Evidence map›Paper›PMID 39104961›Full record

ArticleERJ open research2024

Untargeted metabolomic analysis reveals different metabolites associated with response to mepolizumab and omalizumab in asthma.

Tanawin Nopsopon, Yulu Chen, Qingwen Chen, Craig E Wheelock, Scott T Weiss, Michael McGeachie, Jessica Lasky-Su, Ayobami Akenroye

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ERJ open research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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.

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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Biomarkers for selecting biologic therapies in asthma.Therapeutic advances in respiratory disease
    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

8 authors.

Tanawin NopsoponDivision of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Yulu ChenChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Qingwen ChenChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Craig E WheelockUnit of Integrative Metabolomics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID https://orcid.org/0000-0002-8113-0653
Scott T WeissChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID https://orcid.org/0000-0001-7196-303X
Michael McGeachieChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID https://orcid.org/0000-0001-5566-2712
Jessica Lasky-SuChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Ayobami AkenroyeDivision of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID https://orcid.org/0000-0002-1909-1470

Funding

Multi-omic approaches to mechanisms of vitamin D, environmental influences, and the microbiome on asthmaUH3OD023268 · OD · BRIGHAM AND WOMEN'S HOSPITAL · PI LITONJUA, AUGUSTO A, WEISS, SCOTT T · 2018 to 2022
$13.5M
Systems Biology of Airway DiseaseP01HL132825 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI WEISS, SCOTT T · 2016 to 2020
$12.6M
Leveraging Pharmacogenomics in Asthma for Predication, Mechanism and EndotypingR01HL161362 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EUGENE ROLAND BLEECKER, GEOFFREY L CHUPP · 2022 to 2026
$8.4M
Integrative Metabolomics of Asthma SeverityR01HL123915 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LASKY-SU, JESSICA A · 2014 to 2023
$7.0M
Pharmacogenomics of Adrenal Suppression with Inhaled Corticosteroids (PhASIC)R01HL152244 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI DAHLIN, AMBER · 2020 to 2024
$4.4M
Mechanistic insights into asthma pathogenesis through the integration of asthma genes, risk exposures, and metabolomicsR01HL141826 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LASKY-SU, JESSICA A · 2018 to 2021
$3.4M
Synthesizing Trial and Real-world Data on the Use of Biologics in Patients with Severe AsthmaR00MD015767 · NIMHD · BRIGHAM AND WOMEN'S HOSPITAL · PI AKENROYE, AYOBAMI T · 2023 to 2025
$677k
NHLBI NIH HHS P01 HL132825NHLBI NIH HHS R01 HL123915NHLBI NIH HHS R01 HL141826NHLBI NIH HHS R01 HL152244NHLBI NIH HHS R01 HL161362NIH HHS UH3 OD023268NIMHD NIH HHS R00 MD015767
6 · The paper itself

Abstract

Background: There is limited evidence on biomarkers associated with response to the monoclonal antibodies currently approved for asthma treatment. We sought to identify circulatory metabolites associated with response to treatment with mepolizumab or omalizumab. Methods: We conducted global metabolomic profiling of pre-treatment plasma samples from 100 patients with moderate-to-severe asthma who initiated mepolizumab (n=31) or omalizumab (n=69). The primary outcome was the change in exacerbations within 12 months of therapy. Negative binomial models were used to assess the association between each metabolite and exacerbations, adjusting for age, sex, body mass index, baseline exacerbations and inhaled corticosteroid use. Chemical similarity enrichment analysis (ChemRICH) was conducted to identify chemical subclasses associated with treatment response. Results: The mean age of the mepolizumab group was 58.7 years with on average 2.9 exacerbations over the year prior to initiation of biologic therapy. The mean age in the omalizumab group was 48.8 years with 1.5 exacerbations in the preceding year. Patients with higher levels of two tocopherol metabolites were associated with more exacerbations on mepolizumab (δ-carboxyethyl hydroxychroman (CEHC) (p=2.65E-05, false discovery rate (FDR=0.01) and δ-CEHC glucuronide (p=2.47E-06, FDR=0.003)). Higher levels of six androgenic steroids, three carnitine metabolites and two bile acid metabolites were associated with decreased exacerbations in the omalizumab group. In enrichment analyses, xanthine metabolites (cluster FDR=0.0006) and tocopherol metabolites (cluster FDR=0.02) were associated with worse mepolizumab response, while androgenic steroids (cluster FDR=1.9E-18), pregnenolone steroids (cluster p=3.2E-07, FDR=1.4E-05) and secondary bile acid metabolites (cluster p=0.0003, FDR=0.006) were the top subclasses associated with better omalizumab response. Conclusion: This study identifies distinct metabolites associated with response to mepolizumab and omalizumab, with androgenic steroids associated with response to both mepolizumab and omalizumab.

Identifiers

PMID39104961
PMCPMC11298997

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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.