title: Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort.
abstract: OBJECTIVE
  To define the rate, timing, and clinical risk factors for the development of autoimmune disease (AID) after alemtuzumab treatment for multiple sclerosis (MS).
  
  
  METHODS
  We analyzed prospective clinical and serologic data from 248 patients with MS treated with alemtuzumab, with median follow-up of 34.3 months (range 6.7-107.3).
  
  
  RESULTS
  Novel AID developed in 22.2%. Thyroid AID was most frequent (15.7%). A range of hematologic, renal, and dermatologic AID were also observed as was asymptomatic development of novel autoantibodies. AID was seen from 2 weeks after initial treatment and was most frequent 12-18 months after first treatment. No new cases of AID were identified 60 months or more after initial treatment and risk of AID was independent of total alemtuzumab dose or interval of dosage. While established risk factors for AID including sex and age had no impact on AID frequency, both family history (odds ratio = 7.31, 95% confidence interval 3.02-17.68) of AID and a personal smoking history (odds ratio = 3.05, 95% confidence interval 1.50-6.19) were predictive of AID expression.
  
  
  CONCLUSIONS
  Cumulative risk for AID in MS following alemtuzumab is 22.2%, most frequent between 12 and 18 months following first dose and evident for up to 5 years. Individual risk is modified by smoking and family history, which should be incorporated within the counseling process prior to treatment.
  
  
  METHODS
  This study provides Class IV evidence that the risk of AID after alemtuzumab treatment for MS is time-limited and modified by external factors.
authors.affiliation: Department of Psychological Medicine and Neurology, Cardiff University, University Hospital of Wales, Heath Park, Cardiff, UK.
authors.forename: M
authors.initials: M
authors.lastname: Cossburn
authors.forename: A A
authors.initials: AA
authors.lastname: Pace
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.forename: R
authors.initials: R
authors.lastname: Ali
authors.forename: G
authors.initials: G
authors.lastname: Ingram
authors.forename: K
authors.initials: K
authors.lastname: Baker
authors.forename: C
authors.initials: C
authors.lastname: Hirst
authors.forename: J
authors.initials: J
authors.lastname: Zajicek
authors.forename: N
authors.initials: N
authors.lastname: Scolding
authors.forename: M
authors.initials: M
authors.lastname: Boggild
authors.forename: T
authors.initials: T
authors.lastname: Pickersgill
authors.forename: Y
authors.initials: Y
authors.lastname: Ben-Shlomo
authors.forename: A
authors.initials: A
authors.lastname: Coles
authors.forename: N P
authors.initials: NP
authors.lastname: Robertson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000235:genetics; D015331:Cohort Studies; D003376:Counseling; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications* / Q000188:drug therapy*; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking; D013959:Thyroid Diseases / Q000139:chemically induced / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D001323:Autoantibodies; D000074323:Alemtuzumab; D008775:Methylprednisolone