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

Published on Jan 1, 2014in Gastroenterology19.809
· DOI :10.1053/j.gastro.2013.05.048
WilliamJSandborn142
Estimated H-index: 142
(UCSD: University of California, San Diego),
Brian G. Feagan95
Estimated H-index: 95
(UWO: University of Western Ontario)
+ 12 AuthorsPaul Rutgeerts138
Estimated H-index: 138
(Katholieke Universiteit Leuven)
Sources
Abstract
Background & Aims Little is known about the efficacy of golimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF) −α, for treatment of ulcerative colitis (UC). We evaluated subcutaneous golimumab induction therapy in TNF−α 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. ClinicalTrials.gov Number: NCT00487539.
  • References (22)
  • Citations (423)
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References22
Newest
#1WilliamJSandbornH-Index: 142
#2Brian G. FeaganH-Index: 95
Last. Paul RutgeertsH-Index: 138
view all 13 authors...
3 CitationsSource
#1Ingrid Ordás (University of Barcelona)H-Index: 25
#2Brian G. Feagan (UWO: University of Western Ontario)H-Index: 95
Last. WilliamJSandborn (UCSD: University of California, San Diego)H-Index: 142
view all 3 authors...
Although tumor necrosis factor (TNF) antagonists have shown clear benefits over conventional treatments for inducing and maintaining clinical remission in both Crohn's disease and ulcerative colitis, a high proportion of patients lose response over time. Given the scarce alternative of treatments when treatment failure occurs, it is highly desirable to optimize both initial response and long-term continuation of TNF antagonists. One of the most well-characterized factors associated with loss of ...
140 CitationsSource
#1Arthur Kavanaugh (UCSD: University of California, San Diego)H-Index: 78
#2D. van der Heijde (LUMC: Leiden University Medical Center)H-Index: 129
Last. Anna Beutler (Janssen Pharmaceutica)H-Index: 25
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Objective Golimumab, administered subcutaneously every 4 weeks, has been shown to be effective in reducing the signs and symptoms of active psoriatic arthritis (PsA) through week 24 of the GO-REVEAL study. Herein we report 1-year clinical, radiographic, and safety findings. Methods Adult patients with active PsA (≥3 swollen and ≥3 tender joints) were randomly assigned to receive subcutaneous placebo, golimumab 50 mg, or golimumab 100 mg every 4 weeks through week 20. At week 16, patients with <1...
137 CitationsSource
#1Jürgen BraunH-Index: 88
Last. Benjamin HsuH-Index: 19
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Objective To assess the efficacy and safety of golimumab over 104 weeks in patients with active ankylosing spondylitis. Methods At baseline, patients with active ankylosing spondylitis (n=356) were randomly assigned (1:1.8:1.8) to subcutaneous injections of placebo (group 1), golimumab 50 mg (group 2) or golimumab 100 mg (group 3) every 4 weeks. At week 16, patients in groups 1 and 2 with Results At week 104, 38.5%, 60.1% and 71.4% of patients in groups 1, 2 and 3, respectively, had at least 20%...
92 CitationsSource
#1WilliamJSandborn (UCSD: University of California, San Diego)H-Index: 142
#2G. Van Assche (Katholieke Universiteit Leuven)H-Index: 82
Last. Roopal ThakkarH-Index: 20
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Background & Aims Adalimumab is a fully human monoclonal antibody that binds tumor necrosis factor (TNF)-α. Its efficacy as maintenance therapy for patients with ulcerative colitis has not been studied in a controlled, double-blind trial. Methods Ulcerative colitis long-term remission and maintenance with adalimumab 2 (ULTRA 2) was a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of adalimumab in induction and maintenance of clinical remission in 494 patients with mo...
631 CitationsSource
#1Yanli Zhuang (Janssen Pharmaceutica)H-Index: 6
#2Zhenhua Xu (Janssen Pharmaceutica)H-Index: 23
Last. Honghui Zhou (Janssen Pharmaceutica)H-Index: 19
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Abstract Background The pharmacokinetics of golimumab, a human monoclonal antibody that inhibits the activity of tumor necrosis factor α, after a single subcutaneous (SC) or intravenous (IV) administration have been previously studied. Objectives The purpose of this study was to assess the pharmacokinetics of golimumab after multiple SC or IV administrations in patients with active rheumatoid arthritis (RA). The effect of concomitant methotrexate (MTX) use on golimumab pharmacokinetics was evalu...
49 CitationsSource
#1Walter Reinisch (Medical University of Vienna)H-Index: 74
#2WilliamJSandborn (Mayo Clinic)H-Index: 142
Last. Roopal ThakkarH-Index: 20
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Objective The aim of this study was to assess the efficacy and safety of adalimumab (ADA), a recombinant human monoclonal antibody against tumour necrosis factor a (TNF), for the induction of clinical remission in anti-TNF nao¨ve patients with moderately to severely active ulcerative colitis. Methods This 8-week, multicentre, randomised, doubleblind, placebo-controlled study (NCT00385736), conducted at 94 centres in North America and Europe, enrolled ambulatory adult patients with Mayo score of ...
487 CitationsSource
#1David ShealyH-Index: 9
#2Ann CaiH-Index: 5
Last. Jill Giles-KomarH-Index: 12
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We prepared and characterized golimumab (CNTO148), a human IgG1 tumor necrosis factor alpha (TNFα) antagonist monoclonal antibody chosen for clinical development based on its molecular properties. Golimumab was compared with infliximab, adalimumab and etanercept for affinity and in vitro TNFα neutralization. The affinity of golimumab for soluble human TNFα, as determined by surface plasmon resonance, was similar to that of etanercept (18 pM versus 11 pM), greater than that of infliximab (44 pM) ...
177 CitationsSource
#1Edward C. Keystone (MSH: Mount Sinai Hospital, Toronto)H-Index: 68
#2Mark C. Genovese (Stanford University)H-Index: 69
Last. Mahboob Rahman (UPenn: University of Pennsylvania)H-Index: 57
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Objective To evaluate the efficacy and safety of golimumab to 52 weeks in patients with active rheumatoid arthritis despite methotrexate. Methods Patients were randomly assigned to receive placebo plus methotrexate (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus methotrexate (group 3) and golimumab 100 mg plus methotrexate (group 4). At week 16, patients in groups 1, 2 and 3 who had less than 20% improvement in tender and swollen joints entered early escape. At week 24, ...
119 CitationsSource
#1Paul Emery (University of Leeds)H-Index: 143
#2Roy Fleischmann (UTSW: University of Texas Southwestern Medical Center)H-Index: 60
Last. Mahboob Rahman (UPenn: University of Pennsylvania)H-Index: 57
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Objective. To assess the safety and efficacy of golimumab in methotrexate (MTX)-naive patients with active rheumatoid arthritis (RA). Methods. MTX-naive patients with RA (n = 637) were randomized to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Subcutaneous injections of golimumab or placebo were administered every 4 weeks. The dosage of MTX/placebo capsules started at 10 mg/week and escala...
317 CitationsSource
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BACKGROUND Significant associations between serum golimumab concentrations and favourable outcomes have been observed during both induction and maintenance therapy in ulcerative colitis (UC). However, data regarding optimal therapeutic serum golimumab concentration thresholds are limited. AIMS To identify optimal serum golimumab concentration thresholds during induction and maintenance treatment with golimumab. METHODS GO-LEVEL was an open label, phase IV study that included a prospective cohort...
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#1Minkyung HanH-Index: 6
#2Yoon Suk JungH-Index: 14
Last. Sohee ParkH-Index: 33
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PURPOSE: The optimal timing of anti-tumor necrosis factor (anti-TNF) initiation in patients with ulcerative colitis (UC) remains unclear. Very little is known about the clinical outcomes after the early versus late initiation of anti-TNF therapy, especially in Asian UC patients. Here we aimed to assess whether earlier anti-TNF treatment initiation results in favorable clinical outcomes in Korean UC patients. MATERIALS AND METHODS: Using the Korean National Health Insurance claims database, we st...
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#2Rahul Kalla (Edin.: University of Edinburgh)H-Index: 9
Last. Gwo-Tzer Ho (Edin.: University of Edinburgh)H-Index: 16
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Inflammatory bowel diseases are common, complex, immune-mediated conditions with a sharply rising global prevalence. While major advances since 2000 have provided strong mechanistic clues implicating a de-regulation in the normal interaction among host genetics, immunity, microbiome, and the environment, more recent progress has generated entirely new hypotheses and also further refined older disease concepts. In this review, we focus specifically on these novel developments in the pathogenesis ...
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#2Christopher Ma (U of C: University of Calgary)H-Index: 13
ABSTRACTIntroduction: The management of patients with ulcerative colitis (UC) has evolved over the past few decades. While aminosalicylates remain the mainstay of induction and maintenance therapy ...
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#2Jessica R. Allegretti (Brigham and Women's Hospital)H-Index: 14
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BACKGROUND: Few data exist to select a second biologic agent in patients with refractory ulcerative colitis (UC). AIM: To compare the efficacy of infliximab (IFX) and vedolizumab (VDZ) in UC patients who failed a first subcutaneous anti-tumor necrosing factor (TNF) agent. METHODS: Consecutive UC patients from 12 French centres starting IFX or VDZ after at least one injection of adalimumab or golimumab have been included in a retrospective study. Outcomes were clinical remission at week 14, survi...
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