Evidence map›Paper›PMID 39880410›Full record

ArticleRMD open2025

Prediction of long-term drug-free outcomes in ACPA-positive and ACPA-negative rheumatoid arthritis by combined clinical and ultrasound assessment of residual disease: a 5-year prospective study.

Antonio Manzo, Emanuele Bozzalla Cassione, Carlomaurizio Montecucco, Garifallia Sakellariou, Blerina Xoxi, Terenzj Luvaro, Ylenia Sammali, Ludovico De Stefano, Claudia Alpini, Catherine Klersy and 1 more

Abstract read
In one paragraph

Article in RMD open, 2025. 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. 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

11 authors.

Antonio Manzo *Rheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy antonio.manzo@unipv.it.
Emanuele Bozzalla Cassione *Rheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy.ORCID 0000-0001-6578-6938
Carlomaurizio MontecuccoRheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy.
Garifallia SakellariouRheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy.ORCID 0000-0002-1849-5123
Blerina XoxiRheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy.
Terenzj LuvaroRheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy.
Ylenia SammaliRheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy.
Ludovico De StefanoRheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy.ORCID 0000-0002-2312-2161
Claudia AlpiniLaboratory of Biochemical-Clinical Analyses, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Catherine KlersyBiostatistics and Clinical Trial Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Serena BugattiRheumatology and Translational Immunology Research Laboratories (LaRIT), Department of Internal Medicine and Therapeutics, Universita di Pavia, Pavia, Italy.ORCID 0000-0002-5396-7077

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo delineate, within the framework of current clinical practice and criteria, the sustainability of first-line immuno-suppressive treatment discontinuation in rheumatoid arthritis (RA) and the impact of residual disease in remission on long-term drug-free (DF) outcomes.

methodsRA patients, referring to the Pavia early arthritis clinic (EAC) between 2009 and 2021 and achieving remission after Disease Activity Score-driven methotrexate (MTX) monotherapy, were recruited. Eligible patients underwent DF follow-up at 3-month intervals over 5 years after MTX discontinuation. Pre-selected clinical, serological and ultrasound (US) exposure variables at MTX withdrawal were analysed using multivariable Cox regression to predict time-to-flare.

resultsOf 761 EAC patients with RA, 132 started DF follow-up (person-months: 3678). 62 experienced a flare after a median (range) of 9 (3-60) months, resulting in a progressive decline in flare-free survival throughout the observation period. Whole-cohort multivariate Cox regression identified anti-citrullinated protein antibody (ACPA) positivity (HR: 4.20, 95% CI 2.37 to 7.44) and hands' joints with grey scale (US-GS) alterations (GS>1; HR: 2.18, 95% CI 1.20 to 3.93) as independent predictors. ACPA-positive patients in Simplified Disease Activity Index (SDAI) remission displayed a flare-free survival estimate at 5 years of 6.4% (95% CI 1.2 to 35.7) versus 78.2% (95% CI 67.4 to 90.8) for ACPA-negative patients in SDAI remission without residual US-GS alteration in hands' joints (n=59); the latter group showing no evidence of radiographic progression and functional deterioration.

conclusionsLong-term DF remission is attainable in a niche subset of ACPA-negative RA. Examining clinical and subclinical residual synovial abnormalities during remission allows for effective preemptive identification of this subset in real life.

Indexed as

Anti-Citrullinated Protein AntibodiesAntirheumatic AgentsArthritis, RheumatoidAdultAgedDisease ProgressionFemaleFollow-Up StudiesHumansMaleMethotrexateMiddle AgedPrognosisProspective StudiesRemission InductionTreatment OutcomeAnti-Citrullinated Protein AntibodiesAntirheumatic AgentsMethotrexateAnti-Citrullinated Protein AntibodiesMethotrexateRecurrenceRheumatoid ArthritisRisk Factors

Identifiers

PMID39880410
PMCPMC11781140

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Registered trials

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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.