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

被引：61

作者：

Herfarth, Hans ^{[1
,2
]}

Barnes, Edward L. ^{[1
,2
]}

Valentine, John F. ^{[3
]}

Hanson, John ^{[4
]}

Higgins, Peter D. R. ^{[5
]}

Isaacs, Kim L. ^{[1
,2
]}

Jackson, Susan ^{[1
,2
]}

Osterman, Mark T. ^{[6
]}

Anton, Kristen ^{[1
,7
,8
]}

Ivanova, Anastasia ^{[9
]}

Long, Millie D. ^{[1
,2
]}

Martin, Christopher ^{[7
]}

Sandler, Robert S. ^{[1
,7
]}

Abraham, Bincy ^{[10
]}

Cross, Raymond K. ^{[11
]}

Dryden, Gerald ^{[12
]}

Fischer, Monika ^{[13
]}

Harlan, William ^{[14
]}

Levy, Campbell ^{[15
]}

McCabe, Robert ^{[16
]}

Polyak, Steven ^{[17
]}

Saha, Sumona ^{[18
]}

Williams, Emmanuelle ^{[19
]}

Yajnik, Vijay ^{[20
,21
]}

Serrano, Jose ^{[22
]}

Sands, Bruce E. ^{[23
]}

Lewis, James D. ^{[6
,24
]}

机构：

[1] Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC 27515 USA

[2] Univ N Carolina, Multidisciplinary Ctr Inflammatory Bowel Dis, Chapel Hill, NC 27515 USA

[3] Univ Utah, Div Gastroenterol Hepatol & Nutr, Salt Lake City, UT USA

[4] Atrium Hlth, Charlotte, NC USA

[5] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA

[6] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[7] Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC 27515 USA

[8] Geisel Sch Med Dartmouth, Hanover, NH USA

[9] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA

[10] Houston Methodist Weill Cornell, Div Gastroenterol & Hepatol, Houston, TX USA

[11] Univ Maryland, Sch Med, Div Gastroenterol & Hepatol, Baltimore, MD 21201 USA

[12] Univ Louisville, Div Gastroenterol Hepatol & Nutr, Louisville, KY 40292 USA

[13] Indiana Univ, Div Gastroenterol & Hepatol, Indianapolis, IN 46204 USA

[14] Asheville Gastroenterol Associates, Asheville, NC USA

[15] Dartmouth Hitchcock Med Ctr, Sect Gastroenterol & Hepatol, Lebanon, NH 03766 USA

[16] Minnesota Gastroenterol, Plymouth, MN USA

[17] Univ Iowa, Div Gastroenterol Hepatol & Nutr, Iowa City, IA USA

[18] Univ Wisconsin, Div Gastroenterol & Hepatol, Madison, WI USA

[19] Penn State Milton S Hershey Med Ctr, Div Gastroenterol & Hepatol, Hershey, PA USA

[20] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA

[21] Harvard Med Sch, Boston, MA USA

[22] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD USA

[23] Icahn Sch Med Mt Sinai, Dr Henry D Janowitz Div Gastroenterol, New York, NY 10029 USA

[24] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA

来源：

GASTROENTEROLOGY | 2018年 / 155卷 / 04期

基金：

美国国家卫生研究院;

关键词：

Active Ulcerative Colitis; IBD Therapy; Immunosuppressive Agent; Inflammatory Bowel Diseases; INFLAMMATORY-BOWEL-DISEASE; RANDOMIZED CONTROLLED-TRIAL; PEDIATRIC CROHNS-DISEASE; RHEUMATOID-ARTHRITIS; COMBINATION THERAPY; CLINICAL REMISSION; AZATHIOPRINE; EFFICACY; MAINTENANCE; INFLIXIMAB;

D O I：

10.1053/j.gastro.2018.06.046

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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.

引用

页码：1098 / +

页数：20

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