OBJECTIVES: To assess the comparative risk of adverse effects (AEs) across common treatment regimens for Parkinson’s disease (PD) in a large, real-world population.
METHODS: Retrospective analyses were conducted using the MarketScan database, an employer-based source of inpatient, outpatient, and pharmacy claims for >30 million lives. Patients had ≥1 PD diagnosis (ICD-9-CM 332.0) during 2000-2011 and ≥1 of the following anti-PD regimens: levodopa monotherapy (L-dopa), dopamine agonist monotherapy (DA), anticholinergic monotherapy (AC), L-dopa+DA, MAOB-inhibitor monotherapy (MAOB), L-dopa+COMT-inhibitor (L-dopa+COMT), L-dopa+AC, L-dopa+MAOB, or amantadine monotherapy (AMTD). Index groups were assigned based on first regimen exposed to. Patients had ≥6 months pre-index plan enrollment and were followed from index until AE or earliest of new regimen start, disenrollment, or database end. Cox models were estimated for each AE with covariates for index regimen (reference: MAOB), demographics, and pre-index comorbidities and AEs.
RESULTS: 41,652 patients met the inclusion criteria (mean[SD] age: 73.4[11.0] years, 57.5% male). Index regimen distribution was: L-dopa (n=28,249), DA (n=7,775), AC (n=1,496), L-dopa+DA (n=578), MAOB (n=1,498), L-dopa+COMT (n=343), L-dopa+AC (n=106), L-dopa+MAOB (n=198), AMTD (n=1,409). AC, L-dopa+AC, and AMTD carried increased dyskinesia risk versus MAOB (hazard ratios (HRs) [95% CIs]: 2.1[1.8-2.5 ], 1.7[1.1-2.7], and 1.9[1.6-2.2], respectively). L-dopa+DA and L-dopa+MAOB had increased risk of orthostatic hypotension (HRs: 2.2[1.4-3.5] and 2.5[1.3-5.0]). L-dopa+DA carried the highest edema risk (HR: 2.1[1.6-2.6]). L-dopa+DA and AMTD had increased risk of hallucinations (HRs: 2.6[1.3-5.1] and 3.0[1.8-4.8]). For 6 of 9 AEs examined, L-dopa+DA had significantly (p<0.05) increased risk versus MAOB; in 4 of these (orthostatic hypotension, edema, nausea, hallucinations), L-dopa+DA carried the highest or second highest HR versus MAOB amongst all regimens examined.
CONCLUSIONS: Treatments with high dopaminergic levels (L-dopa+DA) generally carried increased AE risk versus MAOB monotherapy. However, other dopamine-containing and non-dopaminergic regimens also carried increased AE risk versus MAOB. These findings highlight practical challenges presented by current PD treatments.
