Evidence map›Paper›PMID 21982514›Full record

ArticleArthritis research & therapy2011

Human epidermal growth factor receptor bispecific ligand trap RB200: abrogation of collagen-induced arthritis in combination with tumour necrosis factor blockade.

Luke L Gompels, Nasser M Malik, Leigh Madden, Pei Jin, Marc Feldmann, H Michael Shepard, Ewa M Paleolog

Open access · goldAbstract readComparative Study
In one paragraph

Article in Arthritis research & therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 31% 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.

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

6 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
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  4. HBEGFScience translational medicine · 2019
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  5. Review
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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

7 authors at 5 institutions in 4 countries.

Luke L GompelsFaculty of Medicine, Kennedy Institute of Rheumatology, 65 Aspenlea Road, London, W6 8LH, Imperial College London, London, UK.
Nasser M Malik
Leigh Madden
Pei Jin
Marc Feldmann
H Michael Shepard
Ewa M Paleolog
Imperial College London · GBUniversity of Oxford · GBHalozyme Therapeutics (United States) · USNovartis (China) · CNWilliam Harvey Research Institute · GB

Funding

Arthritis Research UK
6 · The paper itself

Abstract

introductionRheumatoid arthritis (RA) is a chronic disease associated with inflammation and destruction of bone and cartilage. Although inhibition of TNFα is widely used to treat RA, a significant number of patients do not respond to TNFα blockade, and therefore there is a compelling need to continue to identify alternative therapeutic strategies for treating chronic inflammatory diseases such as RA. The anti-epidermal growth factor (anti-EGF) receptor antibody trastuzumab has revolutionised the treatment of patients with EGF receptor-positive breast cancer. Expression of EGF ligands and receptors (known as HER) has also been documented in RA. The highly unique compound RB200 is a bispecific ligand trap that is composed of full-length extracellular domains of HER1 and HER3 EGF receptors. Because of its pan-HER specificity, RB200 inhibits responses mediated by HER1, HER2 and HER3 in vitro and in vivo. The objective of this study was to assess the effect of RB200 combined with TNF blockade in a murine collagen-induced arthritis (CIA) model of RA.

methodsArthritic mice were treated with RB200 alone or in combination with the TNF receptor fusion protein etanercept. We performed immunohistochemistry to assess CD31 and in vivo fluorescent imaging using anti-E-selectin antibody labelled with fluorescent dye to elucidate the effect of RB200 on the vasculature in CIA.

resultsRB200 significantly abrogated CIA by reducing paw swelling and clinical scores. Importantly, low-dose RB200 combined with a suboptimal dose of etanercept led to complete abrogation of arthritis. Moreover, the combination of RB200 with etanercept abrogated the intensity of the E-selectin-targeted signal to the level seen in control animals not immunised to CIA.

conclusionsThe human pan-EGF receptor bispecific ligand trap RB200, when combined with low-dose etanercept, abrogates CIA, suggesting that inhibition of events downstream of EGF receptor activation, in combination with TNFα inhibitors, may hold promise as a future therapy for patients with RA.

Indexed as

AnimalsArthritis, ExperimentalCattleErbB ReceptorsEtanerceptHumansImmunoglobulin GLigandsMaleMiceMice, Inbred DBAReceptor, ErbB-3Receptors, Tumor Necrosis FactorTumor Necrosis Factor-alphaEGFR protein, humanErbB ReceptorsEtanerceptImmunoglobulin GLigandsReceptor, ErbB-3Receptors, Tumor Necrosis FactorTumor Necrosis Factor-alpha

Identifiers

PMID21982514
PMCPMC3308094
OpenAlexW2088747468

What OpenQuestion holds

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LicenceCC BY
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.