Safety Profile Similar in Upadacitinib and Adalimumab for Patients With PsA

Upadacitinib 15 mg and adalimumab reported similar safety profiles, including malignancies, venous thromboembolic events (VTEs), major adverse cardiovascular events (MACEs), and death, in patients with psoriatic arthritis (PsA), according to a study published in Springer.¹ Exceptions included rates of opportunistic infections (OIs) and herpes zoster (HZ). No new safety risks were observed with longer-term upadacitinib treatment.

“As the therapeutic landscape for PsA evolves, evaluating the long-term safety of treatments is essential to understand benefit–risk profiles and inform patient care,” investigators explained.

Data was collected from 2 randomized, placebo-controlled phase 3 trials, SELECT-PsA 1 (NCT03104400) and SELECT-PsA 2 (NCT03104374). Patients received either upadacitinib 15 mg daily, upadacitinib 30 mg daily, adalimumab 40 mg every other week (SELECT-PsA 1 only), or placebo until Week 24, followed by upadacitinib 15 mg or 30 mg daily. Eligible patients were aged 18 years or older and had active PsA with an inadequate response or intolerance to 1 or more non-biologic (SELECT-PsA 1) or biologic (SELECT-PsA 2) disease-modifying antirheumatic drug (DMARD). Patients were followed for up to 3 years.

Treatment-emergent adverse events (TEAEs) and laboratory data, including hematology and chemistry values, were compared across treatment groups. Adverse events (AEs) were determined by the Common Terminology Criteria for Adverse Events (CTCAE) and adverse events of special interest (AESIs) were assessed.

A total of 907 patients received at least 1 dose of upadacitinib 15 mg, 921 patients received at least 1 dose of upadacitinib 30 mg, and 429 were placed in the adalimumab group. The average duration of disease was 6 to 8 years, and most were treated concomitantly with methotrexate (MTX). Demographics and disease characteristics were similar among all groups.

TEAEs were higher in the upadacitinib 30 mg group. However, rates were comparable in both upadacitinib 15 mg and adalimumab cohorts. The most common TEAE was upper respiratory tract infection. Discontinuation rates due to AEs were similar across all groups.

Serious infections occurred more frequently in patients treated with upadacitinib 30 mg (5.2 E/100 PY) when compared with both upadacitinib 15 mg (2.3 E/100 PY) and adalimumab (1.3 E/100 PY). Pneumonia was the most common serious infection reported.

HZ rates were higher in both upadacitinib groups when compared with adalimumab. However, they were more frequent in those receiving upadacitinib 30 mg and were non-serious. Fewer than 1% of participants permanently discontinued upadacitinib due to developing HZ.

OIs, the most common of which was mucosal candida infection, were only observed in patients receiving upadacitinib, with higher rates in the upadacitinib 30 mg cohort.

Hepatic disorders were similar between upadacitinib groups and higher in patients treated with adalimumab. Apart from 4 patients, cases were temporary and non-serious.

Malignancies observed were those expected in patients with PsA and were seen at similar rates across both upadacitinib and adalimumab groups. MACE and VTE, all of which were non-fatal, were comparable across groups. Additionally, patients receiving upadacitinib who reported MACE or VTE had ≥ 1 risk factor at baseline.

CTCAE grade 3 or grade 4 were infrequent across all treatment groups. However, a decrease in lymphocytes and an increase in creatine phosphokinase (CPK) were higher in patients receiving upadacitinib when compared with adalimumab or placebo. Most changes did not lead to discontinuation of treatment.

Anemia was seen more in the upadacitinib 30 mg group. Neutropenia was lower in the upadacitinib 15 mg cohort; however, rates were similar for those receiving upadacitinib 30 mg and adalimumab.

Information regarding long-term exposure to upadacitinib compared with placebo could not be evaluated. However, adalimumab data can be utilized to compare upadacitinib with standard PsA therapy. Further, a level of bias may have been introduced as sample size variations and exposure time were greater in the upadacitinib group.

“These results support an acceptable safety profile of upadacitinib 15 mg for the treatment of PsA in patients who had an inadequate response or intolerance to ≥ 1 non-biologic or biologic DMARD. The safety of upadacitinib will continue to be monitored in the long-term extensions of the SELECT-PsA trials.”

Reference:

Burmester GR, Winthrop K, Blanco R, et al. Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials [published online ahead of print, 2021 Dec 30]. Rheumatol Ther. 2021;1-19. doi:10.1007/s40744-021-00410-z