Evidence map›Paper›PMID 27481309›Full record

Trial reportThe American journal of gastroenterology2016

A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Brodalumab in Patients With Moderate-to-Severe Crohn's Disease.

Stephan R Targan, Brian Feagan, Severine Vermeire, Remo Panaccione, Gil Y Melmed, Carol Landers, Dalin Li, Chris Russell, Richard Newmark, Nan Zhang and 4 more

Abstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The American journal of gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
201citing papers in PubMed, 4 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

201 citing papers in PubMed, 4 syntheses or guidelines pooled it.

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141 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Stephan R TarganDivision of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Brian FeaganRobarts Research Institute, University of Western Ontario, London, Ontario, Canada.
Severine VermeireDepartment of Gastroenterology, University Hospitals KU Leuven, Leuven, Belgium.
Remo PanaccioneUniversity of Calgary, Calgary, Alberta, Canada.
Gil Y MelmedDivision of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Carol LandersDivision of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Dalin LiDivision of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Chris RussellAmgen, Thousand Oaks, California, USA.
Richard NewmarkAmgen, Thousand Oaks, California, USA.
Nan ZhangAmgen, Thousand Oaks, California, USA.
Yun ChonAmgen, Thousand Oaks, California, USA.
Yi-Hsiang HsuAmgen, Thousand Oaks, California, USA.
Shao-Lee LinAmgen, Thousand Oaks, California, USA.
Paul KlekotkaAmgen, Thousand Oaks, California, USA.

Funding

Using polygenic scores to enhance both variant discovery, and understanding of functional consequences of genetic variation in IBD.P01DK046763 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI TARGAN, STEPHAN R. · 1992 to 2020
$31.1M
Identify Serological Markers defined subgroups in CD patients using Bigdata toolsR21DK108140 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI LI, DALIN · 2016 to 2017
$481k
NIDDK NIH HHS R21 DK108140
6 · The paper itself

Abstract

objectivesTo assess the safety and efficacy of brodalumab, a human anti-interleukin-17 receptor monoclonal antibody, in patients with moderate-to-severe Crohn's disease (CD).

methodsPhase 2, randomized, double-blind, placebo-controlled, dose-ranging study in patients with moderate-to-severe CD and evidence of active inflammation. Patients were randomized 1:1:1:1 to receive brodalumab (210, 350, or 700 mg at baseline and week 4) or placebo. The primary end point was proportion of patients achieving Crohn's disease activity index (CDAI) remission (≤150) at week 6. Secondary end points included proportion of patients with CDAI response (reduction from baseline of ≥100) at week 6 and change from baseline in CDAI at week 6.

resultsThe study was terminated early based on an imbalance in worsening CD in active treatment groups. At the time of termination, 130 patients had been randomized. At week 6, remission rates were 3% (210 mg), 15% (350 mg), 9% (700 mg), and 3% (placebo) and CDAI response occurred in 16% (210 mg), 27% (350 mg), 15% (700 mg), and 13% (placebo) of patients. Mean change in CDAI at week 6 was -8.7 (95.3) (210 mg), -35.4 (105.6) (350 mg), -0.6 (105.9) (700 mg), and -28.2 (86.0) (placebo). Besides worsening of CD, overall incidences of adverse events were similar across treatment groups.

conclusionsTreatment with brodalumab resulted in a disproportionate number of cases of worsening CD in patients with active CD and no evidence of meaningful efficacy. These analyses did not suggest additional safety risks of brodalumab beyond worsening of CD symptoms in patients with active CD.

Indexed as

AdultAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCrohn DiseaseDouble-Blind MethodEarly Termination of Clinical TrialsFemaleHumansMaleMiddle AgedReceptors, Interleukin-17Remission InductionSeverity of Illness IndexTreatment OutcomeYoung AdultAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedbrodalumabIL17RA protein, humanReceptors, Interleukin-17

Identifiers

PMID27481309

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.