Apomorphine Infusions Improve Off Time Associated With Parkinson Disease
Continuous infusion of apomorphine may allow for a reduction in required concomitant oral dose of antiparkinsonian medications.
Apomorphine infusions increased off time (the amount of time medications do not impact Parkinson disease symptoms) by reducing uncontrolled motor fluctuation in patients with Parkinson disease, according to a study published in Lancet Neurology.
The researchers of this double-blind, placebo-controlled trial randomly assigned 106 patients with Parkinson disease, who experienced motor fluctuations currently not managed with other medications, into a subcutaneous apomorphine infusion group or a placebo group. The apomorphine infusion group received apomorphine at a rate of 3 to 8 mg/hour for an average of 16 hours per day. The control arm received a placebo saline infusion for 16 hours per day. The first 4 weeks consisted of the titration period where the dosage was slowly increased to 8 mg/hour or to the highest tolerated dose. The next 8 weeks consisted of the maintenance phase where the dosage remained consistent.
Patients completed hospital visits at baseline, 2, 3, 4, 6, 8, 10, and 12 weeks where vital signs, standard blood tests, and adverse events were assessed. Patients completed diaries at home containing information on motor control and sleeping patterns. The primary endpoint was efficacy shown through a change in off time recorded in patient's diary. Secondary endpoints were changes in quality of life and adverse events.
The mean apomorphine dose was 4.68 mg/hour (SD 1.50), and 12 patients in the intervention arm and 23 patients in the control arm discontinued treatment before the end of the 12 weeks. The apomorphine infusion significantly reduced off time by -2.47 hours per day (SD 3.70) and -0.58 (SD 2.80) hours per day for the placebo group, for a total treatment difference of -1.89 hours per day (95% CI, –3.16 to –0.62; P=.0025).
Apomorphine infusions also significantly decreased time of dyskinesia (treatment difference 1.97 hours per day, 95% CI, 0.69-3.24; P=.0008), improved Patient Global Impression of Change scores (P<.0001), and improved self-evaluated general health in 71% of the patients. Oral levodopa doses decreased significantly in the apomorphine infusion from baseline to 12 weeks (P=.0014). Adverse events occurred in 93% of the patients receiving the apomorphine infusion, and most of these were mild or moderate. Skin reactions, nausea, and somnolence were the most common adverse events. Severe adverse events were noted in 5 patients.
Limitations of this study included a possible degree of attrition bias due to the number of patients who withdrew early from the study, adverse events due to oral dopamine agonists not completely discontinued, and complete trial blinding could have been compromised due to the quick and notable effects of apomorphine.
In conclusion, apomorphine infusions significantly reduced off time and provided patients with Parkinson disease who experienced uncontrolled motor fluctuations a treatment option that is effective and safe.
This study was supported by Britannia Pharmaceuticals Ltd. Please refer to reference for a complete list of authors' disclosures.
Katzenschlager R, Poewe W, Rascol O, et al. Apomorphine subcutaneous infusion in patients with Parkinson's disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial [published online July 25, 2018]. Lancet Neurol. doi: 10.1016/S1474-4422(18)30239-4