PMID- 35241426 OWN - NLM STAT- MEDLINE DCOM- 20220519 LR - 20220722 IS - 1468-2060 (Electronic) IS - 0003-4967 (Print) IS - 0003-4967 (Linking) VI - 81 IP - 6 DP - 2022 Jun TI - Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis. PG - 815-822 LID - 10.1136/annrheumdis-2021-221664 [doi] AB - OBJECTIVE: To evaluate the efficacy and safety of an oral selective tyrosine kinase 2 (TYK2) inhibitor, deucravacitinib, in patients with active psoriatic arthritis (PsA). METHODS: In this double-blind, phase II trial, 203 patients with PsA were randomised 1:1:1 to placebo, deucravacitinib 6 mg once a day or 12 mg once a day. The primary endpoint was American College of Rheumatology-20 (ACR-20) response at week 16. RESULTS: ACR-20 response was significantly higher with deucravacitinib 6 mg once a day (52.9%, p=0.0134) and 12 mg once a day (62.7%, p=0.0004) versus placebo (31.8%) at week 16. Both deucravacitinib doses resulted in significant improvements versus placebo (p/=5%) in deucravacitinib-treated patients were nasopharyngitis, upper respiratory tract infection, sinusitis, bronchitis, rash, headache and diarrhoea. There were no serious AEs and no occurrence of herpes zoster, opportunistic infections and major adverse cardiovascular events, or differences versus placebo in mean changes in laboratory parameters with deucravacitinib treatment. CONCLUSIONS: Treatment with the selective TYK2 inhibitor deucravacitinib was well tolerated and resulted in greater improvements than placebo in ACR-20, multiplicity-controlled secondary endpoints and other exploratory efficacy measures in patients with PsA. Larger trials over longer periods of time with deucravacitinib are warranted to confirm its safety profile and benefits in PsA. TRIAL REGISTRATION NUMBER: NCT03881059. CI - (c) Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. FAU - Mease, Philip J AU - Mease PJ AUID- ORCID: 0000-0002-6620-0457 AD - Swedish Medical Center/Providence St. Joseph Health and University of Washington, Seattle, Washington, USA pmease@philipmease.com. FAU - Deodhar, Atul A AU - Deodhar AA AUID- ORCID: 0000-0002-2130-1246 AD - Oregon Health & Science University, Portland, Oregon, USA. FAU - van der Heijde, Desiree AU - van der Heijde D AUID- ORCID: 0000-0002-5781-158X AD - Leiden University Medical Center, Leiden, The Netherlands. FAU - Behrens, Frank AU - Behrens F AD - Rheumatology and Fraunhofer Institute, Translational Medicine and Pharmacology (ITMP) & Fraunhofer Cluster of Excellence Immune-Mediated Diseases (CIMD), Goethe University, Frankfurt, Germany. FAU - Kivitz, Alan J AU - Kivitz AJ AD - Department of Rheumatology, Altoona Center for Clinical Research, Duncansville, Pennsylvania, USA. FAU - Neal, Jeffrey AU - Neal J AD - Arthritis Center of Lexington, University of Kentucky School of Medicine, Lexington, Kentucky, USA. FAU - Kim, Jonghyeon AU - Kim J AD - Bristol Myers Squibb, Princeton, New Jersey, USA. FAU - Singhal, Shalabh AU - Singhal S AD - Bristol Myers Squibb, Princeton, New Jersey, USA. FAU - Nowak, Miroslawa AU - Nowak M AD - Bristol Myers Squibb, Princeton, New Jersey, USA. FAU - Banerjee, Subhashis AU - Banerjee S AD - Bristol Myers Squibb, Princeton, New Jersey, USA. LA - eng SI - ClinicalTrials.gov/NCT03881059 PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20220303 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (Antirheumatic Agents) RN - 0 (Heterocyclic Compounds) RN - EC 2.7.10.2 (TYK2 Kinase) RN - EC 2.7.10.2 (TYK2 protein, human) RN - N0A21N6RAU (deucravacitinib) SB - IM MH - *Antirheumatic Agents/therapeutic use MH - *Arthritis, Psoriatic/chemically induced/drug therapy MH - Double-Blind Method MH - Heterocyclic Compounds MH - Humans MH - Severity of Illness Index MH - TYK2 Kinase MH - Treatment Outcome PMC - PMC9120409 OTO - NOTNLM OT - arthritis OT - inflammation OT - psoriatic OT - therapeutics COIS- Competing interests: PJM: research grants: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma and UCB; consulting and/or speaker fees: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma and UCB. AAD: consulting and/or advisory boards: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer and UCB; research grants: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer and UCB. DvdH: consulting fees: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB Pharma; Director: Imaging Rheumatology. FB: research grants: Pfizer, Janssen, Chugai, Celgene and Roche; consultancies/speaker fees: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche, Chugai, Bristol Myers Squibb and UCB Pharma. AJK: shareholder: Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences and Novartis; paid consultant: AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research and Gilead Sciences; speakers bureau: Celgene, Merck, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion and AbbVie. JN: research grants to foundation: AbbVie, Amgen, Eli Lilly, Genentech, Novartis, UCB, Pfizer, Gilead and Bristol Myers Squibb. SS, MN, SB: employees and shareholders of Bristol Myers Squibb. JK: employee of Bristol Myers Squibb at time of the study conduct. EDAT- 2022/03/05 06:00 MHDA- 2022/05/20 06:00 PMCR- 2022/05/20 CRDT- 2022/03/04 05:36 PHST- 2021/10/12 00:00 [received] PHST- 2022/01/18 00:00 [accepted] PHST- 2022/03/05 06:00 [pubmed] PHST- 2022/05/20 06:00 [medline] PHST- 2022/03/04 05:36 [entrez] PHST- 2022/05/20 00:00 [pmc-release] AID - annrheumdis-2021-221664 [pii] AID - 10.1136/annrheumdis-2021-221664 [doi] PST - ppublish SO - Ann Rheum Dis. 2022 Jun;81(6):815-822. doi: 10.1136/annrheumdis-2021-221664. Epub 2022 Mar 3.