POS1048 SAFETY AND EFFICACY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE TYROSINE KINASE 2 INHIBITOR, IN PATIENTS WITH PSORIATIC ARTHRITIS: 52-WEEK RESULTS FROM A RANDOMISED PHASE 2 TRIAL

Abstract

BackgroundDeucravacitinib (DEUC) is a novel, oral, selective, allosteric inhibitor of tyrosine kinase 2 (TYK2) that acts by binding to the unique TYK2 regulatory domain, thereby suppressing signalling of key cytokines (eg, IL-23) involved in skin psoriasis and psoriatic arthritis (PsA) pathogenesis. Results from the initial 16-week (wk), placebo (PBO)-controlled period (Part A) of a 52-wk, blinded Phase 2 trial in PsA showed that DEUC was significantly more efficacious than PBO.1 The Psoriatic Arthritis Disease Activity Score (PASDAS), a validated comprehensive measure assessing a variety of PsA clinical domains, was used to assess efficacy of DEUC up to 52 wks.ObjectivesEvaluate the safety and efficacy of DEUC in Part B (Wks 16-52) in the Phase 2 PsA trial.MethodsPatients (pts) with PsA were randomised 1:1:1 to PBO, DEUC 6 mg once daily (QD), or 12 mg QD. After Wk 16 (Part A), pts could enrol in an optional, double-blind period until Wk 52 (Part B). In Part B, pts receiving DEUC who had achieved minimal disease activity (MDA) at Wk 16 continued DEUC treatment and those who had not achieved MDA were switched to ustekinumab (UST) at the approved PsA dose. All pts treated with PBO in Part A switched to UST in Part B. Pts were assessed up to 52 wks for adverse events (AEs) and exploratory efficacy endpoints including change in PASDAS. Analyses were descriptive using data as observed.ResultsOf 203 pts randomised in Part A, 180 (89%) completed 16 wks of treatment and 173 (96%) of these pts chose to enrol in Part B. Of 118 pts initially randomised to DEUC, 25% (29/118; 6 mg QD, 22% [13/60]; 12 mg QD, 28% [16/58]) achieved MDA at Wk 16 and continued at the same dose. All other pts switched to UST in Part B: PBO, 100% (55/55; including 5 pts who had achieved MDA at Wk 16); DEUC 6 mg QD, 78% (47/60); DEUC 12 mg QD, 72% (42/58). The safety profile of DEUC in Part B (Table 1) was consistent with that in Part A, and all AEs were mild or moderate except 2 AEs in 1 pt with severe cataract/macular fibrosis. There were no opportunistic infections, herpes zoster, malignancy, thrombotic events, or treatment-related serious AEs reported in pts who remained on DEUC. Decreases in mean PASDAS score observed at Wk 16 were maintained at Wk 52 in pts who continued on DEUC (Figure 1). Improvements in other outcomes, including ACR components, PASI, and FACIT-Fatigue, were also sustained at Wk 52 in pts who continued DEUC treatment. Pts who had not achieved MDA on DEUC at Wk 16 showed a decrease in mean PASDAS score at Wk 52 after switching to UST.Table 1.Overall summary of safety in Part B (Weeks 16 to 52)AE, n (%)aDEUC 6 mg QD n = 13DEUC 12 mg QD n = 16DEUC 6 mg QD →UST n = 47DEUC 12 mg QD → UST n = 42PBO → UST n = 55Total AEs11 (84.6)8 (50.0)26 (55.3)26 (61.9)30 (54.5)Deaths001 (2.1)d1 (2.4)d0SAE1 (7.7)b03 (6.4)4 (9.5)0Treatment-related SAE00000Discontinued due to AE01 (6.3)c02 (4.8)c,e0Includes all treated patients in Part B. Medical Dictionary for Regulatory Activities version 23.0 was used. an is the number of patients who experienced an event. bOne patient had SAEs of psoriatic arthropathy in 1 joint and peripheral neuropathy. cPatient had an AE of COVID-19 infection leading to discontinuation. dDeaths in UST arms were due to car accident and sudden death in a 71-year-old patient with hypertension. ePatient had an AE of urinary tract infection leading to discontinuation.AE, adverse event; DEUC, deucravacitinib; PBO, placebo; QD, once daily; SAE, serious adverse event; UST, ustekinumab.ConclusionIn the 16- to 52-wk blinded Part B of a Phase 2 study in pts with PsA, no new safety signals were observed with continuous DEUC treatment vs the earlier Part A period. Efficacy in PASDAS, as well as other key efficacy measures, was maintained with continued DEUC treatment through Wk 52.