Comparable risk of major adverse cardiovascular events in patients with autoimmune diseases receiving upadacitinib, methotrexate and adalimumab

Upadacitinib is a Janus kinase (JAK) inhibitor proven to be an effective treatment for adults with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis, and ulcerative colitis. Additionally, it has demonstrated effectiveness in treating both adults and adolescents with atopic dermatitis. 

According to a recent study published in Rheumatic and Musculoskeletal Diseases Open, the rates of venous thromboembolism (VTE) events and major adverse cardiovascular events (MACEs) associated with upadacitinib were equivalent to those of active comparators methotrexate and adalimumab. These rates were consistent with previously published data for patients using traditional synthetic and biologic disease-modifying antirheumatic medications. 

The study, conducted by Charles-Schoeman and colleagues, analyzed and summarized data from clinical trials of RA, PsA, and AS patients treated with upadacitinib 15 mg QD and 30 mg QD as of June 30th, 2021. The analysis also included data from the adalimumab and methotrexate arms as comparators. A total of 4298 patients received upadacitinib 15 mg (RA n=3209, PsA n=907, and AS n=182), and 2125 patients received upadacitinib 30 mg (RA n=1204 and PsA n=921). The study found that rates of MACE and VTE were similar across upadacitinib doses in RA and PsA patients, while no MACEs and only one VTE event occurred in AS patients. Most patients who experienced MACEs or VTE events had two or more baseline cardiovascular risk factors. Furthermore, rates of MACEs and VTE events were similar across RA and PsA groups. 

In the ORAL Surveillance trial, which focused on RA patients aged 50 and older with at least one cardiovascular risk factor, a combination of tofacitinib doses (5 and 10 mg) did not meet non-inferiority standards compared to tumor necrosis factor (TNF) inhibitor therapy in terms of incidence rates for MACE and malignancy, excluding non-melanoma skin cancer. Following a post hoc analysis of the study, it was found that the 10 mg dose of tofacitinib had a slightly increased risk of VT) compared to patients using TNF inhibitor therapy, irrespective of a history of atherosclerotic cardiovascular disease. Furthermore, the 5 mg dose of tofacitinib exhibited a trend towards an increased risk of MACE in patients with a history of atherosclerotic cardiovascular disease, though this trend was not observed in those without such a history. 

 The study offers a comprehensive understanding of the medication’s safety profile and may assist clinicians in treatment decision-making. By considering factors such as the patient’s specific autoimmune condition, baseline cardiovascular risk factors, and potential predisposition to adverse events, clinicians can better identify suitable candidates for upadacitinib therapy. 


  1. Charles-Schoeman C, Choy E, McInnes IB, Mysler E, Nash P, Yamaoka K, et al. MACE and VTE across upadacitinib clinical trial programmes in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. RMD Open. 2023 Nov;9(4):e003392.  
  1. Ytterberg SR, Bhatt DL, Mikuls TR, Koch GG, Fleischmann R, Rivas JL, et al. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. New England Journal of Medicine. 2022 Jan 27;386(4):316–26.