Parkinson Disease Symptoms Improved With Modification of Advanced Therapies


A new retrospective analysis revealed that modifying advanced therapies led to improved motor and subjective symptoms, emphasizing the importance of considering combination therapies when efficacy declines or adverse events arise.

Paul Lingor, MD, professor of neurology at the Technical University of Munich (TUM), in Germany

Paul Lingor, MD

A nationwide retrospective analysis newly published in Neurology showed that modification or combination of advanced therapies used in later stages of Parkinson disease (PD) was associated with improvement in motor symptoms or subjective symptoms among patients with PD. These findings suggest that an advanced therapy combination, either simultaneous or sequential, should be considered when the first advanced therapy decreases in efficacy over time or has adverse effects.1

Of 148 advanced treatments used in 116 patients, modifications were associated with significantly improved objective (median decrease, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS] Part III, 4.0 points; P <.001; MDS-UPDRS Part IV, 6.0 points; P <.001; MDS-UPDRS Part IV-off-time item, 1.0 points; P <.001) and subjective clinical outcome as well as decreased rates of adverse events (AEs). Notably, insufficient symptom control and adverse effects of the previous therapy were described as the main reasons reported for the modification of the advanced therapies.

Clinical Takeaways

  • Modification of advanced therapies for Parkinson disease offers substantial improvements in both motor and subjective symptoms.
  • The study highlights the importance of considering combination therapies, either simultaneous or sequential, when addressing insufficient symptom control or adverse effects.
  • Investigators emphasize the need for further large-scale studies to develop evidence-based clinical decision pathways and a recommendation to consider a change in treatment if advanced therapy fails to produce desired effects.

“With patients living longer, we will be faced more and more often with the question of what we can do for patients when an advanced treatment fails,” senior author Paul Lingor, MD, professor of neurology at the Technical University of Munich (TUM), in Germany, said in a statement.2 “We were able to show improvement for patients from a change in treatments is almost the same as when the original treatment is introduced. This is an enormous benefit.”

READ MORE: Short- and Long-Duration Response to Levodopa Critical to Improving Motor Performance in Parkinson Disease

Investigators assessed simultaneous or sequential advanced therapy combinations among patients with PD at the start of the initiation of the second advanced therapies in Germany since 2005. The data were gathered retrospectively by modular questionnaires from 22 PD centers based on information about the centers’ patients such as on their clinical and therapeutical data. The clinical data aspects included Mini-Mental Status Test/Montréal Cognitive Assessment, MDS-UPDRS, adverse effects, reasons for advanced therapies modification while the therapeutics aspects gathered included advanced therapies with specifications and oral medication.

In the subgroup analyses conducted by the investigators of the current study, the findings suggest addition of deep brain stimulation (DBS) or pump therapies in patients administered advanced therapies with leading dyskinesia, addition of levodopa/carbidopa intestinal gel (LCIG) for leading other cardinal motor symptoms, and addition of LCIG or continuous subcutaneous apomorphine infusion for dominant off-time. Based on the gathered data, the researchers observed that DBS was the most long-lasting therapy-until requiring a modification.

All told, the collected information for the study had incomplete data sets, which led to smaller sample sizes than the overall cohort in some of the analyses. Furthermore, the data sets for the clinical evaluation of the additional modifications were smaller than for the first one, which prevented statistically robust clinical conclusions for the changes. The authors noted it was not possible to determine whether the clinical assessment was documented during ON or OFF for some of the patients. Additionally, a matched control group was not available in this case collection because the authors relied on nonblinded clinical routine data. The investigators also noted expectancy of clinical success after any modifications might have resulted in better scoring and variability in clinical outcome as some patients did not benefit from the modification.

“Based on the results of our study, we can now make a clear recommendation for action,” Lingor, also codirector of the Parkinson’s Outpatient Center at the TUM, said in a statement.2 “If an advanced treatment does not produce results or bring about the desired effects, a change in treatment should be considered. This insight is far from trivial, because it would have been entirely possible that all available treatments would fail at an advanced stage of the disease.” Lingor and colleagues noted that further and prospective large scale studies are needed for detailed outcome analyses including subgroup analyses, and for the development of evidence based clinical decision pathways.

1. Pürner D, Hormozi M, Weiß D, et al. Nationwide Retrospective Analysis of Combinations of Advanced Therapies in Patients With Parkinson Disease. Neurology. 2023;101(21):e2078-e2093. doi:10.1212/WNL.0000000000207858
2. Parkinson's: New hope when treatment options seem exhausted. News Release. Technical University of Munich. Published November 6, 2023. Accessed December 15, 2023.
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