Malignancy in the Upadacitinib Clinical Trials for Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis

Andrea Rubbert-Roth; Adriana M Kakehasi; Tsutomu Takeuchi; Marc Schmalzing; Hannah Palac; Derek Coombs; Jianzhong Liu; Samuel I Anyanwu; Ralph Lippe; Jeffrey R Curtis

doi:10.1007/s40744-023-00621-6

Malignancy in the Upadacitinib Clinical Trials for Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis

Rheumatol Ther. 2024 Feb;11(1):97-112. doi: 10.1007/s40744-023-00621-6. Epub 2023 Nov 20.

Authors

Affiliations

¹ Division of Rheumatology, Cantonal Clinic St Gallen, Rorschacherstrasse 95, St Gallen, Switzerland. andrea.rubbert-roth@kssg.ch.
² Hospital das Clínicas, Federal University of Minas Gerais, Belo Horizonte, Brazil.
³ Keio University School of Medicine, Tokyo, Japan.
⁴ Saitama Medical University, Saitama, Japan.
⁵ Rheumatology/Clinical Immunology, Department of Internal Medicine II, University of Wϋrzburg, Würzburg, Germany.
⁶ AbbVie Inc., North Chicago, IL, USA.
⁷ AbbVie Deutschland GmbH & Co. KG, Wiesbaden, Germany.
⁸ Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.

Abstract

Introduction: This article aims to describe malignancies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) treated with upadacitinib (UPA) or active comparators.

Methods: This integrated safety analysis includes data from 11 phase 3 UPA trials across RA (6 trials), PsA (2 trials), AS (2 trials; one phase 2b/3), and nr-axSpA (1 trial). Treatment-emergent adverse events (TEAEs) were summarized for RA (pooled UPA 15 mg [UPA15], pooled UPA 30 mg [UPA30], adalimumab 40 mg [ADA], methotrexate monotherapy [MTX]), PsA (pooled UPA15, pooled UPA30, ADA), AS (pooled UPA15), and nr-axSpA (UPA15). TEAEs were reported as exposure-adjusted event rates (events/100 patient-years).

Results: Median treatment duration ranged from 1.0 to 4.0 years (with a maximum of 6.6 years in RA). Across treatments and indications, rates of malignancy excluding nonmelanoma skin cancer (NMSC) ranged from 0.2 to 1.1, while NMSC ranged from 0.0 to 1.4. In RA, rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX (breast and lung cancer were the most common). In RA and PsA, Kaplan-Meier analyses revealed no differences in event onset of malignancy excluding NMSC with UPA15 versus UPA30 over time. In RA, NMSC rates were higher with UPA30 than UPA15; both UPA15 and UPA30 were higher than ADA and MTX. In PsA, rates of malignancy excluding NMSC and NMSC were generally similar between UPA15, UPA30, and ADA. In AS and nr-axSpA, malignancies were reported infrequently. Few events of lymphoma were reported across the clinical programs.

Conclusion: Rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX and were consistent across RA, PsA, AS, and nr-axSpA. A dose-dependent increased rate of NMSC was observed with UPA in RA.

Trial registration: ClinicaTrials.gov identifier: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847, NCT03086343, NCT03104400, NCT03104374, NCT03178487, and NCT04169373.

Keywords: Ankylosing spondylitis (AS); Janus kinase (JAK) inhibitor; Malignancy; Non-radiographic axial spondyloarthritis (nr-axSpA); Nonmelanoma skin cancer (NMSC); Psoriatic arthritis (PsA); Rheumatoid arthritis (RA); Risk factors; Spondyloarthritis (SpA); Upadacitinib (UPA).

Associated data

ClinicalTrials.gov/NCT02706873
ClinicalTrials.gov/NCT02675426
ClinicalTrials.gov/NCT02629159
ClinicalTrials.gov/NCT02706951
ClinicalTrials.gov/NCT02706847
ClinicalTrials.gov/NCT03086343
ClinicalTrials.gov/NCT03104400
ClinicalTrials.gov/NCT03104374
ClinicalTrials.gov/NCT03178487
ClinicalTrials.gov/NCT04169373