AT A GLANCE

A new study published in Advances in Therapy reports on the long-term safety of upadacitinib in seven chronic diseases.¹

As part of a descriptive analysis, study authors Burmester et al. sought to uncover the long-term safety of upadacitinib (oral, selective, and reversible Janus kinase inhibitor) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), atopic dermatitis (AD), Crohn's disease (CD), and ulcerative colitis (UC).

For study purposes, data from 16 studies (data cutoff, August 15, 2024) were analyzed. Each treatment group was pooled across studies within each indication, and active comparator arms included adalimumab (RA/PsA) and methotrexate (RA). Treatment-emergent adverse events (TEAEs) were reported as exposure-adjusted incidence rates per 100 patient-years (n/100 PY).

Ultimately, the analysis included 8632 upadacitinib-treated patients (RA, n = 3209; PsA, n = 907; AS, n = 596; nr-axSpA, n = 286; AD, n = 2683; CD, n = 450; UC, n = 501) over 27,164.2 patient-years (range, 199.4–12,315.8 PY across indications).

Rates (n/100 PY) of any TEAEs ranged from 112.0 (AS) to 401.1 (RA), with the most frequently reported TEAEs including COVID-19, upper respiratory tract infection, nasopharyngitis, herpes zoster, urinary tract infection, and acne. Separately, rates of serious TEAEs ranged from 4.5 (AD) to 11.0 (UC), with rates of those leading to discontinuation ranging from 2.9 (AS) to 8.3 (UC). Finally, rates of TEAEs leading to death ranged from 0 (nr-axSpA, UC) to 0.7 (RA).

Among upadacitinib-treated patients across indications, rates of adverse events of special interest ranged from 1.3–4.6 (serious infection), 2.4–6.6 (herpes zoster), 0.2–0.9 (malignancy excluding non-melanoma skin cancer [NMSC]), 0–1.4 (NMSC), 0–0.5 (major adverse cardiovascular events [MACEs]), 0–0.9 (venous thromboembolism [VTE]), and 0–9.2 (elevated creatine kinase).

The authors note that, in RA and PsA, rates of herpes zoster, NMSC, and elevated creatine kinase levels were numerically higher with upadacitinib versus the active comparators. Meanwhile, rates of serious infections, herpes zoster, malignancies (excluding NMSC), NMSC, MACE, and VTE remained stable over time.

“This descriptive analysis indicates a long-term safety profile of upadacitinib consistent with previous reports, further supporting long-term treatment of chronic diseases with upadacitinib. Variations in TEAE rates across indications likely reflected differences in populations and underlying comorbidities,” conclude the authors.

Reference

1.     Burmester GR, Deodhar A, Irvine AD, et al. Safety Profile of upadacitinib: descriptive analysis in over 27,000 patient-years across rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, and inflammatory bowel disease (online ahead of print August 28, 2025. Adv Ther.