Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorATAGA, K. I.
dc.contributor.authorKUTLAR, A.
dc.contributor.authorKANTER, J.
dc.contributor.authorLILES, D.
dc.contributor.authorCANCADO, R.
dc.contributor.authorFRIEDRISCH, J.
dc.contributor.authorGUTHRIE, T. H.
dc.contributor.authorKNIGHT-MADDEN, J.
dc.contributor.authorALVAREZ, O. A.
dc.contributor.authorGORDEUK, V. R.
dc.contributor.authorGUALANDRO, S.
dc.contributor.authorCOLELLA, M. P.
dc.contributor.authorSMITH, W. R.
dc.contributor.authorROLLINS, S. A.
dc.contributor.authorSTOCKER, J. W.
dc.contributor.authorROTHER, R. P.
dc.date.accessioned2017-06-09T15:18:20Z
dc.date.available2017-06-09T15:18:20Z
dc.date.issued2017
dc.description.abstractBACKGROUND The up-regulation of P-selectin in endothelial cells and platelets contributes to the cell-cell interactions that are involved in the pathogenesis of vaso-occlusion and sickle cell-related pain crises. The safety and efficacy of crizanlizumab, an antibody against the adhesion molecule P-selectin, were evaluated in patients with sickle cell disease. METHODS In this double-blind, randomized, placebo-controlled, phase 2 trial, we assigned patients to receive low-dose crizanlizumab (2.5 mg per kilogram of body weight), high-dose crizanlizumab (5.0 mg per kilogram), or placebo, administered intravenously 14 times over a period of 52 weeks. Patients who were receiving concomitant hydroxyurea as well as those not receiving hydroxyurea were included in the study. The primary end point was the annual rate of sickle cell-related pain crises with high-dose crizanlizumab versus placebo. The annual rate of days hospitalized, the times to first and second crises, annual rates of uncomplicated crises (defined as crises other than the acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism) and the acute chest syndrome, and patient-reported outcomes were also assessed. RESULTS A total of 198 patients underwent randomization at 60 sites. The median rate of crises per year was 1.63 with high-dose crizanlizumab versus 2.98 with placebo (indicating a 45.3% lower rate with high-dose crizanlizumab, P = 0.01). The median time to the first crisis was significantly longer with high-dose crizanlizumab than with placebo (4.07 vs. 1.38 months, P = 0.001), as was the median time to the second crisis (10.32 vs. 5.09 months, P = 0.02). The median rate of uncomplicated crises per year was 1.08 with high-dose crizanlizumab, as compared with 2.91 with placebo (indicating a 62.9% lower rate with high-dose crizanlizumab, P = 0.02). Adverse events that occurred in 10% or more of the patients in either active-treatment group and at a frequency that was at least twice as high as that in the placebo group were arthralgia, diarrhea, pruritus, vomiting, and chest pain. CONCLUSIONS In patients with sickle cell disease, crizanlizumab therapy resulted in a significantly lower rate of sickle cell-related pain crises than placebo and was associated with a low incidence of adverse events.
dc.description.indexMEDLINE
dc.description.sponsorshipSelexys Pharmaceuticals
dc.description.sponsorshipNational Heart, Lung, and Blood Institute of the National Institutes of Health [5R44HL093893]
dc.description.sponsorshipOrphan Products Grant Program of the Food and Drug Administration [R01FD004805]
dc.description.sponsorshipPfizer
dc.description.sponsorshipEmmaus Life Sciences
dc.description.sponsorshipMast Therapeutics
dc.description.sponsorshipGlycoMimetics
dc.description.sponsorshipHema-Quest Pharmaceuticals
dc.description.sponsorshipApoPharma
dc.identifier.citationNEW ENGLAND JOURNAL OF MEDICINE, v.376, n.5, p.429-439, 2017
dc.identifier.doi10.1056/NEJMoa1611770
dc.identifier.eissn1533-4406
dc.identifier.issn0028-4793
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/19944
dc.language.isoeng
dc.publisherMASSACHUSETTS MEDICAL SOC
dc.relation.ispartofNew England Journal of Medicine
dc.rightsrestrictedAccess
dc.rights.holderCopyright MASSACHUSETTS MEDICAL SOC
dc.subject.othernonsteroidal antiinflammatory drugs
dc.subject.otherp-selectin
dc.subject.otheradhesion
dc.subject.otheranemia
dc.subject.otherflow
dc.subject.othervasoocclusion
dc.subject.othererythrocytes
dc.subject.otherendothelium
dc.subject.otherhydroxyurea
dc.subject.otherleukocytes
dc.subject.wosMedicine, General & Internal
dc.titleCrizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.author.externalATAGA, K. I.:Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA
hcfmusp.author.externalKUTLAR, A.:Augusta Univ, Med Coll Georgia, Sickle Cell Ctr, Augusta, GA USA
hcfmusp.author.externalKANTER, J.:Med Univ South Carolina, Div Pediat, Charleston, SC USA
hcfmusp.author.externalLILES, D.:East Carolina Univ, Div Hematol Oncol, Greenville, NC USA
hcfmusp.author.externalCANCADO, R.:Santa Casa Med Sch Sao Paulo, Dept Hematol Oncol, Sao Paulo, Brazil
hcfmusp.author.externalFRIEDRISCH, J.:Hosp Clin Porto Alegre, Hematol & Bone Marrow Transplantat Serv, Porto Alegre, RS, Brazil
hcfmusp.author.externalGUTHRIE, T. H.:Baptist Med Ctr, Baptist Canc Inst, Jacksonville, FL USA
hcfmusp.author.externalKNIGHT-MADDEN, J.:Univ West Indies, Sickle Cell Unit, Jamaica, NY USA
hcfmusp.author.externalALVAREZ, O. A.:Univ Miami, Div Pediat Hematol Oncol, Miami, FL USA
hcfmusp.author.externalGORDEUK, V. R.:Univ Illinois, Dept Med, Chicago, IL USA
hcfmusp.author.externalCOLELLA, M. P.:Univ Estadual Campinas, Hematol & Hemotherapy Ctr, Campinas, SP, Brazil
hcfmusp.author.externalSMITH, W. R.:Virginia Commonwealth Univ, Div Gen Internal Med, Richmond, VA USA
hcfmusp.author.externalROLLINS, S. A.:Selexys Pharmaceut, Oklahoma City, OK USA
hcfmusp.author.externalSTOCKER, J. W.:Selexys Pharmaceut, Oklahoma City, OK USA
hcfmusp.author.externalROTHER, R. P.:Selexys Pharmaceut, Oklahoma City, OK USA
hcfmusp.citation.scopus504
hcfmusp.contributor.author-fmusphcSANDRA FATIMA MENOSI GUALANDRO
hcfmusp.description.beginpage429
hcfmusp.description.endpage439
hcfmusp.description.issue5
hcfmusp.description.volume376
hcfmusp.origemWOS
hcfmusp.origem.pubmed27959701
hcfmusp.origem.scopus2-s2.0-85011901148
hcfmusp.origem.wosWOS:000393507200006
hcfmusp.publisher.cityWALTHAM
hcfmusp.publisher.countryUSA
hcfmusp.relation.referenceAtaga KI, 2011, BRIT J HAEMATOL, V153, P92, DOI 10.1111/j.1365-2141.2010.08520.x
hcfmusp.relation.referenceBallas SK, 2012, BLOOD, V120, P3647, DOI 10.1182/blood-2012-04-383430
hcfmusp.relation.referenceBallas SK, 2005, AM J HEMATOL, V79, P17, DOI 10.1002/ajh.20336
hcfmusp.relation.referenceBunn HF, 1997, NEW ENGL J MED, V337, P762
hcfmusp.relation.referenceCandrilli SD, 2011, AM J HEMATOL, V86, P273, DOI 10.1002/ajh.21968
hcfmusp.relation.referenceChang CH, 2010, STROKE, V41, P1884, DOI 10.1161/STROKEAHA.110.585828
hcfmusp.relation.referenceCHARACHE S, 1995, NEW ENGL J MED, V332, P1317, DOI 10.1056/NEJM199505183322001
hcfmusp.relation.referenceChuang SY, 2015, STROKE, V46, P996, DOI 10.1161/STROKEAHA.114.007932
hcfmusp.relation.referenceEmbury SH, 2004, BLOOD, V104, P3378, DOI 10.1182/blood-2004-02-0713
hcfmusp.relation.referenceFrenette PS, 2004, MICROCIRCULATION, V11, P167, DOI 10.1080/10739680490278556
hcfmusp.relation.referenceGutsaeva DR, 2011, BLOOD, V117, P727, DOI 10.1182/blood-2010-05-285718
hcfmusp.relation.referenceHEBBEL RP, 1980, NEW ENGL J MED, V302, P992, DOI 10.1056/NEJM198005013021803
hcfmusp.relation.referenceHeeney MM, 2016, NEW ENGL J MED, V374, P625, DOI 10.1056/NEJMoa1512021
hcfmusp.relation.referenceKutlar A, 2012, AM J HEMATOL, V87, P536, DOI 10.1002/ajh.23147
hcfmusp.relation.referenceLAWRENCE MB, 1991, CELL, V65, P859, DOI 10.1016/0092-8674(91)90393-D
hcfmusp.relation.referenceManwani D, 2013, BLOOD, V122, P3892, DOI 10.1182/blood-2013-05-498311
hcfmusp.relation.referenceMatsui NM, 2002, BLOOD, V100, P3790, DOI 10.1182/blood-2002-02-0626
hcfmusp.relation.referenceMatsui NM, 2001, BLOOD, V98, P1955, DOI 10.1182/blood.V98.6.1955
hcfmusp.relation.referencePLATT OS, 1994, NEW ENGL J MED, V330, P1639, DOI 10.1056/NEJM199406093302303
hcfmusp.relation.referencePolanowska-Grabowska R, 2010, ARTERIOSCL THROM VAS, V30, P2392, DOI 10.1161/ATVBAHA.110.211615
hcfmusp.relation.referenceRees DC, 2010, LANCET, V376, P2018, DOI 10.1016/S0140-6736(10)61029-X
hcfmusp.relation.referenceSteinberg MH, 2003, JAMA-J AM MED ASSOC, V289, P1645, DOI 10.1001/jama.289.13.1645
hcfmusp.relation.referenceTurhan A, 2002, P NATL ACAD SCI USA, V99, P3047, DOI 10.1073/pnas.052522799
hcfmusp.relation.referencevan Tuijn CFJ, 2010, AM J HEMATOL, V85, P532, DOI 10.1002/ajh.21731
hcfmusp.relation.referenceWun T, 1997, J LAB CLIN MED, V129, P507, DOI 10.1016/S0022-2143(97)90005-6
hcfmusp.relation.referenceZarbock A, 2007, BLOOD REV, V21, P99, DOI 10.1016/j.blre.2006.06.001
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