Evidence map›Paper›PMID 36137735›Full record

Trial reportAnnals of the rheumatic diseases2023

Risk of major adverse cardiovascular events with tofacitinib versus tumour necrosis factor inhibitors in patients with rheumatoid arthritis with or without a history of atherosclerotic cardiovascular disease: a post hoc analysis from ORAL Surveillance.

Christina Charles-Schoeman, Maya H Buch, Maxime Dougados, Deepak L Bhatt, Jon T Giles, Steven R Ytterberg, Gary G Koch, Ivana Vranic, Joseph Wu, Cunshan Wang and 6 more

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled TrialClinical Trial, Phase IV
PubMed Full text at PMC Publisher
In one paragraph

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. It is linked to trial NCT02092467 (PHASE 3B/4 RANDOMIZED SAFETY ENDPOINT STUDY OF 2 DOSES OF TOFACITINIB IN COMPARISON TO A TUMOR NECROSIS FACTOR), which is not on this map. Cited by 118 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed, 2 pooled it
29.3field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT02092467 phase4completednot on this map

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

TypeinterventionalSponsorPfizerRan2014 to 2020Enrolled4,372ConditionsArthritis, RheumatoidArmstofacitinib, adalimumab, etanercept
3 · Its place in the literature

Who cites it

118 citing papers in PubMed, 2 syntheses or guidelines pooled it, 189 citations in OpenAlex.

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58 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 11 institutions in 5 countries.

Christina Charles-SchoemanDivision of Rheumatology, Department of Medicine, University of California, Los Angeles, Los Angeles, California, USA ccharles@mednet.ucla.edu.ORCID 0000-0002-1768-7019
Maya H BuchCentre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.ORCID 0000-0002-8962-5642
Maxime DougadosUniversité de Paris; Department of Rheumatology, Hôpital Cochin; Assistance Publique-Hôpitaux de Paris, Paris, France.ORCID 0000-0003-3009-6229
Deepak L BhattDivision of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0002-1278-6245
Jon T GilesDivision of Rheumatology, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA.
Steven R YtterbergDivision of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA.
Gary G KochDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Ivana VranicPfizer Ltd, Tadworth, UK.
Joseph WuPfizer Inc, Groton, Connecticut, USA.
Cunshan WangPfizer Inc, Groton, Connecticut, USA.
Kenneth KwokPfizer Inc, New York, New York, USA.
Sujatha MenonPfizer Inc, Groton, Connecticut, USA.
Jose L RivasPfizer SLU, Madrid, Spain.
Arne YndestadPfizer Inc, Oslo, Norway.
Carol A ConnellPfizer Inc, Groton, Connecticut, USA.
Zoltan SzekaneczDivision of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.ORCID 0000-0002-7794-6844
Pfizer (United States) · USBrigham and Women's Hospital · USColumbia University · USInserm · FRManchester Academic Health Science Centre · GBMayo Clinic · USPfizer (United Kingdom) · GBSaint Louis University · ESUniversity of California, Los Angeles · USUniversity of Debrecen · HUUniversity of North Carolina at Chapel Hill · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesEvaluate risk of major adverse cardiovascular events (MACE) with tofacitinib versus tumour necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA) with or without a history of atherosclerotic cardiovascular disease (ASCVD) in ORAL Surveillance.

methodsPatients with RA aged ≥50 years with ≥1 additional CV risk factor received tofacitinib 5 mg or 10 mg two times per day or TNFi. Hazard rations (HRs) were evaluated for the overall population and by history of ASCVD (exploratory analysis).

resultsRisk of MACE, myocardial infarction and sudden cardiac death were increased with tofacitinib versus TNFi in ORAL Surveillance. In patients with history of ASCVD (14.7%; 640/4362), MACE incidence was higher with tofacitinib 5 mg two times per day (8.3%; 17/204) and 10 mg two times per day (7.7%; 17/222) versus TNFi (4.2%; 9/214). HR (combined tofacitinib doses vs TNFi) was 1.98 (95% confidence interval (CI) 0.95 to 4.14; interaction p values: 0.196 (for HR)/0.059 (for incidence rate difference)). In patients without history of ASCVD, MACE HRs for tofacitinib 5 mg two times per day (2.4%; 30/1251) and 10 mg two times per day (2.8%; 34/1234) versus TNFi (2.3%; 28/1237) were, respectively, 1.03 (0.62 to 1.73) and 1.25 (0.76 to 2.07).

conclusionsThis post hoc analysis observed higher MACE risk with tofacitinib versus TNFi in patients with RA and history of ASCVD. Among patients without history of ASCVD, all with prevalent CV risk factors, MACE risk did not appear different with tofacitinib 5 mg two times per day versus TNFi. Due to the exploratory nature of this analysis and low statistical power, we cannot exclude differential MACE risk for tofacitinib 5 mg two times per day versus TNFi among patients without history of ASCVD, but any absolute risk excess is likely low. TRIAL REGISTRATION NUMBER: NCT02092467.

Indexed as

Antirheumatic AgentsArthritis, RheumatoidAtherosclerosisCardiovascular DiseasesHumansMiddle AgedPiperidinesPyrimidinesTumor Necrosis Factor InhibitorsAntirheumatic AgentsPiperidinesPyrimidinestofacitinibTumor Necrosis Factor InhibitorsAntirheumatic AgentsArthritis, RheumatoidCardiovascular DiseasesTherapeutics

Identifiers

PMID36137735
PMCPMC9811099
OpenAlexW4296696831

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

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.