Apomorphine Improves Parkinson Disease Control In Combination With DBS And Alone

February 13, 2019

The authors concluded that when DBS is insufficient to manage motor symptoms, apomorphine, whether alone or in combination with DBS, is a good choice to improve the disease control.

Angel Sesar, MD

New research has suggested that the use of deep brain stimulation (DBS) in patients with advanced Parkinson disease may not be sufficient enough, or may fail entirely, to control motor symptoms to an adequate extent, though continuous subcutaneous apomorphine infusion in conjunction with DBS or alone, can improve disease control.1

The descriptive, retrospective, single-center analysis ultimately found that in Group 4 of the 4 groups included in the study, the 13 patients treated with DBS and apomorphine in combination displayed significant improvements in motor function between treatment with DBS alone (off-hours, 3.9 ±2.6) compared to combination therapy (off-hours, 2.2 ±1.3; P = .03).

“Advanced [Parkinson] is a tough situation for patients but also clinicians. Fortunately, there are effective treatments for this stage,” Ángel Sesar, MD, a neurologist at Hospital Clínico Universitario Santiago de Compostela, and colleagues, wrote. “Although we always recommend DBS as the first option, sometimes, this therapy is not sufficient or fails. In these cases, [apomorphine], whether alone as a temporary solution, alone indefinitely, or in combination with DBS, is an excellent choice to ensure that the patients have a reasonably good quality of life.”

Sesar told NeurologyLive that the research was prompted to "analyze different scenarios in which we use at the same or at different times apomorphine or DBS in a given patient," and that ultimately, "advanced Parkinson disease is a complex situation and sometimes you need to combine 2 therapies specific for this stage."

In total, the study assessed data from 71 patients treated with DBS and apomorphine, together or sequentially, from February 2006 to June 2018. The patients were placed into 4 groups, with 17 patients discontinuing apomorphine for various reasons. The groups consisted of the following: Group 1 (n = 18), patients on the waiting list for DBS treatment who were treated with apomorphine until surgery; Group 2 (n = 11), patients treated temporarily with apomorphine following DBS device removal; Group 3 (n = 12), patients treated with apomorphine after the permanent removal of a DBS device; and Group 4 (n = 13), patients who were treated with both DBS and apomorphine.

In Group 1, no significant differences in Unified Parkinson Disease Rating Scale (UPDRS) II and III scores between the 3 treatment periods of pre-apomorphine treatment, apomorphine treatment, and DBS treatment. Although, a significant decrease in off-hours was observed between the period prior to being treated with apomorphine and treatment with apomorphine (P <.001), as well as the pre-apomorphine and DBS periods (P <.001). However, no difference was shown between the time they were with apomorphine and with DBS. Off-hours before apomorphine were 5.4 ±1.4 compared to 1.4 ±1.2 after apomorphine and 0.7 ±0.8 after DBS.

Sesar and colleagues noted that “similarly, for oral levodopa dose, significant decreases were observed” for the pre-apomorphine and post-apomorphine periods (P = .003) and the pre-apomorphine and post-DBS periods (P = .002), but not between the post-apomorphine and post-DBS periods. Nine out of 12 patients in the pre-apomorphine group experienced dyskinesia, and this remained unchanged after treatment with apomorphine, but with DBS treatment, significantly fewer patients (5 out of 12) experienced dyskinesia (P = .023).

“In our study, the results observed in Group 1 are a consequence of too long waiting lists. To avoid prolonged periods with untreated advanced disease, we always offer [apomorphine] before DBS,” the investigators explained. “We achieved a good improvement in daily on time with [apomorphine] that was not significantly different to the improvement showed with DBS. However, the sample number is small, and the study is retrospective.”

In Group 2, no significant differences UPDRS II and III scores were observed between the initial DBS device period, the apomorphine period, and the final DBS device period. Off-hours were significantly reduced between the initial DBS device period and the apomorphine period (P = .02), and between the apomorphine period and the final DBS device period (P = .02). There was no difference between the initial and final DBS periods, though, with less off-time recorded during both treatment periods. Overall, patients were observed to have 0.7 ±1.0 off-hours during the first DBS treatment, compared to 2.2 ±1.5 off-hours during the apomorphine period and 0.6 ±0.8 off-hours with the second DBS period (P = .03 compared to apomorphine).

In Group 3, patients had mild but significant worsening of motor function between the DBS period (off hours, 1.1 ±1.0) and the apomorphine period (off hours, 2.0 ±0.9; P = .03). No significant differences UPDRS II and III scores were observed between the 2 periods.

“A significant increase in daily off-hours was observed in patients treated with [apomorphine] following DBS removal (W+ = 41.5; P = .03) accompanied by a significant decrease in levodopa dose (t = −3.33; P = .01),” Sesar and colleagues wrote.

In addition to the previously mentioned findings from Group 4, a significant decrease in daily off-hours was observed for patients treated with the combination (t = −2.53; P = .03) compared with DBS alone. There was also significant worsening of cognitive decline in the combination period (W+ = 15.0; P = .04), compared with DBS alone.

Sesar and colleagues determined that in advanced Parkinson, DBS may be not sufficient or may fail to control motor symptoms satisfactorily. “In these cases, [apomorphine], whether alone or in combination with DBS, is a good choice to improve the disease control,” they concluded.

"In patients in early-advanced stage, it seems that both apomorphine and DBS get very similar symptomatic disease control. This does not happen in more advanced patients. In these cases, DBS seems superior," Sesar told NeurologyLive.

REFERENCES

1. Sesar A, Fernandez&#8209;Pajarin G, Ares B, et al. Continuous subcutaneous apomorphine in advanced Parkinson’s disease patients treated with deep brain stimulation. J Neurol. Published online January 7, 2019. doi: 10.1007/s00415-019-09184-5.