Methotrexate Is Not Superior to Placebo in Maintaining Steroid-Free Response or Remission in Ulcerative Colitis

Clinical Research Alliance of the Crohn's and Colitis Foundation

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 after 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 of 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/wk) and a 12-week steroid taper. At week 16, steroid-free responders were randomly assigned to groups that either continued methotrexate (25 mg/wk, 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/wk) was not superior to placebo in preventing relapses of UC in patients who achieved steroid-free response during induction therapy. ClinicalTrials.gov, Number: NCT01393405.

Original languageEnglish (US)
Pages (from-to)1098-1108.e9
JournalGastroenterology
Volume155
Issue number4
DOIs
StatePublished - Oct 1 2018

Fingerprint

Ulcerative Colitis
Methotrexate
Steroids
Placebos
Recurrence
Maintenance
Biological Therapy
Endoscopy
Therapeutics
Randomized Controlled Trials
Inflammation
Safety

Keywords

  • Active Ulcerative Colitis
  • IBD Therapy
  • Immunosuppressive Agent
  • Inflammatory Bowel Diseases

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Methotrexate Is Not Superior to Placebo in Maintaining Steroid-Free Response or Remission in Ulcerative Colitis. / Clinical Research Alliance of the Crohn's and Colitis Foundation.

In: Gastroenterology, Vol. 155, No. 4, 01.10.2018, p. 1098-1108.e9.

Research output: Contribution to journalArticle

Clinical Research Alliance of the Crohn's and Colitis Foundation. / Methotrexate Is Not Superior to Placebo in Maintaining Steroid-Free Response or Remission in Ulcerative Colitis. In: Gastroenterology. 2018 ; Vol. 155, No. 4. pp. 1098-1108.e9.
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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 after 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 of 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/wk) and a 12-week steroid taper. At week 16, steroid-free responders were randomly assigned to groups that either continued methotrexate (25 mg/wk, 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/wk) was not superior to placebo in preventing relapses of UC in patients who achieved steroid-free response during induction therapy. ClinicalTrials.gov, Number: NCT01393405.",
keywords = "Active Ulcerative Colitis, IBD Therapy, Immunosuppressive Agent, Inflammatory Bowel Diseases",
author = "{Clinical Research Alliance of the Crohn's and Colitis Foundation} and Hans Herfarth and Barnes, {Edward L.} and Valentine, {John F.} and John Hanson and Higgins, {Peter D.R.} and Isaacs, {Kim L.} and Susan Jackson and Osterman, {Mark T.} and Kristen Anton and Anastasia Ivanova and Long, {Millie D.} and Christopher Martin and Sandler, {Robert S.} and Bincy Abraham and Cross, {Raymond K.} and Gerald Dryden and Monika Fischer and William Harlan and Campbell Levy and Robert McCabe and Steven Polyak and Sumona Saha and Emmanuelle Williams and Vijay Yajnik and Jose Serrano and Sands, {Bruce E.} and Lewis, {James D.}",
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AU - Clinical Research Alliance of the Crohn's and Colitis Foundation

AU - Herfarth, Hans

AU - Barnes, Edward L.

AU - Valentine, John F.

AU - Hanson, John

AU - Higgins, Peter D.R.

AU - Isaacs, Kim L.

AU - Jackson, Susan

AU - Osterman, Mark T.

AU - Anton, Kristen

AU - Ivanova, Anastasia

AU - Long, Millie D.

AU - Martin, Christopher

AU - Sandler, Robert S.

AU - Abraham, Bincy

AU - Cross, Raymond K.

AU - Dryden, Gerald

AU - Fischer, Monika

AU - Harlan, William

AU - Levy, Campbell

AU - McCabe, Robert

AU - Polyak, Steven

AU - Saha, Sumona

AU - Williams, Emmanuelle

AU - Yajnik, Vijay

AU - Serrano, Jose

AU - Sands, Bruce E.

AU - Lewis, James D.

PY - 2018/10/1

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N2 - 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 after 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 of 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/wk) and a 12-week steroid taper. At week 16, steroid-free responders were randomly assigned to groups that either continued methotrexate (25 mg/wk, 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/wk) was not superior to placebo in preventing relapses of UC in patients who achieved steroid-free response during induction therapy. ClinicalTrials.gov, Number: NCT01393405.

AB - 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 after 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 of 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/wk) and a 12-week steroid taper. At week 16, steroid-free responders were randomly assigned to groups that either continued methotrexate (25 mg/wk, 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/wk) was not superior to placebo in preventing relapses of UC in patients who achieved steroid-free response during induction therapy. ClinicalTrials.gov, Number: NCT01393405.

KW - Active Ulcerative Colitis

KW - IBD Therapy

KW - Immunosuppressive Agent

KW - Inflammatory Bowel Diseases

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