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.References[1]Mease PJ et al. Efficacy and Safety of Selective TYK2 Inhibitor, Deucravacitinib, in a Phase 2 Trial in Psoriatic Arthritis. Ann Rheum Dis. (In Press).AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Julianne Hatfield, PhD at Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Bristol Myers Squibb. The authors acknowledge Jonghyeon Kim, PhD, who was employed by Bristol Myers Squibb at the time the study was conducted, for his statistical assistance.Disclosure of InterestsPhilip J Mease Consultant of: Consulting and/or speaker fees: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB., Grant/research support from: Research grants: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB;, Atul Deodhar Consultant of: Consulting and/or advisory boards: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, MoonLake, Novartis, Pfizer, UCB, Grant/research support from: Research grants: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB., Désirée van der Heijde Consultant of: Consulting fees: AbbVie, Bayer, Bristol Myers Squibb, Cyxone, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB Pharma; Director: Imaging Rheumatology BV., Frank Behrens Consultant of: Consultancies/speaker fees: AbbVie, Amgen, Boehringer, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly, Boehringer, Sandoz, and Sanofi., Grant/research support from: Research Support: AbbVie, Pfizer, Roche, Chugai, Prophylix, Novartis, and Amgen, Alan Kivitz Shareholder of: Shareholder: Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc., Novartis, Consultant of: Paid Consultant: AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc., Speakers bureau: Celgene, Merck, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion, AbbVie., Jeffrey Neal Grant/research support from: Research grants to foundation: AbbVie, Amgen, Eli Lilly, Genentech, Novartis, UCB, Pfizer, Gilead, and Bristol Myers Squibb., Marleen Nys Shareholder of: Bristol Myers Squibb., Employee of: Bristol Myers Squibb., Thomas Lehman Shareholder of: Bristol Myers Squibb., Employee of: Bristol Myers Squibb., Nikolay Delev Shareholder of: Bristol Myers Squibb., Employee of: Bristol Myers Squibb., Shimon Korish Shareholder of: Bristol Myers Squibb., Employee of: Bristol Myers Squibb., Miroslawa Nowak Shareholder of: Bristol Myers Squibb., Employee of: Bristol Myers Squibb., Subhashis Banerjee Shareholder of: Bristol Myers Squibb., Employee of: Bristol Myers Squibb.

Deucravacitinib for the treatment of psoriatic arthritis: the evidence so far

“…In a phase II clinical trial including patients with active PsA, deucravacitinib, given at 6 mg or 12 mg daily, showed higher efficacy in several domains of PsA, namely arthritis, enthesitis and dactylitis. 29 , 30 Furthermore, an improvement in multiple patient-reported outcomes, including physical function (assessed by HAQ) and quality of life (assessed by SF-36 PCS), was observed as early as week 4 of treatment. 29 On the psoriasis development programme, deucravacitinib showed a higher efficacy versus apremilast.…”

“…All other patients switched to ustekinumab in part B, 100% ( n =55) from the placebo group, 78% (47/60 patients) from the deucravacitinib 6 mg group and 72% (42/58 patients) from the deucravacitinib 12 mg group. 30 …”

“…Improvements in other outcomes, namely ACR responses, PASI, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and DAPSA, were also sustained at week 52. 30 …”

“…No thrombotic events, opportunistic infections, herpes zoster, malignancy or death were reported in patients treated with long-term deucravacitinib. 30 …”