title: Morbidity and mortality in rheumatoid arthritis patients with prolonged therapy-induced lymphopenia: twelve-year outcomes.
abstract: OBJECTIVE
  To assess immunologically relevant outcomes in a cohort of rheumatoid arthritis (RA) patients with prolonged therapy-induced lymphopenia.
  
  
  METHODS
  Morbidity (infection or malignancy) and mortality were assessed in 53 RA patients who were treated with the lymphocytotoxic monoclonal antibody alemtuzumab between 1991 and 1994. Data were obtained by interview, medical record review, and Office for National Statistics mortality monitoring. Lymphocyte subsets were enumerated by flow cytometry. A retrospective, matched-cohort study of mortality was performed with 102 control subjects selected from the European League Against Rheumatism database of patients with rheumatic disorders.
  
  
  RESULTS
  Lymphopenia persisted in the patients: median CD3+CD4+, CD3+CD8+, CD19+, and CD56+ lymphocyte counts measured at a median followup of 11.8 years from the first administration of alemtuzumab were 0.50 x 10(9)/liter, 0.26 x 10(9)/liter, 0.11 x 10(9)/liter, and 0.09 x 10(9)/liter, respectively. Twenty-seven of 51 cases and 46 of 101 controls with available data had died, yielding a mortality rate ratio of 1.20 (95% confidence interval 0.72-1.98). Causes of death were similar to those that would be expected in a hospital-based RA cohort. No opportunistic infections were noted, and only 3 infections were documented following 36 elective orthopedic procedures.
  
  
  CONCLUSIONS
  Despite continued lymphopenia 11.8 years after therapy, our patient cohort did not exhibit excess mortality or unusual infection-related morbidity, and surgery was well tolerated. These data should be reassuring for clinicians and patients who are considering lymphocytotoxic or other immunomodulatory therapy for RA.
authors.affiliation: Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: Alice R
authors.initials: AR
authors.lastname: Lorenzi
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Clarke
authors.forename: Tom
authors.initials: T
authors.lastname: Wooldridge
authors.forename: Herman
authors.initials: H
authors.lastname: Waldmann
authors.forename: Geoff
authors.initials: G
authors.lastname: Hale
authors.forename: Deborah
authors.initials: D
authors.lastname: Symmons
authors.forename: Brian L
authors.initials: BL
authors.lastname: Hazleman
authors.forename: John D
authors.initials: JD
authors.lastname: Isaacs
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000401:mortality* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007239:Infections / Q000401:mortality; D053208:Kaplan-Meier Estimate; D016131:Lymphocyte Subsets / Q000187:drug effects; D008231:Lymphopenia / Q000139:chemically induced* / Q000401:mortality; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009017:Morbidity; D009369:Neoplasms / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab