Switching and Combining Device-Aided Therapies in Advanced Parkinson’s Disease: A Double Centre Retrospective Study

Abstract

Background: Device-aided therapies (DAT), such as continuous subcutaneous apomorphine infusion (CSAI), levodopa-carbidopa intestinal gel infusion (LCIG), and deep brain stimulation of the subthalamic nucleus (STN-DBS), have markedly changed the treatment landscape of advanced Parkinson’s disease (aPD). In some patients, it is necessary to switch or combine DATs for various reasons. The aim of this retrospective study was to explore the frequency and reasons for switching between or combining DATs in two movement disorders centres in Slovenia and Israel. Methods: We collected and analysed demographic and clinical data from aPD patients who switched between or combined DATs. Motor and non-motor reasons, adverse events for switching/combining, and their frequency were examined, as was the effect of DAT using the Global Improvement subscale of the Clinical Global Impression Scale, Movement Disorders Society Unified Parkinson’s Disease Rating Scale part III, Mini Mental State Examination, and Parkinson’s Disease Questionnaire 39. Descriptive statistics and non-parametric tests were used to analyse the data. Results: Of 505 aPD patients treated with DATs at both centres between January 2009 and June 2021, we identified in a total of 30 patients (6%) who either switched DAT (n = 24: 7 LCIG-to-STN−DBS, 1 LCIG-to-CSAI, 5 CSAI-to STN−DBS, 8 CSAI-to-LCIG, 1 STN−DBS-to-LCIG, 1 LCIG-to-CSAI-to-STN−DBS, and 1 STN−DBS-to-CSAI-to-LCIG) or combined DATs (n = 6:5 STN−DBS+LCIG and 1 STN−DBS+CSAI-to-STN−DBS+LCIG). In most of these patients, an inadequate control of motor symptoms was the main reason for switching or combining DATs, but non-motor reasons (related to the disease and/or DAT) were also identified. Conclusions: Switching between and combining DATs is uncommon, but in some patients brings substantial clinical improvement and should be considered in those who have either inadequate symptom control on DAT treatment or have developed DAT-related complications.

Adverse effects of levodopa/carbidopa intrajejunal gel treatment: A single‐center long‐term follow‐up study

“…LCIG treatment was discontinued in case of severe adverse effects, in case of switch to another device‐aided treatment, 20 lack of caregiver, unrelated severe diseases that interfered with treatment also in case of reduced effectiveness of LCIG in very advanced disease stage. The decision to discontinue treatment was made by a multidisciplinary team and in agreement with patient and/or caregiver after a detailed in hospital evaluation of the patient and taking into consideration the efficiency of LCIG on multiple aspects of advanced PD with an emphasis on patient's and caregiver's quality of life.…”

Advanced therapies in Parkinson’s disease: an individualized approach to their indication

“…This is also supported by several recent studies, which have shown that patients also benefit from a combination or sequential application of various intensified therapies. Several retrospective case series show that both the combination and the sequential use of intensified therapeutic procedures can lead to significant clinical improvement (Sesar et al 2019;Georgiev et al 2022;Pürner et al 2023). This is supported by a small prospective case series that showed a significant decrease in motor impairment with the addition of LCIG in patients with DBS and therapy-refractory symptoms (Regidor et al 2017).…”

Nationwide Retrospective Analysis of Combinations of Advanced Therapies in Patients With Parkinson Disease

“…33 Only few analyses consider patients with more than 1 AT change. 22,[31][32][33] No randomized blinded trials are available. The vast majority of studies to date attribute the decision to combine ATs to insufficient motor control [21][22][23][24][25][26][29][30][31][32][33][34][35] and adverse effects of the previous AT 21,25,26,[31][32][33][34][35] and document a relevant clinical improvement by combining ATs, in regard to main symptoms of PD 20,24,30,32 or motor complications.…”

“…22,[31][32][33] No randomized blinded trials are available. The vast majority of studies to date attribute the decision to combine ATs to insufficient motor control [21][22][23][24][25][26][29][30][31][32][33][34][35] and adverse effects of the previous AT 21,25,26,[31][32][33][34][35] and document a relevant clinical improvement by combining ATs, in regard to main symptoms of PD 20,24,30,32 or motor complications. [20][21][22][23]25,26,29,30,35 In 2 studies, CSAI was used as bridging therapy to DBS, 20,33 2 special cases used DBS for controlling biphasic-like dyskinesias induced by LCIG therapy, 27,28 and 1 study used LCIG as a rescue for DBSunresponsive new freezing of gait after STN-DBS.…”

“…Previously, AT combinations were mostly described in retrospective case collections with a limited sample size (n < 10). [21][22][23][24][25][26][27][28][29][30] To date, only 5 cohort studies (n > 10) have been published, 20,[31][32][33][34] the largest one comprising 54 evaluated individuals. 33 Only few analyses consider patients with more than 1 AT change.…”