Survey explores how patients balance treatment benefits, burdens

Off time therapies need to avoid bodily fluid discoloration, Parkinson's patients say

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by Steve Bryson, PhD |

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Adults with Parkinson’s disease are willing to take additional medicine to manage daily off times — when the benefits of standard levodopa therapy wear off — as long as it does not increase the risk of their bodily fluids becoming discolored, according to a patient survey.

Survey respondents also said reducing daily dyskinesia, the involuntary movements associated with long-term levodopa use, and more on time —  when levodopa is working — also were important features of a medicine that potentially reduces off times.

The survey study, “Patients’ Preferences for Adjunctive Parkinson’s Disease Treatments: A Discrete-Choice Experiment,” was published in the journal Patient Preference and Adherence.

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Levodopa is a first-line therapy to treat symptoms associated with Parkinson’s disease, which is caused by the death of nerve cells in the brain that make the chemical messenger dopamine. While effective at controlling symptoms, most patients will experience a return of symptoms between scheduled doses, referred to as off time.

Secondary, or adjunctive therapies, have been developed to reduce this burdensome off time, such as so-called catechol-o-methyl transferase (COMT) inhibitors. These medications block the breakdown of levodopa, thereby prolonging its therapeutic effects. Approved COMT inhibitors include Comtan (entacapone), Ongentys (opicapone), and Tasmar (tolcapone).

Still, little is known about patients’ preferences regarding the potential benefits and side effects of these adjunctive medications.

Balancing treatment benefits and burdens

“This study aimed to explore how individuals with [Parkinson’s disease] balance treatment benefits and burdens, such as adverse effects, when considering adjunctive treatment with a COMT inhibitor,” wrote a team based in the U.S. and Canada, led by scientists at Neurocrine Biosciences. This company, which funded the study, markets Ongentys in North America.

Parkinson’s patients, ages 30-83, who experienced off periods, were recruited through Fox Insight, a study led by the Michael J. Fox Foundation for Parkinson’s Research, to complete a survey.

Participants were presented with a series of questions, each offering a choice between two hypothetical adjunctive therapy profiles and the option “no additional medicine.”

Hypothetical treatment profiles were defined by five attributes: increase in daily on time (when levodopa is working); additional daily minutes with dyskinesia (uncontrolled movements caused by long-term levodopa use); risk of diarrhea; risk of change in urine, sweat, or saliva color; and frequency of daily administration.

480 Parkinson’s patients surveyed

A total of 480 adults completed the survey, with an average age of 67 years and 69% receiving a Parkinson’s diagnosis at least five years before the survey. Among them, 27% reported two or more hours of daily off time, 34% experienced bodily fluid discoloration, and 44% reported dyskinesia.

Survey results showed that a lower risk of change in urine, sweat, or saliva color, was the most important feature of a medicine to reduce off time. This was followed by less time with dyskinesia each day, then an increase in daily on time. A change associated with a 40% increase in the risk of change in bodily fluid color was five times higher than a change for 25 additional minutes of on time.

Respondents said that more than 60 minutes of additional daily on time would compensate for a 40% increased risk, from no risk, of a change in urine, sweat, or saliva color, as well as a worsening in the levels of risks or frequency of therapy administration.

An additional 40 minutes of on time would offset a 10% increased risk of diarrhea, while an added 22 minutes of on time would balance switching from one other daily to one pill with each levodopa dose.

While still a significant concern, patients who experienced a side effect, such as bodily fluid discoloration or dyskinesia, said these effects were less important than those who had not experienced these side effects. Respondents who have experienced bodily fluid discoloration ranked avoiding dyskinesia as the most important attribute.

Patients with dyskinesia ranked avoiding a 40% risk of bodily fluid discoloration as the most important, followed by increasing their daily on time by 60 minutes, then avoiding 10 additional daily minutes of dyskinesia. Respondents with two or more hours of daily off time thought increasing daily on time was more important than those who experienced less than two hours of off time.

The most important attribute among both men and women was avoiding the risk of bodily fluid discoloration, while taking additional medicine each day was the least important. In men, no differences were reported between the risk of bodily fluid discoloration and the relative importance of additional minutes with dyskinesia. Preferences were similar, regardless of age.

Respondents preferred an additional medication over no additional medication. Also, data predicted that 59.1% of patients would select a hypothetical treatment profile similar to Ongentys, followed by no additional medicines (27.5%) and a hypothetical treatment profile similar to Comtan (13.4%). Of note, Ongentys is taken once daily, while Comtan is administered up to eight times daily and is associated with urine discoloration.

“Our results demonstrate that patients with [Parkinson’s disease] are willing to add adjunctive therapy with a COMT inhibitor to manage OFF time,” the researchers concluded. “Nuances of safety, efficacy, and administration frequency in combination may result in large differences in patients’ preference for medications.”

“Future research should explore patient preferences for attributes associated with other adjunctive treatment options,” they added.