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

TY - JOUR

T1 - Nationwide Retrospective Analysis of Combinations of Advanced Therapies in Patients With Parkinson Disease

AU - Pürner, Dominik

AU - Hormozi, Mohammad

AU - Weiß, Daniel

AU - Barbe, Michael T

AU - Jergas, Hannah

AU - Prell, Tino

AU - Gülke, Eileen

AU - Pötter-Nerger, Monika

AU - Falkenburger, Björn

AU - Klingelhöfer, Lisa

AU - Gutsmiedl, Pia K

AU - Haslinger, Bernhard

AU - Jochim, Angela M

AU - Wolff, Andreas

AU - Schröter, Nils

AU - Rijntjes, Michael

AU - van Riesen, Christoph

AU - Scheller, Ute

AU - Wolz, Martin

AU - Amouzandeh, Ali

AU - Ebersbach, Georg

AU - Gruber, Doreen

AU - Kohl, Zacharias

AU - Maetzler, Walter

AU - Paschen, Steffen

AU - Pérez-González, Pablo

AU - Rozanski, Verena

AU - Schwarz, Johannes

AU - Südmeyer, Martin

AU - Torka, Elisabeth

AU - Wesbuer, Simone

AU - Bornmann, Sarah

AU - Flöel, Agnes

AU - Ip, Chi Wang

AU - Krause, Patricia

AU - Kühn, Andrea A

AU - Csoti, Ilona

AU - Herting, Birgit

AU - van de Loo, Simone

AU - Basheer, Aniz Ahammed

AU - Liszka, Robert

AU - Jost, Wolfgang H

AU - Koschel, Jiri

AU - Haller, Bernhard

AU - Lingor, Paul

PY - 2023/11/21

Y1 - 2023/11/21

N2 - BACKGROUND AND OBJECTIVES: Advanced therapies (ATs; deep brain stimulation [DBS] or pump therapies: continuous subcutaneous apomorphine infusion [CSAI], levodopa/carbidopa intestinal gel [LCIG]) are used in later stages of Parkinson disease (PD). However, decreasing efficacy over time and/or side effects may require an AT change or combination in individual patients. Current knowledge about changing or combining ATs is limited to mostly retrospective and small-scale studies. The nationwide case collection Combinations of Advanced Therapies in PD assessed simultaneous or sequential AT combinations in Germany since 2005 to analyze their clinical outcome, their side effects, and the reasons for AT modifications.METHODS: Data were acquired retrospectively by modular questionnaires in 22 PD centers throughout Germany based on clinical records and comprised general information about the centers/patients, clinical (Mini-Mental Status Test/Montréal Cognitive Assessment, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS], side effects, reasons for AT modification), and therapeutical (ATs with specifications, oral medication) data. Data assessment started with initiation of the second AT.RESULTS: A total of 148 AT modifications in 116 patients were associated with significantly improved objective (median decrease of MDS-UPDRS Part III 4.0 points [p < 0.001], of MDS-UPDRS Part IV 6.0 points [p < 0.001], of MDS-UPDRS Part IV-off-time item 1.0 points [p < 0.001]) and subjective clinical outcome and decreasing side effect rates. Main reasons for an AT modification were insufficient symptom control and side effects of the previous therapy. Subgroup analyses suggest addition of DBS in AT patients with leading dyskinesia, addition of LCIG for leading other cardinal motor symptoms, and addition of LCIG or CSAI for dominant off-time. The most long-lasting therapy-until requiring a modification-was DBS.DISCUSSION: Changing or combining ATs may be beneficial when 1 AT is insufficient in efficacy or side effects. The outcome of an AT combination is comparable with the clinical benefit by introducing the first AT. The added AT should be chosen dependent on dominant clinical symptoms and adverse effects. Furthermore, prospective trials are needed to confirm the results of this exploratory case collection.CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, in patients with PD, changing or combining ATs is associated with an improvement in the MDS-UPDRS or subjective symptom reporting.

AB - BACKGROUND AND OBJECTIVES: Advanced therapies (ATs; deep brain stimulation [DBS] or pump therapies: continuous subcutaneous apomorphine infusion [CSAI], levodopa/carbidopa intestinal gel [LCIG]) are used in later stages of Parkinson disease (PD). However, decreasing efficacy over time and/or side effects may require an AT change or combination in individual patients. Current knowledge about changing or combining ATs is limited to mostly retrospective and small-scale studies. The nationwide case collection Combinations of Advanced Therapies in PD assessed simultaneous or sequential AT combinations in Germany since 2005 to analyze their clinical outcome, their side effects, and the reasons for AT modifications.METHODS: Data were acquired retrospectively by modular questionnaires in 22 PD centers throughout Germany based on clinical records and comprised general information about the centers/patients, clinical (Mini-Mental Status Test/Montréal Cognitive Assessment, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS], side effects, reasons for AT modification), and therapeutical (ATs with specifications, oral medication) data. Data assessment started with initiation of the second AT.RESULTS: A total of 148 AT modifications in 116 patients were associated with significantly improved objective (median decrease of MDS-UPDRS Part III 4.0 points [p < 0.001], of MDS-UPDRS Part IV 6.0 points [p < 0.001], of MDS-UPDRS Part IV-off-time item 1.0 points [p < 0.001]) and subjective clinical outcome and decreasing side effect rates. Main reasons for an AT modification were insufficient symptom control and side effects of the previous therapy. Subgroup analyses suggest addition of DBS in AT patients with leading dyskinesia, addition of LCIG for leading other cardinal motor symptoms, and addition of LCIG or CSAI for dominant off-time. The most long-lasting therapy-until requiring a modification-was DBS.DISCUSSION: Changing or combining ATs may be beneficial when 1 AT is insufficient in efficacy or side effects. The outcome of an AT combination is comparable with the clinical benefit by introducing the first AT. The added AT should be chosen dependent on dominant clinical symptoms and adverse effects. Furthermore, prospective trials are needed to confirm the results of this exploratory case collection.CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, in patients with PD, changing or combining ATs is associated with an improvement in the MDS-UPDRS or subjective symptom reporting.

U2 - 10.1212/WNL.0000000000207858

DO - 10.1212/WNL.0000000000207858

M3 - SCORING: Journal article

C2 - 37914414

VL - 101

SP - e2078-e2093

JO - NEUROLOGY

JF - NEUROLOGY

SN - 0028-3878

IS - 21

ER -