Apomorphine as Steady Infusion of Benefit in Advanced Parkinson’s

Two years of continuous treatment with apomorphine as an under-the-skin infusion safely preserved quality of life and effectively eased motor fluctuations in people with advanced Parkinson’s disease, according to a single-center, real-life study in France.

Notably, patients with poor life quality before starting with continuous apomorphine were more likely to improve in this domain.

Reductions in dyskinesia — the involuntary, jerky movements that mark this disease — were mild and temporary.

These findings shed light on what can be expected in advanced Parkinson’s patients on continuous apomorphine treatment, and suggest that the best candidates for this type of therapy are those with a 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 the levels of dopamine — the brain messenger molecule that is progressively lost in Parkinson’s patients — are considered gold standards of Parkinson’s treatment.

When used for long periods of time, however, these dopaminergic therapies are associated with a faster wearing-off of effects, causing so-called “off” episodes in which symptoms return.

These motor fluctuations can be managed with continuous administration of dopaminergic therapies such as apomorphine (brand name Apokyn, as a subcutaneously injection) and Duodopa/Duopa (a gel given via a tube surgically inserted into the intestines).

The safety and effectiveness of continuous apomorphine infusion in Parkinson’s patients was established in an appropriately controlled, short-term clinical trial. Several uncontrolled studies also support its efficacy “in managing motor complications and nonmotor symptoms in patients with advanced PD [Parkinson’s disease],” the researchers wrote.

However, the long-term effects of this therapy on patients’ health-related quality of life (HRQoL) and the predictors of apomorphine discontinuation remain largely unknown.

To fill this knowledge gap, researchers in Paris retrospectively analyzed demographic, clinical, and HRQoL data covering 110 adults (55 men and 55 women) with advanced Parkinson’s disease who were given continuous apomorphine infusion at a single center.

Patients, with a mean age of 62.9 and experiencing motor fluctuations for a mean of 4.5 years, were followed for two years after apomorphine initiation.

The researchers mainly assessed changes in patients’ HRQoL, motor fluctuations, and dyskinesia, and aimed to identify predictors of apomorphine discontinuation and HRQoL improvement.

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 domains of life.

In most patients, apomorphine was administered at relatively low doses, and used as an add-on treatment to oral dopaminergic medications.

A total of 39 (35%) patients stopped with apomorphine during the two-year period, with a mean treatment duration of 7.4 months. Of the 71 patients who continued treatment for two years, 57 had complete, longitudinal PDQ-39 data and were included in the final analysis.

Most (71%) were given a 24-hour continuous apomorphine infusion, while 15 patients (21%) were infused during daytime hours only.

Results showed that among these 57 people, health-related quality of life remained generally stable over the two years of treatment. Specifically, HRQoL improved in 26 patients (45.6%), was stable in one (1.8%), and worsen in 30 patients (52.6%).

Notably, a significant improvement in PDQ-39’s mobility domain was observed at one year, but was no longer statistically significant at two years. In turn, social support and communication domains were generally worse after two years of treatment.

Continuous apomorphine treatment was also associated with a significant reduction in motor fluctuations, while its beneficial effects on dyskinesia were found to be mild and transient.

It is likely that the observed “oral dose reduction and apomorphine flow rate were not sufficient to induce a large improvement in dyskinesias,” the researchers wrote.

Greatest overall improvements were perceived by patients after one year of treatment, with motor fluctuations reductions being reported by 91% of them and quality of life improvements by 82%. These were assessed with a home-made satisfaction self-questionnaire that mainly focused on motor aspects, which may explain the overall improvements in life quality.

PDQ-39 score before apomorphine’s continuous use was the only predictor of HRQoL improvement after two years of treatment, with patients with a worse quality of life at treatment start being more likely to achieve greater HRQoL improvements over time.

Patients also reported an overall satisfaction with the administration device, with moderate comfort and no significant pain.

Two patients were able to completely discontinue oral dopaminergic medications. Six others were able to stop at some point, but eventually resumed levodopa.

The most common adverse event was injection site skin nodules (about 55% of patients), followed by daytime sleepiness or drowsiness (about 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 an opposite trend.

Impulse control disorders may include gambling, compulsive shopping, overeating, and compulsive sexual behaviors. Patients with preexisting impulse control disorders showed an overall good tolerability to continuous apomorphine.

Most treatment discontinuations were associated with adverse events (14%) or insufficient benefit (13%).

The researchers also found that male sex, shorter disease duration, the presence of dyskinesia, poorer mental health (poorer psychological status), and worse “off” episodes were independent predictors of treatment discontinuation.

“Our findings are important for clinical practice,” the team wrote, adding that “they provide a broad overview of what can be expected in advanced PD patients treated with [continuous apomorphine] in a routine care setting and clues to identify patients who are more likely to benefit from this treatment.”

Based on these data, the researchers suggested that Parkinson’s patients with poor quality of life and pronounced motor fluctuations may benefit the most from continuous apomorphine infusion.

“Adequate support from the family and friends might also be critical” for these patients, they wrote.