Abstract

Methotrexate is not superior to placebo in maintaining steroid-free response or remission in ulcerative colitis

Herfarth H1, Barnes EL2, Valentine JF3, Hanson J4, Higgins PD5, Isaacs KL2, Jackson S2, Osterman MT6, Anton K7, Ivanova A8, Long MD2, Martin C9, Sandler RS10, Abraham B11, Cross RK12, Dryden G13, Fischer M14, Harlan W15, Levy C16, McCabe R17, Polyak S18, Saha S19, Williams E20, Yajnik V21, Serrano J22, Sands BE23, Lewis JD24; Clinical Research Alliance of the Crohn’s and Colitis Foundation. Gastroenterology. 2018 Jun 29. pii: S0016-5085(18)34688-2. doi: 10.1053/j.gastro.2018.06.046. [Epub ahead of print]
 
     

Author information

1 Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC; University of North Carolina Multidisciplinary Center for Inflammatory Bowel Diseases, Chapel Hill, NC. Electronic address: hherf@med.unc.edu.

2 Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC; University of North Carolina Multidisciplinary Center for Inflammatory Bowel Diseases, Chapel Hill, NC.

3 Division of Gastroenterology, Hepatology and Nutrition, University of Utah, Salt Lake City, UT.

4 Atrium Health, Charlotte, NC.

5 Division of Gastroenterology University of Michigan Ann Arbor, MI.

6 Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.

7 Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC; Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC; Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.

8 Department of Biostatistics, University of North Carolina, Chapel Hill, NC.

9 Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC.

10 Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC; Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC.

11 Division of Gastroenterology and Hepatology, Houston Methodist - Weill Cornell, Houston, TX.

12 Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD.

13 Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, KY.

14 Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, IN.

15 Asheville Gastroenterology Associates, Asheville, NC.

16 Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH.

17 Minnesota Gastroenterology, Plymouth, MN.

18 Division of Gastroenterology, Hepatology and Nutrition, University of Iowa, Iowa City, IA.

19 Division of Gastroenterology and Hepatology, University of Wisconsin, Madison, WI.

20 Division of Gastroenterology and Hepatology, Penn State Milton S. Hershey Medical Center, Hershey, PA.

21 Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

22 Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.

23 Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.

24 Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.

Abstract

BACKGROUND & AIMS: Parenteral methotrexate induces clinical remission but not endoscopic improvement of mucosal inflammation in patients with ulcerative colitis (UC). We performed a randomized, placebo-controlled trial to assess the efficacy of parenteral methotrexate in maintaining steroid-free response or remission in patients with UC following induction therapy with methotrexate and steroids.

METHODS: We performed a 48-week trial, from February 2012 through May 2016, of 179 patients with active UC (Mayo score 6-12 with endoscopy subscore ≥2) despite previous conventional or biological therapy. The study comprised a 16-week open-label methotrexate induction period followed by a 32-week double-blind placebo-controlled maintenance period. Patients were given subcutaneous methotrexate (25 mg/week) and a 12-week steroid taper. At week 16, steroid-free responders were randomly assigned to groups that either continued methotrexate (25 mg/week, n=44) or were given placebo (n=40) until week 48. We compared the efficacy of treatment by analyzing the proportion of patients who remained relapse free and were in remission at week 48 without use of steroids or other medications to control disease activity.

RESULTS: Ninety-one patients (51%) achieved response at week 16, and 84 patients were included in the maintenance period study. During this period, 60% of patients in the placebo group (24/40) and 66% in the methotrexate group (29/44) had a relapse of UC (P=.75). At week 48, 30% of patients in the placebo group (12/40) and 27% of patients in the methotrexate group (12/44) were in steroid-free clinical remission without need for additional therapies (P=.86). No new safety signals for methotrexate were detected.

CONCLUSIONS: Parenteral methotrexate (25 mg/week) was not superior to placebo in preventing relapses of UC in patients who achieved steroid-free response during induction therapy.

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