title: Association of time-to-levodopa with initial Parkinsonian medication: a retrospective cohort study.
abstract: OBJECTIVE
  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.
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Reese
authors.forename: Hajo
authors.initials: H
authors.lastname: Hamer
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.forename: Adam
authors.initials: A
authors.lastname: Strzelczyk
authors.forename: Ulrich O
authors.initials: UO
authors.lastname: Mueller
authors.forename: Christina
authors.initials: C
authors.lastname: Heilmaier
authors.forename: Karel
authors.initials: K
authors.lastname: Kostev
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy*; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D008996:Monoamine Oxidase Inhibitors; D007980:Levodopa