Evidence map›Paper›PMID 37721470›Full record

Trial reportThe Journal of infectious diseases2024

The Cyclooxygenase 2 Inhibitor Etoricoxib as Adjunctive Therapy in Tuberculosis Impairs Macrophage Control of Mycobacterial Growth.

Kristin G Nore, Claire Louet, Marit Bugge, Alexandre Gidon, Marthe Jøntvedt Jørgensen, Synne Jenum, Anne Ma Dyrhol-Riise, Kristian Tonby, Trude Helen Flo

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02503839 (Therapeutic Vaccination and Immune Modulation - New Treatment Strategies for the Multidrug-resistant Tuberculosis Pandemic; an Open Label Phase I Clinical Trial of the Therapeutic TB H56), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.2field-weighted citation impact, top 22% 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.

NCT02503839 phase1completednot on this map

Therapeutic Vaccination and Immune Modulation - New Treatment Strategies for the Multidrug-resistant Tuberculosis Pandemic; an Open Label Phase I Clinical Trial of the Therapeutic TB H56:IC31 Vaccine and Cyclooxygenase-inhibitors

TypeinterventionalSponsorAnne Margarita Dyrhol RiiseRan2015 to 2020Enrolled39ConditionsTuberculosisArmsetoricoxib, H56:IC31
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
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

9 authors at 3 institutions in 1 country.

Kristin G NoreInstitute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.ORCID 0000-0002-1592-7613
Claire LouetCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Marit BuggeCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Alexandre GidonCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Marthe Jøntvedt JørgensenInstitute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Synne JenumDepartment of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
Anne Ma Dyrhol-RiiseInstitute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Kristian TonbyInstitute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Trude Helen FloCentre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Norwegian University of Science and Technology · NOOslo University Hospital · NOUniversity of Oslo · NO

Funding

Olav Thon FoundationOslo University HospitalResearch Council Of Norway 234493University of Oslo 2017009
6 · The paper itself

Abstract

backgroundCurrent tuberculosis treatment regimens could be improved by adjunct host-directed therapies (HDT) targeting host responses. We investigated the antimycobacterial capacity of macrophages from patients with tuberculosis in a phase 1/2 randomized clinical trial (TBCOX2) of the cyclooxygenase-2 inhibitor etoricoxib.

methodsPeripheral blood mononuclear cells from 15 patients with tuberculosis treated with adjunctive COX-2i and 18 controls (standard therapy) were collected on day 56 after treatment initiation. The ex vivo capacity of macrophages to control mycobacterial infection was assessed by challenge with Mycobacterium avium, using an in vitro culture model. Macrophage inflammatory responses were analyzed by gene expression signatures, and concentrations of cytokines were analyzed in supernatants by multiplex.

resultsMacrophages from patients receiving adjunctive COX-2i treatment had higher M. avium loads than controls after 6 days, suggesting an impaired capacity to control mycobacterial infection compared to macrophages from the control group. Macrophages from the COX-2i group had lower gene expression of TNF, IL-1B, CCL4, CXCL9, and CXCL10 and lowered production of cytokines IFN-β and S100A8/A9 than controls.

conclusionsOur data suggest potential unfavorable effects with impaired macrophage capacity to control mycobacterial growth in patients with tuberculosis receiving COX-2i treatment. Larger clinical trials are required to analyze the safety of COX-2i as HDT in patients with tuberculosis. CLINICAL TRIALS REGISTRATION: NCT02503839.

Indexed as

Mycobacterium tuberculosisTuberculosisCyclooxygenase 2 InhibitorsCytokinesEtoricoxibHumansLeukocytes, MononuclearMacrophagesCyclooxygenase 2 InhibitorsCytokinesEtoricoxibCOX-2 inhibitorhost-directed therapyinflammationinnate immunitymacrophagesMycobacterium aviumMycobacterium tuberculosis

Identifiers

PMID37721470
PMCPMC10938220
OpenAlexW4386817455

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.