Trial reportAnnals of the rheumatic diseases2023
Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: an analysis of the open label, randomised controlled study ORAL Surveillance.
Trial report in Annals of the rheumatic diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 32 registered trials, which are not on this map. Cited by 66 papers, 4 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 Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Compare 3 Dose Levels Of CP-690,550 Versus Placebo, Administered Orally Twice Daily (BID) For 6 Weeks, In The Treatment Of The Signs And Symptoms Of Subjects With Active Rheumatoid Arthritis
A Phase 2B, Randomized, Double Blind, Placebo-Controlled, Multicenter Study To Compare 6 Dose Regimens Of CP-690,550 Vs. Placebo, Each Combined With Methotrexate, Administered For 6 Months In The Treatment Of Subjects With Active Rheumatoid Arthritis Who Have Had An Inadequate Response To Methotrexate Alone
A Long-term, Open-label Follow-up Study Of Tofacitinib (Cp-690,550) For Treatment Of Rheumatoid Arthritis
A Phase 2b, Randomized, Double Blind, Placebo Controlled Active Comparator, Multicenter Study To Compare 5 Dose Regimens Of CP- 690,550 And Adalimumab Versus Placebo, Administered For 6 Months In The Treatment Of Subjects With Active Rheumatoid Arthritis
A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Confirm Dose Responsiveness Following 12 Weeks of the Administration of CP-690,550 (4 Doses) or Placebo in Subjects With Active Rheumatoid Arthritis Inadequately Controlled With Methotrexate Alone
A Long-term, Open-label Study Of Cp-690,550 to Confirm The Safety Following Long Term Administration Of Cp-690,550 In The Treatment Of Rheumatoid Arthritis
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Confirm Dose Responsiveness Following 12 Weeks Of The Administration Of CP-690,550 (5 Doses) Or Placebo In Subjects With Active Rheumatoid Arthritis Inadequately Responding To At Least 1 DMARD
A Randomized, Placebo Controlled, Double Blind, Parallel Group Multi-Center Study In Order To Investigate Safety And Efficacy Of CP- 690 550 In Subjects With Moderate To Severe Ulcerative Colitis.
Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Of The Efficacy And Safety Of 2 Doses Of CP-690,550 Monotherapy In Patients With Active Rheumatoid Arthritis
Phase 3 Randomized, Double Blind, Placebo Controlled Study Of The Efficacy And Safety Of 2 Doses Of CP-690,550 In Patients With Active Rheumatoid Arthritis On Background Methotrexate
Phase 3 Randomized, Double-Blind, Active Comparator, Placebo-Controlled Study Of The Efficacy And Safety Of 2 Doses Of CP 690,550 In Patients With Active Rheumatoid Arthritis On Background Methotrexate
Phase 3, Randomized, Double Blind, Placebo Controlled Study Of The Safety And Efficacy Of 2 Doses Of CP 690,550 In Patients With Active Rheumatoid Arthritis On Background DMARDS
Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Of The Safety And Efficacy Of 2 Doses Of CP-690,550 In Patients With Active Rheumatoid Arthritis On Background Methotrexate With Inadequate Response To TNF Inhibitors
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
Phase 3 Randomized, Double-blind Study Of The Efficacy And Safety Of 2 Doses Of Cp-690,550 Compared To Methotrexate In Methotrexate Navie Patients With Rheumatoid Arthritis
Phase 2 Study Of The Effects Of Open-Label CP-690,550 And Double-Blind Atorvastatin On Lipids In Patients With Active Rheumatoid Arthritis
An Exploratory Phase 2, Randomized, Double-blind, Multicenter Study To Assess The Effects Of Tofacitinib (Cp-690,550) On Magnetic Resonance Imaging Endpoints, In Methotrexate Naive Subjects With Early Active Rheumatoid Arthritis
An Exploratory Phase 1, Fixed Sequence, Open-Label Study To Assess The Effects Of CP-690,550 On The Kinetics Of Cholesterol Flux Through The High Density Lipoprotein/Reverse Cholesterol Transport Pathway In Patients With Active Rheumatoid Arthritis
A Randomized, Double Blind, Placebo Controlled Phase 2 Study To Assess The Immune Response Following Administration Of Influenza And Pneumococcal Vaccines To Subjects With Rheumatoid Arthritis Receiving Cp-690,550 Or Placebo Cp-690,550 With And Without Background Methotrexate
A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As A Maintenance Therapy In Subjects With Ulcerative Colitis
A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As An Induction Therapy In Subjects With Moderate To Severe Ulcerative Colitis.
A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As An Induction Therapy In Subjects With Moderate To Severe Ulcerative Colitis
A multi-center, open-label study of cp-690,550 in subjects with moderate to severe ulcerative colitis
A Phase 1, Randomized, Placebo-Controlled, Two-Period, Fixed Sequence Study To Evaluate The Effect Of CP-690,550 On Measured Glomerular Filtration Rate In Patients With Active Rheumatoid Arthritis
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Of The Efficacy And Safety Of 2 Doses Of Tofacitinib (CP-690,550) Or Adalimumab In Subjects With Active Psoriatic Arthritis
A Phase 3, Randomized, Double-blind, Placebo-controlled Study Of The Efficacy And Safety Of 2 Doses Of Tofacitinib (Cp-690,550) In Subjects With Active Psoriatic Arthritis And An Inadequate Response To At Least One Tnf Inhibitor
A long-term, open-label extension study of tofacitinib (cp-690,550) for the treatment of psoriatic arthritis
Phase 3b/4 randomized safety endpoint study of 2 doses of tofacitinib in comparison to a tumor necrosis factor (tnf) inhibitor in subjects with rheumatoid arthritis
A Randomized, Double-blind, Placebo-controlled, Phase 2 Study To Assess The Immune Response Following Administration Of Zoster Vaccine To Subjects With Rheumatoid Arthritis Receiving Tofacitinib (Cp-690,550) Or Placebo With Background Methotrexate Treatment
A Phase 3b/4 Randomized Double Blind Study Of 5 Mg Of Tofacitinib With And Without Methotrexate In Comparison To Adalimumab With Methotrexate In Subjects With Moderately To Severely Active Rheumatoid Arthritis
A Multicenter, Randomized, Double-blind, Parallel-group, Phase 3 Study To Demonstrate Non-inferiority For The Efficacy Of A Once Daily Dose Of Tofacitinib Modified Release Tablet To A Twice Daily Dose Of The Immediate Release Tablet In Adult Patients With Rheumatoid Arthritis On Background Methotrexate
A phase 3b/4 randomized double blind placebo controlled study of methotrexate (mtx) withdrawal in subjects with rheumatoid arthritis (ra) treated with tofacitinib 11mg modified release (mr) formulation
Who cites it
66 citing papers in PubMed, 4 syntheses or guidelines pooled it, 112 citations in OpenAlex.
- Therapeutic approaches for difficult-to-treat rheumatoid arthritis: a systematic literature review of current evidence.RMD open · 2026Pooled it
- Meta-Analysis of the Incidence and Influencing Factors of Malignant Tumors in Patients with Rheumatoid Arthritis.Journal of epidemiology and global health · 2026Pooled it
- EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update.Annals of the rheumatic diseases · 2024Guideline
- Efficacy and safety of tofacitinib for chronic plaque psoriasis and psoriatic arthritis: a systematic review and meta-analysis of randomized controlled trials.Clinical rheumatology · 2024Pooled it
- Trial
- Unsupervised machine learning with Cluster Analysis in patients with rheumatoid arthritis: insights in CV risk phenotypes from a multicentre Italian cohort.Internal and emergency medicine · 2026Article
- Comparative Safety Analysis of Targeted Synthetic and Biologic Disease-Modifying Antirheumatic Drugs Among Patients With Rheumatoid Arthritis: A Nationwide Cohort Study in Japan.International journal of rheumatic diseases · 2026Article
- Comparative efficacy and safety of tofacitinib versus adalimumab in patients with Behçet's uveitis: a real-world retrospective study.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- Effectiveness and Safety of Tofacitinib Up to 36 Months in Canadian Patients with Rheumatoid Arthritis: Final Results from the CANTORAL Study.Rheumatology and therapy · 2026Article
- Chemotherapy-Induced Alopecia Beyond Cytotoxicity: Hair Follicle Immune Privilege Collapse and JAK-STAT Signaling.International journal of molecular sciences · 2026Review
- Post-marketing surveillance of tofacitinib in patients with ulcerative colitis in Japan: a post hoc analysis of safety and effectiveness in older (≥65 years) and younger (<65 years) patients.Intestinal research · 2026Article
- Risk of serious infections, myocardial infarction or stroke, venous thromboembolic events, and malignancy in patients with psoriatic arthritis treated with tofacitinib compared with biologic treatments in the United States.Arthritis research & therapy · 2026Article
- From Convenience to Clinical Efficacy: Selective TYK2 Inhibition in Psoriasis and the Evolving Role of Next-Generation Oral Targeted Therapies.Pharmaceutics · 2026Review
- Observational
- Venous thromboembolism events associated with tofacitinib in rheumatoid arthritis patients: a real-world study from FAERS database.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Risk Factors for Major Adverse Cardiovascular Events, Malignancies, and Serious Infections With Tofacitinib in Rheumatoid Arthritis: Post Hoc Analysis of a 3-Year J-Post-Marketing Surveillance.International journal of rheumatic diseases · 2026Article
- Tumor safety of biologic agents and targeted therapies in immune-mediated inflammatory arthritides.Frontiers in immunology · 2026Review
- Venous Thromboembolism Risk in Patients with Atopic Dermatitis Treated with Abrocitinib: A Review of Female Patients on Oral Contraception and Nicotine Exposure From the JADE Clinical Trial Program.The Journal of clinical and aesthetic dermatology · 2026Article
- Tofacitinib does not affect platelet function or coagulation in patients with ulcerative colitis.Frontiers in immunology · 2026Article
- Safety of JAK inhibitors versus other biologic therapies following anti-TNF failure in patients with rheumatoid arthritis.Arthritis research & therapy · 2025Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedCorrection:2024
Authors and funding
8 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesBased on primary results from ORAL Surveillance, an event-driven clinical trial of risk-enriched patients, identify subpopulations with different relative risk (ie, 'high-risk' and 'low-risk') with tofacitinib versus tumour necrosis factor inhibitors (TNFi).
methodsPatients with rheumatoid arthritis aged ≥50 years with ≥1 additional cardiovascular risk factor received tofacitinib 5 or 10 mg two times a day or TNFi. Prior analyses had identified age and smoking as risk factors of particular interest across safety outcomes. Hazard ratios (HRs) and incidence rates were evaluated by age and smoking individually and in combination. Results were validated across tofacitinib development programmes.
results'Age ≥65 years or ever smoker' defined a group ('high-risk') with increased risk of malignancies (excluding non-melanoma skin cancer), major adverse cardiovascular events, myocardial infarction, venous thromboembolism and all-cause death with tofacitinib (combined doses) versus TNFi (HRs 1.41-5.19). In patients 'aged <65 years and never smokers' ('low-risk'), there was no detectable risk increase with tofacitinib versus TNFi (HRs ≈1.0) up to 6 years of follow-up, and absolute risk remained low and was corroborated across tofacitinib rheumatoid arthritis, psoriatic arthritis and ulcerative colitis programmes with up to 10 years of observation.
conclusionsThis posthoc analysis of ORAL Surveillance identified two tofacitinib subpopulations with different relative risk versus TNFi. High risk was confined to patients defined by distinct risk factors age ≥65 years or smoking, and these differentiating risk factors accounted for the excess risk observed with tofacitinib versus TNFi. These findings can guide individualised benefit/risk assessment and clinical decision-making on treatment with tofacitinib. TRIAL REGISTRATION NUMBERS: NCT02092467, NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT02147587, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT02281552, NCT02187055, NCT02831855, NCT00413699, NCT00661661, NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612, NCT01877668, NCT01882439, NCT01976364.
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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.