Apomorphine as a continuous infusion beneficial in advanced Parkinson’s disease
According to a real-life, single-center study in France, two years of continuous treatment with apomorphine by subcutaneous infusion safely preserved quality of life and effectively reduced motor fluctuations in people with Parkinson’s disease. an advanced stage.
Notably, patients with poor quality of life before starting continuous apomorphine were more likely to improve in this area.
The reductions in dyskinesia – the involuntary jerky movements that mark this disease – were mild and temporary.
These results highlight what to expect in advanced Parkinson’s patients on continuous treatment with apomorphine and suggest that the best candidates for this type of therapy are those with poor quality of life and marked motor fluctuations.
The study, “Long-term effect of apomorphine infusion in advanced Parkinson’s disease: a real-life study, ”Was published in the journal NPJ Parkinson’s disease.
Oral levodopa and carbidopa, which work to increase levels of dopamine – the brain messenger molecule that is gradually lost in patients with Parkinson’s disease – are considered gold standards in the treatment of Parkinson’s disease. .
However, when used for long periods of time, these dopaminergic therapies are associated with a faster reduction of effects, causing so-called “off” episodes in which symptoms reappear.
These motor fluctuations can be managed by the continued administration of dopamine therapies such as apomorphine (brand name Apokyn, injected under the skin) and Duodopa / Duopa (a gel given through a tube surgically inserted into the intestines).
The safety and efficacy of continuous apomorphine infusion in patients with Parkinson’s disease has been established in an appropriately controlled short-term clinical trial. Several uncontrolled studies also support its effectiveness “in the management of motor complications and non-motor symptoms in patients with advanced PD.” [Parkinson’s disease]The researchers wrote.
However, the long-term effects of this therapy on the health-related quality of life (HRQoL) of patients and the predictors of apomorphine discontinuation remain largely unknown.
To fill this knowledge gap, Paris researchers retrospectively analyzed demographic, clinical and quality of life data covering 110 adults (55 men and 55 women) with advanced Parkinson’s disease who received a continuous infusion of apomorphine in a single center.
Patients, with a mean age of 62.9 years and with motor fluctuations for an average of 4.5 years, were followed for two years after initiation of apomorphine.
The researchers primarily assessed changes in patients’ HRQO, motor fluctuations, and dyskinesias, and aimed to identify predictors of apomorphine discontinuation and improvement in HRQO.
Health-related quality of life was measured using the 39-item Parkinson’s disease questionnaire (PDQ-39), which covers several aspects of HRQoL, including physical, mental and social areas of life. .
In most patients, apomorphine has been administered in relatively low doses and used as an adjunct to oral dopaminergic drugs.
A total of 39 (35%) patients discontinued apomorphine within the two-year period, with an average treatment duration of 7.4 months. Of the 71 patients who continued treatment for two years, 57 had complete and longitudinal PDQ-39 data and were included in the final analysis.
Most (71%) received a continuous infusion of apomorphine over 24 hours, while 15 patients (21%) received an infusion during the day only.
The results showed that among these 57 people, the health-related quality of life remained broadly stable over the two years of treatment. Specifically, HRQoL improved in 26 patients (45.6%), was stable in one (1.8%) and worsened in 30 patients (52.6%).
Notably, a significant improvement in the PDQ-39 mobility domain was observed at one year, but was no longer statistically significant at two years. In turn, the areas of social support and communication were generally worse after two years of treatment.
Continued treatment with apomorphine has also been associated with a significant reduction in motor fluctuations, while its beneficial effects on dyskinesia have been shown to be mild and transient.
It is likely that “the observed oral dose reduction and apomorphine output was not sufficient to induce a great improvement in dyskinesias,” the researchers wrote.
The most significant overall improvements were seen by patients after one year of treatment, with reductions in motor fluctuations reported by 91% and improvements in quality of life by 82%. These were assessed using a homemade satisfaction self-questionnaire, mainly focusing on motor aspects, which may explain the overall improvements in quality of life.
The PDQ-39 score before continued apomorphine use was the only predictor of improvement in HRHL after two years of treatment, with patients with poorer quality of life at the start of treatment being more likely to achieve greater improvements in HRQL over time.
Patients also reported overall satisfaction with the delivery device, with moderate comfort and no significant pain.
Two patients were able to completely stop oral dopaminergic drugs. Six others were able to quit at some point, but eventually resumed levodopa.
The most common adverse event was skin nodules at the injection site (approximately 55% of patients), followed by drowsiness or daytime sleepiness (approximately 30% of patients). Mild to moderate hallucinations and impulse control disorders were also common, with the former becoming more frequent over time, while the latter generally showed the opposite pattern.
Impulse control disorders can include gambling, compulsive shopping, overeating, and compulsive sexual behavior. Patients with pre-existing impulse control disorders showed good overall tolerance to continuous apomorphine.
Most of the treatment discontinuations were associated with adverse events (14%) or insufficient benefit (13%).
The researchers also found that male gender, shorter duration of illness, presence of dyskinesia, poor mental health (poorer psychological state), and worse ‘off’ episodes were independent predictors of treatment discontinuation. .
“Our results are important for clinical practice,” the team wrote, adding that “they provide a broad overview of what to expect in patients with advanced PD treated with [continuous apomorphine] in a routine care setting and clues to identify patients most likely to benefit from this treatment.
Based on this data, the researchers suggested that Parkinson’s disease patients with poor quality of life and pronounced motor fluctuations could benefit the most from continuous apomorphine infusion.
“Adequate support from family and friends could also be essential” for these patients, they wrote.