title: A distinctive form of immune thrombocytopenia in a phase 2 study of alemtuzumab for the treatment of relapsing-remitting multiple sclerosis.
abstract: In a phase 2 clinical trial of annual alemtuzumab for treatment of relapsing-remitting multiple sclerosis, 6 of 216 patients (2.8%) developed immune thrombocytopenia (ITP). Over mean follow-up of 4.5 years, the incidence rate of ITP was 6.2 (95% confidence interval, 2.3-13.3) per 1000 person-years. Median times from initial and last alemtuzumab exposure to ITP diagnosis were 24.5 and 10.5 months, respectively. Five patients developed severe thrombocytopenia. Four were symptomatic, including fatal intracranial hemorrhage in the index case. Four patients received standard first-line ITP therapy, all of whom responded to treatment within 1 week. All 5 surviving patients achieved complete remission and remained in complete remission without need for ongoing ITP therapy for a median duration of 34 months at last follow-up. A monitoring plan for the early detection of ITP, implemented after presentation of the index case, identified all 5 subsequent cases before serious hemorrhagic morbidity or mortality occurred. In conclusion, we describe a distinctive form of ITP associated with alemtuzumab treatment characterized by delayed presentation after drug exposure, responsiveness to conventional ITP therapies, and prolonged remission. Clinicians should maintain a high level of vigilance and consider routine monitoring for ITP in patients treated with this agent. This trial was registered at www.clinicaltrials.gov as #NCT00050778.
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA. adam.cuker@uphs.upenn.edu
authors.forename: Adam
authors.initials: A
authors.lastname: Cuker
authors.forename: Alasdair J
authors.initials: AJ
authors.lastname: Coles
authors.forename: Herman
authors.initials: H
authors.lastname: Sullivan
authors.forename: Edward
authors.initials: E
authors.lastname: Fox
authors.forename: Mark
authors.initials: M
authors.lastname: Goldberg
authors.forename: Pedro
authors.initials: P
authors.lastname: Oyuela
authors.forename: Annie
authors.initials: A
authors.lastname: Purvis
authors.forename: Diana S
authors.initials: DS
authors.lastname: Beardsley
authors.forename: David H
authors.initials: DH
authors.lastname: Margolin
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; D015331:Cohort Studies; D016903:Drug Monitoring; D057239:Early Termination of Clinical Trials; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000037:antagonists & inhibitors; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000517:prevention & control; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000139:chemically induced / Q000453:epidemiology / Q000276:immunology* / Q000628:therapy; D012074:Remission Induction; D055502:Secondary Prevention; D012720:Severity of Illness Index; D014481:United States / Q000453:epidemiology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D007155:Immunologic Factors; D000074323:Alemtuzumab