Trial reportRMD open2020
Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme.
Trial report in RMD open, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 21 registered trials, which are not on this map. Cited by 98 papers, 6 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
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 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 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
Who cites it
98 citing papers in PubMed, 6 syntheses or guidelines pooled it.
- 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
- Efficacy and safety of Advanced Combination Treatment in immune-mediated inflammatory disease: A systematic review and meta-analysis of randomized controlled trials.Journal of autoimmunity · 2024Pooled it
- Pooled it
- Herpes zoster in patients with inflammatory arthritides or ulcerative colitis treated with tofacitinib, baricitinib or upadacitinib: a systematic review of clinical trials and real-world studies.Rheumatology international · 2023Pooled it
- Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database.Annals of the rheumatic diseases · 2022Pooled it
- Effectiveness and Safety of JAK Inhibitors in Autoinflammatory Diseases: A Systematic Review.Frontiers in medicine · 2022Pooled it
- Exposure-Response Analysis of Tofacitinib in Active Psoriatic Arthritis: Results from Two Phase 3 Studies.Journal of clinical pharmacology · 2025Trial
- Olokizumab plus methotrexate: safety and efficacy over 106 weeks of treatment.Annals of the rheumatic diseases · 2024Trial
- Trial
- Long-term Risk of Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib.Inflammatory bowel diseases · 2023Trial
- Infections in patients with rheumatoid arthritis receiving tofacitinib versus tumour necrosis factor inhibitors: results from the open-label, randomised controlled ORAL Surveillance trial.Annals of the rheumatic diseases · 2022Trial
- Waiting for JAK inhibitor safety data.RMD open · 2022Trial
- Trajectory of lipid profiles in rheumatoid arthritis patients receiving tofacitinib: Evidence from the prospective CENTRA cohort.British journal of clinical pharmacology · 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 Effectiveness of Upadacitinib vs. Other JAK Inhibitors in Patients With Rheumatoid Arthritis in a Global Real-World Setting.Rheumatology and therapy · 2026Article
- Mycobacterium intracellulare Infection in a Japanese Patient with Signal Transducer and Activator of Transcription-3 Gain-of-function Syndrome.Internal medicine (Tokyo, Japan) · 2026Article
- Janus Kinase Inhibitors and Body Weight: Current Evidence and Potential.Life (Basel, Switzerland) · 2026Review
- Observational
- JAK/STAT signaling pathway inhibitors in neurodegenerative diseases: current status and future perspectives.Frontiers in aging neuroscience · 2026Review
- JAK inhibitors and adverse cardiovascular events: Class effect or molecule-specific risk?Frontiers in pharmacology · 2026Review
38 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.
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). We report the largest integrated safety analysis of tofacitinib, as of March 2017, using data from phase I, II, III, IIIb/IV and long-term extension studies in adult patients with RA.
methodsData were pooled for patients with RA who received ≥1 tofacitinib dose. Incidence rates (IRs; patients with events/100 patient-years [PY]; 95% CIs) of first-time occurrences were obtained for adverse events (AEs) of interest.
results7061 patients received tofacitinib (total exposure: 22 875 PY; median [range] exposure: 3.1 [0 to 9.6] years). IRs (95% CI) for serious AEs, serious infections, herpes zoster (all), opportunistic infections (excluding tuberculosis [TB]) and TB were 9.0 (8.6 to 9.4), 2.5 (2.3 to 2.7), 3.6 (3.4 to 3.9), 0.4 (0.3 to 0.5) and 0.2 (0.1 to 0.2), respectively. IRs (95% CI) for malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC and lymphomas were 0.8 (0.7 to 0.9), 0.6 (0.5 to 0.7) and 0.1 (0.0 to 0.1), respectively. IRs (95% CI) for gastrointestinal perforations, deep vein thrombosis, pulmonary embolism, venous thromboembolism, arterial thromboembolism and major adverse cardiovascular events were 0.1 (0.1 to 0.2), 0.2 (0.1 to 0.2), 0.1 (0.1 to 0.2), 0.3 (0.2 to 0.3), 0.4 (0.3 to 0.5) and 0.4 (0.3 to 0.5), respectively. IR (95% CI) for mortality was 0.3 (0.2 to 0.3). IRs generally remained consistent across 6-month intervals to >78 months.
conclusionThis represents the largest clinical dataset for a JAK inhibitor in RA to date. IRs remained consistent with previous reports from the tofacitinib RA clinical development programme, and stable over time. TRIAL REGISTRATION NUMBERS: NCT01262118; NCT01484561; NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01164579; NCT00976599; NCT01059864; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT00413699; NCT00661661.For summary of phase I, phase II, phase III, phase IIIb/IV and LTE studies included in the integrated safety analysis, see online supplemental table 1.
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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.