Timing of myelosuppression during thiopurine therapy for inflammatory bowel disease: implications for monitoring recommendations.
OBJECTIVE
Thiopurines (azathioprine and 6-mercaptopurine) can induce life-threatening myelosuppression. This study determined the frequency, timing, and outcomes of mild and severe myelosuppression after initiation of thiopurine therapy.


METHODS
This retrospective cohort study included patients with inflammatory bowel disease who were new users of thiopurines; those tested for thiopurine methyltransferase levels before therapy were excluded. Patients were followed from their first thiopurine prescription until the earliest of severe leukopenia (white blood cell count, <1.0 x 10(9)/L), severe thrombocytopenia (platelet level, <20 x 10(9)/L), the end of therapy, the first gap in therapy, disenrollment, or December 31, 2006.


RESULTS
Among 1997 new users, the incidence of severe leukopenia per 100 person-months was 0.16 (95% confidence interval [CI], 0.03-0.29; n = 6) in weeks 0 to 8, 0.00 in weeks 9 to 24, and 0.01 (95% CI, 0-0.03; n = 3) after week 26 of therapy. The incidence of severe neutropenia and severe thrombocytopenia per 100 person-months during the first 8 weeks of therapy was 0.51 (95% CI, 0.31-0.80; n = 19) and 0.08 (95% CI, 0.02-0.23; n = 3), respectively. During the first 8 weeks, the median duration from a normal white blood cell count to severe leukopenia was 13 days (range, 8-26 d) and to severe neutropenia was 14 days (range, 7-23 d).


CONCLUSIONS
The high incidence of severe myelosuppression justifies frequent monitoring during the first 8 weeks of therapy. Subsequently, the rate of severe myelosuppression and the proportion of patients who progress from mild to severe myelosuppression decrease, justifying less-frequent monitoring.
Lewis
James D
JD
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6021, USA. lewisjd@mail.med.upenn.edu
Abramson
Oren
O
Pascua
Monina
M
Liu
Liyan
L
Asakura
Laura M
LM
Velayos
Fernando S
FS
Hutfless
Susan M
SM
Alison
James E
JE
Herrinton
Lisa J
LJ
D000328:Adult; D000368:Aged; D000963:Antimetabolites / Q000009:adverse effects / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects*; D015331:Cohort Studies; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D007970:Leukopenia / Q000139:chemically induced*; D008137:Longitudinal Studies; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced*; D013997:Time Factors; D016896:Treatment Outcome
D000963:Antimetabolites; D015122:Mercaptopurine; D001379:Azathioprine