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dc.creatorRodríguez P.C., Prada D.M., Moreno E., Aira L.E., Molinero C., López A.M., Gómez J.A., Hernández I.M., Martínez J.P., Reyes Y., Milera J.M., Hernández M.V., Torres R., Avila Y., Barrese Y., Viada C., Montero E., Hernández P.spa
dc.date.accessioned2018-04-13T16:35:19Z
dc.date.available2018-04-13T16:35:19Z
dc.date.created2018spa
dc.identifier.issn99104spa
dc.identifier.urihttp://hdl.handle.net/11407/4574
dc.description.abstractItolizumab is a humanized anti-CD6 monoclonal antibody (mAb) that has previously shown encouraging results, in terms of safety and positive clinical effects, in a 6-week monotherapy clinical trial conducted in rheumatoid arthritis (RA) patients. The current Phase I study evaluated the safety and clinical response for a longer treatment of 12 itolizumab intravenous doses in subjects with active RA despite previous disease-modifying anti-rheumatic drug (DMARD) therapy. Twenty-one subjects were enrolled into four dosage groups (0·1, 0·2, 0·4 and 0·8 mg/kg). Efficacy end-points including American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates and disease activity score in 28 joints (DAS28) were monitored at baseline and at specific time-points during a 10-week follow-up period. Itolizumab was well tolerated up to the highest tested dose. No related serious adverse events were reported and most adverse events were mild. Remarkably, itolizumab treatment did not produce lymphopenia and, therefore, was not associated with infections. All patients achieved a clinical response (ACR20) at least once during the study. Eleven subjects (55%) achieved at least a 20% improvement in ACR just 1 week after the first itolizumab administration. The clinical response was observed from the beginning of the treatment and was sustained during 24 weeks. The efficacy profile of this 12-week treatment was similar to that of the previous study (6-week treatment). These results reinforce the safety profile of itolizumab and provide further evidence on the clinical benefit from the use of this anti-CD6 mAb in RA patients. © 2017 British Society for Immunologyeng
dc.language.isoengspa
dc.publisherBlackwell Publishing Ltdspa
dc.relation.isversionofhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85034243118&doi=10.1111%2fcei.13061&partnerID=40&md5=3d8a9bf433217b5046abeabe052ba9d2spa
dc.sourceScopusspa
dc.titleThe anti-CD6 antibody itolizumab provides clinical benefit without lymphopenia in rheumatoid arthritis patients: results from a 6-month, open-label Phase I clinical trialspa
dc.typeArticlespa
dc.typeinfo:eu-repo/semantics/publishedVersionspa
dc.typeinfo:eu-repo/semantics/articlespa
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessspa
dc.contributor.affiliationDivision of Clinical Research, Center of Molecular Immunology, Havana, Cuba; Service for Rheumatology, 10 de Octubre Hospital, Havana, Cuba; Facultad de Ciencias Básicas, Universidad de Medellin, Medellin, Colombia; Department of Clinical Trials, National Coordinating Center of Clinical Trials, Havana, Cuba; Experimental Immunotherapy Department, Center of Molecular Immunology, Havana, Cubaspa
dc.identifier.doi10.1111/cei.13061spa
dc.subject.keywordCD6; clinical trial; itolizumab; Phase I; rheumatoid arthritiseng
dc.publisher.facultyFacultad de Ciencias Básicasspa
dc.abstractItolizumab is a humanized anti-CD6 monoclonal antibody (mAb) that has previously shown encouraging results, in terms of safety and positive clinical effects, in a 6-week monotherapy clinical trial conducted in rheumatoid arthritis (RA) patients. The current Phase I study evaluated the safety and clinical response for a longer treatment of 12 itolizumab intravenous doses in subjects with active RA despite previous disease-modifying anti-rheumatic drug (DMARD) therapy. Twenty-one subjects were enrolled into four dosage groups (0·1, 0·2, 0·4 and 0·8 mg/kg). Efficacy end-points including American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates and disease activity score in 28 joints (DAS28) were monitored at baseline and at specific time-points during a 10-week follow-up period. Itolizumab was well tolerated up to the highest tested dose. No related serious adverse events were reported and most adverse events were mild. Remarkably, itolizumab treatment did not produce lymphopenia and, therefore, was not associated with infections. All patients achieved a clinical response (ACR20) at least once during the study. Eleven subjects (55%) achieved at least a 20% improvement in ACR just 1 week after the first itolizumab administration. The clinical response was observed from the beginning of the treatment and was sustained during 24 weeks. The efficacy profile of this 12-week treatment was similar to that of the previous study (6-week treatment). These results reinforce the safety profile of itolizumab and provide further evidence on the clinical benefit from the use of this anti-CD6 mAb in RA patients. © 2017 British Society for Immunologyeng
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An observational study (2012) Bol Asoc Med P R, 104, pp. 34-41; Hernández, P., Moreno, E., Aira, L.E., Rodríguez, P.C., Therapeutic targeting of CD6 in autoimmune diseases: a review of Cuban clinical studies with the antibodies IOR-T1 and itolizumab (2016) Curr Drug Targets, 17, pp. 666-677; Pinto, M., Carmo, A.M., CD6 as a therapeutic target in autoimmune diseases: successes and challenges (2013) BioDrugs, 27, pp. 191-202; Brucklacher-Waldert, V., Steinbach, K., Lioznov, M., Kolster, M., Holscher, C., Tolosa, E., Phenotypical characterization of human Th17 cells unambiguously identified by surface IL-17A expression (2009) J Immunol, 183, pp. 5494-5501; Leipe, J., Grunke, M., Dechant, C., Role of Th17 cells in human autoimmune arthritis (2010) Arthritis Rheum, 62, pp. 2876-2885; van Hamburg, J.P., Asmawidjaja, P.S., Davelaar, N., Th17 cells, but not Th1 cells, from patients with early rheumatoid arthritis are potent inducers of matrix metalloproteinases and proinflammatory cytokines upon synovial fibroblast interaction, including autocrine interleukin-17A production (2011) Arthritis Rheum, 63, pp. 73-83spa
dc.creator.affiliationRodríguez, P.C., Division of Clinical Research, Center of Molecular Immunology, Havana, Cuba; Prada, D.M., Service for Rheumatology, 10 de Octubre Hospital, Havana, Cuba; Moreno, E., Facultad de Ciencias Básicas, Universidad de Medellin, Medellin, Colombia; Aira, L.E., Division of Clinical Research, Center of Molecular Immunology, Havana, Cuba; Molinero, C., Service for Rheumatology, 10 de Octubre Hospital, Havana, Cuba; López, A.M., Service for Rheumatology, 10 de Octubre Hospital, Havana, Cuba; Gómez, J.A., Service for Rheumatology, 10 de Octubre Hospital, Havana, Cuba; Hernández, I.M., Service for Rheumatology, 10 de Octubre Hospital, Havana, Cuba; Martínez, J.P., Service for Rheumatology, 10 de Octubre Hospital, Havana, Cuba; Reyes, Y., Service for Rheumatology, 10 de Octubre Hospital, Havana, Cuba; Milera, J.M., Service for Rheumatology, 10 de Octubre Hospital, Havana, Cuba; Hernández, M.V., Service for Rheumatology, 10 de Octubre Hospital, Havana, Cuba; Torres, R., Service for Rheumatology, 10 de Octubre Hospital, Havana, Cuba; Avila, Y., Department of Clinical Trials, National Coordinating Center of Clinical Trials, Havana, Cuba; Barrese, Y., Department of Clinical Trials, National Coordinating Center of Clinical Trials, Havana, Cuba; Viada, C., Division of Clinical Research, Center of Molecular Immunology, Havana, Cuba; Montero, E., Experimental Immunotherapy Department, Center of Molecular Immunology, Havana, Cuba; Hernández, P., Division of Clinical Research, Center of Molecular Immunology, Havana, Cubaspa
dc.relation.ispartofesClinical and Experimental Immunologyspa


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