Whitney Sunseri1, Jeffrey S Hyams, Trudy Lerer, David R Mack, Anne M Griffiths, Anthony R Otley, Joel R Rosh, Ryan Carvalho, Andrew B Grossman, Jose Cabrera, Marian D Pfefferkorn, James Rick, Neal S Leleiko, Meredith C Hitch, Maria Oliva-Hemker, Shehzad A Saeed, Michael Kappelman, James Markowitz, David J Keljo. 1. 1Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania; 2Department of Pediatrics, Connecticut Children's Medical Center, Hartford, Connecticut; 3Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada; 4Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, ON, Canada; 5Department of Pediatrics, I.W.K. Health Center, Halifax, NS, Canada; 6Pediatric Gastroenterology, Goryeb Children's Hospital, Morristown, New Jersey; 7Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio; 8Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; 9Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin; 10Section of Gastroenterology/Hepatology/Nutrition, Riley Hospital for Children, Indianapolis, Indiana; 11Department of Gastroenterology, Dayton Children's, Dayton, Ohio; 12Division of Pediatric Gastroenterology, Nutrition and Liver Diseases, Hasbro Children's Hospital, Providence, Rhode Island; 13Department of Pediatrics, Russell Children's Hospital, Birmingham, Alabama; 14Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, Maryland; 15Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Medical Center, Cincinnati, Ohio; 16Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina; and 17Department of Pediatrics, Cohen Children's Medical Center, New Hyde Park, New York.
Abstract
BACKGROUND: Methotrexate (MTX) use as an alternative to thiopurines in the treatment of Crohn's disease (CD) in children is increasing. This study was undertaken to assess safety and efficacy of MTX in children with CD. METHODS: Patients treated with MTX with a minimum of 1-year follow-up were identified in the Pediatric IBD Collaborative Research Group Registry, a prospective inception cohort study started in 2002. The clinical efficacy and safety of MTX were analyzed retrospectively. RESULTS: Two hundred ninety patients treated with MTX were identified. One hundred seventy-two patients received at least 3 months of MTX without thiopurine or biologicals and had ≥1 year of follow-up. Eighty-one of 172 patients (47%) received MTX as first immunomodulator (IMM), of which 22 (27%) achieved ≥12 months of sustained clinical remission without surgery, thiopurine, biologicals, or corticosteroids. Those receiving MTX as second IMM achieved similar remission rate (35%, P = not significant). Fourteen percent received MTX as first IMM in 2002 and 60% in 2010 (P = 0.005). Disease location did not affect outcomes. MTX doses were equivalent in both groups. Fifteen percent of patients developed an alanine aminotransferase >60 international units/liter and 12% developed a white blood cell <4000 cells per microliter while on MTX. Only 4% of these discontinued MTX completely. A small group of 6 centers, which contributed only about one-third of patients with CD in the registry, contributed nearly two-thirds of the patients receiving MTX (P < 0.001). CONCLUSIONS: MTX use as first choice IMM is increasing in pediatric CD. MTX provided sustained clinical remission in nearly one-third of patients with minimal toxicity. There is large center-to-center variability in its use.
BACKGROUND:Methotrexate (MTX) use as an alternative to thiopurines in the treatment of Crohn's disease (CD) in children is increasing. This study was undertaken to assess safety and efficacy of MTX in children with CD. METHODS:Patients treated with MTX with a minimum of 1-year follow-up were identified in the Pediatric IBD Collaborative Research Group Registry, a prospective inception cohort study started in 2002. The clinical efficacy and safety of MTX were analyzed retrospectively. RESULTS: Two hundred ninety patients treated with MTX were identified. One hundred seventy-two patients received at least 3 months of MTX without thiopurine or biologicals and had ≥1 year of follow-up. Eighty-one of 172 patients (47%) received MTX as first immunomodulator (IMM), of which 22 (27%) achieved ≥12 months of sustained clinical remission without surgery, thiopurine, biologicals, or corticosteroids. Those receiving MTX as second IMM achieved similar remission rate (35%, P = not significant). Fourteen percent received MTX as first IMM in 2002 and 60% in 2010 (P = 0.005). Disease location did not affect outcomes. MTX doses were equivalent in both groups. Fifteen percent of patients developed an alanine aminotransferase >60 international units/liter and 12% developed a white blood cell <4000 cells per microliter while on MTX. Only 4% of these discontinued MTX completely. A small group of 6 centers, which contributed only about one-third of patients with CD in the registry, contributed nearly two-thirds of the patients receiving MTX (P < 0.001). CONCLUSIONS:MTX use as first choice IMM is increasing in pediatric CD. MTX provided sustained clinical remission in nearly one-third of patients with minimal toxicity. There is large center-to-center variability in its use.