Evolution of thiopurine use in pediatric inflammatory bowel disease in an academic center.
OBJECTIVE
We evaluated how our use of thiopurines was altered by determination of thiopurine methyltransferase (TPMT) level and drug dose adjustment guided by a 6-mercaptopurine metabolite assay. We further examined whether these resulted in better selection of the drug dose, improved control of disease, and decreased corticosteroid use in pediatric inflammatory bowel disease (IBD).


METHODS
This is a retrospective review of 101 pediatric patients with IBD receiving a stable dose of azathioprine (AZA) for 4 months or longer. The study group (n = 64) consisted of patients who received AZA and had metabolite levels measured. The comparison group (n = 37) consisted of patients who were receiving AZA before the availability of metabolite measurement. The TPMT level was measured in study group patients before starting AZA.


RESULTS
Patients with normal TPMT level received a higher starting dose of AZA than in patients who were heterozygous for TPMT deficiency (1.7 vs 0.9 mg/[kg x d], P < 0.0001). Study group patients received a higher starting dose (1.6 vs 1.2 mg/[kg x d], P = 0.001) and a higher final dose of AZA (2.4 vs 1.7 mg/[kg x d], P < 0.0001) compared with patients in the comparison group. These patients also had more dose adjustments (0.8 vs 0.4 mg/kg, P < 0.002). The number of disease exacerbations per patient per year was 55% less in the study group (95% CI, 17%-76%, P < 0.0001). The study group patients received less prednisone (P < 0.0001) and had lower disease activity scores (P < 0.05). There was no difference between groups in infliximab use or surgery rate.


CONCLUSIONS
Azathioprine dose adjustment using a 6-mercaptopurine metabolite assay was associated with use of higher doses, improved control of disease and decreased corticosteroid use in pediatric patients with IBD.
Banerjee
Sanjoy
S
Children's Hospital of Iowa, Department of Pediatric Gastroenterology, Iowa City, Iowa, USA.
Bishop
Warren P
WP
D000293:Adolescent; D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy; D004912:Erythrocytes / Q000737:chemistry / Q000201:enzymology; D005260:Female; D006150:Guanine Nucleotides / Q000097:blood; D006579:Heterozygote; D006801:Humans; D007223:Infant; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood; D008780:Methyltransferases / Q000097:blood / Q000172:deficiency / Q000235:genetics; D011241:Prednisone / Q000008:administration & dosage; D012074:Remission Induction; D012189:Retrospective Studies; D013873:Thionucleotides / Q000097:blood
D006150:Guanine Nucleotides; D013873:Thionucleotides; C003964:6-thioguanylic acid; C010240:6-methylthiopurine; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine; D011241:Prednisone