In an abstract presented at EULAR 2020, investigators find more serious adverse events in the upadacitinib treatment arms compared to placebo.
Mark C. Genovese, MD
Upadacitinib (UPA), an oral, reversible, JAK inhibitor currently approved for treatment of moderate to severe rheumatoid arthritis, might also be effective to treat psoriatic arthritis (PsA).
In data planned for presentation during the European Congress of Rheumatology (EULAR) 2020 meeting, a team, led by Mark C. Genovese, MD, Division of Immunology & Rheumatology, Stanford University School of Medicine, assessed the efficacy and safety of upadacitinib compared to placebo in patients with psoriatic arthritis with prior inadequate response or intolerance to at least 1 biologic disease-modifying anti-rheumatic drug (bDMARD).
In the SELECT-PsA-2 trial, 641 patients were equally randomized to receive upadacitinib 15 mg (UPA15), 30 mg (UPA30), or placebo. The investigators stratified patients by baseline biologic disease-modifying anti-rheumatic drug use, number of failed attempts, and extent of psoriasis.
The mean age of the study population was 53.4 years old and the mean duration since PsA diagnosis was 10.1 years. Of the included patients, 61% failed at least 1 bDMARD, 18% failed 2 bBMARDs, and 13% failed at least 3 bBMARDs. In addition, 543 patients completed the 24 week study period with the intended study drug.
The team sought primary endpoints of the proportion of patients achieving ACR20 response at week 12.
They also sought multiplicity controlled secondary endpoints, such as change in HAQ-DI, FACIT-Fatigue (FACIT-F), and SF-36 Physical Component Summary (PCS) at week 12, static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at least a 2-point improvement from baseline, PASI75, and change in Self-Assessment of Psoriasis Symptoms (SAPS) at week 16, and proportion of patients achieving MDA at week 24.
There were also additional secondary endpoints including ACR50 and ACR70 at week 12 and ACR20 at week 2.
The investigators also reported treatment-emergent adverse events for patients who received at least 1 dose of the study drug.
Overall, a significantly greater proportion receiving either dosage of upadacitinib compared to placebo achieved ACR20 at week 12 (56.9% and 63.8% vs 24.1%; P < .0001 for both comparisons).
The investigators observed statistically significant improvements in both upadacitinib treatment arms compared to placebo in all multiplicity controlled secondary endpoints including ΔHAQ-DI (PBO, -0.10; UPA15, -0.30; UPA30, -0.41), ΔSF-36 PCS (PBO, 1.6; UPA15, 5.2; UPA30, 7.1), ΔFACIT-F (PBO, 1.3; UPA15, 5.0; UPA30, 6.1), and ΔSAPS (PBO, -1.5; UPA15, -24.4; UPA30, -29.7; P < .0001 for all endpoints).
They also saw a greater proportion of patients achieving ACR50 and ACR70 at week 12 receiving the study treatment than placebo.
Treatment-emergent adverse events were reported at similar frequencies between the placebo and UPA15 groups, but were reported at a higher frequency in the UPA30 arm. Also, higher frequencies of serious adverse events were
reported in both treatment arms, with herpes zoster more frequently found in the UPA30 arm.
The investigators also observed 3 malignancies in each of the UPA arms and 1 adjudicated non-fatal myocardial infarction and 1 adjudicated pulmonary embolism in the UPA15 arm.
“In this bDMARD-IR PsA population, UPA15 and UPA30 demonstrated significant improvements across PsA domains including improvements in joint and skin signs and symptoms vs PBO through week 24 with improvement observed by week 2,” the authors wrote. “A greater percentage of pts treated with UPA achieved MDA and ACR50/70, stringent composite measures of disease control. No new safety signals were identified compared to what has been observed with UPA in RA.”
The study, “Efficacy and Safety of Upadacitinib in Patients with Active Psoriatic Arthritis and Inadequate Response to Biologic Disease-Modifying Anti-Rheumatic Drugs (SELECT-PSA-2): a Double-Blind, Randomized Controlled Phase 3 Trial,” was published online by EULAR.