Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis

William J Sandborn, Brian G Feagan, Colleen W Marano, Hongyan Zhang, Richard Strauss, Jewel Johanns, Omoniyi J Adedokun, Cynthia A Guzzo, Jean-Frederic Colombel, Walter Reinisch, Peter Raymond Gibson, Judith F Collins, Gunnar Jarnerot, Toshifumi Hibi, Paul Rutgeerts

Research output: Contribution to journalArticleResearchpeer-review

429 Citations (Scopus)

Abstract

Background Aims Little is known about the efficacy of golimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF) -a, for treatment of ulcerative colitis (UC). We evaluated subcutaneous golimumab induction therapy in TNF-a antagonist-naive patients with moderate-to-severe UC despite conventional treatment. Methods We integrated double-blind phase 2 dose-finding and phase 3 dose-confirmation trials in a study of 1064 adults with UC (Mayo score: 6-12; endoscopic subscore =2; 774 patients in phase 3). Patients were randomly assigned to groups given golimumab doses of 100 mg and then 50 mg (phase 2 only), 200 mg and then 100 mg, or 400 mg and then 200 mg, 2 weeks apart. The phase 3 primary end point was week-6 clinical response. Secondary end points included week-6 clinical remission, mucosal healing, and Inflammatory Bowel Disease Questionnaire (IBDQ) score change. Results In phase 2, median changes from baseline in the Mayo score were -1.0, -3.0, -2.0, and -3.0, in the groups given placebo, 100 mg/50 mg, 200/100 mg, and 400/200 mg golimumab, respectively. In phase 3, rates of clinical response at week 6 were 51.0 and 54.9 among patients given 200 mg/100 mg and 400 mg/200 mg golimumab, respectively, vs 30.3 among those given placebo (both, P =.0001). Rates of clinical remission and mucosal healing and mean changes in IBDQ scores were significantly greater in both golimumab groups vs the placebo group (P =.0014, all comparisons). Rates of serious adverse events were 6.1 and 3.0 , and rates of serious infection were 1.8 and 0.5 , in the placebo and golimumab groups, respectively. One patient in the 400 mg/200 mg group died as a result of surgical complications of an ischiorectal abscess. Conclusions Treatment with subcutaneous golimumab induces clinical response, remission, and mucosal healing, and increases quality of life in larger percentages of patients with active UC than placebo.
Original languageEnglish
Pages (from-to)85 - 95
Number of pages11
JournalGastroenterology
Volume146
Issue number1
DOIs
Publication statusPublished - 2014

Cite this

Sandborn, W. J., Feagan, B. G., Marano, C. W., Zhang, H., Strauss, R., Johanns, J., ... Rutgeerts, P. (2014). Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology, 146(1), 85 - 95. https://doi.org/10.1053/j.gastro.2013.05.048
Sandborn, William J ; Feagan, Brian G ; Marano, Colleen W ; Zhang, Hongyan ; Strauss, Richard ; Johanns, Jewel ; Adedokun, Omoniyi J ; Guzzo, Cynthia A ; Colombel, Jean-Frederic ; Reinisch, Walter ; Gibson, Peter Raymond ; Collins, Judith F ; Jarnerot, Gunnar ; Hibi, Toshifumi ; Rutgeerts, Paul. / Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. In: Gastroenterology. 2014 ; Vol. 146, No. 1. pp. 85 - 95.
@article{59d4ffaf51834c7e9156756e115aac69,
title = "Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis",
abstract = "Background Aims Little is known about the efficacy of golimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF) -a, for treatment of ulcerative colitis (UC). We evaluated subcutaneous golimumab induction therapy in TNF-a antagonist-naive patients with moderate-to-severe UC despite conventional treatment. Methods We integrated double-blind phase 2 dose-finding and phase 3 dose-confirmation trials in a study of 1064 adults with UC (Mayo score: 6-12; endoscopic subscore =2; 774 patients in phase 3). Patients were randomly assigned to groups given golimumab doses of 100 mg and then 50 mg (phase 2 only), 200 mg and then 100 mg, or 400 mg and then 200 mg, 2 weeks apart. The phase 3 primary end point was week-6 clinical response. Secondary end points included week-6 clinical remission, mucosal healing, and Inflammatory Bowel Disease Questionnaire (IBDQ) score change. Results In phase 2, median changes from baseline in the Mayo score were -1.0, -3.0, -2.0, and -3.0, in the groups given placebo, 100 mg/50 mg, 200/100 mg, and 400/200 mg golimumab, respectively. In phase 3, rates of clinical response at week 6 were 51.0 and 54.9 among patients given 200 mg/100 mg and 400 mg/200 mg golimumab, respectively, vs 30.3 among those given placebo (both, P =.0001). Rates of clinical remission and mucosal healing and mean changes in IBDQ scores were significantly greater in both golimumab groups vs the placebo group (P =.0014, all comparisons). Rates of serious adverse events were 6.1 and 3.0 , and rates of serious infection were 1.8 and 0.5 , in the placebo and golimumab groups, respectively. One patient in the 400 mg/200 mg group died as a result of surgical complications of an ischiorectal abscess. Conclusions Treatment with subcutaneous golimumab induces clinical response, remission, and mucosal healing, and increases quality of life in larger percentages of patients with active UC than placebo.",
author = "Sandborn, {William J} and Feagan, {Brian G} and Marano, {Colleen W} and Hongyan Zhang and Richard Strauss and Jewel Johanns and Adedokun, {Omoniyi J} and Guzzo, {Cynthia A} and Jean-Frederic Colombel and Walter Reinisch and Gibson, {Peter Raymond} and Collins, {Judith F} and Gunnar Jarnerot and Toshifumi Hibi and Paul Rutgeerts",
year = "2014",
doi = "10.1053/j.gastro.2013.05.048",
language = "English",
volume = "146",
pages = "85 -- 95",
journal = "Gastroenterology",
issn = "0016-5085",
number = "1",

}

Sandborn, WJ, Feagan, BG, Marano, CW, Zhang, H, Strauss, R, Johanns, J, Adedokun, OJ, Guzzo, CA, Colombel, J-F, Reinisch, W, Gibson, PR, Collins, JF, Jarnerot, G, Hibi, T & Rutgeerts, P 2014, 'Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis', Gastroenterology, vol. 146, no. 1, pp. 85 - 95. https://doi.org/10.1053/j.gastro.2013.05.048

Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. / Sandborn, William J; Feagan, Brian G; Marano, Colleen W; Zhang, Hongyan; Strauss, Richard; Johanns, Jewel; Adedokun, Omoniyi J; Guzzo, Cynthia A; Colombel, Jean-Frederic; Reinisch, Walter; Gibson, Peter Raymond; Collins, Judith F; Jarnerot, Gunnar; Hibi, Toshifumi; Rutgeerts, Paul.

In: Gastroenterology, Vol. 146, No. 1, 2014, p. 85 - 95.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis

AU - Sandborn, William J

AU - Feagan, Brian G

AU - Marano, Colleen W

AU - Zhang, Hongyan

AU - Strauss, Richard

AU - Johanns, Jewel

AU - Adedokun, Omoniyi J

AU - Guzzo, Cynthia A

AU - Colombel, Jean-Frederic

AU - Reinisch, Walter

AU - Gibson, Peter Raymond

AU - Collins, Judith F

AU - Jarnerot, Gunnar

AU - Hibi, Toshifumi

AU - Rutgeerts, Paul

PY - 2014

Y1 - 2014

N2 - Background Aims Little is known about the efficacy of golimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF) -a, for treatment of ulcerative colitis (UC). We evaluated subcutaneous golimumab induction therapy in TNF-a antagonist-naive patients with moderate-to-severe UC despite conventional treatment. Methods We integrated double-blind phase 2 dose-finding and phase 3 dose-confirmation trials in a study of 1064 adults with UC (Mayo score: 6-12; endoscopic subscore =2; 774 patients in phase 3). Patients were randomly assigned to groups given golimumab doses of 100 mg and then 50 mg (phase 2 only), 200 mg and then 100 mg, or 400 mg and then 200 mg, 2 weeks apart. The phase 3 primary end point was week-6 clinical response. Secondary end points included week-6 clinical remission, mucosal healing, and Inflammatory Bowel Disease Questionnaire (IBDQ) score change. Results In phase 2, median changes from baseline in the Mayo score were -1.0, -3.0, -2.0, and -3.0, in the groups given placebo, 100 mg/50 mg, 200/100 mg, and 400/200 mg golimumab, respectively. In phase 3, rates of clinical response at week 6 were 51.0 and 54.9 among patients given 200 mg/100 mg and 400 mg/200 mg golimumab, respectively, vs 30.3 among those given placebo (both, P =.0001). Rates of clinical remission and mucosal healing and mean changes in IBDQ scores were significantly greater in both golimumab groups vs the placebo group (P =.0014, all comparisons). Rates of serious adverse events were 6.1 and 3.0 , and rates of serious infection were 1.8 and 0.5 , in the placebo and golimumab groups, respectively. One patient in the 400 mg/200 mg group died as a result of surgical complications of an ischiorectal abscess. Conclusions Treatment with subcutaneous golimumab induces clinical response, remission, and mucosal healing, and increases quality of life in larger percentages of patients with active UC than placebo.

AB - Background Aims Little is known about the efficacy of golimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF) -a, for treatment of ulcerative colitis (UC). We evaluated subcutaneous golimumab induction therapy in TNF-a antagonist-naive patients with moderate-to-severe UC despite conventional treatment. Methods We integrated double-blind phase 2 dose-finding and phase 3 dose-confirmation trials in a study of 1064 adults with UC (Mayo score: 6-12; endoscopic subscore =2; 774 patients in phase 3). Patients were randomly assigned to groups given golimumab doses of 100 mg and then 50 mg (phase 2 only), 200 mg and then 100 mg, or 400 mg and then 200 mg, 2 weeks apart. The phase 3 primary end point was week-6 clinical response. Secondary end points included week-6 clinical remission, mucosal healing, and Inflammatory Bowel Disease Questionnaire (IBDQ) score change. Results In phase 2, median changes from baseline in the Mayo score were -1.0, -3.0, -2.0, and -3.0, in the groups given placebo, 100 mg/50 mg, 200/100 mg, and 400/200 mg golimumab, respectively. In phase 3, rates of clinical response at week 6 were 51.0 and 54.9 among patients given 200 mg/100 mg and 400 mg/200 mg golimumab, respectively, vs 30.3 among those given placebo (both, P =.0001). Rates of clinical remission and mucosal healing and mean changes in IBDQ scores were significantly greater in both golimumab groups vs the placebo group (P =.0014, all comparisons). Rates of serious adverse events were 6.1 and 3.0 , and rates of serious infection were 1.8 and 0.5 , in the placebo and golimumab groups, respectively. One patient in the 400 mg/200 mg group died as a result of surgical complications of an ischiorectal abscess. Conclusions Treatment with subcutaneous golimumab induces clinical response, remission, and mucosal healing, and increases quality of life in larger percentages of patients with active UC than placebo.

UR - http://www.sciencedirect.com/science/article/pii/S0016508513008469

U2 - 10.1053/j.gastro.2013.05.048

DO - 10.1053/j.gastro.2013.05.048

M3 - Article

VL - 146

SP - 85

EP - 95

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 1

ER -