Fw: Requip Slows Progression of PD

[Hans van der Genugten <genugten@xxxxxxxxxxxxx>]

(abstract was modified by Dr. Lieberman to make it more readable for lay
people.)

The REAL-PET Study:
Slower progression in Early Parkinson's Disease
Treated with Ropinirole Compared with L-Dopa
Presented American Academy of Neurology, April 2002 Denver Colorado

Authors
Alan L. Whone, Philippe Remy, Margaret R. Davis, Michael Sabolek, Claude
Nahmias, A. Jon Stoessl, Ray L. Watts, David J. Brooks

Countries
London, United Kingdom, Orsay, France, Atlanta, GA, Ulm, Germany,
Hamilton, Ontario, Vancouver, British Columbia

OBJECTIVE:
To investigate the relative progression of early PD patients treated with
the dopamine agonist ropinirole (Requip) versus L-dopa as evidenced by brain
18F-dopa uptake.

BACKGROUND:
Currently, there is no medication proven to have disease modifying
properties in PD. Preclinical studies have shown ropinirole (Requip) to have
neuro-protective properties. Pilot 18F-dopa PET data from a cohort of 45 PD
patients showed a trend towards 20% slower disease progression in ropinirole
(Requip) versus L-dopa treated patients. The REAL-PET study was designed to
confirm this potential.

DESIGN/METHODS:
This was a 2 year, double-blind, multinational study of 186 de novo
(untreated) PD patients subsequently treated with ropinirole (Requip) or
L-dopa (Sinemet). The randomization was 1:1 half were treated with
ropinirole, half with L-dopa. .

Patients with insufficient therapeutic benefit could supplement medication
with additional L-dopa and continue in the study. The primary endpoint was
the change in putamen 18F-dopa uptake measured with 3D PET.

Scan data were transformed into standard stereo-tactic space to normalize
brain position and shape and analyzed by:
1. Placing regions of interest on an MRI template.
2. Using statistical parametric mapping to localize and compare peak
changes between groups.

Local regions of interest analyses were also performed by individual
centers.

Clinical progression scored with the Unified Parkinson Disease Rating
Scale and incidence of dyskinesias were secondary endpoints.

RESULTS:
93 PD patients were randomized to each treatment
73% of the ropinirole and 74% of the L-dopa patients completed the 2 year
study.

The mean daily doses after 2 years were:
12.2 mg of ropinirole ( +/- 6.1 mg)
558.7 mg of L-dopa (+/- 180.8 mg)

Blinded review of baseline and follow-up PET identified 11% of subjects as
having normal caudate and putamen 18F-dopa uptake. These were considered
separately.

14% of ropinirole and 8% of L-dopa patients required additional L-dopa.

Central region of interest analysis of putamen 18F-dopa uptake showed
significantly slower progression with ropinirole:
-13% progression with ropinirole versus
-20% progression with L-dopa (p value of significance=0.022).

Statistical parametric mapping detected significantly slower progression
in two regions with ropinirole (Requip).

In the putamen there was
-14% progression with ropinirole versus
-20% progression with L-dopa (p value of significance =0.034)

In the substantia nigra there was: +3% progression with ropinirole
versus -8% progression with L-dopa ( p = 0.035).

Local region of interest analysis of 18F-dopa uptake showed a trend in
favor of ropinirole
-15% progression with ropinirole versus
-18% progression with L-dopa (p =0.354).
The incidence of dyskinesia was: 3% with ropinerole 27% with L-dopa (p less
than 0.001)

Although overall the PD symptoms of both groups were adequately controlled,
changes in the Unified Parkinson Disease Rating Scale favored the L-dopa
group by 6 points.

CONCLUSIONS:
Both blinded central region of interest analysis and spacial parametric
mapping on spatially normalized 18F-dopa PET data provide clear evidence
of significantly slower disease progression in PD patients taking
ropinirole (Requip) compared with L-dopa.

Furthermore, a significantly lower incidence of dyskinesias was seen in
patients taking ropinirole(Requip) compared with L-dopa.

Supported By: Glaxo SmithKline

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