Case Based Insights: Parkinson Disease OFF Episodes - Episode 6
Fernando L. Pagan, MD: This particular case is a 63-year-old teacher—currently active, still teaching, still working, still has a family life—and there was an unpredictable nature to her off episodes. Just going up on her medications didn’t make a lot of sense, although you can sometimes increase the medicines and also use an on-demand therapy.
We chose the inhalation levodopa powder to manage her off episodes because, No. 1, she’s still very active. It was easy for her to put together and be able to administer it fairly quickly throughout her day. She had a good idea of the start of her off episodes: she starts feeling the tremor, and then if she doesn’t get control of it, she knows that the rest of the day becomes more difficult.
That’s one of the important parts about the inhalation powder: recognizing that you’re beginning to have an off episode and being able to inhale it. As long as somebody does not have COPD [chronic obstructive pulmonary disease] or asthma, which our patient did not have, and no other lung problems, this was an appropriate use of the inhalation powder to manage her off episodes. This was a good choice to be able to give her more control of these off episodes.
The SPAN-PD trial looked at patients who were having off time and off episodes, and these patients were able to use this inhalation levodopa powder up to 5 times a day. The average time of using it was about 2 times per day in the SPAN-PD trial. The SPAN-PD trial also showed that, if you used it at the onset of when one felt to have an off episode, within about 10 minutes, with a peak effect at 30 minutes, you saw a resolution of these off episodes or improvement in the Unified Parkinson’s Disease Rating Scale.
It gives us a new tool to be able to help treat our Parkinson’s disease patients to get better control of these off episodes. With this on-demand therapy, even though patients were able to use it up to 5 times a day, the average was about 2 times per day.
It lets our patients choose when to manage these off episodes, and some of our patients’ off episodes are very unpredictable. Some of them are a little more predictable. There could be a gastrointestinal component, they can be a little late on their medication, or they could be wearing off. We can do more than one thing for our patients, and that’s what is new to Parkinson’s disease. We always need to take a look at those maintenance therapies, but when these off episodes come, and they’re going to come in most of our Parkinson’s disease patients, they have something to be able to get better control of their symptoms and overall better their quality of life.
When you’re using this inhalation levodopa powder, it is very important to go over how to administer it as you are using a device to be able to inhale, so it’s an inhaler. It’s very simple to put each capsule in and put it together, but for the actual inhalation, when you bring it up to the mouth, you have to take a deep breath in, deep breath out, and then a nice slow deep breath in, and then hold it in, and you want to hear for that whirl. Go over that with the patient. There is a great video online on how to use it. Some patients will cough when you use this. With a smoother, slower, inhalation, there’s less irritation to the back of the throat, so you see less cough. The first time, I think I see 100% of people cough a little. It’s very mild, but then you get used to it, and then it gets better from there. Each patient learns a little. I usually require my patients to drink a little bit of water afterward. Sometimes, drinking a little water right before can diminish that feeling of dry powder hitting the back of the throat. These are some of the things I do for my patients. A nice slow inhalation and then holding your breath for a few seconds afterward, about 5 seconds, has led to the best efficacy for my patients and more ease of use with it.
If powder is left inside the mouth, that can oxidize, so it can turn the tongue or some of the teeth black, so I usually ask them just to drink a cup of water after inhaling.
My personal experience with this is that our patients who are able to use this really love it. They get control of their symptoms. Every patient is different, and there are some patients who are better at inhaling than others. It is something that’s out there for our patients, and as a neurologist, I’ve become more comfortable offering on-demand therapies for our patients in addition to giving them their maintenance treatment. It’s important to be offering these patients different medications that we have. There’s more than 1 drug available for Parkinson’s disease, so it’s important to have these discussions with our patients and get them used to more of a “cocktail approach” or a rational polypharmacy approach to treat off time and off episodes in Parkinson’s disease.
The biggest unmet need in treating off episodes in Parkinson’s disease is all about education. No matter what we do as physicians or no matter how many medications our Parkinson’s disease patients take, over time, they are going to have off episodes. It is very reasonable to do the things we normally do by increasing carbidopa-levodopa, by using COMT inhibitors, MAO-B inhibitors, dopamine agonists, and now A2aR antagonists. All these things are aimed to reducing off time and improving on time, but no matter what we do over time, we’re still going to have these off episodes.
Thinking about the rationale of having those maintenance therapies and then on-demand therapies, right now we have 2 on-demand therapies. In the future, we’re going to see other on-demand therapies coming out, and it’s linking up our patients to the appropriate on-demand therapy. This is what we’re going to be learning more and more: which on-demand therapy is going to be best for a particular individual. We as neurologists have to start getting more comfortable in approaching Parkinson’s disease as having a maintenance therapy and an on-demand therapy.