Evidence map›Paper›PMID 29644082›Full record

ArticleLupus science & medicine2018

Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus.

Jeffrey M Riggs, Richard N Hanna, Bhargavi Rajan, Kamelia Zerrouki, Jodi L Karnell, Divya Sagar, Inna Vainshtein, Erika Farmer, Kimberly Rosenthal, Chris Morehouse and 6 more

Open access · goldAbstract read
In one paragraph

Article in Lupus science & medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 2 pooled it
9.7field-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.

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

82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 142 citations in OpenAlex.

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  16. Keratinocytes: pleiotropic orchestrators of cutaneous immunity and Inflammation - Emerging therapeutic paradigms in dermatological pathologies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
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22 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

16 authors.

Jeffrey M Riggs *Respiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, Maryland, USA.
Richard N Hanna *Respiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, Maryland, USA.
Bhargavi RajanClinical Pharmacology and DMPK, MedImmune LLC, Mountain View, California, USA.
Kamelia ZerroukiRespiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, Maryland, USA.
Jodi L KarnellRespiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, Maryland, USA.
Divya SagarRespiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, Maryland, USA.
Inna VainshteinClinical Pharmacology and DMPK, MedImmune LLC, Mountain View, California, USA.
Erika FarmerAnalytical Sciences, MedImmune LLC, Gaithersburg, Maryland, USA.
Kimberly RosenthalAntibody Discovery and Protein Engineering, MedImmune LLC, Gaithersburg, Maryland, USA.
Chris MorehouseTranslational Medicine, MedImmune LLC, Gaithersburg, Maryland, USA.
Melissa de Los ReyesTranslational Medicine, MedImmune LLC, Gaithersburg, Maryland, USA.
Kevin SchifferliRespiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, Maryland, USA.
Meina LiangClinical Pharmacology and DMPK, MedImmune LLC, Mountain View, California, USA.
Miguel A SanjuanRespiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, Maryland, USA.
Gary P SimsRespiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, Maryland, USA.
Roland KolbeckRespiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, Maryland, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveWe investigated the mechanistic and pharmacological properties of anifrolumab, a fully human, effector-null, anti-type I interferon (IFN) alpha receptor 1 (IFNAR1) monoclonal antibody in development for SLE.

methodsIFNAR1 surface expression and internalisation on human monocytes before and after exposure to anifrolumab were assessed using confocal microscopy and flow cytometry. The effects of anifrolumab on type I IFN pathway activation were assessed using signal transducer and activator of transcription 1 (STAT1) phosphorylation, IFN-stimulated response element-luciferase reporter cell assays and type I IFN gene signature induction. The ability of anifrolumab to inhibit plasmacytoid dendritic cell (pDC) function and plasma cell differentiation was assessed by flow cytometry and ELISA. Effector-null properties of anifrolumab were assessed in antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) assays with B cells.

resultsAnifrolumab reduced cell surface IFNAR1 by eliciting IFNAR1 internalisation. Anifrolumab blocked type I IFN-dependent STAT1 phosphorylation and IFN-dependent signalling induced by recombinant and pDC-derived type I IFNs and serum of patients with SLE. Anifrolumab suppressed type I IFN production by blocking the type I IFN autoamplification loop and inhibited proinflammatory cytokine induction and the upregulation of costimulatory molecules on stimulated pDCs. Blockade of IFNAR1 suppressed plasma cell differentiation in pDC/B cell co-cultures. Anifrolumab did not exhibit CDC or ADCC activity.

conclusionsAnifrolumab potently inhibits type I IFN-dependent signalling, including the type I IFN autoamplification loop, and is a promising therapeutic for patients with SLE and other diseases that exhibit chronic dysfunctional type I IFN signalling.

Indexed as

cytokinesdmards (biologic)interferonsystemic lupus erythematosustreatment

Identifiers

PMID29644082
PMCPMC5890856
OpenAlexW2796401459

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.