Publications

Risk of extended major adverse cardiovascular event endpoints with tofacitinib versus TNF inhibitors in patients with rheumatoid arthritis: A post hoc analysis of a Phase 3b/4 randomised safety study

RMD Open 2024;10:e003912 doi: 10.1136/rmdopen-2023-003912

Buch MH,

Bhatt DL,

Charles-Schoeman C,

Giles JT,

Mikuls T,

Koch GG,

Ytterberg S,

Nagy E,

Jo H,

Kwok K,

Connell CA,

Masri KM,

Yndestad A

Risk of composite CV endpoints combining all ischaemic CV events and heart failure were similar for individual and combined TOF doses versus TNFi. The totality of CV risk (MACE-8 plus VTE) was higher with TOF 10mg twice daily versus TNFi. Buch et al conducted a post-hoc analysis on the ORAL Surveillance trial to assess risk across extended MACE endpoints in RA patients treated with either TOF 5mg, TOF 10mg, or TNFi.

Keywords:

• Cardiovascular,
• Dosing,
• Safety,
• TNF,
• Tofacitinib

Risk of venous thromboembolism with tofacitinib versus tumor necrosis factor inhibitors in cardiovascular risk-enriched rheumatoid arthritis patients

Arthritis Rheumatol 2024 doi: 10.1002/art.42846 Epub ahead of print https://pubmed.ncbi.nlm.nih.gov/38481002/

Charles-Schoeman C,

Fleischmann R,

Mysler E,

Greenwald M,

Ytterberg SR,

Koch GG,

Bhatt DL,

Wang C,

Mikuls TR,

Chen AS,

Connell CA,

Woolcott JC,

Menon S,

Chen Y,

Lee K,

Szekanecz Z

This post hoc analysis of ORAL Surveillance showed that incidence of venous thromboembolism (VTE) events was higher in patients with RA treated with tofacitinib (10>5mg BID) versus TNFi. Across treatments, VTE risk factors (age, BMI, and VTE history) were aligned with previous studies in the general RA population.

Keywords:

• Adalimumab,
• Safety,
• Outcomes,
• Tofacitinib

Rheumatoid Arthritis Disease Activity and Adverse Events in Patients Receiving Tofacitinib or Tumor Necrosis Factor Inhibitors: A Post Hoc Analysis of ORAL Surveillance

Ther Adv Musculoskelet Dis. 2023;15:1759720X231201047 doi: 10.1177/1759720X231201047

Karpouzas GA,

Szekanecz Z,

Baecklund E,

Mikuls TR,

Bhatt DL,

Wang C,

Sawyerr GA,

Chen Y,

Menon S,

Connell CA,

Ytterberg SR,

Mortezavi M

Post hoc analysis of ORAL Surveillance data highlights that active disease in RA leads to higher risk of adverse medical events, regardless of medication used.

Keywords:

• Outcomes

Malignancy Risk with Tofacitinib versus TNF Inhibitors in Rheumatoid Arthritis: Results from the Open-Label, Randomised Controlled Oral Surveillance Trial

Ann Rheum Dis. 2023;82(3):331–343 doi: 10.1136/ard-2022-222543

Curtis JR,

Yamaoka K,

Chen YH,

Bhatt DL,

Gunay LM,

Sugiyama N,

Connell CA,

Wang C,

Wu J,

Menon S,

Vranic I,

Gómez-Reino JJ

Results from the open-label, randomised controlled ORAL Surveillance trial find increased risk of malignancies with tofacitinib versus TNFi, highlighting the highest incidence in patients with a history of atherosclerotic cardiovascular disease or increasing cardiovascular risk.

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Malignancy

Impact of Cardiovascular Risk Enrichment on Incidence of Major Adverse Cardiovascular Events in the Tofacitinib Rheumatoid Arthritis Clinical Programme

Ann Rheum Dis. 2023;82(4):575–577 doi: 10.1136/ard-2022-223406

Dougados M,

Charles-Schoeman C,

Szekanecz Z,

Giles JT,

Ytterberg SR,

Bhatt DL,

Koch GG,

Vranic I,

Wu J,

Wang C,

Kwok K,

Menon S,

Connell CA,

Yndestad A,

Rivas JL,

Buch MH

Data suggest that an important difference between P123LTE and ORAL Surveillance was the proportion of patients with a history of atherosclerotic CV disease (ASCVD).

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Cardiovascular

Risk of MACE with Tofacitinib Versus TNFi in Patients with RA With or Without a History of Atherosclerotic CV: A Post Hoc Analysis from ORAL Surveillance

Ann Rheum Dis. 2022. doi: 10.1136/ard-2022-222259

Charles-Schoeman C,

Buch MH,

Dougados M,

Bhatt DL,

Giles JT,

Ytterberg SR,

Koch GG,

Vranic I,

Wu J,

Wang C,

Kwok K,

Menon S,

Rivas JL,

Yndestad A,

Connell CA,

Szekanecz Z.

Post hoc analysis from ORAL Surveillance observes higher major adverse cardiovascular events (MACE) risk with tofacitinib vs TNFi in patients with RA and history of atherosclerotic cardiovascular disease (ASCVD).

Keywords:

• JAK,
• Tildrakizumab,
• Safety,
• Cardiovascular

Infections in patients with rheumatoid arthritis receiving tofacitinib versus tumour necrosis factor inhibitors: results from the open-label, randomised controlled ORAL Surveillance trial

doi: 10.1136/ard-2022-222405

Balanescu AR,

Citera G,

Pascual-Ramos V,

Bhatt DL,

Connell CA,

Gold D,

Chen AS,

Sawyerr G,

Shapiro AB,

Pope JE,

Schulze-Koops H

Post hoc analysis, using the final dataset from ORAL Surveillance, reveals a higher risk of non-serious infections and herpes zoster with tofacitinib vs TNFi, and higher risk of serious infection events with tofacitinib 10 mg BID versus TNFi, particularly in patients aged ≥65 years.

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Infections

Cardiovascular and Cancer Risk With Tofacitinib in Rheumatoid Arthritis

N Engl J Med 2022;386:316–26. doi: 10.1056/NEJMc2202778

Ytterberg SR,

Bhatt DL,

Mikuls TR,

Koch GG,

Fleischmann R,

Rivas JL,

Germino R,

Menon S,

Sun Y,

Wang C,

Shapiro AB,

Kanik KS,

Connell CA

In this paper, Ytterberg et al. compare incidence of MACE and cancers (excluding NMSC) with tofacitinib 5 mg BID, tofacitinib 10 mg BID and TNFi. They found that risk of MACE and cancer were higher with tofacitinib versus TNFi, and did not meet noninferiority criteria.This prospective head-to-head safety trial compared tofacitinib to TNFi, and was required by the FDA after increases in lipid levels and cancers were observed during tofacitinib drug development. ...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Malignancy,
• Cardiovascular

Post-Approval Comparative Safety Study of Tofacitinib and Biological Disease-Modifying Antirheumatic Drugs: 5-Year Results from a United States–Based Rheumatoid Arthritis Registry

ACR Open Rheumatol. 2021 Feb 11.

Kremer JM,

Bingham CO 3rd,

Cappelli LC,

Greenberg JD,

Madsen AM,

Geier J,

Rivas JL,

Onofrei AM,

Barr CJ,

Pappas DA,

Litman HJ,

Dandreo KJ,

Shapiro AB,

Connell CA,

Kavanaugh A

Analysis from the US Corrona RA registry has provided the longest-term real-world safety data for a JAK inhibitor to date. The analysis showed that the cohorts had similar adverse events, except for higher herpes zoster rates for tofacitinib initiators vs bDMARDs.Kremer JM, et al. analysed adult patients with RA newly initiating tofacitinib, or a bDMARD, to compare incidence rates of MACE, SIEs, HZ, malignancies and death. VTE data were also collected prospectively and assessed descriptively thr...

Keywords:

• JAK,
• Tildrakizumab,
• Real-World

Age-Based (<65 vs ≥65 years) Incidence of Infections and Serious Infections with Tofacitinib Versus Biological DMARDs in Rheumatoid Arthritis Clinical Trials and the US Corrona RA Registry

Ann Rheum Dis 2020; DOI: 10.1136/annrheumdis-2020-218992

Winthrop KL,

Citera G,

Gold D,

Henrohn D,

Connell CA,

Shapiro AB,

Shi H,

Onofrei AM,

Pappas DA,

Schulze-Koops H

Reports from clinical trials and the US Corrona RA registry showed that serious infection event (SIE) incidence was higher in older versus younger patients with RA receiving 10 mg BID of TOF and ADA, however, SIE risk was similar between age groups with TOF 5 mg BID and ADA.Data were collected from Phase II–IV tofacitinib studies, and the US Corrona RA registry. The clinical data set evaluated patients receiving TOF 5 and 10 mg BID versus TNFi (ADA/ETN) in RA patients aged ≥50 years. The EMA rec...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Real-World,
• Infections