Trial reportClinical rheumatology2025
Split vs single-dose oral methotrexate in rheumatoid arthritis: a randomized controlled trial (SMART study).
Trial report in Clinical rheumatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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.
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.
Who cites it
2 citing papers in PubMed.
- Chronotherapy in Inflammatory Bowel Disease: Biological Rationale, Human Evidence, and a Clinical Implementation Framework.Digestive diseases and sciences · 2026Review
- Split vs. single-dose oral methotrexate in rheumatoid arthritis: a meta-analysis of randomized controlled trial.Inflammopharmacology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivePharmacokinetic evidence suggests split dose of oral methotrexate increases bioavailability, but unproven to improve efficacy. Thus, we planned to compare clinical response of split vs single-dose oral methotrexate in rheumatoid arthritis (RA).
methodsThis pragmatic, open-label (blinded assessor) randomized controlled trial was conducted across six university hospitals in India and enrolled patients with seropositive RA with active disease (TJC
resultsTwo hundred fifty-three patients [83% female, mean age 42.2 years, mean disease duration 2.1 yrs] were randomized to receive either split-dose (n = 128) or single-dose (n = 125) methotrexate. Primary outcome, good response at 24 weeks, was not significantly higher with split-dose methotrexate (+ 6.5%, 95% CI - 4.2 to 17.2%, p = 0.263). However, key secondary outcome, good response at 16 weeks, was significantly higher with split-dose methotrexate (+ 12.3%, 95% CI 3.5 to 21.3%, p = 0.008). Also, less patients in split-dose group required addition of second DMARD at 16 weeks (- 19.5%, p = 0.003). Numerically higher transaminitis and intolerance occurred with split-dose MTX.
conclusionAlthough the primary outcome was not met, we found faster response and better efficacy at 16 weeks with split-dose oral MTX, and reduced need for a second DMARD. Key Points • This was the first RCT to compare split-dose (same-day, morning, evening) to single-dose oral methotrexate (MTX) and included 253 patients of RA. • Primary outcome was not met, i.e., split-dose MTX was not superior in terms of EULAR good response at 24 weeks. • However, key secondary outcome was met, i.e., split-dose MTX met led to significantly higher EULAR good response at 16 weeks; also it reduced need for addition of a second DMARD. • Split-dose MTX was associated with higher adverse effects (numerically) in terms of both intolerance and transaminitis.
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Identifiers
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Registered trials
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.