Unmet Needs in Managing OFF Episodes in Parkinson Disease


Robert A. Hauser, MD, MBA, and Laxman Bahroo, DO, review unmet needs in managing OFF episodes for patients with Parkinson Disease.

Stuart Isaacson, MD: With all these different options Dr Raj just described, Bob, tell me, what do you think of the unmet needs for managing OFF episodes in patients who continue to have the OFF? And how do you assess the unmet needs for your individual patients in terms of reducing the frequency or duration of OFF episodes? The severity of OFF episodes would be another goal. Rating the time to onset of therapies, the reliability of response. How do you look at all these things and then see if there’s still unmet needs for our patients?

Robert A. Hauser, MD, MBA: Yes. I think the unmet need is generally there’s not one simple easy answer. If you heard Raj’s great summary, we have a lot of partial answers and they’re all helpful but none of them are really the solution. That’s the big issue. I agree with Raj that a lot of patients who are on IR 3 times a day, we can go up to IR and that does great initially. A lot of patients we can convert over to levodopa or carbidopa extended release and that will be good if they have a limited number of OFF hours, and then we can add on adjuncts. For people whose IR lasts 2 1/2, 3 hours, we’re doing 3 or 4 things, and No. 1 you have to be aggressive to take all those steps. The cost is high. They’re not always available. And you don’t always get to the result you need. Those are the patients then that are generally going to deep brain stimulation, which I guess in a sense is the closest we have to a single solution. I don’t know that I’d call it simple or inexpensive, but that’s the biggest issue, Stu, is that it’d be nice to have 1 really great drug that would be robust in its effect and last all or most of the day that we could give it once or twice and it solved the problem.

Stuart Isaacson, MD: Laxman, how do you assess the effectiveness of your OFF treatments in your patients? Are there certain populations of patients that seem to respond better than others or do you think it’s very individualized?

Laxman Bahroo, DO: It’s very individualized. I suspect there’s so many variabilities in Parkinson’s that many times we have to look at different targets. If somebody is on levodopa, they’re on a moderate dosage of levodopa, can I get more out of that levodopa dosage by using a COMT [catechol-o-methyl transferase] inhibitor? Can I squeeze more out of it by using an MAO-B [monoamine oxidase type B] inhibitor in that sense and making it last longer? The mainstay is to differentiate and say these are peripheral OFF episodes. If I can figure that out, I tend to go towards on-demand therapies. Choosing the right therapy has an art and a science to it. The science component is trying to figure out where the OFFs are coming from, where they would benefit. The art is trying to convince your patients to take yet another medication when they’re on so many for their Parkinson’s and many other medications. This is the art of the science of it and being able to set reasonable expectations, which I think is also an art and a science of what I’m going to expect to get out of it. As Bob mentioned, if you have somebody who’s a fluctuater at every 2 1/2 hours, you’d have to pile them on full of adjuncts and or every single thing that’s on the list and maybe you don’t get the result. Maybe you don’t get the result period. Maybe you don’t get the result because they can’t tolerate all those medications. Trying to get a realistic assessment of this is important to say, have I made a meaningful difference? That’s the phrase I ask. Have I made a meaningful difference at the OFFs? You were having 6 or 7 OFF episodes a day. Several of them were very bad. We’ve got you on therapies. Have we reduced those OFFs? Yes. Now I’m having maybe 4 episodes, but they’re not as severe, or I’m still having 4 episodes but I’m having less severe ones. The more severe ones are covered by on-demand therapy. It’s a question of asking and the patient is one component of it but in that population the patients who were fluctuating were what I call moderate to advancing populations of Parkinson’s patients. From a motor point of view, I it’s important to ask the caregiver or the spouse and say, “Is this person now having less OFFs? In other words, are they able to do things more. Are the OFFs less interfering? These are all subjective questions with subjective answers, but ultimately at that stage you have a lot of subjective reporting to use to try and see how effective your OFF therapies are.

Transcript Edited for Clarity

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