Randomized Clinical Trial
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World J Gastroenterol. Jul 21, 2014; 20(27): 9185-9190
Published online Jul 21, 2014. doi: 10.3748/wjg.v20.i27.9185
Routine use of thiopurines in maintaining remission in pediatric Crohn’s disease
Brendan M Boyle, Michael D Kappelman, Richard B Colletti, Robert N Baldassano, David E Milov, Wallace V Crandall
Brendan M Boyle, Wallace V Crandall, Nationwide Children’s Hospital, Columbus, OH 43205, United States
Michael D Kappelman, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
Richard B Colletti, University of Vermont, Burlington, VT 05405, United States
Robert N Baldassano, Children’s Hospital of Philadelphia, Philadelphia, PA 19146, United States
David E Milov, Nemours Children’s Clinic, Orlando, FL 32806, United States
Author contributions: Boyle BM, Crandall WV and Kappelman MD wrote the paper; Colletti RB, Baldassano RN, and Milov DE provided the manuscript review and designed the development of the PIBDNet cohort registry.
Correspondence to: Brendan M Boyle, MD, MPH, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, United States. brendan.boyle@nationwidechildrens.org
Telephone: +1-614-7223473 Fax: +1-614-7223454
Received: November 7, 2013
Revised: February 28, 2014
Accepted: April 15, 2014
Published online: July 21, 2014
Processing time: 256 Days and 15.9 Hours
Abstract

AIM: To evaluate the effectiveness of thiopurines in maintaining steroid-free remission in routine clinical practice.

METHODS: The multi-center Pediatric Inflammatory Bowel Disease Network (PIBDNet) cohort study prospectively collected data on thiopurine naïve patients initiating mercaptopurine (6MP) or azathioprine. Patients with a diagnosis of Crohn’s disease (CD) were included in our study upon entering remission as determined by physician global assessment (PGA) within 365 d of initiation of thiopurines. The primary outcome of the study was maintenance of steroid-free remission (SFR) at each follow up visit. Patients were considered treatment failures if there had been a change in PGA from remission to mild, moderate or severe disease; disease relapse between visits; need for rescue therapy (biologic therapy, methotrexate, steroids); thiopurine discontinuation, hospitalization or surgical intervention. A secondary outcome defined treatment failure as a change from remission to moderate or severe (not mild) in addition to the previously defined criteria.

RESULTS: Sixty-five of 182 patients in the PIBDNet registry met criteria for inclusion in this study. Forty-five of 65 (69%) of included patients achieved remission within 180 d of thiopurine initiation. For the primary outcome, 47% and 23% of patients remained in SFR at 6 and 12 mo. The mean thiopurine dose at initiation for the 65 included patients was 0.89 ± 0.31 mg/kg per day. Metabolite levels were obtained in 48% (31/65) of the included patients with a mean 6TG level of 258 pmole/8 × 108 RBC ± 147. For the secondary outcome, 65% and 42% of patients remained in SFR at 6 and 12 mo.

CONCLUSION: Thiopurines were less effective in maintaining remission for pediatric CD in this “real world” cohort than has been previously described. Variation in thiopurine dosing and metabolite measurement was found among practitioners.

Keywords: Crohn’s disease; Pediatric; Remission; Thiopurines; Mercaptopurine

Core tip: This manuscript describes the real world effectiveness of thiopurines in maintaining remission for pediatric Crohn’s disease. The outcomes differ in comparison to the initially published randomized controlled trial for pediatric Crohn’s but are similar to more recently published studies evaluating the effectiveness of thiopurines. The study evaluates data from a pediatric inflammatory bowel disease registry and is representative of real world clinical care. Varitation in practitioner approach to thiopurine dosage and metabolite measurement was found. Implementation of a more standardized approach to use of thiopurines could impact clinical outcomes.