Evidence map›Paper›PMID 29275332›Full record

Trial reportAnnals of the rheumatic diseases2018

Dual IL-17A and IL-17F neutralisation by bimekizumab in psoriatic arthritis: evidence from preclinical experiments and a randomised placebo-controlled clinical trial that IL-17F contributes to human chronic tissue inflammation.

Sophie Glatt, Dominique Baeten, Terry Baker, Meryn Griffiths, Lucian Ionescu, Alastair D G Lawson, Ash Maroof, Ruth Oliver, Serghei Popa, Foteini Strimenopoulou and 5 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of the rheumatic diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02141763 (A Subject-blind, Investigator-blind, Randomized, Placebo-controlled Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of UCB4940 in Subjects With Psoriatic Arthritis), which is not on this map. Cited by 137 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
137citing papers in PubMed, 6 pooled it
9.2field-weighted citation impact, top 1% of its field
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.

NCT02141763 phase1completednot on this map

A Subject-blind, Investigator-blind, Randomized, Placebo-controlled Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of UCB4940 in Subjects With Psoriatic Arthritis

TypeinterventionalSponsorUCB CelltechRan2014 to 2015Enrolled53ConditionsPsoriatic ArthritisArmsUCB4940 40 mg, UCB4940 80 mg, UCB4940 160 mg, UCB4940 240 mg, UCB4940 320 mg
3 · Its place in the literature

Who cites it

137 citing papers in PubMed, 6 syntheses or guidelines pooled it, 251 citations in OpenAlex.

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77 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

15 authors at 5 institutions in 5 countries.

Sophie GlattGlobal Exploratory Development, UCB Pharma, Slough, UK.
Dominique BaetenDepartment of Clinical Immunology and Rheumatology, University of Amsterdam, Amsterdam, The Netherlands.
Terry BakerStructural Biology, UCB Pharma, Slough, UK.
Meryn GriffithsNew Medicines, UCB Pharma, Slough, UK.
Lucian IonescuImmunology Patient Value Unit, UCB Pharma, Brussels, Belgium.
Alastair D G LawsonStructural Biology, UCB Pharma, Slough, UK.
Ash MaroofNew Medicines, UCB Pharma, Slough, UK.
Ruth OliverGlobal Exploratory Development, UCB Pharma, Slough, UK.
Serghei PopaDepartment of Rheumatology and Nephrology, Nicolae Testemiţanu State University of Medicine and Pharmacy, Chisinau, Republic of Moldova.
Foteini StrimenopoulouGlobal Exploratory Development, UCB Pharma, Slough, UK.
Pavan VajjahGlobal Exploratory Development, UCB Pharma, Slough, UK.
Mark I L WatlingGlobal Exploratory Development, UCB Pharma, Slough, UK.
Nataliya YeremenkoDepartment of Clinical Immunology and Rheumatology, University of Amsterdam, Amsterdam, The Netherlands.
Pierre MiossecDepartment of Clinical Immunology and Rheumatology, University of Lyon, Lyon, France.
Stevan ShawNew Medicines, UCB Pharma, Slough, UK.
UCB Pharma (United Kingdom) · GBUCB Pharma (Belgium) · BENicolae Testemițanu State University of Medicine and Pharmacy · MDUniversité Claude Bernard Lyon 1 · FRUniversity of Amsterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveInterleukin (IL)-17A has emerged as pivotal in driving tissue pathology in immune-mediated inflammatory diseases. The role of IL-17F, sharing 50% sequence homology and overlapping biological function, remains less clear. We hypothesised that IL-17F, together with IL-17A, contributes to chronic tissue inflammation, and that dual neutralisation may lead to more profound suppression of inflammation than inhibition of IL-17A alone.

methodsPreclinical experiments assessed the role of IL-17A and IL-17F in tissue inflammation using disease-relevant human cells. A placebo-controlled proof-of-concept (PoC) clinical trial randomised patients with psoriatic arthritis (PsA) to bimekizumab (n=39) or placebo (n=14). Safety, pharmacokinetics and clinical efficacy of multiple doses (weeks 0, 3, 6 (240 mg/160 mg/160 mg; 80 mg/40 mg/40 mg; 160 mg/80 mg/80 mg and 560 mg/320 mg/320 mg)) of bimekizumab, a humanised monoclonal IgG1 antibody neutralising both IL-17A and IL-17F, were investigated.

resultsIL-17F induced qualitatively similar inflammatory responses to IL-17A in skin and joint cells. Neutralisation of IL-17A and IL-17F with bimekizumab more effectively suppressed

conclusionsThese data support IL-17F as a key driver of human chronic tissue inflammation and the rationale for dual neutralisation of IL-17A and IL-17F in PsA and related conditions. TRIAL REGISTRATION NUMBER: NCT02141763; Results.

Indexed as

AdultAntibodies, Monoclonal, HumanizedAntibodies, NeutralizingArthritis, PsoriaticDouble-Blind MethodFemaleHumansInflammationInterleukin-17MaleMiddle AgedProof of Concept StudySeverity of Illness IndexTreatment OutcomeAntibodies, Monoclonal, HumanizedAntibodies, NeutralizingbimekizumabIL17A protein, humanIL17F protein, humanInterleukin-17autoimmune diseasescytokinesinflammationpsoriatic arthritis

Identifiers

PMID29275332
PMCPMC5890624
OpenAlexW2779290422

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

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.