Should We Consider Subcutaneous Apomorphine Infusions for Parkinson’s Disease Patients Who Do Not Want Deep Brain Stimulation or a Dopamine Pump?
There has been a growing interest among patients and families for a “nonsurgical” alternative to deep brain stimulation or to Duopa pump therapy. The idea of brain surgery or of a feeding tube have been cited as being undesirable for large numbers of PD patients. The hope is that ultimately pharmacological therapies may one day provide a strong enough treatment alternative for moderate to severe Parkinson’s related motor fluctuations and dyskinesia. For many PD patients, optimizing medical therapy has failed to provide enough relief from these disabling PD manifestations. Regina Katzenschlager and colleagues recently released the findings from a multicenter study (the TOLEDO study) of a subcutaneous apomorphine infusion therapy. In this month’s What’s Hot column we will discuss this new approach.
Katzenschlager and colleagues performed a double-blind randomized placebo-controlled Phase III study on the use of an apomorphine subcutaneous infusion to address “off” dopaminergic times in Parkinson’s disease patients. This therapy works much like a standard handheld diabetic pump. There is a small device/pump which can be clipped to the belt or to the clothing and a wire is fed under the skin and provides apomorphine on a regular and automatic schedule. In a diabetic patient the wire carries insulin.
Twenty-three centers participated and centers randomized patients to receive either apomorphine infusion (n=53) or a saline placebo (n=53). The Parkinson’s patients were allowed to continue their normal medications, but in some cases the medications needed to be adjusted for motor fluctuations. The primary outcome for the study was the change in “off” medication time from before the subcutaneous infusion was installed compared to three months after infusion treatment was started. There was an improvement of more than 2 hours in off time in the infusion group as compared to the placebo group. There was also less troublesome dyskinesia reported in the group with the apomorphine infusions.
Single apomorphine shots have been FDA approved and already available in the U.S., however access to a subcutaneous infusion could provide a practical alternative to patients not interested in surgically based therapies (DBS and pumps). Over time it will be necessary to monitor apomorphine infusion therapy for safety and for skin related side effects (inflammation, nodules, rashes, infections). The data suggest that this therapy will be useful for some patients but will not replace deep brain stimulation or duopa pumps, which will still be required for severe motor fluctuations and dyskinesia. It should be stressed that the apomorphine infusion therapy results were presented last week at the American Academy of Neurology meeting in Boston and that there has not been a full research publication completed or an application to the FDA for U.S. approval.
Regina Katzenschlager, Werner Poewe, Olivier Rascol, Claudia Trenkwalder, Guenther Deuschl, Kallol Chaudhuri, Tove Henriksen, Teus Van Laar, Kevin Spivey, Senthil Vel, Andrew Lees Double blind, randomized, placebo controlled, Phase III study (TOLEDO) to evaluate the efficacy of apomorphine subcutaneous infusion in reducing OFF time in Parkinson’s disease patients with motor fluctuations not well controlled on optimized medical treatment. AAN 69th Annual Meeting, Boston MA, April 2017.