Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study
| Autor: | Paul McCrone, Marc Verny, Gilles CHOPARD, Christoph Schrader, Jörg B. Schulz, Jan Kassubek, Nicholas Wood, Karen Elaine Morrison, Thomas Gasser, Martin Skalej, Beate Winner, Jürgen Winkler, David Burn, Arno Villringer, Richard Brown, K Ray Chaudhuri, Ammar Al-Chalabi, Georg Bernhard Landwehrmeyer, Claire Donnellan, Klaus Gröschel, Danielle Seilhean, Sue Evans |
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| Přispěvatelé: | Immunologie - Immunopathologie - Immunothérapeutique (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institute of Psychiatry, Institute of psychiatry, Neuroépidémiologie Tropicale et Comparée (NETEC), Université de Limoges (UNILIM)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de Neurologie [CHU Limoges], CHU Limoges, Service de Radiologie et Imagerie Médicale [CHU Limoges], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fédération des Maladies du Système Nerveux, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
MESH: Multiple System Atrophy multiple system atrophy MESH: Epidemiologic Methods Severity of Illness Index law.invention 0302 clinical medicine MESH: Riluzole Randomized controlled trial law Clinical endpoint MESH: Treatment Outcome MESH: Aged 0303 health sciences education.field_of_study Riluzole MESH: Middle Aged MESH: Neuroprotective Agents Middle Aged Prognosis 3. Good health Neuroprotective Agents Treatment Outcome natural history Disease Progression Female MESH: Disease Progression Supranuclear Palsy Progressive MESH: Parkinson Disease Secondary medicine.drug medicine.medical_specialty Psychometrics Population Placebo MESH: Prognosis 03 medical and health sciences MESH: Psychometrics Internal medicine MESH: Severity of Illness Index Severity of illness medicine Humans Parkinson Disease Secondary education Aged 030304 developmental biology Intention-to-treat analysis MESH: Humans business.industry Original Articles progressive supranuclear palsy eye diseases MESH: Male Surgery Relative risk randomized controlled trial MESH: Supranuclear Palsy Progressive [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie Neurology (clinical) Epidemiologic Methods business MESH: Female 030217 neurology & neurosurgery |
| Zdroj: | Brain-A Journal of Neurology Brain-A Journal of Neurology, 2009, 132 (Pt 1), pp.156-71. ⟨10.1093/brain/awn291⟩ Brain-A Journal of Neurology, Oxford University Press (OUP), 2009, 132 (Pt 1), pp.156-71. ⟨10.1093/brain/awn291⟩ Brain |
| ISSN: | 0006-8950 1460-2156 |
| Popis: | International audience; Parkinson plus diseases, comprising mainly progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are rare neurodegenerative conditions. We designed a double-blind randomized placebo-controlled trial of riluzole as a potential disease-modifying agent in Parkinson plus disorders (NNIPPS: Neuroprotection and Natural History in Parkinson Plus Syndromes). We analysed the accuracy of our clinical diagnostic criteria, and studied prognostic factors for survival. Patients with an akinetic-rigid syndrome diagnosed as having PSP or MSA according to modified consensus diagnostic criteria were considered for inclusion. The psychometric validity (convergent and predictive) of the NNIPPS diagnostic criteria were tested prospectively by clinical and pathological assessments. The study was powered to detect a 40% decrease in relative risk of death within PSP or MSA strata. Patients were randomized to riluzole or matched placebo daily and followed up to 36 months. The primary endpoint was survival. Secondary efficacy outcomes were rates of disease progression assessed by functional measures. A total of 767 patients were randomized and 760 qualified for the Intent to Treat (ITT) analysis, stratified at entry as PSP (362 patients) or MSA (398 patients). Median follow-up was 1095 days (range 249-1095). During the study, 342 patients died and 112 brains were examined for pathology. NNIPPS diagnostic criteria showed for both PSP and MSA excellent convergent validity with the investigators' assessment of diagnostic probability (point-biserial correlation: MSA r(pb) = 0.93, P < 0.0001; PSP, r(pb) = 0.95, P < 0.0001), and excellent predictive validity against histopathology [sensitivity and specificity (95% CI) for PSP 0.95 (0.88-0.98) and 0.84 (0.77-0.87); and for MSA 0.96 (0.88-0.99) and 0.91 (0.86-0.93)]. There was no evidence of a drug effect on survival in the PSP or MSA strata (3 year Kaplan-Meier estimates PSP-riluzole: 0.51, PSP-placebo: 0.50; MSA-riluzole: 0.53, MSA-placebo: 0.58; P = 0.66 and P = 0.48 by the log-rank test, respectively), or in the population as a whole (P = 0.42, by the stratified-log-rank test). Likewise, rate of progression was similar in both treatment groups. There were no unexpected adverse effects of riluzole, and no significant safety concerns. Riluzole did not have a significant effect on survival or rate of functional deterioration in PSP or MSA, although the study reached over 80% power to detect the hypothesized drug effect within strata. The NNIPPS diagnostic criteria were consistent and valid. They can be used to distinguish between PSP and MSA with high accuracy, and should facilitate research into these conditions relatively early in their evolution. |
| Databáze: | OpenAIRE |
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