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Association of time-to-levodopa with initial Parkinsonian medication: a retrospective cohort study

Jens Peter Reese, Hajo Hamer, Wolfgang H. Oertel, Adam Strzelczyk,Ulrich O. Mueller, Christina Heilmaier, and Karel Kostev

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Volume 53 p. 107 - 114

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 2/2015 (107-114)

Association of time-to-levodopa with initial Parkinsonian medication: a retrospective cohort study

Jens Peter Reese¹,², Hajo Hamer², Wolfgang H. Oertel², Adam Strzelczyk², Ulrich O. Mueller¹, Christina Heilmaier³, and Karel Kostev⁴

¹Institute of Medical Sociology and Social Medicine, ²Department of Neurology, Philipps-University Marburg, Marburg, Germany, ³City Hospital Zuerich, Switzerland, and ⁴IMS Health, Epidemiology, Frankfurt, Germany
Objectives: To determine the initial distribution of medication in patients with de novo Parkinson’s disease (PD), to estimate the share of patients who not receive a recommended initial therapy according to current German guidelines, and to compare the time-to-levodopa. Methods: We used the Disease Analyzer database (IMS HEALTH), containing basic medical data from ~ 20 million patients in Germany. The primary outcome was the therapy change rate from initial treatment to levodopa estimated by Kaplan-Meier analyses. A Cox proportional hazards model was used to estimate the relationship between time-to-levodopa and confounders for a maximum follow-up of 10 years (between January 2002 and December 2011). Adjusted hazard ratios (HR) and 95% confidence intervals (CI) are presented for change-to-levodopa rate. Results: A representative sample of de-novo patients diagnosed with PD was drawn (n = 108,885). 71.8% of patients received levodopa as a first line treatment. 29,708 patients started with other anti-PD substances: 13.3% with dopamine agonists (DA), 3.6% with amantadine, 5.9% with anticholinergics, and 0.8% with monoamine oxidase B (MAO-B) inhibitors. Therefore, the proportion of patients who not receive a recommended initial therapy according to current German guidelines was ~ 10%. 29.0% of patients not starting with levodopa switched to levodopa within 5 years. After 5 years, more than 80% of PD patients using anticholinergics as their initial treatment remained levodopa-free. MAOB- inhibitors and DAs showed significantly lower proportions of levodopa-free patients after 5 years (35% and 55%, respectively). Compared to MAO-B inhibitors, the HR for switching to levodopa was 0.38 (CI 0.34 – 0.43; p < 0.001) for anticholinergics and 0.85 (CI 0.75 – 0.97; p = 0.017) for nonergot DA. Conclusions: Surprisingly, initial treatment with anticholinergics is correlated with the longest delay of levodopa treatment among all monotherapies. Our results suggest re-evaluating the comparative effectiveness of all initial PD treatments in head-tohead comparisons.Correspondence to:
Dr. Karel Kostev
IMS Health, Epidemiology
Darmstädter Str. 108, 60598 Frankfurt, Germany
Email: [email protected]

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