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03-08-2018 | Parkinson's disease | News | Article

Apomorphine infusion reduces ‘off time’ in patients with Parkinson’s disease

medwireNews: Subcutaneous apomorphine infusion meaningfully reduces the time in which a patient’s medication is not working optimally and parkinsonian symptoms return, reports the placebo-controlled, multicentre TOLEDO trial.

A total of 106 patients with Parkinson’s disease who had motor fluctuations that were inadequately controlled with optimal medical treatment were randomly assigned to receive 3–8 mg/hour apomorphine or placebo, delivered by a pump for around 16 hours of each patient’s waking day for 12 weeks.

Apomorphine infusion significantly reduced off time (ie, time with returning symptoms prior to next medication dose) compared with placebo, by 2.47 versus 0.58 hours/day, from respective baselines of 6.69 and 6.76 hours/day, giving a difference of 1.89 hours/day.

This magnitude of effect, write Regina Katzenschlager (Danube Hospital, Vienna, Austria) and colleagues in The Lancet Neurology, “exceeds that seen with oral or transdermal medication […] and is around two times the change in off time identified as clinically meaningful to patients.”

Importantly, the improvement in off time was achieved without worsening of dyskinesias. In fact, apomorphine infusion significantly increased on time without troublesome dyskinesia, with an absolute mean change of 2.77 hours/day in the apomorphine group versus 0.80 hours/day in the placebo group.

Week 12 Patient Global Impression of Change scores were significantly improved with apomorphine versus placebo, which the researchers suggest may be related to the significantly greater reduction in oral levodopa-equivalent dose between baseline and week 12 with apomorphine. They comment: “This reduction is probably clinically relevant to patients with motor complications because it might alleviate the burden of complex oral treatment regimens.”

The infusions were well tolerated and adverse events were similar to those reported in previous observational studies. Nonetheless, six patients, all in the apomorphine group, discontinued the study because of adverse events, all of which were reversed upon treatment discontinuation.

In an accompanying editorial, Peter LeWitt (Henry Ford Hospital, West Bloomfield, Michigan, USA) says that “the study’s findings should help guide clinicians in making decisions about management of patients with advanced Parkinson’s disease, particularly when considering use of deep brain stimulation or intestinal infusion of levodopa–carbidopa gel. In view of its efficacy and safety profile, apomorphine infusion should be considered before embarking on other invasive therapies.”

The researchers conclude: “We hope that treatment guidelines will be developed to guide physicians, and apomorphine infusion will be offered and reimbursed more widely as an effective treatment option.”

By Catherine Booth

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