Should we consider subcutaneous apomorphine infusions for Parkinson’s disease patients who do not want deep brain stimulation or a dopamine pump? There is a growing interest among people with Parkinson’s disease (PD) and families for a “nonsurgical” alternative to deep brain stimulation (DBS) surgery or to Duopa pump therapy. The idea of brain surgery or 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 in PD? 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. This type of device is what carries insulin to a diabetic patient.
Twenty-three centers participated in the study. 53 patients in the test group received apomorphine infusion and 53 patients in the control group received a saline placebo. The patients were allowed to continue their normal medications, but in some cases medications were 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 two 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 U.S. Food and Drug Administration (FDA) approved and are already available in the U.S. 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). Data suggests that this therapy will be useful for some patients, but will not replace DBS or Duopa pumps, which will still be required for severe motor fluctuations and dyskinesia. It should be stressed that 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.
Okun MS. Subcutaneous Apomorphine Subcutaneous Infusions and Parkinson’s Disease. NEJM Journal Watch, 2017.
You can find out more about PF's National Medical Director, Dr. Michael S. Okun, by also visiting the Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life and 10 Breakthrough Therapies for Parkinson's Disease. You can read more from Dr. Okun in the What's Hot in PD? archives.