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Researchers Identify Intensified Therapy as Marker of Advanced PD


Intensified treatment for Parkinson disease (PD) as noted in patients' electronic medical records can serve as an indicator of more advanced disease.

Treatment intensity can be considered an objective and robust indicator of more advanced Parkinson disease (APD), according to findings of a recent retrospective analysis.

As such, this marker can be integrated into electronic medical record alerts to actively target patients with more advanced disease and better guide-risk appropriate care, authors said. Results were published in Movement Disorders.

Once patients with PD progress beyond early stages of the disease, responses to oral treatments wane and device-assisted therapies (DAT) may be helpful in improving motor function, while timely interventions for patients with PD can help reduce symptoms, maintain quality of life, and reduce direct health care costs, researchers explained.

“Yet, the existing instruments for the identification of patients with APD are complicated, involve multiple subjective and objective factors, and generally fail to comprehensively assess the full range of PD manifestations,” they said.

To address the gap in clinical profiling of patients with APD, investigators assessed real-world data from a health care organization in Israel to see whether presence of intensified drug regimens serves as a proxy for ADP.

The Maccabi Health Service (MHC) covers 26% of the Israeli population and the system’s electronic medical records (EMRs) database includes information on medical prescriptions, consultations, hospitalizations, and other metrics.

Anonymous medical data recorded between January 2000 and January 2018 were assessed for the current analysis. "Date of first diagnosis or first anti-PD medication purchase, the earliest of the two, was defined as the first indication of PD,” authors wrote.

In addition, non-intensified therapy (NIT) was defined as oral levodopa <5 times/day and <1000 mg levodopa equivalent dose/day (LEDD), and intensified therapy (IT) as oral levodopa ≥5 times/day and/or ≥ 1000 mg LEDD based on Tomlinson’s proposal and expert opinion, they added.

Individuals who switched from NIT to IT during the timeframe were classified as IT only. A total of 2037 individuals made up the IT cohort and 3402 were classified as NIT. Mean age at index for both cohorts was around 72 years and more than half in each were men.

Analyses revealed:

  • IT was associated with significantly (P <.05) higher use of health care resources including visits to the neurologist, geriatrician, physiotherapist, speech therapist and occupational therapist
  • Risk for mortality (17%; 95% CI, 5%–30%), disability (57%; 95% CI, 41%–75%), and hospitalization (16%; 95% CI, 7%–27%) was increased for the IT patients compared with the NIT patients
  • IT patients were 4.7 times more likely to be treated with DAT compared with NIT patients (HR, 4.7; 95% CI, 2.9–7.8)
  • A higher prevalence of cognitive dysfunction (7.5%vs. 4.1%) and sleep disorders (30% vs. 23.5%) was noted among IT compared with NIT patients
  • In the 12 months following the index date, IT patients had 1.5 times (95% CI, 1.2–1.8; P < .001) more hospitalization events and 1.9-fold longer lengths of stay at hospital (95% CI, 1.8–2.1; P <.001) compared with NIT patients

Data also showed health care expenditures were 21.5% higher for IT patients, with higher costs most significant in medication purchases, hospital stays, and emergency room visits. Patients with IT were more likely to have underlying sleep disorders and cognitive dysfunction at baseline, with sleep disorders serving as one of the most frequently reported non-motor symptoms of PD.

“Close monitoring of this highly accessible indicator can facilitate identification of progressing PD and dictate referral to specialized care to improve clinical outcomes and decrease potential health hazards,” researchers wrote.

A lack of verification ensuring prescribed medications were actually taken marks a limitation to the analysis, and authors were unable to account for major complications of advanced disease including psychosis, autonomic disturbances, cognitive deterioration, and balance impaitment, all of which can elevate disease burden.

“Early identification of failing effectiveness of current treatments using a simple and easily accessible indicator will assist in optimizing PD treatment strategies andstandardizingclinicalpracticewhilereducing health care expenditures,” they said.

“Such a proxy model can potentially serve as a meaningful end point for assessing the impact of investigational products on disease progression in future disease-modifying trials,” authors concluded.


Barer Y, Gurevich T, Chodick G, et al. Advanced-stage Parkinson’s disease” from identification to characterization using a nationwide data base. Mov Disord. Published online April 29, 2022. doi:10.1002/mdc3.13458

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