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The EuroInf survey

Posted in Sponsored Feature on 10th Dec 2012

A grant was provided by Britannia Pharmaceuticals Ltd as a contribution towards the production and design costs of this article. Britannia Pharmaceuticals sponsored the Webinar held during the Movement Disorder Society’s 16th International Congress of Parkinson’s Disease and Movement Disorders held 17-21 June 2012. 

Speaking at an interactive webinar, Professor Ray Chaudhuri discussed the European Infusion (EuroInf) survey, part of the EUROPAR project endorsed by the EPDA and involving over 14 centres across Europe. This survey was presented as a poster at the MDS meeting in Dublin and also presented as one of the highlights at the Dublin congress earlier this year in June.This ongoing multi-centre observational study across several centres in the UK and Europe compares the two infusional therapies for advanced Parkinson’s disease – subcutaneous apomorphine and intrajejunal levodopa.

The study focuses on motor and non-motor symptoms and their cumulative effect, namely quality of life. While not a randomised placebo-controlled study, the outcome measures used (UPDRS III and IV for motor symptoms, NMSS for non-motor symptoms and PDQ-8 for quality of life) reflect good clinical practice in a ‘real-life’ population.Aiming ultimately to have 50 patients in each treatment arm,the study has already recruited over 40 patients on levodopa and 37 on apomorphine. Because the two groups do not match identically, the study looks at the effect size of the two interventions and numbers needed to treat.

With regard to inclusion criteria, these reflect existing clinical practice across Europe for treatment with advanced therapies, said Professor Chaudhuri. Not included are patients who are demented or have significant cognitive problems, those with a diagnosis other than Parkinson’s disease or where the Parkinson’s diagnosis is uncertain, and patients whose response to levodopa is failing. Patients included in the study are therefore essentially those considered fit for further therapy in whom deep brain stimulation using the subthalamic nucleus or globus pallidus internus is not appropriate.

Summarising the observations from the EuroInf survey Professor Chaudhuri outlined that infusions of both apomorphine and levodopa worked well in terms of UPDRS-III, but apomorphine had a very strong effect on motor symptoms, perhaps not surprisingly since previous studies have shown that apomorphine can often quite dramatically return a patient who is otherwise ‘off’ and bradykinetic to essentially normal motor function. In addition, the study found that apomorphine improved certain non-motor symptoms, though the effect on dyskinesias was not quite as good as might have been expected, perhaps because apomorphine therapy was given as monotherapy in only a few centres and was often associated with concomitant use of oral dopaminergic treatment. Levodopa on the other hand was generally given as monotherapy. However, the effect of apomorphine on the non-motor symptoms scale, as well as on quality of life, was as strong as in the levodopa arm.

Addressing the availability of infusion treatments

Professor Chaudhuri noted that even in well established Parkinson’s disease treatment centres the number of patients receiving these therapies is low. Clearly a significant number of patients suitable for apomorphine or levodopa are not being offered these interventions. This may be due to non-availability of the relevant expertise or the supporting services required, but perhaps also because clinicians are not familiar with these treatment strategies. By contrast, deep brain stimulation is a well recognised therapeutic option with a good evidence base from randomised controlled trials. However, to Professor Chaudhuri’s knowledge, deep brain stimulation therapy has yet to be examined holistically using the validated non-motor scale used for apomorphine and levodopa in the EuroInf survey. For patients who cannot undergo deep brain stimulation because of their age, or because they have cognitive impairment or depression, infusion with apomorphine or levodopa provides an alternative therapeutic option.

Looking to the future the aim is therefore to add a third arm to the EuroInf survey to compare a matched group of patients undergoing deep brain stimulation, as well as a fourth comparator arm comprising patients who have not received any of these advanced therapies and who instead continue on conventional best medical therapy.Such a cohort exists in the UK, where funding streams are some-what different to other countries in Europe. Professor Chaudhuri stressed that access to treatment with apomorphine, levodopa and deep brain stimulation is very variable. A good state-of-the-art Parkinson’s disease centre should be able to provide access to all three therapies, based on informed patient choice. This is not currently the case. Patients can be influential here. Professor Chaudhuri noted that, empowered by initiatives such as expert patient groups, patients are becoming better educated about Parkinson’s disease and its potential treatments. In addition, the media has considerable influence in this area.

Impulse control disorders continue to be a major topic of discussion in Parkinson’s disease. Professor Chaudhuri outlined that the relationship between impulse control disorders and oral therapy, particularly dopamine agonist therapy, remains unclear. However data from his own group suggest that the rate of impulse control disorders occurring with longer-acting dopaminergic therapies, particularly dopamine agonists, is actually low compared to the overall prevalence. Single infusional therapies (as possible with apomorphine) appear not to be associated with a high rate of impulse control disorders. Professor Chaudhuri stressed that this is an anecdotal observation, however, which needs to be supported by evidence from a controlled study or data from a large case series like the EuroInf survey.


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