2202: Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, in Patients with Moderate to Severe Psoriasis: Long-Term Efficacy in Placebo Crossovers

Richard B. Warren¹, Mark Lebwohl², Shinichi Imafuku³, Jerry Bagel⁴, April W. Armstrong⁵, Thierry Passeron⁶, Misti Linaberry⁷, Kim Hoyt⁷, Andrew Napoli⁷, Renata M. Kisa⁷, Diamant Thaçi⁸ and Andrew Blauvelt⁹, ¹Dermatology Centre, Northern Care Alliance NHS Foundation Trust; NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom, ²Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, ³Fukuoka University Faculty of Medicine, Fukuoka, Japan, ⁴Psoriasis Treatment Center of New Jersey, East Windsor, NJ, ⁵Keck School of Medicine of University of Southern California, Los Angeles, CA, ⁶Université Côte d’Azur, University Hospital of Nice, Nice, France, ⁷Bristol Myers Squibb, Princeton, NJ, ⁸Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany, ⁹Oregon Medical Research Center, Portland, OR

Background/Purpose: Deucravacitinib, a first-in-class, oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in multiple countries for the treatment of adults with plaque psoriasis; it is currently being investigated in several immune-mediated diseases and has shown efficacy in phase 2 trials for SLE and PsA (NCT03252587 and NCT03881059, respectively). Deucravacitinib was superior to placebo and apremilast in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials in moderate to severe plaque psoriasis. Patients who completed PSO-1 and PSO-2 could enroll in the ongoing POETYK long-term extension (LTE) trial (NCT04036435). Patients treated with continuous deucravacitinib in PSO-1 maintained long-term efficacy responses through week 112. In the present analysis, we assessed the efficacy of deucravacitinib for up to 112 weeks among patients from PSO-1 who crossed over from placebo to deucravacitinib at week 16.

Methods: Patients in PSO-1 were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily (QD), or apremilast 30 mg twice daily. Patients randomized to placebo at baseline crossed over to deucravacitinib at week 16. At week 52, patients who completed the parent trial were able to enroll in the LTE trial and receive open-label deucravacitinib 6 mg QD. Efficacy outcomes included ≥ 75%/≥ 90% reductions from baseline in Psoriasis Area and Severity Index (PASI 75/90) and static Physician's Global Assessment (sPGA) score of
0 (clear) or 1 (almost clear) with a ≥ 2-point improvement from baseline. Efficacy is reported using modified nonresponder imputation; patients who had not reached the week 112 assessment or had not discontinued as of October 1, 2021, were excluded. As-observed data and results by treatment failure rule imputation were also analyzed.

Results: At week 16, PASI 75, PASI 90, and sPGA 0/1 response rates in patients treated with placebo were 12.7%, 4.2%, and 7.2%, respectively. A total of 126 patients randomized to placebo at baseline crossed over to deucravacitinib at week 16 and received open-label deucravacitinib in the LTE through week 112. At week 112, PASI 75 and PASI 90 response rates were 81.4% and 50.6%, respectively, and the sPGA 0/1 response rate was 58.2%. These results were similar to those at week 112 in patients who were treated with deucravacitinib from day 1.

Conclusion: Deucravacitinib treatment is associated with long-term efficacy in patients who originally received placebo and crossed over to deucravacitinib after 16 weeks in PSO-1, with results replicating those with continuous deucravacitinib treatment from day 1. These findings further indicate that the once-daily, oral treatment of deucravacitinib is an effective long-term therapy for moderate to severe plaque psoriasis.


R. Warren: AbbVie, 2, 5, 6, Almirall, 2, 5, 6, Amgen, 2, 5, 6, Arena, 2, 6, Astellas, 2, 6, Avillion, 2, 6, Biogen, 2, 6, BMS, 2, 6, Boehringer Ingelheim, 2, 6, Celgene, 2, 5, DiCE, 6, Eli Lilly, 2, 5, 6, GSK, 2, 6, Janssen, 2, 5, 6, LEO Pharma, 2, 5, 6, Novartis, 2, 5, 6, Pfizer, 2, 5, 6, Sanofi, 2, 6, Sun Pharma, 6, UCB Pharma, 2, 5, 6, Union, 6; M. Lebwohl: Mark Lebwohl is an employee of Mount Sinai and receives research funds fromAbbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara therapeutics,, 2; S. Imafuku: AbbVie, 5, Amgen (Celgene), 12, Personal fees, Boehringer Ingelheim, 12, Personal fees, Bristol Myers Squibb, 12, Personal fees, Daiichi Sankyo, 12, Personal fees, Eisai, 5, Eli Lilly, 12, Personal fees, GSK, 12, Personal fees, Janssen, 5, Kyowa Kirin, 5, Leo Pharma, 5, Maruho, 5, Novartis, 12, Personal fees, Sun Pharma, 5, Taiho Yakuhin, 5, Tanabe Mitsubishi, 5, Torii Yakuhin, 5, UCB, 12, Personal fees; J. Bagel: AbbVie, 2, 6, 12, Research funds, Amgen, 2, 12, Research funds, Arcutis, 12, Research funds, Boehringer-Ingelheim, 12, Research funds, Bristol-Myers Squibb(BMS), 12, Research funds, Celgene, 2, 6, 12, Research funds, CorEvitas' (Corrona) Psoriasis Registry, 12, Research funds, Dermavant, 12, Research funds, Dermira/UCB, 12, Research funds, Eli Lilly, 2, 6, 12, Research funds, Glenmark, 12, Research funds, Janssen Biotech, 2, 6, 12, Research funds, Kadmon, 12, Research funds, Leo Pharma, 12, Research funds, Lycera, 12, Research funds, Menlo Therapeutics, 12, Research funds, Novartis, 2, 6, 12, Research funds, Pfizer, 12, Research funds, Regeneron, 12, Research funds, Sun Pharma, 2, 12, Research funds, Taro, 12, Research funds, Valeant, 2, 12, Research funds; A. Armstrong: AbbVie, 5, Almirall, 1, 6, Arcutis, 1, 6, Aslan Pharmaceuticals, 1, 1, 6, 6, Beiersdorf, 1, 6, Boehringer Ingelheim/Parexel, 12, Personal fees, Bristol-Myers Squibb(BMS), 5, Celgene, 12, Personal fees, Dermavant, 1, 6, 12, Personal fees, Dermira, 1, 5, 6, Eli Lilly, 5, EPI Health, 1, 6, Genentech, 12, Personal fees, GSK, 12, Personal fees, Incyte, 1, 6, Janssen, 5, Kyowa Kirin, 5, Leo Pharma, 5, Lilly, 1, 6, Menlo Therapeutics, 12, Personal fees, Merck, 12, Personal fees, Mindera Health, 1, 6, Modernizing Medicine, 12, Personal fees, Nimbus, 1, 6, Novartis, 5, Ortho Dermatologics, 12, Personal fees, Pfizer, 12, Personal fees, Regeneron, 12, Personal fees, Sanofi Genzyme, 12, Personal fees, Science 37, 12, Personal fees, Sun, 1, 6, Sun Pharma, 12, Personal fees, UCB, 5, Valeant, 12, Personal fees; T. Passeron: AbbVie/Abbott, 2, 6, Amgen, 6, Boehringer-Ingelheim, 6, Bristol-Myers Squibb(BMS), 1, 5, 6, Celgene, 6, Eli Lilly, 1, 6, Janssen, 1, 6, Novartis, 1, 6, Pfizer, 6, UCB, 1, 5, 6; M. Linaberry: Bristol-Myers Squibb(BMS), 3, 12, Shareholder; K. Hoyt: Bristol-Myers Squibb(BMS), 2; A. Napoli: Bristol-Myers Squibb(BMS), 3, 11; R. Kisa: Bristol-Myers Squibb(BMS), 3, 12, Shareholder; D. Thaçi: AbbVie, 1, 2, 5, 12, Investigator, Almirall, 1, 2, 12, Investigator, Amgen, 1, 2, 12, Investigator, Boehringer-Ingelheim, 1, 2, 12, Investigator, Bristol-Myers Squibb(BMS), 1, 2, 12, Investigator, Celltrion, 1, 2, 12, Investigator, Eli Lilly, 1, 2, 12, Investigator, Galapagos, 1, 2, 12, Investigator, Galderma, 1, 2, 5, 12, Investigator, Janssen-Cilag, 1, 2, 12, Investigator, LEO Pharma, 1, 2, 5, 12, Investigator, Novartis, 1, 2, 5, 12, Investigator, Pfizer, 1, 2, 12, Investigator, Regeneron, 1, 2, 12, Investigator, Samsung, 1, 2, 12, Investigator, Sandoz, 1, 2, 12, Investigator, Sanofi, 1, 2, 12, Investigator, Target-Solution, 1, 2, 12, Investigator, UCB, 1, 2, 12, Investigator; A. Blauvelt: AbbVie/Abbott, 5, 6, Abcentra, 6, Acelyrin, 12, Clinical study investigator, Aclaris, 6, Affibody, 6, Aligos, 6, Allakos, 12, Clinical study investigator, Almirall, 6, Alumis, 6, Amgen, 5, 6, Anaptysbio, 6, Apogee, 6, Arcutis, 5, 6, Arena, 6, Aslan, 6, Athenex, 5, 6, 12, Clinical study investigator, Bluefin, 6, Boehringer-Ingelheim, 5, 6, Bristol-Myers Squibb(BMS), 5, 6, Cara Therapeutics, 6, Concert, 12, Clinical study investigator, CTI Biopharma, 6, Dermavant, 5, 6, EcoR1, 6, Eli Lilly, 5, 6, Escient, 6, Evelo, 6, Evommune, 6, Forte, 6, Galderma, 5, 6, Highlightll Pharma, 6, Incyte, 5, 6, InnoventBio, 6, Janssen, 5, 6, Landos, 6, Leo, 5, 6, Merck/MSD, 5, 6, Novartis, 5, 6, Pfizer, 5, 6, Rani, 6, Rapt, 6, Regeneron, 5, 6, Sanofi Genzyme, 6, Spherix Global Insights, 6, Sun Pharma, 5, 6, TLL Pharmaceutical, 6, TrialSpark, 6, UCB, 5, 5, 6, 6, Union, 6, Ventyx, 6, Vibliome, 6, Xencor, 6.