Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials

Abstract

Introduction: This integrated analysis describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, at 15 and 30 mg once daily for up to 3 years of exposure in patients with active psoriatic arthritis (PsA) who had a prior inadequate response or intolerance to ≥ 1 non-biologic or biologic disease-modifying antirheumatic drug.

Methods: Safety data were pooled and analyzed from two randomized, placebo-controlled phase 3 trials. Both trials evaluated upadacitinib 15 mg and 30 mg once daily, and one trial also evaluated adalimumab 40 mg every other week. Treatment-emergent adverse events (TEAEs) and laboratory data were summarized for four groups: pooled placebo, pooled upadacitinib 15 mg, pooled upadacitinib 30 mg, and adalimumab. TEAEs were reported as exposure-adjusted event rates (events per 100 patient-years [E/100 PY]) up to a data cut-off of June 29, 2020.

Results: A total of 2257 patients received ≥ 1 dose of upadacitinib 15 mg (N = 907) or 30 mg (N = 921) for 2504.6 PY of exposure or adalimumab (N = 429) for 549.7 PY of exposure. Upper respiratory tract infection, nasopharyngitis, and increased creatine phosphokinase (CPK) were the most common TEAEs with upadacitinib. Rates of malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs), and deaths were similar across treatment groups. Rates of herpes zoster (HZ) and opportunistic infections (OI; excluding tuberculosis, HZ, and oral candidiasis) were higher with upadacitinib versus adalimumab. Serious infection, anemia, and CPK elevations were most frequent with upadacitinib 30 mg. Potentially clinically significant laboratory abnormalities were uncommon.

Conclusions: Upadacitinib 15 mg and adalimumab had similar safety profiles with the exception of HZ and OIs, consistent with what was observed in rheumatoid arthritis. Rates of malignancies, MACEs, VTEs, and deaths were comparable among patients receiving upadacitinib and adalimumab. No new safety risks emerged with longer-term exposure to upadacitinib.

Trial registration numbers: SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374.

Keywords: Adalimumab; JAK inhibitor; Psoriatic arthritis; SELECT-PsA 1; SELECT-PsA 2; Safety; Upadacitinib.

© 2021. The Author(s).

Figures

Fig. 1

Event rates per 100 patient years for adverse events of special interest (a–l). Events are presented as exposure-adjusted event rates per 100 patient-years (E/100 PY), calculated as the total number of events adjusted for total exposure to UPA, ADA, or PBO. UPA 15 mg and UPA 30 mg QD groups include patients who were originally assigned to UPA and patients originally assigned to PBO who switched to UPA at week 24. aOpportunistic infections excluded tuberculosis, herpes zoster, and oral candidiasis. bMACE was defined as CV death, non-fatal MI, and non-fatal stroke. cVTE was defined as deep vein thrombosis and pulmonary embolism. ADA adalimumab, CPK creatine phosphokinase, E/100 PY event per 100 patient-years, EOW every other week, MACE major adverse cardiovascular event, MI myocardial infarction, NMSC non-melanoma skin cancer, PBO placebo, UPA upadacitinib, VTE venous thromboembolism

Fig. 2

Mean changes in hemoglobin, platelets, neutrophils, and lymphocytes levels (a–d). Baseline mean includes patients with non-missing baseline and at least one post-baseline value. ADA adalimumab, EOW every other week, UPA upadacitinib