Evidence map›Paper›PMID 40197512›Full record

ArticleBMC rheumatology2025

Long-term effectiveness and safety of methotrexate-tacrolimus combination therapy versus methotrexate monotherapy in reducing rheumatoid arthritis flares after TNF inhibitor discontinuation: a retrospective cohort study.

Taio Naniwa, Mikiko Kajiura

Abstract read
In one paragraph

Article in BMC 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.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

2 authors.

Taio NaniwaDivision of Rheumatology, Department of Internal Medicine, Nagoya City University Hospital, and Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, 467-8601, Japan. tnaniwa@med.nagoya-cu.ac.jp.ORCID https://orcid.org/0000-0002-0489-2611
Mikiko KajiuraTakeuchi Orthopedics & Internal Medicine, Chita, Aichi, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThis study evaluates the long-term effectiveness and safety of methotrexate-tacrolimus combination therapy compared to methotrexate monotherapy in maintaining successful tumor necrosis factor (TNF) inhibitor discontinuation in rheumatoid arthritis (RA) patients.

methodsWe retrospectively analyzed consecutive RA patients who discontinued TNF inhibitors after achieving disease control by October 2022 and received either methotrexate monotherapy or methotrexate-tacrolimus combination therapy for up to 10 years. Per-observation time-to-event analyses assessed treatment failure, treatment intensification, first disease flare, and irreversible functional deterioration. Mixed-effects Cox models, time-dependent Cox models without random effects, and Kaplan-Meier estimates with inverse probability weighting were applied. Safety assessment included treatment-limiting adverse events and renal function trends.

resultsA total of 147 treatment lines (96 methotrexate monotherapy and 51 combination therapy) in 116 patients were analyzed. The combination therapy significantly reduced treatment failure (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.24-0.72), treatment intensification with the index drugs (HR, 0.38; 95% CI, 0.22-0.67) and with biologics or Janus kinase inhibitors (HR, 0.39; 95% CI, 0.22-0.71), and first flare (HR, 0.55; 95%CI 0.36-0.84), with consistent findings across models. The benefit was most pronounced in patients with prior flares during methotrexate monotherapy after TNF inhibitor discontinuation, with HRs as low as 0.04-0.12 across outcomes. No significant differences in treatment-limiting adverse events were observed. The annual increase in serum creatinine for tacrolimus users was 0.0032 mg/dL, suggesting minimal long-term renal impact.

conclusionsMethotrexate-tacrolimus combination therapy significantly reduces relapse risk following TNF inhibitor discontinuation without compromising safety, offering a potentially sustainable treatment alternative after achieving remission with TNF inhibitor therapy.

Indexed as

Biological therapyClinical remissionRecurrenceRheumatoid arthritisWithdrawing treatment

Identifiers

PMID40197512
PMCPMC11974236

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.