Apomorphine formulation may influence subcutaneous complications from continuous subcutaneous apomorphine infusion in Parkinson's disease

Abstract

Continuous subcutaneous (s.c.) apomorphine infusion is an effective therapy for Parkinson's disease (PD), but a limitation is the formation of troublesome s.c. nodules. Various chemically non-identical apomorphine formulations are available. Anecdotal experiences have suggested that shifting from one of these (Apo-Go PumpFill^®; apoGPF) to another (Apomorphine PharmSwed^®; apoPS) may influence the occurrence and severity of s.c. nodules. We, therefore, followed 15 people with advanced PD (median PD-duration, 15 years; median "off"-phase Hoehn and Yahr, IV) on apoGPF and with troublesome s.c. nodules who were switched to apoPS. Data were collected at baseline, at the time of switching, and at a median of 1, 2.5, and 7.3 months post-switch. Total nodule numbers (P < 0.001), size (P < 0.001), consistency (P < 0.001), skin changes (P = 0.058), and pain (P ≤ 0.032) improved over the observation period. PD severity and dyskinesias tended to improve and increase, respectively. Apomorphine doses were stable, but levodopa doses increased by 100 mg/day. Patient-reported apomorphine efficacy tended to increase and all participants remained on apoPS throughout the observation period; with the main patient-reported reason being improved nodules. These observations suggest that patients with s.c. nodules caused by apoGPF may benefit from switching to apoPS in terms of s.c. nodule occurrence and severity. Alternatively, observed benefits may have been due to the switch itself. As nodule formation is a limiting factor in apomorphine treatment, a controlled prospective study comparing local tolerance with different formulations is warranted.

Keywords: Apomorphine; Complications; Nodules; Parkinson’s disease; Safety; Skin.

Fig. 1

Development of subcutaneous (s.c.) nodules over time in relation to switching from one apomorphine formulation (Apo-Go Pumpfill^® 5 mg/ml) to another (Apomorfin PharmSwed^® 5 mg/ml) among 15 people on continuous s.c. apomorphine infusion with troublesome s.c. nodules. a Depicts the total number of s.c. nodules at the various time points; b through d depict the (b) median nodule diameter (mm) and total sums of ratings of nodule (c) consistency (rated 0–3; 0 = none, 3 = hard) and d associated skin changes (rated 0–4; 0 = none, 4 = ulceration) of the five most pronounced nodules for each individual at the respective time points. P values in the respective panels are for comparisons (Skillings-Mack tests) across all time points. Pairwise comparisons (Wilcoxon signed-ranks tests) yielded the following results: (a) P = 0.042 vs baseline; (b) P = 0.011 vs. baseline, P = 0.030 vs. switch; (c) P = 0.002 vs baseline, P = 0.033 vs. switch, P = 0.497 vs. follow-up 1; (d) P = 0.002 vs baseline, P = 0.003 vs. switch, P = 0.053 vs. f ollow-up 1, P = 0.232 vs. follow-up 2; (e) P = 0.755 vs baseline; (f) P = 0.004 vs. baseline, P = 0.002 vs. switch; (g) P = 0.016 vs baseline, P = 0.009 vs. switch, P = 0.133 vs. follow-up 1; (h) P = 0.002 vs baseline, P = 0.003 vs. switch, P = 0.041 vs. follow-up 1, P = 0.724 vs. follow-up 2; (i) P = 0.261 vs baseline; (j) P = 0.019 vs. baseline, P = 0.008 vs. switch; (k) P = 0.002 vs baseline, P = 0.006 vs. switch, P = 0.112 vs. follow-up 1; (l) P = 0.040 vs baseline, P = 0.082 vs. switch, P = 0.373 vs. follow-up 1, P = 0.964 vs. follow-up 2; (m) P = 0.167 vs baseline; (n) P = 0.142 vs. baseline, P = 0.136 vs. switch; (o) P = 0.217 vs baseline, P = 0.124 vs. switch, P = 0.249 vs. follow-up 1; (p) P = 0.370 vs baseline, P = 0.245 vs. switch, P = 0.298 vs. follow-up 1, and P = 0.341 vs. follow-up 2. Solid horizontal lines are median values, boxes are inter-quartile ranges (25th–75th percentiles), error bars are ranges, and dots are outliers