Evidence map›Paper›PMID 39516929›Full record

ArticleArthritis research & therapy2024

Timely escalation to second-line therapies after failure of methotrexate in patients with early rheumatoid arthritis does not reduce the risk of becoming difficult-to-treat.

Bernardo D'Onofrio, Ludovico De Stefano, Emanuele Bozzalla Cassione, Valentina Morandi, Francesca Cuzzocrea, Garifallia Sakellariou, Antonio Manzo, Carlomaurizio Montecucco, Serena Bugatti

Abstract read
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Article in Arthritis research & therapy, 2024. 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

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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

2 citing papers in PubMed.

  1. Article
  2. JAK/STAT inhibition reprograms T cell activation and metabolism in inflammatory arthritis patients.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
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

9 authors.

Bernardo D'Onofrio *Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Ludovico De Stefano *Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Emanuele Bozzalla CassioneDepartment of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Valentina MorandiDepartment of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Francesca CuzzocreaDepartment of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Garifallia SakellariouDepartment of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Antonio ManzoDepartment of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Carlomaurizio MontecuccoDepartment of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Serena BugattiDepartment of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy. serena.bugatti@unipv.it.ORCID 0000-0002-5396-7077

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTo investigate the frequency of difficult-to-treat (D2T) rheumatoid arthritis (RA) in patients early escalated to biologic/targeted synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs) after failure of treat-to-target with methotrexate (MTX).

methodsFrom a prospective cohort of early RA, all patients with their first access in the years 2005-2018, and eventually starting a b/tsDMARD before the end of 2022, were included and followed-up until April 2024. Study outcomes included drug survival on each consecutive b/tsDMARDs, development of D2T (according to the EULAR definition and subsequent modifications), and its predictors.

resultsOf a total cohort of 722 early RA patients treated with initial MTX and followed-up for at least 3 years from diagnosis, 155 (21.5%) had started a b/tsDMARD after a median of 19 months. In more than 70% of the cases, RA was uncontrolled despite optimal doses of MTX of ≥ 15 mg/day. The retention rates of the first and the second b/tsDMARD were approximatively 70% after 1 year but dropped to 40% after 5 years. After a median (IQR) follow up of 72.6 (34.5-134.2) months, 45 patients (29%) fulfilled the EULAR D2T criteria. At multivariable analysis, higher number of swollen joints and worse pain scores were confirmed as predictors of D2T. Furthermore, in this early RA cohort, shorter disease duration at the start of treatment with b/tsDMARDs, together with negativity for autoantibodies, were also independent predictors of D2T.

conclusionsEarly implementation of treatment after failure of treat-to-target with MTX may not prevent the development of D2T in RA. Patients showing early refractoriness to conventional drugs and those lacking autoantibodies are at higher risk of multiple treatment failures.

Indexed as

Antirheumatic AgentsArthritis, RheumatoidMethotrexateTreatment FailureAdultAgedBiological ProductsCohort StudiesFemaleFollow-Up StudiesHumansMaleMiddle AgedProspective StudiesAntirheumatic AgentsBiological ProductsMethotrexateACPAAnti-citrullinated protein antibodiesDifficult-to-treatEarlyMethotrexateRefractoryRheumatoid arthritisRheumatoid factorSeronegativeTreat-to-target

Identifiers

PMID39516929
PMCPMC11545058

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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.