Apomorphine formulation influences subcutaneous complications in continuous apomorphine pump therapy for Parkinson’s disease

Objective: To explore if the occurrence and severity of subcutaneous (sc) nodules is influenced by the pharmaceutical formulation of apomorphine used for sc infusion in advanced Parkinson’s disease (PD).

Background: Apomorphine infusion is an effective therapy in advanced PD, but a limitation is troublesome sc nodules. Various chemically non-identical apomorphine formulations are available. Anecdotal clinical experience has suggested that shifting from one of these (Apo-Go PumpFill; apoGPF) to another (Apomorphine PharmSwed; apoPS, developed in Sweden) may influence the occurrence and severity of sc nodules.

Methods: In this multicenter open-label prospective observational study, 15 people with advanced PD (mean PD- duration, 13.4 years; median Hoehn & Yahr, IV) on apoGPF since a mean of 2.1 years and with troublesome sc nodules were switched to apoPS. Ongoing interventions to treat existing nodules (ultrasound, massage, Hirudoid cream) continued, and apomorphine as well as other drugs was managed according to clinical routines. Data were collected between May 2015 and March 2017; at baseline, at the time of switching (about 2 weeks later), and up to 1.7-4.2 (mean, 2.5) months post-switch follow-up. Primary outcomes were total nodule numbers, size (mm diameter for the 5 worst nodules), consistency (scored 0-3 for the 5 worst nodules), and associated skin changes (scored 0-4 for the 5 worst nodules) and pain (scored 0-5). Patients also rated their perceived PD severity and motor complications (UPDRS IV). Patient preferences 5-12 months post-switch (2-9 months after follow-up) were also recorded.

Results: Apomorphine and L-dopa doses did not change over the observation period (P≥0.400). Baseline nodule numbers (7.4 vs. 4.6; P<0.003), size (92.9 vs. 54.1 mm; P=0.016), consistency (11 vs. 5; P=0.003), skin changes (3 vs. 1.5; P=0.205), and average pain (1 vs. 0; P=0.020) improved 11 weeks post-switch. Patient-reported PD severity (P=0.020) and motor fluctuations improved (P=0.051), whereas dyskinesias tended to increase (P=0.205). At 5-12 months post-switch, 13 patients had decided to remain on apoPS; mainly due to improved nodules.

Conclusions: These observations suggest that apoPS may have a better safety profile compared to apoGPF in terms of sc nodule occurrence and severity. There is a need for larger, randomized controlled studies for firmer conclusions.