TEMP - Therapy Escalation in M. Parkinson - A German Regional Multicenter Survey

Research Article

Austin J Clin Neurol 2021; 8(3): 1154.

TEMP - Therapy Escalation in M. Parkinson - A German Regional Multicenter Survey

Gandor F1,2*, Kübler D3, Ebersbach G1, Kühn A3, Müller J4, Klostermann F5, Müller Th6, Lipp A3,7, Kivi A4, Jugel C5 and Gruber D1,2

1Movement Disorders Hospital, Kliniken Beelitz GmbH, Beelitz-Heilstätten, Germany

2Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany

3Department of Neurology, Charité - Universitätsmedizin Berlin - Campus Charité Mitte, Section for Movement Disorders and Neuromodulation, Berlin

4Department of Neurology, Vivantes Klinikum Spandau, Berlin

5Department of Neurology, Charité - Universitätsmedizin Berlin - Campus Benjamin Franklin, Berlin

6Department of Neurology, Alexianer St. Joseph-Krankenhaus, Berlin

7Department of Neurology, Park-Klinik Weißensee, Berlin

*Corresponding author: Florin Gandor, Movement Disorders Hospital, Kliniken Beelitz GmbH, Strasse nach Fichtenwalde 16, 14547 Beelitz-Heilstätten, Germany

Received: September 20, 2021; Accepted: October 19, 2021; Published: October 26, 2021

Abstract

Objective: To characterize socio-demographic and disease-specific data of Parkinson’s disease patients before and 1 year after therapy escalation with subcutaneous apomorphine (APO), levodopa/carbidopa intestinal gel (LCIG), or subthalamic deep brain stimulation (STN-DBS) in an observation trial under real life conditions.

Methods: Between 2014-2015, patients undergoing therapy escalation were consecutively included in 5 movement disorders centers. Motor and nonmotor symptoms were scored before and 1 year following initiation of invasive treatments. Therapy adherence, changes of scores and oral medication were evaluated.

Results: In this open-label, prospective, 12-months, multicenter real-lifestudy 63 patients were included. 31 received DBS, 19 were commenced on LCIG, 15 received treatment with APO. 16 patients were lost for follow-up. Therapy adherence after one year in the STN-DBS-group was 100%, in the LCIG-group 87.5%, and in the APO-group 47%. Therapy termination in the APO-cohort was due to onset of hallucinations, orthostatic hypotension and inflammatory skin lesions and necrosis. After one year, UPDRS-III scores improved for STN-DBS patients. All groups gained ON-time with no differences between the 3 arms. STN-DBS patients had less ON-time with dyskinesia compared to APO- and LCIG-patients. Levodopa daily dose was decreased by 50% in STN-DBS patients, and 33% in APO patients, respectively.

Conclusion: All three escalation options improved ON-time. Therapy adherence in the APO-group was less than 50% after 1 year, making it a potential bridging option while awaiting a more invasive treatment.

Keywords: Parkinson’s disease: escalation; apomorphine; Levodopa/ Carbidopa Intestinal Gel; deep brain stimulation

Introduction

In the early stages of Parkinson’s Disease (PD), motor symptoms are usually well controlled by oral or transdermal dopaminergic medication. However, with longer disease duration, the incidence of levodopa induced motor fluctuations increases under dopaminergic treatment [1]. Adjustment of levodopa or dopamine agonist single doses and frequency may transiently improve motor and nonmotor fluctuations, and a combination with COMT-inhibitors or MAO-B-inhibitors might temporarily suffice to control fluctuations. When adjustment of oral medication however does not satisfactorily control motor problems [2], an escalation of therapy with invasive treatment alternatives is considered as a therapeutic option. Subcutaneous apomorphine administration with a pump (APO) [3], levodopa/carbidopa intrajejunal gel-infusion (LCIG) [4] and deep brain stimulation of the subthalamic nucleus (STN-DBS) [5,6] are available. They not only differ in terms of invasiveness, but also in side effect profiles and need for post-interventional care. These different aspects predispose for a specific invasive therapy option based on an individual decision. To date there are some therapy recommendations at hand as to which escalation is recommended to what patient clientel [7-9]. Real-life compliance data of therapy adherence are limited. We therefore performed a real-life observational study on PD patients escalated on either APO, LCIG, or STN-DBS.

Methods

This study was approved by the Ethics Committee of the Brandenburg Medical Board. All participants provided written informed consent.

Between 5/2014 and 1/2015, PD-patients fulfilling the UK Parkinson’s Disease Society Brain Bank Criteria [10] that underwent a therapy escalation with either APO, LCIG, or STN-DBS were consecutively included in five Neurology Departments (two university tertiary medical centers, one tertiary care hospital, one secondary care hospital and one specialized Movement Disorders Hospital) in Berlin and Brandenburg, Germany. Socio-demographic data, Unified Parkinson’s disease rating scale (UPDRS)-III and MDSUPDRS I, II, IV scores to define non-motor, motor impairment and motor complications, percentages of daily OFF-time, daily ON-time and daily ON-time with dyskinesia, Hoehn & Yahr stage [11] to assess the global disease severity, and current dopaminergic treatment were recorded. One year after therapy escalation, changes in diseasespecific scores and oral dopaminergic medication were assessed.

Statistical analysis was performed using IBM SPSS statistics software. Distribution was calculated applying Shapiro-Wilk-Test, variance using the F-test. Difference between groups was assessed applying Kruskal-Wallis and post-hoc Mann-Whitney U-tests, since all values were not normally distributed or normally distributed but unequally variant. Alpha was set at 0.05.

Results

Within the survey period, 63 eligible patients consented to participate. 31 (49%) patients were escalated with STN-DBS, 17 (27%) received LCIG, and 15 (24%) were commenced on APO, respectively. 21 patients were lost for follow up (2/15 APO patients, 12/17 LCIG patients, 7/31 STN-DBS patients). One patient in the LCIG-group died of unrelated cause. Therapy adherence after one year in those patients available for follow-up was 100% for STN-DBS and LCIG. 8/13 (62%) APO patients discontinued treatment due to hallucinations (n=5), orthostatic hypotension (n=2), or cutaneous necrosis at the injection site (n=1).

Citation: Gandor F, Kübler D, Ebersbach G, Kühn A, Müller J, Klostermann F, et al. TEMP - Therapy Escalation in M. Parkinson - A German Regional Multicenter Survey. Austin J Clin Neurol 2021; 8(3): 1154.