Evidence map›Paper›PMID 40388487›Full record

ArticleACR open rheumatology2025

Whole-Blood RNA Sequencing Profiling of Patients With Rheumatoid Arthritis Treated With Tofacitinib.

Chiara Bellocchi, Ennio Giulio Favalli, Gabriella Maioli, Elena Agape, Marzia Rossato, Matteo Paini, Adriana Severino, Barbara Vigone, Martina Biggioggero, Elena Trombetta and 2 more

Abstract read
In one paragraph

Article in ACR open rheumatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

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5 · Who and what money

Authors and funding

12 authors.

Chiara BellocchiFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy.ORCID https://orcid.org/0000-0001-8326-7904
Ennio Giulio FavalliUniversity of Milan and ASST PiniCTO - Presidio Gaetano Pini, Milan, Italy.
Gabriella MaioliUniversity of Milan and ASST PiniCTO - Presidio Gaetano Pini, Milan, Italy.
Elena AgapeUniversity of Milan, Milan, Italy.
Marzia RossatoUniversity of Verona, Verona, Italy.
Matteo PainiUniversity of Verona, Verona, Italy.
Adriana SeverinoFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Barbara VigoneFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Martina BiggioggeroASST PiniCTO - Presidio Gaetano Pini, Milan, Italy.
Elena TrombettaFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Roberto CaporaliUniversity of Milan and ASST PiniCTO - Presidio Gaetano Pini, Milan, Italy.
Lorenzo BerettaFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.ORCID https://orcid.org/0000-0002-6529-6258

Funding

unrestricted investigator-initiated research studies grant-CREARE by Pfizer CREARE by Pfizer
6 · The paper itself

Abstract

objectivePatients with rheumatoid arthritis (RA) often fail to respond to therapies, including JAK inhibitors (JAKi), and treatment allocation is made via a trial-and-error strategy. A comprehensive analysis of responses to JAKi, including tofacitinib, by RNA sequencing (RNAseq) would allow the discovery of transcriptomic markers with a two-fold meaning: (1) an improved knowledge about the mechanisms of response to treatment (inference modeling) and (2) the definition of features that may be useful in treatment optimization and assignment (predictive modeling).

methodsThirty-three patients with active RA were treated with a tofacitinib dose of 5 mg twice a day for 24 weeks and evaluated for EULAR Disease Activity Score in 28 joints using the C-reactive protein level response. Whole-blood RNA was collected before and after treatment to perform RNAseq transcriptome analysis. Linear models were used to determine differentially expressed genes (DEGs) (1) at baseline according to clinical responses and (2) in the pre-post comparison after tofacitinib treatment and in relation to EULAR responses. The capability of DEGs to predict a successful treatment was tested via machine learning modeling after extensive internal validation.

resultsOf 26 patients who completed the study (per-protocol analysis), 15 (57.7%) achieved good responses, and 7 (26.9%) and 4 (15.3%) had moderate and no responses, respectively. Overall, 273 baseline genes were significantly associated with the attainment of good responses, contributing to several pathways linked to the immune system or RA pathogenesis (eg, citrullination processes and the negative regulation of natural killer function). The expression of several molecules was reverted by tofacitinib when good responses were reached, including AKT3, GK5, KLF12, FCRL3, BIRC3, TSPOAP1, and P2RY10. Finally, we isolated 14 markers that singularly were capable of predicting the attainment of good responses, including, NKG2D, CD226, CLEC2D, and CD52.

conclusionWhole-blood transcriptome analysis of patients with RA treated with tofacitinib identified genes whose expression may be relevant in prognostication and understanding the mechanisms of responses to therapy.

Identifiers

PMID40388487
PMCPMC12239517

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