Trial of Deferiprone in Parkinson’s Disease

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Fältnamn	Indikatorer	Metadata
000		05913naa a2201045 4500
001		oai:DiVA.org:uu-491089
003		SwePub
008		221216s2022 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4910892 URI
024	7	a https://doi.org/10.1056/nejmoa22092542 DOI
040		a (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Devos, David4 aut
245	1 0	a Trial of Deferiprone in Parkinson’s Disease
264	1	b Massachusetts Medical Society,c 2022
338		a print2 rdacarrier
520		a BACKGROUNDIron 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.METHODSWe 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.RESULTSA 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<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants.CONCLUSIONSIn participants with early Parkinson's disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng
700	1	a Labreuche, Julien4 aut
700	1	a Rascol, Olivier4 aut
700	1	a Corvol, Jean-Christophe4 aut
700	1	a Duhamel, Alain4 aut
700	1	a Guyon Delannoy, Pauline4 aut
700	1	a Poewe, Werner4 aut
700	1	a Compta, Yaroslau4 aut
700	1	a Pavese, Nicola4 aut
700	1	a Růžička, Evžen4 aut
700	1	a Dušek, Petr4 aut
700	1	a Post, Bart4 aut
700	1	a Bloem, Bastiaan R.4 aut
700	1	a Berg, Daniela4 aut
700	1	a Maetzler, Walter4 aut
700	1	a Otto, Markus4 aut
700	1	a Habert, Marie-Odile4 aut
700	1	a Lehericy, Stéphane4 aut
700	1	a Ferreira, Joaquim4 aut
700	1	a Dodel, Richard4 aut
700	1	a Tranchant, Christine4 aut
700	1	a Eusebio, Alexandre4 aut
700	1	a Thobois, Stéphane4 aut
700	1	a Marques, Ana-Raquel4 aut
700	1	a Meissner, Wassilios G.4 aut
700	1	a Ory-Magne, Fabienne4 aut
700	1	a Walter, Uwe4 aut
700	1	a de Bie, Rob M.A.4 aut
700	1	a Gago, Miguel4 aut
700	1	a Vilas, Dolores4 aut
700	1	a Kulisevsky, Jaime4 aut
700	1	a Januario, Cristina4 aut
700	1	a Coelho, Miguel V.S.4 aut
700	1	a Behnke, Stefanie4 aut
700	1	a Worth, Paul4 aut
700	1	a Seppi, Klaus4 aut
700	1	a Ouk, Thavarak4 aut
700	1	a Potey, Camille4 aut
700	1	a Leclercq, Céline4 aut
700	1	a Viard, Romain4 aut
700	1	a Kuchcinski, Gregory4 aut
700	1	a Lopes, Renaud4 aut
700	1	a Pruvo, Jean-Pierre4 aut
700	1	a Pigny, Pascal4 aut
700	1	a Garçon, Guillaume4 aut
700	1	a Simonin, Ophélie4 aut
700	1	a Carpentier, Jessica4 aut
700	1	a Rolland, Anne-Sophie4 aut
700	1	a Nyholm, Dag,c Professor,d 1974-u Uppsala universitet,Neurologi4 aut0 (Swepub:uu)danyh856
700	1	a Scherfler, Christoph4 aut
700	1	a Mangin, Jean-François4 aut
700	1	a Chupin, Marie4 aut
700	1	a Bordet, Régis4 aut
700	1	a Dexter, David T.4 aut
700	1	a Fradette, Caroline4 aut
700	1	a Spino, Michael4 aut
700	1	a Tricta, Fernando4 aut
700	1	a Ayton, Scott4 aut
700	1	a Bush, Ashley I.4 aut
700	1	a Devedjian, Jean-Christophe4 aut
700	1	a Duce, James A.4 aut
700	1	a Cabantchik, Ioav4 aut
700	1	a Defebvre, Luc4 aut
700	1	a Deplanque, Dominique4 aut
700	1	a Moreau, Caroline4 aut
710	2	a Uppsala universitetb Neurologi4 org
773	0	t New England Journal of Medicined : Massachusetts Medical Societyg 387:22, s. 2045-2055q 387:22<2045-2055x 0028-4793x 1533-4406
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-491089
856	4 8	u https://doi.org/10.1056/nejmoa2209254

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Av författaren/redakt...: Devos, David; Labreuche, Julie ...; Rascol, Olivier; Corvol, Jean-Chr ...; Duhamel, Alain; Guyon Delannoy, ...; visa fler...; Poewe, Werner; Compta, Yaroslau; Pavese, Nicola; Růžička, Evžen; Dušek, Petr; Post, Bart; Bloem, Bastiaan ...; Berg, Daniela; Maetzler, Walter; Otto, Markus; Habert, Marie-Od ...; Lehericy, Stépha ...; Ferreira, Joaqui ...; Dodel, Richard; Tranchant, Chris ...; Eusebio, Alexand ...; Thobois, Stéphan ...; Marques, Ana-Raq ...; Meissner, Wassil ...; Ory-Magne, Fabie ...; Walter, Uwe; de Bie, Rob M.A.; Gago, Miguel; Vilas, Dolores; Kulisevsky, Jaim ...; Januario, Cristi ...; Coelho, Miguel V ...; Behnke, Stefanie; Worth, Paul; Seppi, Klaus; Ouk, Thavarak; Potey, Camille; Leclercq, Céline; Viard, Romain; Kuchcinski, Greg ...; Lopes, Renaud; Pruvo, Jean-Pier ...; Pigny, Pascal; Garçon, Guillaum ...; Simonin, Ophélie; Carpentier, Jess ...; Rolland, Anne-So ...; Nyholm, Dag, Pro ...; Scherfler, Chris ...; Mangin, Jean-Fra ...; Chupin, Marie; Bordet, Régis; Dexter, David T.; Fradette, Caroli ...; Spino, Michael; Tricta, Fernando; Ayton, Scott; Bush, Ashley I.; Devedjian, Jean- ...; Duce, James A.; Cabantchik, Ioav; Defebvre, Luc; Deplanque, Domin ...; Moreau, Caroline; visa färre...

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