Year : 2020 | Volume
: 3 | Issue : 3 | Page : 127--128
Newer therapies for advanced Parkinson’s disease: Choosing among “many rights”
Roopa Rajan1, Kanwaljeet Garg2,
1 Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
Dr. Roopa Rajan
Room 704, 7th Floor, CN Center, All India Institute of Medical Sciences (AIIMS), New Delhi.
|How to cite this article:|
Rajan R, Garg K. Newer therapies for advanced Parkinson’s disease: Choosing among “many rights”.Ann Mov Disord 2020;3:127-128
|How to cite this URL:|
Rajan R, Garg K. Newer therapies for advanced Parkinson’s disease: Choosing among “many rights”. Ann Mov Disord [serial online] 2020 [cited 2022 Sep 30 ];3:127-128
Available from: https://www.aomd.in/text.asp?2020/3/3/127/300259
In this volume of Annals of Movement Disorders, Metta and colleagues discuss in-depth a newly added armament in our fight against Parkinson’s disease (PD) in India. Apomorphine is a drug that has been around for centuries, but widely available for use in PD in its present form only over the past few years and more recently in India. Given the multitude of motor and nonmotor symptoms that increase in frequency as PD advances, apomorphine is a welcome addition to the existing armamentarium. As with any newly introduced intervention, scientific evidence is accumulating, physician expertise is evolving, and patient expectations are rising. Hence, this timely review provides a comprehensive evaluation of apomorphine and its use in the Indian context.
As the authors highlight, apomorphine is now available as a subcutaneous injection for use as a rescue medication or as a continuous subcutaneous infusion for those patients requiring more than 4–6 rescue doses in a day. In the setting of motor and nonmotor fluctuations, the goal of both forms of use is to provide continuous dopaminergic stimulation for control of fluctuations and dyskinesias. The practical aspects of initiation, including apomorphine response assessment, dosing, and maintenance, are lucidly discussed by the authors.
Apart from a number of observational studies, regulatory approval for continuous subcutaneous apomorphine infusion followed a multicenter, double-blind, randomized, placebo-controlled trial: TOLEDO. This trial randomized 107 patients to apomorphine subcutaneous infusion or placebo (saline) infusion for 12 weeks, and assessed the endpoint of absolute change in daily off time from patient diaries. There was a significant reduction in off time with a difference of 1.89h per day (or 29% reduction in off time) in favor of apomorphine. Not only motor symptoms, quality of life, which was assessed as a secondary outcome, too improved significantly. Regarding adverse events, skin nodules (44%), nausea (22%), and somnolence (22%) were reported in a significant number of patients. Impulse control disorders, orthostatic hypotension, QT prolongation, and hemolytic anemia are other known adverse events that need to be monitored.
One of the most important questions for the clinician is patient selection and counseling. Choosing between “two rights” or more is a well-known philosophical dilemma. In this particular context, deep brain stimulation, continuous subcutaneous apomorphine infusion, and intrajejunal levodopa are the options that exist as device-assisted therapies for advanced PD. The last of these three options is presently not available easily in India. How does one choose between the other two? The authors have highlighted the decision-making process and touched on the comparative benefits and risks of both of these procedures. On the apomorphine side, evidence from a moderate-sized randomized controlled trial affirms the benefit on motor symptoms. For effects on quality of life and nonmotor symptoms, the evidence stems from observational studies and secondary outcomes of randomized controlled trials, hence the body of evidence is currently insufficient. On the contrary, deep brain stimulation is now a well-established procedure that has been around for decades with many meta-analyses, including thousands of patients confirming the long-term benefits on motor symptoms, quality of life, and selected nonmotor symptoms.,
There are no head-to-head trials that have compared these two therapies, and the limited comparative evidence we have comes from one randomized controlled trial of deep brain stimulation versus best medical therapy (PD-SURG), in which a number of patients in the best medical therapy arm were receiving apomorphine infusion, and data from prospective real life registries and cohorts such as the EuroInf2 and other smaller studies., These suggest almost similar improvement in off time with both therapies, with larger medication reduction and better control of dyskinesia with subthalamic stimulation. The effect on nonmotor symptoms varies, with a more favorable profile for neuropsychiatric effects suggested for apomorphine infusion.
Deep brain stimulation versus apomorphine infusion may in fact be an unfair comparison to make at this stage, with the large body of evidence and practical experience with thousands of patients for deep brain stimulation on one side and the emerging evidence for apomorphine on the other hand. A quick review of clinicaltrials.gov did not list any ongoing randomized controlled head-to-head studies that may provide an answer in the near future. In this situation, how can clinicians help patients make an informed choice? Advanced age, medication refractory gait problems, cognitive impairment, and otherwise high surgical risks deflect the choice toward apomorphine subcutaneous infusion. In otherwise eligible candidates too, apomorphine infusion can be considered as part of best medical therapy before surgery, given its lesser invasiveness. Published experience from India suggests similar outcomes in Indian patients—being a new entrant to the field, the cost-effectiveness, and specific management issues in our context will be known only as experience rises.
Currently, apomorphine as a rescue medication and as a continuous infusion is a promising therapeutic option that gives clinicians the flexibility to offer additional efficacious choices to their patients. As we await further studies and long-term real-life data, the choice is to be guided by prudent risk–benefit analysis in each individual patient.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
|1||Metta R, Borgohain R, Prasanth LK, Mrudula R, Agarwal P, Kishore A, et al. Subcutaneous apomorphine in advanced Parkinson’s disease: an Indian perspective. Ann Mov Disorders 2020;3:145-55.|
|2||Katzenschlager R, Poewe W, Rascol O, Trenkwalder C, Deuschl G, Chaudhuri KR, et al. Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): A multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol 2018;17:749-59.|
|3||Perestelo-Pérez L, Rivero-Santana A, Pérez-Ramos J, Serrano-Pérez P, Panetta J, Hilarion P Deep brain stimulation in Parkinson’s disease: Meta-analysis of randomized controlled trials. J Neurol 2014;261:2051-60.|
|4||Mansouri A, Taslimi S, Badhiwala JH, Witiw CD, Nassiri F, Odekerken VJJ, et al. Deep brain stimulation for Parkinson’s disease: Meta-analysis of results of randomized trials at varying lengths of follow-up. J Neurosurg 2018;128:1199-213.|
|5||Williams A, Gill S, Varma T, Jenkinson C, Quinn N, Mitchell R, et al; PD SURG Collaborative Group. Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson’s disease (PD SURG trial): A randomised, open-label trial. Lancet Neurol 2010;9:581-91.|
|6||Dafsari HS, Martinez-Martin P, Rizos A, Trost M, Dos Santos Ghilardi MG, Reddy P, et al; EUROPAR and the International Parkinson and Movement Disorders Society Non-Motor Parkinson’s Disease Study Group. Euroinf 2: Subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson’s disease. Mov Disord 2019;34:353-65.|
|7||Prashanth LK, Jaychandran R, Seetharam R, Iyer RB Apomorphine: The initial Indian experience in relation to response tests and pumps. Ann Indian Acad Neurol 2020;23:20-4.|