Evidence map›Paper›PMID 28115015›Full record

Trial reportArthritis research & therapy2017

Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy.

Arndt H Brachat, Alexei A Grom, Nico Wulffraat, Hermine I Brunner, Pierre Quartier, Riva Brik, Liza McCann, Huri Ozdogan, Lidia Rutkowska-Sak, Rayfel Schneider and 17 more

2 registry-linked trialsOpen access · goldAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph

Trial report in Arthritis research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 4% 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.

NCT00886769 phase3terminatednot on this map

A Randomized, Double-blind, Placebo Controlled, Single-dose Study to Assess the Initial Efficacy of Canakinumab (ACZ885) With Respect to the Adapted ACR Pediatric 30 Criteria in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA) and Active Systemic Manifestations

TypeinterventionalSponsorNovartis PharmaceuticalsRan2009 to 2011Enrolled84ConditionsSystemic Juvenile Idiopathic ArthritisArmsCanakinumab, Placebo
NCT00889863 phase3completednot on this map

A Randomized, Double-blind, Placebo Controlled, Withdrawal Study of Flare Prevention of Canakinumab (ACZ885) in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA) and Active Systemic Manifestations

TypeinterventionalSponsorNovartis PharmaceuticalsRan2009 to 2011Enrolled177ConditionsSystemic Juvenile Idiopathic Arthritis With Active FlareArmscanakinumab, placebo
3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.

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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

27 authors at 18 institutions in 12 countries.

Arndt H BrachatNovartis Institutes for Biomedical Research, Basel, Switzerland.
Alexei A GromCincinnati Children's Hospital Medical Center, PRCSG, Cincinnati, OH, USA.
Nico WulffraatWilhelmina Kinderziekenhuis, Department of Pediatric Immunology and Rheumatology, Utrecht, Netherlands.
Hermine I BrunnerCincinnati Children's Hospital Medical Center, PRCSG, Cincinnati, OH, USA.
Pierre QuartierUniversité Paris-Descartes, IMAGINE Institute, Hôpital Necker-Enfants Malades. Centre de référence national pour les Arthrites Juveniles, Unité d'Immunologie, Hématologie et Rhumatologie Pediatrique, Paris, France.
Riva BrikRambam Medical Center, Department of Pediatrics B, Haifa, Israel.
Liza McCannAlder Hey Children's NHS Foundation Trust, Liverpool, UK.
Huri OzdoganCerrahpasa Tip Fakultesi, Ic Hastaliklari ABD, Romatoloji BD, Istanbul, Turkey.
Lidia Rutkowska-SakInstitute of Rheumatology, Paediatric Clinic, Warsaw, Poland.
Rayfel SchneiderHospital for Sick Children, Division of Rheumatology, Toronto, ON, Canada.
Valeria GerloniIstituto Gaetano Pini, Divisione di Reumatologia, Milano, Italy.
Liora HarelSchneider Childrens Medical Center, Pediatric Rheumatology Unit, Petach-Tikvah, Israel.
Maria TerreriUniversidade Federal de São Paulo, Pediatrics, São Paulo, Brazil.
Kristin HoughtonBritish Columbia Children's Hospital, Vancouver, BC, Canada.
Rik JoosUniversitair Ziekenhuis Gent, Centrum Voor Kinderreumatologie, Gent, Belgium.
Daniel KingsburyRandall Children's Hospital at Legacy Emanuel, Portland, OR, USA.
Jorge M Lopez-BenitezFloating Hospital for Children, Rheumatology NEMC 286, Boston, MA, USA.
Stephan BekNovartis Institutes for Biomedical Research, Basel, Switzerland.
Martin SchumacherNovartis Institutes for Biomedical Research, Basel, Switzerland.
Marie-Anne ValentinNovartis Institutes for Biomedical Research, Basel, Switzerland.
Hermann GramNovartis Institutes for Biomedical Research, Basel, Switzerland.
Ken AbramsNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Alberto MartiniUniversity of Genova and Istituto Giannina Gaslini, Pediatria II-PRINTO, Genoa, Italy.
Daniel J LovellCincinnati Children's Hospital Medical Center, PRCSG, Cincinnati, OH, USA.
Nanguneri R NirmalaNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Nicolino RupertoIstituto Giannina Gaslini, Pediatria II-PRINTO, Genoa, Italy. nicolaruperto@gaslini.org.ORCID 0000-0001-8407-7782
Pediatric Rheumatology International Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG)
Novartis (Switzerland) · CHCincinnati Children's Hospital Medical Center · USIstituto Giannina Gaslini · ITNovartis (United States) · USAlder Hey Children's NHS Foundation Trust · GBBC Children's Hospital · CAGhent University Hospital · BEHôpital Necker-Enfants Malades · FRHospital for Sick Children · CAIstanbul University-Cerrahpaşa · TRIstituto Ortopedico Gaetano Pini · ITNational Institute of Geriatrics, Rheumatology and Rehabilitation · PLRambam Health Care Campus · ILRandall Children's Hospital at Legacy Emanuel · USSchneider Children's Medical Center · ILTufts Children's Hospital · USUniversidade Federal de São Paulo · BRWilhelmina Children's Hospital · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCanakinumab is a human anti-interleukin-1β (IL-1β) monoclonal antibody neutralizing IL-1β-mediated pathways. We sought to characterize the molecular response to canakinumab and evaluate potential markers of response using samples from two pivotal trials in systemic juvenile idiopathic arthritis (SJIA).

methodsGene expression was measured in patients with febrile SJIA and in matched healthy controls by Affymetrix DNA microarrays. Transcriptional response was assessed by gene expression changes from baseline to day 3 using adapted JIA American College of Rheumatology (aACR) response criteria (50 aACR JIA). Changes in pro-inflammatory cytokines IL-6 and IL-18 were assessed up to day 197.

resultsMicroarray analysis identified 984 probe sets differentially expressed (≥2-fold difference; P < 0.05) in patients versus controls. Over 50% of patients with ≥50 aACR JIA were recognizable by baseline expression values. Analysis of gene expression profiles from patients achieving ≥50 aACR JIA response at day 15 identified 102 probe sets differentially expressed upon treatment (≥2-fold difference; P < 0.05) on day 3 versus baseline, including IL-1β, IL-1 receptors (IL1-R1 and IL1-R2), IL-1 receptor accessory protein (IL1-RAP), and IL-6. The strongest clinical response was observed in patients with higher baseline expression of dysregulated genes and a strong transcriptional response on day 3. IL-6 declined by day 3 (≥8-fold decline; P < 0.0001) and remained suppressed. IL-18 declined on day 57 (≥1.5-fold decline, P ≤ 0.002).

conclusionsTreatment with canakinumab in SJIA patients resulted in downregulation of innate immune response genes and reductions in IL-6 and clinical symptoms. Additional research is needed to investigate potential differences in the disease mechanisms in patients with heterogeneous gene transcription profiles.

trial registrationClinicaltrials.gov: NCT00886769 (trial 1). Registered on 22 April 2009; NCT00889863 (trial 2). Registered on 21 April 2009.

Indexed as

AdolescentAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedArthritis, JuvenileChildChild, PreschoolDown-RegulationFemaleGene Expression ProfilingHumansImmunoassayInterleukin-18Interleukin-6MaleOligonucleotide Array Sequence AnalysisTranscriptomeAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedcanakinumabIL18 protein, humanIL6 protein, humanInterleukin-18Interleukin-6BiomarkersCanakinumabGene expressionInterleukin-1βJuvenile idiopathic arthritisSJIA

Identifiers

PMID28115015
PMCPMC5260050
OpenAlexW2581236424

What OpenQuestion holds

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LicenceCC BY
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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.