title: Risk of lymphoma in patients with ulcerative colitis treated with thiopurines: a nationwide retrospective cohort study.
abstract: OBJECTIVE
  There is controversy over whether the treatment of patients with ulcerative colitis (UC) with thiopurines increases their risk of lymphoma. We evaluated the risk of lymphoma (ongoing, residual, and per year of therapy) among thiopurine-treated patients with UC.
  
  
  METHODS
  We obtained nationwide data from the Veterans Affairs (VA) health care system from 2001 to 2011. We performed a retrospective cohort study, analyzing data on 36,891 patients from their date of diagnosis of UC in the VA health care system to a diagnosis of lymphoma or October 1, 2011 (subjects followed up for a median of 6.7 years). Thiopurine exposure was assessed using the VA pharmacy database. Patients who developed lymphoma were identified based on ICD-9 codes and confirmed by manual chart review.
  
  
  RESULTS
  In total, 4734 patients with UC (13%) were treated with thiopurines for a median of 1 year. Lymphoma developed in 119 patients who had not been treated with thiopurines, 18 who were treated with thiopurines, and 5 who had discontinued treatment with thiopurines. The incidence rates of lymphoma were 0.60 per 1000 person-years among patients who had not been treated with thiopurines, 2.31 among patients who were treated with thiopurines, and 0.28 among patients who had discontinued treatment with thiopurines. The incidence rates of lymphoma during the first year, second year, third year, fourth year, and >4 years of thiopurine therapy were 0.9, 1.6, 1.6, 5, and 8.9 per 1000 person-years, respectively. The age-, sex-, and race-adjusted hazard ratios of developing lymphoma were 4.2 (95% confidence interval, 2.5-6.8; P < .0001) while being treated with thiopurines and 0.5 (95% confidence interval, 0.2-1.3; P = .17) after discontinuing treatment with thiopurines compared with patients who had not been treated with thiopurines.
  
  
  CONCLUSIONS
  Based on a retrospective, nationwide cohort study, patients with UC have a 4-fold increase in risk of lymphoma while being treated with thiopurines compared with patients who have not been treated with thiopurines. The risk increases gradually for successive years of therapy. Discontinuing thiopurine therapy reduces the risk of lymphoma.
authors.affiliation: Section of Gastroenterology, Department of Internal Medicine, Southeast Louisiana Veterans Health Care System, New Orleans, Louisiana; Section of Gastroenterology and Hepatology, Department of Internal Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana. Electronic address: nabeel.khan@va.gov.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Khan
authors.forename: Ali M
authors.initials: AM
authors.lastname: Abbas
authors.forename: Gary R
authors.initials: GR
authors.lastname: Lichtenstein
authors.forename: Edward V
authors.initials: EV
authors.lastname: Loftus
authors.forename: Lydia A
authors.initials: LA
authors.lastname: Bazzano
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D001379:Azathioprine / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D000069285:Infliximab; D008223:Lymphoma / Q000139:chemically induced* / Q000453:epidemiology*; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D014481:United States; D014493:United States Department of Veterans Affairs
chemical_list: D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D000069285:Infliximab; D015122:Mercaptopurine; D001379:Azathioprine
keywords: 5-ASA; 5-aminosalicylic acid; CI; Cancer Risk; EBV; Epstein–Barr virus; HR; IBD; ICD-9; IQR; Inflammatory Bowel Disease; International Classification of Diseases, Ninth Revision; Medication; SEER; Surveillance Epidemiology and End Results; UC; VA; Veterans Affairs; confidence interval; hazard ratio; inflammatory bowel disease; interquartile range; ulcerative colitis