title: Leukopenia predicts remission in patients with inflammatory bowel disease and Behcet's disease on thiopurine maintenance.
abstract: BACKGROUND
  The thiopurine drugs, azathioprine (AZA), and 6-mercaptopurine (6-MP) are well-established drugs for the treatment of inflammatory bowel disease (IBD). Although leukopenia is a well-recognized side effect of AZA/6-MP treatment, its association with therapeutic effects has yet to be determined. We therefore evaluated the influences of thiopurine-induced leukopenia on the long-term prognosis of IBD.
  
  
  METHODS
  We included 196 IBD patients [45 with ulcerative colitis (UC), 68 with Crohn's disease (CD), and 83 with intestinal Behçet's disease (BD)] who were treated with AZA/6-MP and achieved remission between January 2006 and December 2012. We retrospectively analyzed patient characteristics, AZA/6-MP maintenance dose (mg/kg), the lowest white blood cell (WBC) count during AZA/6-MP treatment, duration of remission, and the occurrence of relapse. We compared the clinical variables between leukopenic (n = 120, WBC count <4,000/μL) and nonleukopenic (n = 76, WBC count ≥ 4,000/μL) patients.
  
  
  RESULTS
  The two groups were well matched for baseline clinical characteristics. The cumulative relapse-free survival rate was higher in the leukopenic group than the nonleukopenic group by Kaplan-Meier survival analysis (log-rank test, P < 0.001). On multivariate analysis, age, duration of AZA/6-MP treatment, presence of macrocytosis, and the presence of leukopenia were negatively associated with relapse (odds ratios 0.975, 0.988, 0.563, and 0.390, respectively). On subgroup analysis, the cumulative relapse-free survival rate was significantly higher in the leukopenic group than in the nonleukopenic group for all types of IBDs, including UC, CD, and intestinal BD (log-rank test, P = 0.032, 0.047, and 0.002, respectively).
  
  
  CONCLUSIONS
  Leukopenia during thiopurine maintenance therapy was associated with prolonged remission in patients with IBD and Behcet's disease.
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.
authors.forename: Mi Sung
authors.initials: MS
authors.lastname: Park
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Duk Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Park
authors.forename: Sung Pil
authors.initials: SP
authors.lastname: Hong
authors.forename: Tae Il
authors.initials: TI
authors.lastname: Kim
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Cheon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D001528:Behcet Syndrome / Q000188:drug therapy* / Q000453:epidemiology*; D003093:Colitis, Ulcerative / Q000453:epidemiology*; D015897:Comorbidity; D003424:Crohn Disease / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007970:Leukopenia / Q000139:chemically induced / Q000453:epidemiology*; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine