Upadacitinib increases risk of herpes zoster, serious infections and skin cancer in RA patients: BMJ

In a recent study examining the safety of upadacitinib in rheumatoid arthritis (RA) patients, researchers have reported an increased risk of serious adverse events (AEs) in individuals aged 50 years and above, with cardiovascular (CV) risk factors. The findings were published in the Annals of the Rheumatic Diseases.

The research analyzed data from six phase III clinical trials involving a total of 3209 patients receiving upadacitinib 15 mg once daily, 579 patients receiving adalimumab (a tumor necrosis factor inhibitor) with concomitant methotrexate (MTX), and 314 patients on MTX monotherapy. Approximately 54% of the patients were included in the higher-risk population, as they were aged 50 years and above and had at least one CV risk factor.

The findings showed that major adverse cardiovascular events (MACE), malignancies (excluding non-melanoma skin cancer), and venous thromboembolism (VTE) were more frequent in the higher-risk groups compared to the overall population. However, the incidence rates of these adverse events were similar between patients treated with upadacitinib and those treated with adalimumab.

Moreover, the study identified higher rates of serious infections in upadacitinib-treated patients within the higher-risk population. Additionally, upadacitinib showed increased rates of non-melanoma skin cancer (NMSC) and herpes zoster (HZ) across all populations compared to the comparators.

The study's post hoc analysis raises concerns about the safety of upadacitinib in RA patients aged 50 years and older with cardiovascular risk factors. While the risk of MACE, malignancies, and VTE was found to be comparable between upadacitinib and adalimumab, the higher rates of serious infections, NMSC, and HZ with upadacitinib demand careful consideration.

Rheumatoid arthritis is a chronic inflammatory disease that affects millions of people worldwide. The advent of novel therapies has improved patient outcomes significantly. However, the safety profiles of these drugs need continuous evaluation to ensure the well-being of patients.

The authors of the study emphasize the importance of individualized treatment decisions, taking into account the patient's age, CV risk factors, and overall health status. Additionally, close monitoring for potential adverse events is crucial during the course of therapy with upadacitinib or other targeted treatments.

Source:

Fleischmann, R., Curtis, J. R., Charles-Schoeman, C., Mysler, E., Yamaoka, K., Richez, C., Palac, H., Dilley, D., Liu, J., Strengholt, S., & Burmester, G. (2023). Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme. In Annals of the Rheumatic Diseases (p. ard-2023-223916). BMJ. https://doi.org/10.1136/ard-2023-223916