Trial of Deferiprone in Parkinson’s Disease.
N Engl J Med. 2022-12-01; 387(22): 2045-2055
DOI: 10.1056/nejmoa2209254
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1. N Engl J Med. 2022 Dec 1;387(22):2045-2055. doi: 10.1056/NEJMoa2209254.
Trial of Deferiprone in Parkinson’s Disease.
Devos D(1), Labreuche J(1), Rascol O(1), Corvol JC(1), Duhamel A(1), Guyon
Delannoy P(1), Poewe W(1), Compta Y(1), Pavese N(1), Růžička E(1), Dušek P(1),
Post B(1), Bloem BR(1), Berg D(1), Maetzler W(1), Otto M(1), Habert MO(1),
Lehericy S(1), Ferreira J(1), Dodel R(1), Tranchant C(1), Eusebio A(1), Thobois
S(1), Marques AR(1), Meissner WG(1), Ory-Magne F(1), Walter U(1), de Bie RMA(1),
Gago M(1), Vilas D(1), Kulisevsky J(1), Januario C(1), Coelho MVS(1), Behnke
S(1), Worth P(1), Seppi K(1), Ouk T(1), Potey C(1), Leclercq C(1), Viard R(1),
Kuchcinski G(1), Lopes R(1), Pruvo JP(1), Pigny P(1), Garçon G(1), Simonin O(1),
Carpentier J(1), Rolland AS(1), Nyholm D(1), Scherfler C(1), Mangin JF(1),
Chupin M(1), Bordet R(1), Dexter DT(1), Fradette C(1), Spino M(1), Tricta F(1),
Ayton S(1), Bush AI(1), Devedjian JC(1), Duce JA(1), Cabantchik I(1), Defebvre
L(1), Deplanque D(1), Moreau C(1); FAIRPARK-II Study Group.
Collaborators: Defebvre L, Rascol O, Tranchant C, Eusebio A, Thobois S, Corvol
JC, Durif F, Meissner W, Yaroslau C, Vilas D, Kulisevsky J, Poewe W, Ruzicka E,
Gago M, Januario C, Vilhena Soares Coelho M, Berg D, Behnke S, Walter U, Worth
P, Pavese N, Post B, de Bie RMA, Abbruzzese G, Accart B, Allain MA, Anheim M,
Ardigo D, Aracil-Bolaños I, Baba P, Bakker M, Balzer-Geldsetzer M, Bargalló N,
Barone P, Basenau S, Beliveau V, Benchetrit E, Best L, Bloem B, Bonicel R,
Boraud T, Bordet R, Bouca R, Bourdain F, Bouzas J, Brefel-Courbon C, Bubenheim
M, Burn D, Bush AI, Cabantchik I, Calvas F, Cámara A, Campolongo A, Carrière N,
Chaigneau V, Matthieu C, Compta Y, Connelly J, Cormier-Dequaire F, Cranston A,
Dean R, De Marzi R, Degos B, Demotes J, Dellapina E, Deplanque D, Devedjian JC,
Devos D, Dexter D, Dodel R, Dongmo C, Duce J, Duhamel A, Dupouy J, Dusek P, El
Mountassir F, Eyvrard F, Fernández M, Ferreira J, Forni GL, Foster V,
Foubert-Samier A, Fradette C, Fréville L, Galitzky M, Gaudebout C, Gelé P,
Giladi N, Grabli D, Gleixner F, Grolez G, Guyon P, Habert MO, Harroch E,
Hartmann A, Hirsch D, Hisbergues M, Hobert MA, Hopfner F, Jurado C, Kaiser A,
Keen G, Klaus S, Kouassi N, Labreuch J, Lacomblez L, Lagha Boukbiza O, Lanthaler
B, Lechatellier G, Le Forestier N, Lehmann F, Lloret T, Le Naour J, Le Toullec
B, Locatelli M, Löhle M, Lomeña F, Longato N, Lützen U, McNichol A, Maetzler C,
Maetzler W, Mahlknecht P, Mangone G, Marín-Lahoz J, Mariani LL, Marques A, Matei
M, Matthias L, Maucourt Bacchi E, Meissner W, Michon A, Moreau C, Nardocci N,
Nosal F, Nyholm D, Oeckl P, Oravska I, Ory F, Otto M, Ouk T, Pagonabarraga J,
Pascual-Sedano B, Peball M, Phillips C, Pineau F, Planellas L, Pop-Ilieva C,
Rabier A, Olivier D, Riedel C, Rodrigues M, Roullet-Solignac I, Rose C, Rozova
A, Růžička E, Salis A, Schäffer E, Scherfler C, Schiefermeier N, Seppi K,
Smagghe D, Silva T, Silva P, Socha J, Souyris C, Spampinato U, Spino M, Steel A,
Sweta B, Thalamas C, Teodor D, Teresa A, Tison F, Tolosa E, Tricta F, Trifirò
Trifirò G, Vidailhet M, Wang Y, Werkmann M, Yilmas R, You H, Zeuner K.
Author information:
(1)From the Departments of Medical Pharmacology (D. Devos, A.-S.R., R.B.,
J.-C.D.), Neuroradiology (R.V., G.K., R.L., J.-P.P.), and Neurology (L.D.,
C.M.), University of Lille, Lille Neuroscience and Cognition, Team DVCD, INSERM
Unité Mixte de Recherche Scientifique (UMRS) 1172, Centre Hospitalier
Universitaire (CHU) de Lille, Expert Center of Parkinson’s Disease, Lille Center
of Excellence for Neurodegenerative Disorders (LiCEND) Network of Centers of
Excellence in Neurodegeneration (CoEN) Center, NS-Park/FCRIN network, the
Department of Biostatistics, University of Lille, CHU de Lille (J.L., A.D.), CHU
de Lille, Direction de la Recherche et de l’Innovation (P.G.D., T.O., C.P.,
C.L.) and Vigilance des Essais Cliniques and Service de Pharmacologie (T.O.,
C.P., C.L.), CHU de Lille, Laboratoire de Biochimie-Hormonologie, Centre de
Biologie Pathologie (P.P.), the University of Lille, CHU de Lille, Institut
Pasteur de Lille, ULR4483-Impact de l’Environnement Chimique sur la Santé
Humaine (G.G., O.S., J.C.), and the University of Lille, INSERM, CHU de Lille,
Unité 1172-Degenerative and Vascular Cognitive Disorders (D. Deplanque), Lille,
Clinical Investigation Center 1436, Departments of Neurosciences and Clinical
Pharmacology, NS-Park/FCRIN network and NeuroToul CoEN Center, University
Hospital of Toulouse, INSERM, University of Toulouse 3, Toulouse (O.R.,
F.O.-M.), Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP),
INSERM, Centre National de la Recherche Scientifique (CNRS), Paris Brain
Institute-Institut du Cerveau et de la Moelle Épinière (ICM), Department of
Neurology, Centre d’Investigation Clinique Neurosciences, Hôpital
Pitié-Salpêtrière (J.-C.C.), Sorbonne Université, CNRS, INSERM, Laboratoire
d’Imagerie Biomédicale, and AP-HP, Hôpital Pitié-Salpêtrière, Department of
Nuclear Medicine (M.-O.H.), Centre pour l’Acquisition et le Traitement des
Images, US52-UAR2031, Commissariat à l’Énergie Atomique et aux Énergies
Alternatives (CEA), ICM, Sorbonne Université, CNRS, INSERM, AP-HP (M.-O.H.,
J.-F.M., M.C.), Paris Brain Institute-ICM, Center for Neuroimaging Research,
Sorbonne Université, INSERM Unité 1127, CNRS 7225, Department of Neuroradiology,
Hôpital Pitié-Salpêtrière, AP-HP (S.L.), and ICM, CNRS UMR 7725, INSERM, Unité
1127, Sorbonne Université (J.-F.M., M.C.), Paris, the Department of Neurology,
NS-Park/FCRIN network, Strasbourg University Hospital, Fédération de Médecine
Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg (C.T.),
Assistance Publique-Hôpitaux de Marseille, Department of Neurology and Movement
Disorders, Timone University Hospital and Institut de Neurosciences de la
Timone, Unité Mixte de Recherche (UMR) 7289, CNRS-Aix Marseille Université,
Marseille (A.E.), University of Lyon, CNRS, UMR 5229, Hospices Civils de Lyon,
Hôpital Neurologique Pierre Wertheimer, Service de Neurologie, Centre Expert
Parkinson NS-Park/FCRIN network, Bron (S.T.), Université Clermont Auvergne,
EA7280, Clermont-Ferrand University Hospital, Neurology Department,
Clermont-Ferrand (A.-R.M.), CHU de Bordeaux, Service de Neurologie des Maladies
Neurodégénératives, Institut des Maladies Neurodégénératives (IMN) Clinique,
University of Bordeaux, CNRS, IMN, UMR 5293, Bordeaux (W.G.M.), and Université
Paris-Saclay, CEA, CNRS, NeuroSpin, Baobab, Gif-sur-Yvette (J.-F.M., M.C.) – all
in France; the Department of Neurology, Medical University Innsbruck, Innsbruck,
Austria (W.P., K.S.); Parkinson’s Disease and Movement Disorders Unit, Hospital
Clínic de Barcelona-Institut d’Investigacions Biomèdiques August Pi I
Sunyer-Centro de Investigación Biomédica en Red sobre Enfermedades
Neurodegenerativas (CIBERNED)-European Reference Network for Rare Neurological
Diseases, Maria de Maeztu Excellence Center-Institut de Neurociències,
Universitat de Barcelona (Y.C.), and the Movement Disorders Unit, Neurology
Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de
Barcelona, Department of Medicine, Sant Pau Biomedical Research Institute, and
CIBERNED (J.K.), Barcelona, and the Movement Disorders Unit, Hospital Germans
Trias i Pujol, Badalona (D.V.) – all in Spain; Clinical Ageing Research Unit,
Newcastle University, Newcastle upon Tyne (N.P.), Addenbrooke’s Hospital (P.W.)
and the ALBORADA Drug Discovery Institute, University of Cambridge, Cambridge
Biomedical Campus (J.A.D.), Cambridge, and Parkinson’s UK, London (D.T.D.) – all
in the United Kingdom; the Department of Neurology and Center of Clinical
Neuroscience, First Faculty of Medicine, Charles University and General
University Hospital, Prague, Czech Republic (E.R., P.D.); Radboud University
Medical Center, Donders Institute for Brain, Cognition, and Behavior, Department
of Neurology, Nijmegen (B.P., B.R.B.), and Amsterdam UMC location University of
Amsterdam, Department of Neurology, and Amsterdam Neuroscience,
Neurodegeneration, Amsterdam (R.M.A.B.) – all in the Netherlands; the Department
of Neurology, Christian Albrechts University Kiel, Kiel (D.B., W.M.), the
Department of Neurology, University Clinic, Ulm (M.O.), the Department of
Geriatric Medicine, University Duisburg-Essen, Essen (R.D.), Rostock University
Medical Center, Department of Neurology, and the German Center for
Neurodegenerative Diseases, Research Site Rostock, Rostock (U.W.), and
University Hospital of the Saarland, Homburg (S.B.) – all in Germany; Centro de
Investigação em Arquitetura, Urbanismo e Design, Faculdade de Arquitetura,
Universidade de Lisboa (J.F.), and Hospital de Santa Maria (M.V.S.C.), Lisbon,
the Department of Neurology, Hospital da Senhora da Oliveira, Guimarães (M.G.),
Life and Health Sciences Research Institute, School of Medicine, University of
Minho, Braga (M.G.), and Hopitais da Universidade de Coimbra, Department of
Neurology, Coimbra (C.J.) – all in Portugal; the Department of Medicine,
University of Otago, Christchurch Campus, and New Zealand Brain Research
Institute – both in Christchurch, New Zealand (W.G.M.); the Department of
Medical Sciences, Neurology, Uppsala University, Uppsala, Sweden (D.N.); Leslie
Dan Faculty of Pharmacy, University of Toronto, ApoPharma, and Chiesi Canada –
all in Toronto (C.F., M.S., F.T.); Melbourne Dementia Research Centre, Florey
Institute of Neuroscience and Mental Health, University of Melbourne, Parkville,
VIC, Australia (S.A., A.I.B., J.A.D.); and the Department of Biological
Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University,
Jerusalem, Israel (I.C.).
Comment in
N Engl J Med. 2022 Dec 1;387(22):2087-2088.
Nat Rev Neurol. 2023 Feb;19(2):67.
BACKGROUND: Iron content is increased in the substantia nigra of persons with
Parkinson’s disease and may contribute to the pathophysiology of the disorder.
Early research suggests that the iron chelator deferiprone can reduce
nigrostriatal iron content in persons with Parkinson’s disease, but its effects
on disease progression are unclear.
METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial
involving participants with newly diagnosed Parkinson’s disease who had never
received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral
deferiprone at a dose of 15 mg per kilogram of body weight twice daily or
matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed
necessary for symptom control. The primary outcome was the change in the total
score on the Movement Disorder Society-sponsored revision of the Unified
Parkinson’s Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores
indicating more severe impairment) at 36 weeks. Secondary and exploratory
clinical outcomes at up to 40 weeks included measures of motor and nonmotor
disability. Brain iron content measured with the use of magnetic resonance
imaging was also an exploratory outcome.
RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive
deferiprone and 186 to receive placebo. Progression of symptoms led to the
initiation of dopaminergic therapy in 22.0% of the participants in the
deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS
total score at baseline was 34.3 in the deferiprone group and 33.2 in the
placebo group and increased (worsened) by 15.6 points and 6.3 points,
respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2;
P