Analysis Finds Similar Safety Profile with Upadacitinib Across Conditions

The Janus kinase (JAK) inhibitor upadacitinib offers a similar long-term safety profile across rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and atopic dermatitis (AD) despite some variations in adverse events, according to an integrated safety analysis published in RMD Open.

“This safety analysis of 6991 patients receiving upadacitinib with a maximum of 5.45 years of follow-up appears largely consistent across RA, PsA, AS, and AD for key adverse events of special interest such as major adverse cardiovascular events, venous thromboembolism, and malignancy excluding non-melanoma skin cancer, and no new or unexpected safety risks were identified compared with previous reports,” wrote corresponding author Gerd R. Burmester, MD, of Charité Universitätsmedizin Berlin in Germany and study coauthors.

For any treatment-emergent adverse event, exposure-adjusted event rates per 100 patient years ranged from 205.5 with upadacitinib 15 mg in patients with RA to 278.1 with upadacitinib 30 mg in patients with AD, according to the study. For treatment-emergent adverse events leading to upadacitinib discontinuation, exposure-adjusted event rates per 100 patient years ranged from 4.5 to 5.4. Serious treatment-emergent adverse events were numerically higher in patients with RA and PsA.

The analysis found that rates of herpes zoster, non-melanoma skin cancer, and elevations in creatine phosphokinase levels were higher with upadacitinib than with active comparators in studies of patients with RA and PsA. Deaths, serious infections, major adverse cardiovascular events, venous thromboembolism, and malignancies occurred; rates tended to be lowest in patients with AS and AD.

Patients with AD had increased rates of acne.

“Some variations in events were observed across diseases, possibly reflecting differences in patient populations and disease-associated comorbidities that impact background risk,” researchers wrote. “Follow-up of patients receiving upadacitinib will continue as these trials are ongoing.”

Reference

Burmester GR, Cohen SB, Winthrop KL, et al. Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. RMD Open. 2023;9(1):e002735. doi:10.1136/rmdopen-2022-002735