Evidence map›Paper›PMID 17673491›Full record

Trial reportAnnals of the rheumatic diseases2008

A single tumour necrosis factor haplotype influences the response to adalimumab in rheumatoid arthritis.

C Miceli-Richard, E Comets, C Verstuyft, R Tamouza, P Loiseau, P Ravaud, H Kupper, L Becquemont, D Charron, X Mariette

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase IIIMulticenter StudyReview
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of the rheumatic diseases, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02878161 (Screening Protein Predictive of Response to Tumor Necrosis Factor-α Inhibitors Treatment in Chinese Rheumatoid Arthritis From "Real World" and Investigating Its Mechanism Through Signal Pathway), which is not on this map. Cited by 26 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 4 pooled it
3.7field-weighted citation impact, top 7% 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.

NCT02878161 phase4unknown statusnot on this mapstarted 2016, after this paper: background citation

Screening Protein Predictive of Response to Tumor Necrosis Factor-α Inhibitors Treatment in Chinese Rheumatoid Arthritis From "Real World" and Investigating Its Mechanism Through Signal Pathway

TypeinterventionalSponsorFen LiRan2016 to 2019Enrolled240ConditionsRheumatoid ArthritisArmsmethotrexate(necessary), infliximab, etanercept, adalimumab, leflunomide (permitted, not necessary)
3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 4 syntheses or guidelines pooled it, 75 citations in OpenAlex.

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  15. Methotrexate treatment efficacy in sarcoidosis might be related to TNF-α polymorphism: real life preliminary study.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2019
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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

10 authors at 6 institutions in 2 countries.

C Miceli-RichardRhumatologie, Institut Pour la Santé et la Recherche Médicale U 802, Université Paris-Sud 11, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.
E Comets
C Verstuyft
R Tamouza
P Loiseau
P Ravaud
H Kupper
L Becquemont
D Charron
X Mariette
Bicêtre Hospital · FRHôpital Saint-Louis · FRAbbott (Germany) · DEAssistance Publique – Hôpitaux de Paris · FRInserm · FRUniversité Paris Cité · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo determine whether tumour necrosis factor (TNF) gene polymorphisms and/or the shared epitope are genetic predictors of the response to adalimumab (ADA) in rheumatoid arthritis (RA).

methodsThis ancillary study to the Research in Active Rheumatoid Arthritis (ReAct) Phase IIIb study included a large cohort of Caucasian patients with RA from France (n = 388) treated with ADA plus methotrexate (MTX) (n = 182), ADA plus any other DMARD (n = 98) or ADA alone (n = 108). The primary outcome was ACR50 at 12 weeks. Patients underwent genotyping for HLA-DRB1 and three TNF gene polymorphisms (-238A/G,-308A/G and-857C/T). Extended haplotypes involving HLA-DRB1 and TNF loci were reconstructed using the PHASE program.

resultsA total of 151 patients (40%) had an ACR50 response at week 12. Neither the number of HLA-DRB1 shared epitope copies nor presence of the three TNF polymorphisms tested separately was significantly associated with ACR50 response at week 12. However, haplotype reconstruction of the TNF locus revealed that the GGC haplotype (-238G/-308G/-857C) in a homozygous form (i.e. present in more than half of the patients) was significantly associated with a lower ACR50 response to ADA at 12 weeks (34% vs. 50% in patients without the haplotype) (p = 0.003; pa = 0.015). This effect was more important in the subgroup of patients concomitantly treated with MTX.

conclusionThis large pharmacogenetic study provides preliminary data indicating that a single TNF locus haplotype (-238G/-308G/-857C), present on both chromosomes is associated with a lower response to ADA, mainly in patients treated with ADA and MTX.

Indexed as

AdalimumabAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntirheumatic AgentsArthritis, RheumatoidDrug Therapy, CombinationFemaleGenotypeHaplotypesHLA-DR AntigensHLA-DRB1 ChainsHumansMaleMethotrexateAdalimumabAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntirheumatic AgentsHLA-DR AntigensHLA-DRB1 ChainsMethotrexateTumor Necrosis Factor-alpha

Identifiers

PMID17673491
PMCPMC2750008
OpenAlexW2158854507

What OpenQuestion holds

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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.