Real-world evidence on levodopa dose escalation in patients with Parkinsons disease treated with istradefylline

ObjectiveIstradefylline, a selective adenosine A2A receptor antagonist, is indicated in the US and Japan as adjunctive treatment to levodopa/decarboxylase inhibitors in adults with Parkinsons disease (PD) experiencing OFF time. This study aimed to observe patterns of dose escalation of levodopa over time in patients initiated on istradefylline. MethodsUsing Japanese electronic health record data, interrupted time series analyses were used to compare levodopa daily dose (LDD, mg/day) gradients in patients before and after initiation of istradefylline. Data were analyzed by period relative to istradefylline initiation (Month 1): pre-istradefylline (Months -72 to 0), early istradefylline (Months 1 to 24), and late istradefylline (Months 25 to 72). Subgroup analyses included LDD before istradefylline initiation (<400, [&ge;]400 to <600, [&ge;]600 mg/day) and treatment with or without monoamine oxidase-B inhibitors (MAO-BIs), catechol-O-methyltransferase inhibitors (COMTIs), or dopamine agonists before istradefylline initiation. ResultsThe analysis included 4026 patients; mean (SD) baseline LDD was 419.27 mg (174.19). Patients receiving [&ge;]600 mg/day levodopa or not receiving MAO-BIs or COMTIs demonstrated a significant reduction in LDD increase gradient for pre-istradefylline vs late-phase istradefylline ([&ge;]600 mg/day levodopa, -6.259 mg/day each month, p<0.001; no MAO-BIs, -1.819 mg/day each month, p=0.004; no COMTIs, -1.412 mg/day each month, p=0.027). ConclusionsThis real-world analysis of Japanese prescription data indicated that slowing of LDD escalation was observed in patients initiated on istradefylline, particularly in those receiving [&ge;]600 mg/day levodopa, suggesting istradefylline may slow progressive LDD increases. These findings suggest that initiating istradefylline before other levodopa-adjunctive therapies may mitigate LDD increases, potentially reducing occurrence or severity of levodopa-induced complications in long-term istradefylline treatment.