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.

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BackgroundUpadacitinib (UPA) was previously evaluated in two Phase 2, randomized, controlled trials (RCTs) in patients (pts) with rheumatoid arthritis (RA) and inadequate response to tumor necrosis factor inhibitors (BALANCE-1) or methotrexate (BALANCE-2).ObjectivesTo assess the final safety and efficacy of UPA in BALANCE-EXTEND, a 312-week open-label extension (OLE) enrolling pts who completed either BALANCE-1 or BALANCE-2.MethodsAll pts initially received UPA 6 mg twice daily (BID). Increase to 12 mg BID was required for pts with <20% improvement in swollen or tender joint counts (S/TJC) at Week 6 or 12, and permitted for those not achieving Clinical Disease Activity Index (CDAI) low disease activity (LDA). Pts with <20% improvement in SJC or TJC 6 weeks after escalation, or at any two consecutive visits, discontinued. Return to 6 mg BID was permitted for safety or tolerability reasons. After January 2017, the 6 and 12 mg BID doses were replaced by 15 and 30 mg once-daily (QD) extended-release equivalents. As-observed efficacy data are shown at Week 312 for three subgroups: pts who received 6 mg BID/15 mg QD throughout (“Never titrated”), those titrated up to 12 mg BID/30 mg QD for efficacy (“Titrated up”), and those titrated up to 12 BID/30 mg QD and then back to 6 mg BID/15 mg QD due to safety concerns (“Titrated up and down”). Exposure-adjusted adverse events (EAERs) per 100 patient-years (PY) of exposure were summarized from OLE Day 1 in all pts who received UPA (Any UPA).ResultsOverall, 493 pts entered the OLE, receiving UPA for ≤6.2 years (Never titrated, n=306; Titrated up, n=149; Titrated up and down, n=38), and 270 pts (54.8%) discontinued, mostly due to withdrawal of consent (16.8%; n=83) or AEs (14.6%; n=72). Mean (standard deviation) duration of UPA exposure was 3.8 (2.4) years (range <1–6.2 years); cumulative exposure was 1863 PY. The AE profile in pts receiving UPA 15 mg was generally similar to the Any UPA population, and to that observed in the Phase 3 UPA 15 mg clinical trial population (Table 1). Efficacy was maintained to Week 312, with 84.5% and 86.6% of pts in the Never titrated group achieving DAS28-CRP ≤3.2 and CDAI LDA, respectively (Figure 1).Table 1.Summary of AEs in pts who received UPA 6 mg BID/15 mg QD in the OLE and in the UPA 15 mg Phase 3 study programBALANCE-EXTEND (UPA 6 mg BID/15 mg QD)UPA 15 mg – Phase 3 programbEvents/100 PY (95 CI)aEvents/100 PY (95% CI)aN=493, PY=1277N=3209, PY=9079Any AE138.4 (132.0, 145.0)205.5 (202.5, 208.5)Any SAE7.9 (6.4, 9.6)12.4 (11.7, 13.2)AE leading to discontinuation4.2 (3.2, 5.5)4.9 (4.4, 5.3)Death0.4 (0.1, 0.9)0.5 (0.4, 0.7)cInfection49.2 (45.5, 53.2)63.9 (62.3, 65.6) Serious infection1.4 (0.8, 2.2)2.8 (2.4, 3.1) Opportunistic infection0.2 (0.0, 0.6)0.3 (0.2, 0.4) Herpes zoster2.0 (1.3, 3.0)3.0 (2.6, 3.3)Anemia1.1 (0.6, 1.8)3.0 (2.7, 3.4)Neutropenia1.3 (0.8, 2.1)2.1 (1.8, 2.5)Lymphopenia1.7 (1.1, 2.6)1.7 (1.4, 1.9)Gastrointestinal perforation0<0.1 (0.0, 0.1)Any malignancy1.2 (0.7, 1.9)1.1 (0.9, 1.4)Non-melanoma skin cancer (NMSC)0.4 (0.1, 0.9)0.4 (0.3, 0.5) Excluding NMSC0.8 (0.4, 1.4)0.7 (0.6, 0.9)Creatinine phosphokinase elevation3.4 (2.5, 4.6)4.4 (4.0, 4.9)Hepatic disorder4.1 (3.0, 5.3)10.2 (9.5, 10.8)Venous thromboembolism0.5 (0.2, 1.0)0.4 (0.3, 0.6)Major adverse cardiovascular event0.5 (0.2, 1.0)0.4 (0.3, 0.5)aMultiple events occurring in the same pts are counted in the calculation of events/100 PY. bCut-off, June 30, 2021. cBased on 9080 PY.ConclusionIn this OLE, UPA treatment over ~312 weeks showed sustained long-term efficacy in pts with RA who had completed Phase 2 RCTs. Overall safety results showed that UPA was well tolerated over time; the types and frequencies of AEs were consistent with those in pts with similar populations of moderately to severely active RA receiving Janus kinase inhibitors.AcknowledgementsAbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the abstract. AbbVie and the authors thank all study investigators for their contributions and the patients who participated in this study. No honoraria or payments were made for authorship. Medical writing support was provided by Dan Booth, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of InterestsAlan Kivitz Shareholder of: Amgen, Gilead, GlaxoSmithKline, Novartis, Pfizer, and Sanofi (stocks or options), Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Flexion, Genzyme, Gilead, Horizon, Janssen, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sanofi Aventis, SUN Pharma Advanced Research, and UCB, Grant/research support from: AbbVie (his institution received fees for his role as a Principal Investigator in the study), Alvin F. Wells Consultant of: AbbVie, Juan Ignacio Vargas Consultant of: AbbVie, Grant/research support from: AbbVie (as a Principal Investigator in the study), Herbert S.B. Baraf Consultant of: Gilead and Janssen, Grant/research support from: AbbVie, Eli Lilly, Genentech, Gilead, and Janssen, Maureen Rischmueller Consultant of: AbbVie, Bristol-Myers Squibb, CSL Behring, Eli Lilly, Gilead Sciences, Janssen Global Services, Pfizer, Sanofi US Services, and UCB Biosciences, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen Global Services, Novartis, Pfizer, Sanofi Pasteur Biologics, and UCB Biosciences, Justin Klaff Shareholder of: AbbVie (may own stocks or options), Employee of: AbbVie, Nasser Khan Shareholder of: AbbVie (may own stocks or options), Employee of: AbbVie, Yihan Li Shareholder of: AbbVie (may own stocks or options), Employee of: AbbVie, Kyle Carter Shareholder of: AbbVie (may own stocks or options), Employee of: AbbVie, Alan Friedman Shareholder of: AbbVie (may own stocks or options), Employee of: AbbVie, Patrick Durez Speakers bureau: Eli Lilly and Galapagos

2 and -5.6) for CZP 200mg Q2W and 400mg Q4W patients, respectively. ConClusions: Improvements in generic and disease-specific PROs observed over 24 wks were sustained over 48 wks in CZP-treated PsA pts. Improvements were observed regardless of CZP dose regimen. PMS82 ExPanding thE MEaSurEMEnt of trEatMEnt BEnEfit in rhEuMatoid arthritiS: thE rolE of thE PatiEnt-rEPortEd outcoME conSortiuM'S ra Working grouP