OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Deucravacitinib – Sotyktu®

DRUG CLASS

Dermatologic Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

View in own window

DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Deucravacitinib	1609392-27-9	C20-H19-D3-N8-O3

ANNOTATED BIBLIOGRAPHY

References updated: 28 December 2023

Abbreviations: JAK, Janus kinase; STAT, signal transducer activator of transcription; TYK2, Tyrosine Kinase 2.

• Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Review of hepatotoxicity published in 1999 before the availability of tyrosine kinase inhibitors such as deucravacitinib).
• DeLeve LD. Erlotinib. Cancer chemotherapy. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 556.

  (Review of hepatotoxicity of cancer chemotherapeutic agents discusses several tyrosine kinase inhibitors including imatinib, gefitinib, erlotinib and crizotinib, but not deucravacitinib).
• Wellstein A, Giaccone G, Atkins MB, Sausville EA. Pathway-targeted therapies: monoclonal antibodies, protein kinase inhibitors, and various small molecules. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 1203-36.

  (Textbook of pharmacology and therapeutics).
• FDA. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2022/214958Orig1s000MultidisciplineR.pdf

  (Integrated FDA review of the data on safety and efficacy of deucravacitinib that formed the basis of its approval mentions that, in a 24-week controlled trial of deucravacitinib, ALT elevations above 3 times ULN arose at a rate of 3.6 per patient year of exposure, and that analysis of the total safety cohort of 1519 patients identified 24 instances of ALT or AST elevations above 5 times ULN, most of which were transient and unrelated and none of which on thorough evaluation were considered due to drug induced liver injury).
• Chimalakonda A, Burke J, Cheng L, Catlett I, Tagen M, Zhao Q, Patel A, et al. Selectivity profile of the tyrosine kinase 2 inhibitor deucravacitinib compared with Janus kinase 1/2/3 inhibitors. Dermatol Ther (Heidelb). 2021;11:1763–1776. [PMC free article: PMC8484413] [PubMed: 34471993]

  (Among JAK kinase inhibitors, deucravacitinib binds to a regulatory rather than catalytic site on TYK2, which gives it a high selectivity so that it has little or no activity against JAK1, JAK2 or JAK3, and pilot studies suggest that it has fewer adverse side effects and is less likely to affect serum aminotransferase levels compared to other JAK kinase inhibitors).
• Armstrong AW, Gooderham M, Warren RB, Papp KA, Strober B, Thaçi D, Morita A, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial. J Am Acad Dermatol. 2023;88:29–39. [PubMed: 35820547]

  (Among 666 adults with plaque psoriasis treated with deucravacitinib [6 mg daily], apremilast [30 mg twice daily] or placebo for 16 weeks, symptomatic scores improved in 58% vs 54% vs 7-12% on placebo, while overall adverse events were similar in the 3 groups but serious adverse events were less with deucravacitinib [2.1% vs 5.5% with placebo] and mean serum ALT levels did not change in any group).
• Strober B, Thaçi D, Sofen H, Kircik L, Gordon KB, Foley P, Rich P, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 program for evaluation of TYK2 inhibitor psoriasis second trial. J Am Acad Dermatol. 2023;88:40–51. [PubMed: 36115523]

  (Abstract only: Among 1020 adults with moderate to severe plaque psoriasis treated with deucravacitinib [6 mg daily], apremilast [30 mg twice daily], or placebo for up to 52 weeks, 16 week-clinical response rates were highest with deucravacitinib [49.5% vs 33.9% vs 8.6%], and efficacy was maintained to 52 weeks, while adverse events were mostly mild and transient, and serious adverse events and discontinuations were “infrequent”).
• Morand E, Pike M, Merrill JT, van Vollenhoven R, Werth VP, Hobar C, Delev N, et al. Deucravacitinib, a tyrosine kinase 2 inhibitor, in systemic lupus erythematosus: a phase II, randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 2023;75:242–252. [PMC free article: PMC10100399] [PubMed: 36369798]

  (Among 363 adults with systemic lupus erythematosus treated with deucravacitinib [3 or 6 mg twice daily or 12 mg once daily] vs placebo for 48 weeks, symptomatic response rates were higher with deucravacitinib [58% vs 30%], while overall adverse event rates were similar [84% to 93% vs 88%] as were severe adverse events [7.7% to 8.6% vs 12.2%] and discontinuations [6.5% to 12.4% vs 3.3%]; mean ALT levels did not change, and there were no discontinuations for enzyme elevations in treated patients).
• Deucravacitinib (Sotyktu) for plaque psoriasis. Med Lett Drugs Ther. 2023;65:29–31. [PubMed: 36757835]

  (Concise review of the mechanism of action, clinical efficacy, safety, and costs of deucravacitinib shortly after its approval as therapy of psoriasis in 2023, mentions that serum enzyme elevations have occurred in patients taking deucravacitinib).
• Truong TM, Pathak GN, Singal A, Taranto V, Rao BK. Deucravacitinib: The first FDA-approved oral TYK2 inhibitor for moderate to severe plaque psoriasis. Ann Pharmacother. 2023;•••:10600280231153863. [PubMed: 37341177]

  (Summary of the efficacy and safety of deucravacitinib mentions that adverse events appear to be less common than with JAK kinase inhibitors, with an adverse event rate of 75%, only 4% serious, and 3-4% requiring discontinuation, known adverse events being hypersensitivity reactions, infections [29%], viral reactivation [herpes simplex 2% and zoster <1%], tuberculosis [<1%], lymphoma [<1%], liver function test abnormalities [2%], but no mention of hepatotoxicity or clinically apparent liver injury).