital General de Segovia
Gustavo	Fernández‐Pajarín	Complejo Hospitalario Universitario de Santiago de Compostela
Jordi	Casanova Mollá	Hospital Universitario Sant Joan de Reus
Ángela	Monterde Ortega	Hospital Universitario Joan XXIII
Susana	Cantarero Duque	Hospital Universitario de Móstoles
Guillermo	González‐Ortega	Hospital Universitario de Móstoles
Beatriz	Fernández Rodríguez	Hospital Regional Universitario de Málaga
Teresa	Muñoz Ruíz	Hospital Regional Universitario de Málaga
Gloria	Martí Andrés	Hospital Universitario de Navarra, Pamplona, Navarra
Pedro	Clavero Ibarra	Hospital Universitario de Navarra, Pamplona, Navarra
Amaia	Erdocia Goñi	Hospital Universitario de Navarra, Pamplona, Navarra
Ana Carolina	López Veloso	Hospital Universitario Doctor Negrín, Las Palmas de Gran Canaria
Ayoze Nauzet	González Hernández	Hospital Universitario Doctor Negrín, Las Palmas de Gran Canaria
Juan Diego	Guerra Hiraldo	Hospital Universitario Doctor Negrín, Las Palmas de Gran Canaria
Raúl	Rashid López	Hospital Puerta del Mar, Cádiz
Raúl	Espinosa Rosso	Hospital Puerta del Mar, Cádiz
Silvia	Martí Martínez	Hospital General Universitario Alicante
Ángel	Aneiros Díaz	Complejo Hospitalario Universitario de Ferrol
Lydia	Vela	Hospital Fundación de Alcorcón
Javier	Ruíz Martínez	Hospital Universitario Donostia
Elisabet	Mondragón Rezola	Hospital Universitario Donostia
Ana	Vinagre Aragón	Hospital Universitario Donostia
Lara	Pardina Vilella	Hospital Universitario Donostia
David	Campo Caballero	Hospital Universitario Donostia
Javier	Gutiérrez García	Complejo Hospitalario Universitario de Granada San Cecilio
Roberto	López Blanco	Hospital Universitario Severo Ochoa, Leganés, Madrid

Note: The researchers are listed by center in chronological order according to the date they confirmed their participation in the project. * This investigator works at two different centers. All investigators are neurologists except those ones with the symbol: ** SN (specialized nurse); ***graduate in Biology (she will be responsible for remote data monitoring); ****neuropsychologist; *****, study coordinator.

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.