Twenty Years of Apomorphine Therapy – How Does it Compare with Levodopa?

Abstract

Apomorphine administered subcutaneously has provided clinicians with an effective option for the rapid resolution of the symptoms of Parkinson's disease (PD) for over a quarter of a century. It is available for use either as an intermittent injection or a continuous infusion, depending on the severity of the patient's symptoms. This satellite symposium, held during the 18th International Congress of Parkinson's Disease and Movement Disorders in Stockholm, Sweden, from 8-12 June 2014, and chaired by Professor Andrew Lees, set out to review the extensive clinical experience of subcutaneous apomorphine in the management of PD accumulated over the past 25 years. It also aimed to explore why it continues to play such a valuable therapeutic role in this setting. The presenters highlighted key clinical data demonstrating why apomorphine is an effective choice for the management of both motor and non-motor symptoms in PD. Results from the limited number of comparative studies of apomorphine continuous infusion with other therapies for complex PD suggest that it has a robust motor effect, resulting in a reduction of OFF periods comparable to that achieved with more invasive options such as intrajejunal levodopa infusion or deep brain stimulation. In a large European study, apomorphine infusion has been shown to provide similar improvements in health-related quality of life to intrajejunal levodopa infusion but with a superior side-effect profile. In addition, apomorphine infusion has demonstrated beneficial non-motor effects in PD patients and reports suggest it is associated with low rates of impulse control disorders (ICDs). The motor fluctuations that occur over time in PD patients treated with oral levodopa present a management challenge as the disease progresses. Many PD patients experience these OFF periods despite optimised oral therapy and the use of multiple medications. They are due to both end-of-dose wearing OFF and delayed time to ON (TTO). A prolonged TTO is common in PD patients who have gastroparesis (delayed gastric emptying) whereby the levodopa dose is delayed exiting the stomach and is slow in reaching its site of absorption in the small intestine. Alternative non-oral formulations that avoid the gastrointestinal route, such as subcutaneous apomorphine intermittent injection, have therefore been investigated for the relief of motor fluctuations in this setting. Interim results from the ongoing Apokyn for Motor IMProvement of Morning AKinesia Trial (AM IMPAKT) study have shown that subcutaneous apomorphine injection is a valuable treatment option in PD patients with morning akinesia. This is due to a delayed onset of levodopa dose as it produces a rapid and reliable TTO, with 95 % of patients achieving at least a 20-minute reduction in TTO and an average reduction of 40 minutes. Patients also experienced improvements in Unified Parkinson's Disease Rating Scale (UPDRS) motor score and Hoehn and Yahr stage, as well as measures of quality of life and global impression of severity.

Sublingual apomorphine (APL-130277) for the acute conversion of OFF to ON in Parkinson's disease

“…This resulted in a calculated mean time to full ON of approximately 24 minutes, but this is likely to be overinflated because some patients turned ON before 15 minutes and others before the 30‐minute time point. However, even calculating time to full ON in this way, the result is comparable to that seen with an injection of subcutaneous apomorphine in the APO202 and APO301 studies as well as the interim analysis from the AM‐IMPAKT study …”

Effective Delivery of Apomorphine in the Management of Parkinson Disease

“…29 Interim results from the ongoing apokyn for motor improvement of morning akinesia trial study have shown that subcutaneous apomorphine injection produces a rapid and reliable TTO, with 95% of patients with morning akinesia achieving at least a 20-minute reduction in TTO and an average reduction of 40 minutes. 47,48 …”