Real-World Impact of CSAI on Motor Fluctuations in PD

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EP: 1.Real-World Impact of CSAI on Motor Fluctuations in PD

At the 2025 American Academy of Neurology Annual Meeting, held April 5-9, in San Diego, California, movement disorder expert Fernando L. Pagan, MD, sat down with NeurologyLive^® to share some updates on therapeutics for managing motor fluctuations in Parkinson disease (PD) based presentations from meeting. Pagan highlighted real-world findings related to treatment use, including patient experiences, adherence strategies, and adverse effect management with these therapies.

In this first segment, Pagan discussed the use of continuous subcutaneous apomorphine infusion (CSAI) as an adjunctive treatment for managing motor fluctuations in PD. He noted its potential to improve "ON" time, reduce "OFF" periods, and provide more consistent drug delivery. Pagan also referenced clinical studies supporting its long-term use and highlighted its evolving role in treatment strategies.

Transcript below edited for clarity.

Fernando L. Pagan, MD: So CSAIs have been around for about 30 years, so it's a great excitement here in the United States that we finally have this FDA-approved for our patients, because it gives us a different pathway to stimulate those dopamine receptors to help improve on time and reduce off time in patients with significant motor fluctuations.

So, traditionally, it has always been done with levodopa. To have a dopamine agonist that's just as strong as levodopa in reducing the motor symptoms—it allows us the opportunity to really improve that "ON" time, without troublesome dyskinesias. At the same time, we can start to lower other medications, for example, other dopamine agonists. And this is a different type of dopamine agonist than we’ve seen before in the oral formulations, because it's delivered continuously. The profile of the dopamine receptors is very analogous to what regular dopamine is.

In fact, in the 1950s, there were patients at NIH receiving continuous apomorphine infusions, but through an IV. Now, using the same type of technology that we've seen in the diabetic world for insulin delivery, we can do this now—not only for apomorphine but also for carbidopa/levodopa. But this is just a little bit different because this is an adjunctive treatment.

So I think for my patients who are having significant motor fluctuations—they’ve been on dopamine agonists or are on dopamine agonists—and I want to really target those dopa receptors a little bit differently than just levodopa, now I can combine it with apomorphine subcutaneous infusion and really improve that "ON" time and reduce that "OFF" time.

And there are 2 major studies that really have shown this. Number 1, the TOLEDO study that was done in Europe, and then number 2, the InfusON study that was done here in the United States. And the InfusON study here shows us, long-term, we continue to help improve that on time without troublesome dyskinesia, and reduce that off time. So it's a really exciting time in movement disorders.

So, the continuous "ON" time—and especially it's continuous "OFF" time without troublesome dyskinesia—and that reduction of "OFF" time, what that translates to is just improving the daily life of our patients with Parkinson who are going through all these motor fluctuations.

One of the advantages of apomorphine compared to levodopa is you don't have that protein interaction. You bypass the gut, and it can go directly through that blood-brain barrier and find those dopamine receptors.

Of course, it's very patient-specific. It is a dopamine agonist. You have to slowly come up on it to titrate. As you're titrating up that apomorphine, you can start to reduce some of those other medications as well. So it translates to just better drug delivery.