DUOPA, the dopamine pump, was FDA approved in January 2015 as an orphan drug (drugs or products intended for treatment of rare conditions affecting fewer than 200,000 people in the United States). Though there are probably closer to a million people with Parkinson disease (PD) in the U.S., only a minority would be considered for DUOPA use. DUOPA approval was based on a Phase III, 12-week, double-blind, double-placebo, active control, parallel group, multi-center trial with 71 patients (1). In the trial, DUOPA was compared to oral, immediate-release (IR) carbidopa/levodopa tablets in advanced PD patients. At 12 weeks DUOPA patients had reduced daily OFF time (when medications are not working and symptoms are not controlled) an average of about two hours. At the same time, this group had also improved average ON time (when the medication is working and symptoms are controlled) without troublesome dyskinesia (uncontrolled movement that does not interfere with normal daily activities) by two hours (footnote). Use has been limited in the United States for a variety of reasons. We are happy in this interview to hear about the DUOPA pump from someone who is well-versed in medicine and in PD.
Conner Moore, M. D. is a retired pediatrician who practiced for 40 years in the Saco/Biddeford area until 2008, and worked part-time in 2010. That same year he began to notice the signs of PD. Like his mother, who also had the condition, tremors were never a big part of the disease. Over time, his PD progressed and fortunately he responded to carbidopa/levodopa (Sinemet). As far as I know among Maine movement disorder neurologists, he is the first patient in our state to have the DUOPA pump. Dr. Moore took some time to speak with me by phone and describe his experience with DUOPA at the end of February 2018. This was a casual conversation and he was speaking strictly from his own experience, not offering medical advice on a professional basis, and not representing AbbVie Pharmaceuticals. I appreciate his thoughts and insight.
MPDN: What was your PD like in the years prior to getting the pump?
CM: It started out gradually and on one side like most people. But I was always very active, and I knew that there were studies supporting the role of exercise in Parkinson’s. I took a fairly high dose of carbidopa/levodopa to participate in sports and other activities. It was a trade-off and I knew that might also mean dyskinesias might come earlier. It seemed worth it to me. And, I’ve been involved in the New England Parkinson’s Ride (see article in the summer, 2016 issue) and 4 years ago I was able to complete 30 miles. In 2016 I was only able to do 10 miles and took more rest stops, mostly due to fatigue. Last September, 2017 I wasn’t able to participate because of balance and other factors. Also, I wasn’t using the pump yet.
MPDN: I understand that for the two years leading up to the pump dyskinesias had become an increasing problem, sometimes severe enough to be exhausting, and medication failure was an issue. This led to you taking more frequent doses of carbidopa/levodopa. But, this meant trying to work with diet was also a problem because certain foods might interfere with levodopa absorption. How did you manage that before the pump?
CM: I was taking Sinemet every two hours and was very sensitive to protein with the oral drug. I could eat maybe four grams of protein at a time and I’d have to try to get more in later in the day. All the while, weight loss was a problem.
MPDN: Did carbidopa/levodopa work as long as you took it every two hours?
CM: As is often the case after several years, unpredictable OFF times began to occur more frequently, and sometimes I couldn’t leave the house. Even when I was ON, a troublesome issue was that OFF times would come on suddenly, like somebody slammed a window down.
MPDN: Did you consider other options such as deep brain stimulation (DBS) before the pump?
CM: I saw Dr. Kleinman and discussed options. They don’t like to put the wires of DBS in your brain when you’re older, and I asked about other choices. It didn’t take two minutes to decide about the DUOPA pump.
MPDN: When did you go through this process?
CM: I started using the pump in late September 2017 and participated in the PROVIDE study, which monitored bodily movement for two months prior, and three months after starting the pump.
MPDN: How are the results?
CM: Dyskinesia is now less overall. There is less OFF time. I was getting a lot of blank shots with Sinemet, but the pump works every time. My mood is better, and I can do more around the house. There have been adjustments, but it’s been very good so far. The people at AbbVie have been fantastic and there is a number you can call 24/7. The nurse coordinator is very helpful. After the pump I started to put a little weight back on. It is complicated because some people have actually gone off the pump due to weight loss. Since it was already an issue for me I have watched calories to make sure I’m getting enough. I’m up about 10 pounds. I am exercising and using a Theracycle about 30 minutes daily, also using a stationary bike at the gym.
MPDN: Are there other dietary considerations?
CM: Apropos to your article (B6, friend or foe?, fall 2016), there have been reports of neuropathy with dopamine pumps and I have checked my B vitamins. It is a really fascinating disease. The more I learn about this illness, the less I find that I know about it, and there are new questions. But that is often the case in science and medicine.
MPDN: Too true. The pump requires a PEG J tube, a tube that is placed through the upper abdomen (below the ribs) and enters the small intestine downstream from the stomach. Is it difficult to manage?
CM: Care of the pump, tubing, and the PEG tube is not as complicated as I thought it might be. There is also the opening in your skin for the tube, known as a stoma. The only complication I’ve run into has to do with soup. If I eat a little too much there might be a little leakage, not a big problem.
MPDN: How do you get the medication for the pump?
CM: It comes in 16 hour cassettes air shipped frozen from the Midwest and
FedEx has been right on time, even in a snow storm this winter. It runs on AA batteries but they send those too, they send everything you need. The 16 hour daily cassettes contain the carbo/levodopa in gel form and clip onto the pump. The total unit size is 7.5 x 3.5 inches and weighs a pound. There are vests, hip packs and shoulder slings available to hold the pump. I quickly adapted to my new addition and am generally not aware of its presence.
MPDN: Is it difficult to operate?
CM: There are considerations about operating the pump, a learning curve and some getting used to. It takes some dedication to this project. Most people use the pump during the day and turn it off at night.
MPDN: What is a typical day with the pump?
CM: I wake around 5am and feel I am not yet in an OFF state. I’m able to get up and do a few things around the house for about an hour. Then I start to feel the typical tightening of the face and decrease in left arm swing that let me know I’m wearing off. When I attach and turn on the pump after about 20 minutes there may be a brief period of dyskinesia. After that it levels out. During the day the pump provides a base rate of medication such as 40 mg levodopa every hour. It has given me a sense of freedom. I can go into a theatre now, have dinner, and don’t have to worry about wearing off. If that happens it is much more gradual, a slow process that I can feel coming on, unlike before. If that feeling comes on I can give myself a 50 mg bolus by pushing a little button on the pump and it kicks in within minutes. It has improved my quality of life tremendously.
MPDN: Do you still sometimes have wearing OFF?
CM: There might be wearing OFF with a high protein meal, but I can eat about twice as much protein in one sitting than I could before. The other thing is exercise. Sometimes I need to give myself a bolus if I’m working out too hard. Usually I don’t think about it.
MPDN: Are there any personal limitations with the pump?
CM: I don’t think there is anything I would put in that category. I have only tried one overnight away from home, but have talked with PD pump patients who have traveled with the pump. It requires planning because of refrigeration requirements.
MPDN: How about shutting it down for the day?
CM: At first I was concerned I might have to write down a lot of complicated procedure. There are about 15 steps to turning it off and putting everything away at night, but it all becomes so routine that it’s like brushing your teeth. When you shut it off you flush the tubing with tap water and the nice thing about that is that you are flushing medicine into yourself and get about 30 minutes more levodopa from the tube. Then, it is time to sleep. Not everyone shuts it down at bedtime. Some people run it all night. I don’t think I need that at this time.
MPDN: There is a peer mentor program for people considering the pump. What was your experience?
CM: I used the peer mentor program before getting the pump and met people who had been in the study, and had the pump for about six years. They told me the maintenance was low with the equipment and it had generally lasted that long. I wound up signing on myself for that program. People interested in the pump can call and get one of us on the phone to talk about our experience. It’s a good resource because you are talking to a person with experience.
MPDN: Any last thoughts Dr. Moore?
CM: Just that it has been positive for me, and I hope it helps others to know about this.
Dr. Moore also sent me a comment by email after we talked:
We did not talk about the cost. My Medicare and supplemental insurance pays everything. But I think the President is going to look at entitlement programs to balance the budget. The DUOPA is part of the pump package so it falls under Part B durable equipment and does not go through Part D and the drug insurance process. The government gets a discount, but not much.
Comments by Michael Kleinman, D.O.
The most common indication for the pump is for patients with severe motor fluctuations. If someone is taking medication every 3 hours or less and is still with a significant amount of off time then I would consider them for the DUOPA pump. Traditionally these patients would be first considered for deep brain stimulation surgery but for those patients who may not be good candidates for deep brain stimulation surgery or who are not willing to go through the surgery, then this is a good option. The percent increase in ON time is actually similar to that achieved with surgery.
The company which supplies the medication has a support system in place to help patients get used to administering the medication themselves at home. This has run very smoothly in the experience that we have had here. The medication is started for the first time in the office. At that visit the patient will come in without having taken their medication from the prior night. That visit will be 3-6 hours long. The initial bolus dose and continual infusion dose of the DUOPA infusion will be set based on how much oral medication the patient was taking prior to starting DUOPA. We will then monitor how long it takes for the medication to start working, whether there is evidence of too much medication such as dyskinesia, and whether there is any wearing off. The patient and their caregiver are also educated during that visit on how to operate the pump.
Follow up visits will be more frequent than usual in the beginning to fine tune the dose of medication. If the initial programmed dosing is working well then visits can quickly go back to being every few months. Patients can be given a range of settings to work with at home as well. They can call with a report on how they are doing and be instructed on what change to make to their infusion settings without the need to come in for a visit to have the pump settings changed.
Footnote: In the above mentioned phase III trial of DUOPA, the most common adverse events were listed if occurring in more than 7% of patients, and occurring more frequently with DUOPA than carbidopa/levodopa IR and included complication of device insertion, nausea, constipation, incision site erythema (redness), dyskinesia, depression, post procedural discharge, peripheral edema, hypertension, upper respiratory tract infection, oropharyngeal pain, atelectasis, confusional state, anxiety, dizziness and hiatal hernia.
REFERENCES
- Olanow, et al; for LCIG Horizon Study Group. Lancet Neurol. 2014;13(2):141-149.
