Evidence map›Paper›PMID 41052889›Full record

Trial reportRMD open2025

Metabolomic profiling of patients with lupus nephritis reveals unique metabolites that are modulated through type I interferon inhibition by anifrolumab treatment in a phase 2 trial.

Patrick G Gavin, Erik L Allman, David Jayne, Eduardo Mysler, Zahir Amoura, Cristina Di Poto, Xiang Tian, Sonja Hess, Eszter Csomor, Philip Z Brohawn and 9 more

Registry-linked trialAbstract readClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in RMD open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02547922 (A Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 2 Study Evaluating the Efficacy and Safety of Anifrolumab in Adult Subjects With Active Proliferative Lupus Nephritis), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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.

NCT02547922 phase2completednot on this map

A Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 2 Study Evaluating the Efficacy and Safety of Anifrolumab in Adult Subjects With Active Proliferative Lupus Nephritis

TypeinterventionalSponsorAstraZenecaRan2015 to 2021Enrolled147ConditionsLupus NephritisArmsAnifrolumab, Placebo
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
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

19 authors.

Patrick G GavinTranslational Science and Experimental Medicine, Early Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
Erik L AllmanDynamic Omics, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
David JayneUniversity of Cambridge, Cambridge, UK.ORCID 0000-0002-1712-0637
Eduardo MyslerOrganización Médica de Investigación, Buenos Aires, Argentina.
Zahir AmouraFrench National Reference Center for SLE, Hôpital La Pitié-Salpêtrière, Sorbonne University, Paris, France.
Cristina Di PotoDynamic Omics, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
Xiang TianDynamic Omics, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
Sonja HessDynamic Omics, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
Eszter CsomorTranslational Science and Experimental Medicine, Early Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Philip Z BrohawnTranslational Science and Experimental Medicine, Early Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
Daniel MuthasTranslational Science and Experimental Medicine, Early Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Adam PlattTranslational Science and Experimental Medicine, Early Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Consuelo AnzillottiLate Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Heena StoneBioscience Renal, Early Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Asha SethBioscience Renal, Early Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Kevin WoollardBioscience Renal, Early Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Hussein Al-MossawiLate Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Catharina LindholmLate Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Nicola FerrariTranslational Science and Experimental Medicine, Early Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK nicola.ferrari@astrazeneca.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivePatients with systemic lupus erythematosus (SLE) commonly develop lupus nephritis (LN), the most frequent severe organ manifestation of this systemic autoimmune disease. Using serum and urine samples from a phase 2 trial in LN, we investigated that how the LN metabolome is modulated in response to type I interferon receptor blockade with anifrolumab, an approved treatment for moderate to severe SLE.

methodsPatients in TULIP-LN (NCT02547922) received standard therapy plus intravenous anifrolumab or placebo. Untargeted metabolomics analysis was performed on serum and urine samples from 128 and 119 patients, respectively. Metabolites impacted by anifrolumab and their associations with clinical, serological and kidney measures of LN disease activity were examined. An in vitro model was used to validate the impact of anifrolumab on metabolite-induced inflammation.

resultsIn serum, indoxyl sulfate (IS) and cytosine were the metabolites most modulated by anifrolumab, while baseline levels correlated with measures of kidney damage. In urine, uracil and cytosine were the most modulated by anifrolumab and levels of these metabolites were associated with serological markers of disease activity. Anifrolumab reduced markers of vascular dysfunction and inflammation upregulated by IS in in vitro models. Baseline urine uracil levels predicted response to anifrolumab intensive regimen at Week 52.

conclusionOur findings establish a connection between type I interferon signalling, pyrimidine metabolism and uremic toxins in patients with LN and support the evaluation of urine uracil as a potential biomarker of response to anifrolumab.

Indexed as

Antibodies, Monoclonal, HumanizedInterferon Type ILupus NephritisMetabolomeMetabolomicsAdultBiomarkersFemaleHumansMaleMiddle AgedTreatment OutcomeYoung AdultanifrolumabAntibodies, Monoclonal, HumanizedBiomarkersInterferon Type IAutoimmune DiseasesBiological TherapyLupus Nephritis

Identifiers

PMID41052889
PMCPMC12506476

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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.