Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials.

Abstract

BACKGROUND:

Upadacitinib (UPA) is an oral Janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis (RA). JAK inhibitors have been associated with an increased risk of herpes zoster (HZ) in patients with RA.

OBJECTIVES:

To evaluate the incidence and risk factors for HZ in UPA-treated patients with RA from the UPA phase III clinical trial programme.

METHODS:

Exposure-adjusted incidence/event rates for HZ were determined in patients receiving UPA (monotherapy or combination therapy) in six randomised phase III trials (data cut-off on 30 June 2020). HZ incidence and event rates were also determined in patients receiving methotrexate (MTX) monotherapy or adalimumab (ADA) + MTX. Multivariable Cox regression analysis was used to identify HZ risk factors in UPA-treated patients.

RESULTS:

A total of 5306 patients were included in this analysis. The incidence rate of HZ/100 patient-years (95% CI) was 0.8 (0.3 to 1.9), 1.1 (0.5 to 1.9), 3.0 (2.6 to 3.5) and 5.3 (4.5 to 6.2), in the MTX monotherapy, ADA + MTX, UPA 15 mg and UPA 30 mg groups, respectively. The majority of HZ cases with UPA (71%) involved a single dermatome. Prior history of HZ and Asian region were HZ risk factors in UPA-treated patients.

CONCLUSION:

In the UPA phase III RA clinical programme, HZ incidence and event rates were higher with UPA versus ADA + MTX or MTX monotherapy, and higher with the 30 mg versus 15 mg dose. Patients from Asia and those with a history of HZ may be at increased risk of HZ while receiving UPA.

• Authors: Kevin L Winthrop, Peter Nash, Kunihiro Yamaoka, Eduardo Mysler, Nasser Khan, Heidi S Camp, Yanna Song, Jessica L Suboticki, Jeffrey R Curtis
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 81 Issue 2 Pg. 206-213 (02 2022) ISSN: 1468-2060 [Electronic] England
• PMID: 34615638 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Antirheumatic Agents
• Heterocyclic Compounds, 3-Ring
• Janus Kinase Inhibitors
• upadacitinib

Topics

• Adult
• Aged
• Antirheumatic Agents (adverse effects)
• Arthritis, Rheumatoid (drug therapy)
• Clinical Trials, Phase III as Topic
• Female
• Herpes Zoster (chemically induced, epidemiology)
• Heterocyclic Compounds, 3-Ring (adverse effects)
• Humans
• Incidence
• Janus Kinase Inhibitors (adverse effects)
• Male
• Middle Aged
• Risk Factors