ArticleCellular and molecular life sciences : CMLS2026
Monocytes from inflammatory arthritis patients accumulate methotrexate and their transcriptome predicts methotrexate clinical response.
Article in Cellular and molecular life sciences : CMLS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
1 citing paper in PubMed, 1 synthesis or guideline pooled it.
- Subcutaneous methotrexate compared with oral methotrexate in rheumatoid arthritis: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
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Authors and funding
17 authors.
Funding
Abstract
Monocytes and monocyte-derived macrophages play a key pathogenic role in inflammatory arthritis. Methotrexate (MTX) is the first-line disease-modifying antirheumatic drug (DMARD) for arthritis, yet the mechanisms and kinetics of its effects on monocyte/macrophages remain poorly understood. We have now investigated the temporal dynamics of the MTX's anti-inflammatory action by initially performing a phase I clinical trial (METOMAC) on healthy individuals following a single MTX dose, which revealed that MTX plasma levels peak at 1 h after MTX treatment, with maximal suppression of LPS-induced IL-1β and IL-6 in whole blood 5 days after MTX exposure. Building on these findings, we performed an observational clinical study (METOMAC-PAC) on 29 DMARD-naïve early arthritis patients receiving a weekly dose of MTX over a 3 month period. The METOMAC-PAC study revealed that MTX polyglutamates (MTX-PG) accumulates in peripheral blood monocytes, where MTX-PG is detected as early as 5 days post-treatment, and modulates the monocyte gene profile after 4 MTX doses, with specific enrichment of the aryl-hydrocarbon receptor (AhR)-molecular signature and genes coding for anti-inflammatory factors. Importantly, stratification of METOMAC-PAC patients according to their clinical response revealed that Good Responders exhibit increased expression of “non-classical monocyte”-specific genes (MAF, FCGR3B, ICAM4) both before and after MTX treatment, while Partial Responders patients showed a higher baseline expression of genes preferentially expressed by “classical monocytes”. Our results elucidate the kinetics of the anti-inflammatory action of MTX, demonstrate that MTX modulates the monocyte transcriptional signature in vivo, and identify “non-classical monocyte”-associated genes as predictors for an effective MTX clinical response.
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Registered trials
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