title: Safety of thiopurine therapy in inflammatory bowel disease: long-term follow-up study of 3931 patients.
abstract: BACKGROUND
  To evaluate the safety of thiopurines in patients with inflammatory bowel disease. To identify predictive factors associated with the development of thiopurine-induced adverse events.
  
  
  METHODS
  Long-term incidence of adverse events was estimated in patients from a prospectively maintained Spanish nationwide database using Kaplan-Meier analysis. Cox regression analysis was performed to identify potential predictive factors of adverse events.
  
  
  RESULTS
  Three thousand nine hundred and thirty-one patients were included. Ninety-five percent of patients were on azathioprine. The median follow-up with thiopurines was 44 months (range, 0-420). Adverse events occurred at a median of 1 month after starting treatment. The cumulative incidence of adverse events was 26%, with an annual risk of 7% per patient-year of treatment. Most frequent adverse events were nausea (8%), hepatotoxicity (4%), myelotoxicity (4%), and pancreatitis (4%). Four patients had lymphoma. Female and Crohn's disease increased the risk of having nausea. The risk of hepatotoxicity was lower in females and higher in Crohn's disease. The risk of myelotoxicity was significantly higher in patients treated with mercaptopurine and in females. The risk of pancreatitis was higher in Crohn's disease. Overall, 17% of patients discontinued thiopurine treatment due to adverse events. Thirty-seven percent of these patients started thiopurines again and 40% of them had adverse events again.
  
  
  CONCLUSIONS
  As many as 1 of 4 patients on thiopurine therapy had adverse events during follow-up. A relatively high proportion of patients (17%) had to discontinue the treatment with thiopurines due to adverse events. However, more than half of patients that restarted thiopurine treatment after its discontinuation due to adverse events tolerated it. Several predictive factors for some adverse events have been identified.
authors.affiliation: Gastroenterology Unit, La Princesa and Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain. mariachs2005@gmail.com
authors.forename: María
authors.initials: M
authors.lastname: Chaparro
authors.forename: Ingrid
authors.initials: I
authors.lastname: Ordás
authors.forename: Eduard
authors.initials: E
authors.lastname: Cabré
authors.forename: Valle
authors.initials: V
authors.lastname: Garcia-Sanchez
authors.forename: Guillermo
authors.initials: G
authors.lastname: Bastida
authors.forename: Mireia
authors.initials: M
authors.lastname: Peñalva
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomollón
authors.forename: Esther
authors.initials: E
authors.lastname: García-Planella
authors.forename: Olga
authors.initials: O
authors.lastname: Merino
authors.forename: Ana
authors.initials: A
authors.lastname: Gutiérrez
authors.forename: Maria
authors.initials: M
authors.lastname: Esteve
authors.forename: Lucia
authors.initials: L
authors.lastname: Márquez
authors.forename: Maria
authors.initials: M
authors.lastname: Garcia-Sepulcre
authors.forename: Joaquín
authors.initials: J
authors.lastname: Hinojosa
authors.forename: Isabel
authors.initials: I
authors.lastname: Vera
authors.forename: Fernando
authors.initials: F
authors.lastname: Muñoz
authors.forename: Juan L
authors.initials: JL
authors.lastname: Mendoza
authors.forename: Jose L
authors.initials: JL
authors.lastname: Cabriada
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Montoro
authors.forename: Manuel
authors.initials: M
authors.lastname: Barreiro-de Acosta
authors.forename: G
authors.initials: G
authors.lastname: Ceña
authors.forename: Cristina
authors.initials: C
authors.lastname: Saro
authors.forename: Xavier
authors.initials: X
authors.lastname: Aldeguer
authors.forename: Jesús
authors.initials: J
authors.lastname: Barrio
authors.forename: José
authors.initials: J
authors.lastname: Maté
authors.forename: Javier P
authors.initials: JP
authors.lastname: Gisbert
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000009:adverse effects*; D003093:Colitis, Ulcerative / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D003424:Crohn Disease / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D007166:Immunosuppressive Agents; D001379:Azathioprine