Continuous apomorphine infusion effective with advanced Parkinson’s
But almost one-third of study patients in India stopped treatment due to its cost
One year of continuous subcutaneous (under-the-skin) apomorphine infusion (CSAI) reduced the severity of advanced Parkinson’s disease among patients across India, a study showed.
Despite these findings, almost one-third of patients who entered the study discontinued treatment due to a lack of funds, demonstrating that “affordability and cost remains a concern regarding apomorphine use in Indian [Parkinson’s disease] population,” the researchers noted.
The study, “Safety and tolerability of long-term apomorphine infusion in advanced Parkinson’s disease: an Indian multi-center (APO-IND) experience,” was published in the journal Nature Scientific Reports.
Apomorphine as a continuous infusion helps to manage off episodes
Parkinson’s disease is caused by the progressive loss of nerve cells that produce the neurotransmitter dopamine, a signaling molecule essential to control muscle movement.
Standard treatment includes levodopa and its derivatives, which intend to increase dopamine levels in the brain. With long-term use, however, the benefits of these treatments can wear off, and symptoms return between doses, called off episodes. Involuntary and erratic body movements, known as dyskinesia, can occur.
Several therapeutic approaches have been developed to help ease off episodes and dyskinesia, including apomorphine (sold as Apokyn, among other names) that mimics the activity of dopamine. In the U.S., a subcutaneous injection of apomorphine, using a pen, has been approved to manage such off episodes.
CSAI, which can be administered throughout the day via a portable electronic infusion pump, was approved in India in 2019.
Researchers at King’s College Hospital, in the U.K., working with colleagues in India, Romania, and Spain, reported on the efficacy and safety of CSAI treatment in people with advanced Parkinson’s in India. A total of 51 patients, ages 45-80 and 62.7% male, completed one year of treatment. Among them, the disease duration ranged from four to 14 years.
Participants included those who did not completely respond to the conventional oral dopamine-related medications or developed side effects. Each received 14 waking hours of CSAI, at the rate of 2 mg/hour optimized to 3.0 mg/hour at six months and then 3.5 mg/hour at one year. Dose adjustments were driven by an individual’s clinical responsiveness.
Although 90 patients initially were enrolled in the study, 13 (14%) dropped out due to adverse effects after six months, and another 26 patients (29%) were unable to complete a full year of treatment due to cost. This raised the study’s dropout rate to 43%.
“Affordability and availability, major factors for continuity of therapy in Indian patients, are the challenges that need to be overcome … and one that industry needs to take increasing note of by making apomorphine available at affordable costs in developing or low-income countries,” the researchers wrote.
Before continuous apomorphine infusion, most patients had Hoehn and Yahr (H&Y) scores of 3.0 or more, a more advanced disease stage marked by loss of balance and slowness of movement. After one year of sustained treatment, H&Y scores dropped (improved) to 2.5 or less across all participants, and more than one-third had H&Y scores of 2.0.
Improvements noted in motor symptoms, fatigue, depression, and pain
Most clinical assessments showed significant improvements after six months of treatment that were sustained for up to one year. This included measures of motor symptoms, quality of life, and anxiety and depression. Similar results were observed for fatigue and pain (King’s PD pain scale, KPPS).
Motor complications and nonmotor symptoms also significantly eased after six months with such improvements continuing for up to one year, clinical assessments showed. Still, treatment did not affect cognitive abilities or sleep.
Among KPPS subscales, only nighttime and orofacial (mouth and face) pain were significantly lower after six months and one year of the infusion treatment.
Levodopa equivalent daily dose, the combined total of all oral Parkinson’s medications, decreased significantly after six months of CSAI.
Mild injection site reactions were reported as side effects in seven participants, nausea in seven, and skin nodules in two. No deaths were recorded.
“CSAI is safe, effective, with good tolerability in Indian patients with [advanced Parkinson’s disease],” the team concluded. “Patient selection, participation, education and dose optimization enhance improved outcomes and perhaps, implementing cost effectiveness strategies can influence sustainability and continuity of these therapies.”