Evidence map›Paper›PMID 41558803›Full record

Trial reportRMD open2026

Which arthralgia patients benefit most in reduction of subclinical joint inflammation by methotrexate treatment: results from the TREAT EARLIER trial.

Stijn Claassen, Quirine A Dumoulin, Herman K Glas, Esmeralda Molenaar, Hanna W van Steenbergen, Annette Hm van der Helm-van Mil

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in RMD open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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.

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

2 citing papers in PubMed.

  1. Article
  2. Review
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

6 authors.

Stijn ClaassenRheumatology, Leiden University Medical Center, Leiden, The Netherlands s.claassen@lumc.nl.ORCID 0009-0006-6299-7653
Quirine A DumoulinRheumatology, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0003-0318-096X
Herman K GlasRheumatology, Reumazorg Zuid West Nederland, Goes, The Netherlands.
Esmeralda MolenaarRheumatology, Groene Hart Hospital, Gouda, The Netherlands.
Hanna W van SteenbergenRheumatology, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0002-3251-0238
Annette Hm van der Helm-van MilRheumatology, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0001-8572-1437

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesThe TREAT EARLIER trial showed in clinically suspect arthralgia (CSA) that methotrexate induced reductions in subclinical inflammation and related disease burden during the year of treatment, which was sustained thereafter. We studied whether the treatment response defined at the level of subclinical joint inflammation was present in all treated CSA patients and, if not, what characterises the subgroup of responders.

methodsCSA patients with subclinical inflammation were randomised to receive an intramuscular glucocorticoid injection and a 1-year course of methotrexate. Treatment response was defined as a reduction of MRI-detected synovitis, tenosynovitis or osteitis levels beyond the smallest detectable change at 12 months. Baseline clinical and imaging characteristics were studied in relation to treatment response. Predictive values were determined.

results44 of 115 (38%) treated patients had an MRI-defined treatment response. These patients also significantly improved in pain and physical functioning (-22 Visual Analogue Scale pain, -0.29 Health Assessment Questionnaire). Baseline clinical variables were not independently associated with this response, in contrast to the severity of subclinical joint inflammation. Tenosynovitis and osteitis levels in particular were predictive. Patients with ≥2 sites with tenosynovitis or a combination of osteitis and tenosynovitis (with ≥1 of these features at ≥2 sites) had high positive predictive values (PPV 77%, 79%). PPVs were similar in ACPA-positive and ACPA-negative patients at increased risk for rheumatoid arthritis (RA).

conclusionsCSA patients with subclinical inflammation who responded best to methotrexate during the first year were identified by increased levels of subclinical inflammation at diagnosis, primarily due to multiple sites of tenosynovitis with/without osteitis. These data may contribute to personalised medicine for arthralgia at risk for RA.

Indexed as

Antirheumatic AgentsArthralgiaMethotrexateAdultAgedArthritis, RheumatoidFemaleGlucocorticoidsHumansInflammationMagnetic Resonance ImagingMaleMiddle AgedOsteitisPain MeasurementSynovitisAntirheumatic AgentsGlucocorticoidsMethotrexateArthritis, RheumatoidMethotrexateRisk FactorsTherapeutics

Identifiers

PMID41558803
PMCPMC12820865

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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.