Evidence map›Paper›PMID 34913186›Full record

Trial reportAllergy2022

Baseline type 2 biomarker levels and response to tezepelumab in severe asthma.

Jonathan Corren, Tuyet-Hang Pham, Esther Garcia Gil, Kinga Sałapa, Pin Ren, Jane R Parnes, Gene Colice, Janet M Griffiths

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Allergy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02054130 (A Phase 2 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of MEDI9929 in Adult Subjects With Inadequately Controlled, Severe Asthma), which is not on this map. Cited by 68 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 4 pooled it
9.4field-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.

NCT02054130 phase2completednot on this map

A Phase 2 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of MEDI9929 in Adult Subjects With Inadequately Controlled, Severe Asthma

TypeinterventionalSponsorMedImmune LLCRan2013 to 2017Enrolled584ConditionsAsthmaArmsPlacebo, MEDI9929 70 mg, MEDI9929 210 mg, MEDI9929 280 mg
3 · Its place in the literature

Who cites it

68 citing papers in PubMed, 4 syntheses or guidelines pooled it, 114 citations in OpenAlex.

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8 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

8 authors at 5 institutions in 3 countries.

Jonathan CorrenDavid Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California, USA.
Tuyet-Hang PhamTranslational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
Esther Garcia GilGlobal Medical Respiratory, BioPharmaceuticals R&D, AstraZeneca, Barcelona, Spain.
Kinga SałapaBiometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Warsaw, Poland.
Pin RenEarly Biostats and Statistical Innovation, Early-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
Jane R ParnesTranslational Medicine, Amgen, Thousand Oaks, California, USA.
Gene ColiceLate-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
Janet M GriffithsTranslational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA.
AstraZeneca (United States) · USAmgen (United States) · USAstraZeneca (Poland) · PLAstraZeneca (Spain) · ESUniversity of California, Los Angeles · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTezepelumab is a human monoclonal antibody that blocks activity of thymic stromal lymphopoietin (TSLP). In the phase IIb PATHWAY study (NCT02054130), tezepelumab significantly reduced annualized asthma exacerbation rates (AAERs) versus placebo in adults with severe, uncontrolled asthma. We evaluated the effects of tezepelumab in reducing type 2 (T2) inflammatory biomarker levels in the PATHWAY population, and the relationship between baseline T2 biomarker levels and AAER.

methodsAdults with severe, uncontrolled asthma (n = 550) were randomized to tezepelumab (70 mg or 210 mg every 4 weeks, or 280 mg every 2 weeks) or placebo for 52 weeks. Blood eosinophil count, fractional exhaled nitric oxide (FeNO), and serum total immunoglobulin (Ig)E, interleukin (IL)-5, IL-13, periostin, thymus and activation-regulated chemokine (TARC), and TSLP were measured at baseline and over 52 weeks. AAERs were analyzed by baseline threshold (high/low) biomarker levels.

resultsPositive correlations were observed between T2 inflammatory biomarkers (blood eosinophil count, FeNO, IL-5, IL-13 and periostin) at baseline. At Week 52, treatment with tezepelumab 210 mg reduced all biomarker levels measured from baseline versus placebo. Exacerbations were reduced by 55-83% in the pooled tezepelumab cohort versus placebo, irrespective of baseline blood eosinophil count, FeNO, or serum total IgE, IL-5, IL-13, periostin, TARC, or TSLP, when these biomarkers were assessed individually.

conclusionAt baseline, positive correlations between specific T2 inflammatory biomarkers were observed. Tezepelumab reduced multiple T2 inflammatory biomarkers, which indicates decreased airway inflammation, and reduced exacerbations irrespective of baseline T2 biomarker profiles in patients with severe asthma.

Indexed as

AsthmaInterleukin-5AdultAntibodies, Monoclonal, HumanizedBiomarkersDouble-Blind MethodEosinophilsHumansInterleukin-13Antibodies, Monoclonal, HumanizedBiomarkersInterleukin-13Interleukin-5tezepelumabasthmabiomarkersinflammation

Identifiers

PMID34913186
PMCPMC9306691
OpenAlexW4200568464

What OpenQuestion holds

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LicenceCC BY-NC
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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.