Evidence map›Paper›PMID 41989453›Full record

ArticleArchives of rheumatology2026

Early Erythrocyte Methotrexate Polyglutamate-4 Predicts Treatment Response and Is Influenced by GGH 401C>T Genotype in Patients with Rheumatoid Arthritis.

Miho Takahashi, Soshi Takahashi, Ayano Mori, Saori Hatachi, Toshiharu Saito, Masakazu Shinohara, Shunichi Kumagai

Abstract read
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Article in Archives of rheumatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

What it found

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

7 authors.

Miho TakahashiThe Shinko Institute for Medical Research, Shinko Hospital, Kobe, Japan.
Soshi TakahashiThe Shinko Institute for Medical Research, Shinko Hospital, Kobe, Japan,The Center for Rheumatic Disease, Shinko Hospital, Kobe, Japan.
Ayano MoriThe Shinko Institute for Medical Research, Shinko Hospital, Kobe, Japan.
Saori HatachiThe Center for Rheumatic Disease, Shinko Hospital, Kobe, Japan.
Toshiharu SaitoThe Shinko Institute for Medical Research, Shinko Hospital, Kobe, Japan.
Masakazu ShinoharaThe Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, Kobe, Japan,Division of Molecular Epidemiology, Department of Future Medical Sciences, Kobe University Graduate School of Medicine, Kobe, Japan.
Shunichi KumagaiThe Shinko Institute for Medical Research, Shinko Hospital, Kobe, Japan,The Center for Rheumatic Disease, Shinko Hospital, Kobe, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND/

aimsThis study aimed to examine the ability of methotrexate polyglutamate (MTXPG) concentrations in erythrocytes to predict methotrexate (MTX) treatment response and evaluate the association between MTXPG concentrations and single nucleotide polymorphisms (SNPs) involved in MTX metabolism. MATERIALS AND

methodsMethotrexate polyglutamate (MTXPG) concentrations in erythrocytes were measured in 76 MTX-naive patients utilizing liquid chromatography-tandem mass spectrometry. Real-time polymerase chain reaction was conducted to identify solute carrier family 19 member 1, folylpolyglutamate synthase, and gamma-glutamyl hydrolase (GGH) genotypes. Associations between MTXPG concentrations and MTX treatment response and between MTXPG concentrations and SNPs were analyzed.

resultsThis study identified 67 MTX responders and nine non-responders at 24 weeks. MTXPG4 concentrations at four weeks were significantly greater in responders than in non-responders (P < .01). Receiver-operating characteristic analyses for detecting MTX responders at 24 weeks using MTXPG4 at four weeks revealed an area under the curve of 0.77 at a cut-off level of 0.46 nmol/L. The rate of achieving MTXPG4 of ≥0.46 nmol/L at four weeks was significantly higher in patients with CC genotype than those with CT and TT genotypes in GGH 401C>T (P = .032). The adjusted odds ratio of achieving MTXPG4 of ≥0.46 nmol/L at four weeks was significantly greater in patients with the CC genotype than those with the CT and TT genotypes in GGH 401C>T (2.99 [1.16-7.96]).

conclusionThis study indicates that MTXPG4 concentrations at four weeks after MTX initiation predict treatment response at 24 weeks. Further, patients with the CC genotype in GGH 401C>T achieve higher MTXPG4 concentrations. Cite this article as: Takahashi M, Takahashi S, Mori A, et al. Early erythrocyte methotrexate polyglutamate-4 predicts treatment response and is influenced by GGH 401C>T genotype in patients with rheumatoid arthritis. Arch Rheumatol. 2026;41(2):125-133.

Identifiers

PMID41989453
PMCPMC13083763

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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.