Trial reportAnnals of the rheumatic diseases2015
The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis.
Trial report in Annals of the rheumatic diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 147 papers, 8 of them syntheses that pooled 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.
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.
A Long-term, Open-label Follow-up Study Of Tofacitinib (Cp-690,550) For Treatment Of Rheumatoid Arthritis
An Exploratory Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Assess The Pharmacodynamics Of CP-690,550, Administered Orally Twice Daily (BID) For 4 Weeks, In Subjects With Active Rheumatoid Arthritis
Who cites it
147 citing papers in PubMed, 8 syntheses or guidelines pooled it, 291 citations in OpenAlex.
- Combining Aggregate Data and Individual Patient Data in Model-Based Meta-Analysis: An Illustrative Case Study of Tofacitinib in Rheumatoid Arthritis Patients.CPT: pharmacometrics & systems pharmacology · 2026Pooled it
- Pooled it
- A systematic review on disease-drug-drug interactions with immunomodulating drugs: A critical appraisal of risk assessment and drug labelling.British journal of clinical pharmacology · 2022Pooled it
- Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of 24,135 Patients.International journal of molecular sciences · 2022Pooled it
- Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network meta-analysis.The Cochrane database of systematic reviews · 2017Pooled it
- Biologic or tofacitinib monotherapy for rheumatoid arthritis in people with traditional disease-modifying anti-rheumatic drug (DMARD) failure: a Cochrane Systematic Review and network meta-analysis (NMA).The Cochrane database of systematic reviews · 2016Pooled it
- Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to methotrexate or other traditional disease-modifying anti-rheumatic drugs: a systematic review and network meta-analysis.The Cochrane database of systematic reviews · 2016Pooled it
- Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme.Annals of the rheumatic diseases · 2016Pooled it
- Differences and similarities in clinical and functional responses among patients receiving tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus methotrexate: a post hoc analysis of data from ORAL Strategy.Arthritis research & therapy · 2021Trial
- Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials.Digestive diseases and sciences · 2021Trial
- Development of Gut-Selective Pan-Janus Kinase Inhibitor TD-1473 for Ulcerative Colitis: A Translational Medicine Programme.Journal of Crohn's & colitis · 2020Trial
- Toreforant, an orally active histamine HInflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Trial
- Impact of the Sociodemographic Index on Efficacy/Safety of Tofacitinib in Patients with Rheumatoid Arthritis: Post Hoc Analysis of Phase 2/3/3b/4 Studies.Rheumatology and therapy · 2026Article
- Review
- Identification of a metabolic-immune crosstalk in Still's disease: monocyte/macrophage-derived immunometabolite itaconate dictates hepatic immunopathology via the CXCL10-CD8 T cell axis.Experimental & molecular medicine · 2026Article
- Targeting NF-κB and JAK/STAT pathways in rheumatoid arthritis: emerging nanocarrier-based drug delivery approaches.Inflammopharmacology · 2026Review
- A Rationally Designed Novel Bifunctional Human TNF-α- and Janus Kinase-Targeted soloMER Drug Conjugate (SDC) with a Neutrophil Elastase Cleavable Linker Delivering Inflammation Site-Specific Release of Payload.Journal of medicinal chemistry · 2026Article
- Estrogen and progesterone-mediated differential modulation of CD4Frontiers in immunology · 2026Article
- Targeting CXCL8 alleviates intestinal epithelial inflammation by suppressing the JAK-STAT pathway.European journal of medical research · 2025Article
- Molecular Mechanisms of Wound Healing: The Role of Medicinal Plants.Life (Basel, Switzerland) · 2025Review
87 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). The pathways affected by tofacitinib and the effects on gene expression in situ are unknown. Therefore, tofacitinib effects on synovial pathobiology were investigated.
methodsA randomised, double-blind, phase II serial synovial biopsy study (A3921073; NCT00976599) in patients with RA with an inadequate methotrexate response. Patients on background methotrexate received tofacitinib 10 mg twice daily or placebo for 28 days. Synovial biopsies were performed on Days -7 and 28 and analysed by immunoassay or quantitative PCR. Clinical response was determined by disease activity score and European League Against Rheumatism (EULAR) response on Day 28 in A3921073, and at Month 3 in a long-term extension study (A3921024; NCT00413699).
resultsTofacitinib exposure led to EULAR moderate to good responses (11/14 patients), while placebo was ineffective (1/14 patients) on Day 28. Tofacitinib treatment significantly reduced synovial mRNA expression of matrix metalloproteinase (MMP)-1 and MMP-3 (p<0.05) and chemokines CCL2, CXCL10 and CXCL13 (p<0.05). No overall changes were observed in synovial inflammation score or the presence of T cells, B cells or macrophages. Changes in synovial phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT3 strongly correlated with 4-month clinical responses (p<0.002). Tofacitinib significantly decreased plasma CXCL10 (p<0.005) at Day 28 compared with placebo.
conclusionsTofacitinib reduces metalloproteinase and interferon-regulated gene expression in rheumatoid synovium, and clinical improvement correlates with reductions in STAT1 and STAT3 phosphorylation. JAK1-mediated interferon and interleukin-6 signalling likely play a key role in the synovial response. TRIAL REGISTRATION NUMBER: NCT00976599.
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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.