Summary
Methotrexate has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Rheumatoid Arthritis would be drug repurposing rather than first-in-human development. This does not mean it is approved for Rheumatoid Arthritis. ClinicalTrials.gov lists 8 registered trials linking Methotrexate to Rheumatoid Arthritis: 2 are active or not yet recruiting; 5 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT07357649). The largest enrolment is 516 participants (NCT01050998). Registration activity spans 2007 to 2026. The literature layer holds 14 publications for this pair: 5 Cochrane reviews, 3 meta-analyses, 1 systematic review and 5 clinical trial publications. The dated items are from 2026. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
The RepurpOS disease-intelligence file for Rheumatoid Arthritis ranks 544 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: 11% achieve drug-free remission (DFR) at median 74 months; most cohorts show 10-15% DFR ceiling.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 79.0 (trials 29.0, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 0 recruiting, 2 active / not yet recruiting, 5 completed, 1 other |
| Linked publications | 14 (5 Cochrane reviews, 5 clinical trial publications, 3 meta-analyses, 1 systematic review) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | Not recorded |
| Data sources | Open Targets, ChEMBL |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT07357649 | Baricitinib Effects on Procoagulant State in Rheumatoid Arthritis 2026 | not yet recruiting | Phase 4 | 100 |
| NCT04909801 | A Study to Compare the Response to Treatment With Abatacept vs Adalimumab, on Background Methotrexate, in Adults With Early, Seropositive, and Shared Epitope-positive Rheumatoid Arthritis and an Inadequate Response to Methotrexate 2021 | active, not recruiting | Phase 3 | 338 |
| NCT01185301 | Study to Determine the Effects of Different Doses of Methotrexate (MTX) When Taken With Adalimumab in Subjects With Early Rheumatoid Arthritis (RA) 2010 | completed | Phase 3 | 395 |
| NCT00547521 | Phase IIIB Subcutaneous Abatacept Monotherapy Study 2007 | completed | Phase 3 | 119 |
| NCT06073093 | A Study to Evaluate SAR441566 Efficacy and Safety in Adults With Rheumatoid Arthritis 2023 | completed | Phase 2 | 264 |
| NCT00867516 | Safety, Efficacy and Pharmacokinetics Study of ALD518 in Patients With Active Rheumatoid Arthritis 2008 | completed | Phase 2 | 127 |
| NCT01050998 | A Study to Evaluate the Efficacy and Safety of CAM-3001 (Drug) in Subjects With Rheumatoid Arthritis 2010 | completed | Phase 2 | 516 |
| NCT01410695 | Masitinib in Refractory Active Rheumatoid Arthritis 2011 | terminated | PHASE2, PHASE3 | 324 |
Published literature
- Clinical trial publication Long-term safety and efficacy of upadacitinib compared with adalimumab in patients with rheumatoid arthritis: 7-year data from the SELECT-COMPARE studyFleischmann R, Swierkot J, Durez P et al. · RMD open · 2026 · PMID 42342288
- Clinical trial publication Mechanistic study on the reduction of TNF-α and β-CTX levels in RA patients by moxibustion combined with western medication through regulation of the Wnt/β-catenin pathwayWang H, Chen H, Li Y et al. · Frontiers in immunology · 2026 · PMID 42254021
- Clinical trial publication The Kunduan Yimu decoction improves rheumatoid arthritis by targeting microRNA-155-5p to enhance autophagy and reduce inflammationLiu XB, Zou FS, Shi MF et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026 · PMID 42085942
- Clinical trial publication Efficacy and safety of branebrutinib (BMS-986195), an irreversible Bruton's tyrosine kinase inhibitor, for the treatment of rheumatoid arthritis: a phase 2a, randomised, double-blind, placebo-controlled studyØstergaard M, Haavardsholm EA, Nowak M et al. · The Lancet. Rheumatology · 2026 · PMID 42081904
- Clinical trial publication Response of ultrasound-assessed synovitis to baricitinib, in monotherapy and combined with methotrexate, compared with etanercept in rheumatoid arthritis: a randomised, international, multicentre trialNaredo E, Olivas-Vergara O, Borges PE et al. · Annals of the rheumatic diseases · 2026 · PMID 42025496
- Cochrane review Prevalence and risk factors of herpes zoster in patients with rheumatoid arthritis: a systematic review and meta-analysisWang S, Liu Q, Zhou P et al. · Frontiers in immunology · 2026 · PMID 42183272
- Cochrane review Perioperative use of disease-modifying anti-rheumatic drugs (DMARDs) in people with inflammatory arthritisPonkilainen V, Karjalainen TV, Kuitunen I et al. · The Cochrane database of systematic reviews · 2026 · PMID 42159164
- Cochrane review Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2025 update of the EULAR recommendations for the management of rheumatoid arthritisKonzett V, Laskou F, Smolen JS et al. · Annals of the rheumatic diseases · 2026 · PMID 41997804
- Cochrane review Gastrointestinal adverse events among methotrexate users in rheumatoid arthritis patients: a systematic review and meta-analysisHidayat R, Fauzia F, Audrey J et al. · Clinical rheumatology · 2026 · PMID 41653236
- Cochrane review Systematic review of the treatment of rheumatoid arthritis patients of reproductive age: informing the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis-secondary publicationGoto M, Kohno C, Takai C et al. · Modern rheumatology · 2026 · PMID 41060311
- Meta-analysis Efficacy and safety of upadacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysisXu YH, Liu D, Zhang MR et al. · Frontiers in immunology · 2026 · PMID 42245676
- Meta-analysis Association of folylpolyglutamate synthase polymorphisms with methotrexate response and toxicity in rheumatoid arthritis: a meta-analysisLee YH, Song GG · The pharmacogenomics journal · 2026 · PMID 41932892
- Meta-analysis Effect of monotherapy with conventional synthetic disease-modifying anti-rheumatic drugs or glucocorticoids on radiographic progression in rheumatoid arthritis: a network meta-analysis of 64 treatment arms from 31 randomized controlled trialsGuski LS, Pedder H, Andersn SE et al. · Scandinavian journal of rheumatology · 2026 · PMID 41858241
- Systematic review The impact of gene polymorphisms on the response of methotrexate-based treatmentsEsperón P, Vital M, Giletti A · European journal of clinical pharmacology · 2026 · PMID 42104114
Mechanism and notes
No mechanism of action is recorded for this pair in the source databases.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Methotrexate approved for Rheumatoid Arthritis?
Methotrexate has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Rheumatoid Arthritis would be drug repurposing rather than first-in-human development. This does not mean it is approved for Rheumatoid Arthritis. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Methotrexate in clinical trials for Rheumatoid Arthritis?
ClinicalTrials.gov lists 8 registered trials linking Methotrexate to Rheumatoid Arthritis: 2 are active or not yet recruiting; 5 have completed; 1 is terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT07357649). The largest enrolment is 516 participants (NCT01050998). Registration activity spans 2007 to 2026.
What does the evidence show for Methotrexate in Rheumatoid Arthritis?
Methotrexate has both completed registered trials and synthesis-level publications linked to Rheumatoid Arthritis. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.