Deucravacitinib is a first-in-class tyrosine kinase 2 (TYK2) inhibitor recently approved for the treatment of adults with moderate-to-severe plaque psoriasis.
Objective
To discuss the mechanism of action, efficacy, safety, and real-world applications of deucravacitinib for the treatment of psoriasis.
Methods
Literature on the mechanism of action of deucravacitinib is reviewed. The pivotal clinical studies and long-term extension studies for deucravacitinib are also examined.
Results
Deucravacitinib is a novel oral TYK2 inhibitor that binds to the regulatory domain of TYK2, a Janus kinase. By inhibiting TYK2, deucravacitinib interferes with signaling of IL-23, IL-12, and type I interferons, cytokines believed to play important roles in psoriasis pathogenesis. Nearly 60% of patients achieve PASI 75 at 16 weeks of treatment; efficacy improves over 24 weeks and is maintained through 2 years of continuous treatment. In a head-to-head comparison, deucravacitinib efficacy was superior to apremilast, an older yet commonly used oral PDE4 inhibitor approved for the treatment of psoriasis. Of note, patients with moderate-to-severe plaque psoriasis with concomitant involvement of the scalp, nails, and/or palms/soles demonstrated good improvement in these high impact areas. Deucravacitinib has an acceptable safety profile and is generally well-tolerated. Small increases in reactivation of herpesvirus infections, including herpes simplex outbreaks, have been reported. Tuberculosis evaluation, but no other blood tests, is recommended prior to initiation of deucravacitinib. Monitoring of triglyceride levels should be conducted for high-risk patients according to local guidelines.
Conclusion
Deucravacitinib is an effective, safe, and well-tolerated novel oral medication for adults with moderate-to-severe plaque psoriasis.
ArmstrongAWMehtaMDSchuppCW, et al.Psoriasis prevalence in adults in the United States. JAMA Dermatology. 2021;157(8):940-946. doi:10.1001/jamadermatol.2021.2007
2.
ArmstrongAWReadC. Pathophysiology, clinical presentation, and treatment of psoriasis. JAMA. 2020;323(19):1945-1960. doi:10.1001/jama.2020.4006
3.
MenterAStroberBEKaplanDH, et al.Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019;80(4):1029-1072. doi:10.1016/j.jaad.2018.11.057
4.
MenterAGelfandJMConnorC, et al.Joint American academy of dermatology-national psoriasis foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies. J Am Acad Dermatol. 2020;82(6):1445-1486. doi:10.1016/j.jaad.2020.02.044
HowellMDKuoFISmithPA. Targeting the Janus kinase family in autoimmune skin diseases. Front Immunol. 2019;10:2342.
11.
KruegerJGMcInnesIBBlauveltA. Tyrosine kinase 2 and Janus kinase-signal transducer and activator of transcription signaling and inhibition in plaque psoriasis. J Am Acad Dermatol. 2022;86(1):148-157. doi:10.1016/j.jaad.2021.06.869
12.
WinthropKL. The emerging safety profile of JAK inhibitors in rheumatic disease. Nat Rev Rheumatol. 2017;13(4):234-243.
13.
Pérez-JeldresTTylerCJBoyerJD, et al.Targeting cytokine signaling and lymphocyte traffic via small molecules in inflammatory bowel disease: JAK inhibitors and S1PR agonists. Front Pharmacol. 2019;10:212.
14.
BakerKFIsaacsJD. Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis?Ann Rheum Dis. 2018;77(2):175-187.
15.
BurkeJRChengLGilloolyKM, et al.Autoimmune pathways in mice and humans are blocked by pharmacological stabilization of the TYK2 pseudokinase domain. Sci Transl Med. 2019;11(502):1-16.
16.
JiangLLiZRuiL. Leptin stimulates both JAK2-dependent and JAK2-independent signaling pathways. J Biol Chem. 2008;283(42):28066-28073.
17.
XieJLeBaronMJNevalainenMT, et al.Role of tyrosine kinase Jak2 in prolactin-induced differentiation and growth of mammary epithelial cells. J Biol Chem. 2002;277(16):14020-14030.
18.
Kvist-HansenAHansenPRSkovL. Systemic treatment of psoriasis with JAK inhibitors: A review. Dermatology and Therapy. 2020;10(1):29-42.
19.
SchwartzDMKannoYVillarinoA, et al.JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;16(12):843-862.
20.
CIBINQO [package insert]. New York, NY: Pfizer Labs; 2022.
ChimalakondaABurkeJChengL, et al.Selective inhibition of tyrosine kinase 2 with deucravacitinib (BMS-986165) compared with Janus kinase 13 inhibitors. Poster presented at: Annual Fall Clinical Dermatology Conference; October 29 to November 1, 2020; virtual meeting and atLas Vegas, NV.
23.
NogueiraMPuigLTorresT. JAK inhibitors for treatment of psoriasis: Focus on selective TYK2 inhibitors. Drugs. 2020;80(4):341-352.
24.
MoslinRZhangYWrobleskiST, et al.Identification of N-methyl nicotinamide and N-methyl pyridazine-3-carboxamide pseudokinase domain ligands as highly selective allosteric inhibitors of tyrosine kinase 2 (TYK2). J Med Chem. 2019;62(20):8953-8972.
25.
WrobleskiSTMoslinRLinS, et al.Highly selective inhibition of tyrosine kinase 2 (TYK2) for the treatment of autoimmune diseases: Discovery of the allosteric inhibitor BMS-986165. J Med Chem. 2019;62(20):8973-8995.
26.
ClinicalTrials.gov. NCT03624127. Accessed March 29, 2023,2023.
27.
ClinicalTrials.gov. NCT03611751. Accessed March 29, 2023,2023.
28.
ClinicalTrials.gov. NCT04036435. Accessed April 7, 2023,2023.
29.
ArmstrongAWGooderhamMWarrenRB, 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(1):29-39. doi:10.1016/j.jaad.2022.07.002
30.
StroberBThaçiDSofenH, 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(1):40-51.
31.
MerolaJFSofenHThaçiD, et al.Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy analysis by baseline disease characteristics from the phase 3 POETYK PSO-1 and PSO-2 trials. Oral presentation at EADV; September 2021; Milan, ItalyPoster presentation at EADV 2021. Poster 1410.
32.
WarrenRBArmstrongAImafukuS, et al.Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy analysis by prior treatment in the phase 3 POETYK PSO-1 and PSO-2 trials. Oral presentation at EADV; 2021; Switzerland. Presentation FC03.06.
33.
Data on file. BMS-REF-DEU-0010. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
34.
Data on file. BMS-REF-DEU-0020. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
35.
WarrenRBSofenHImafukuS, et al.Deucravacitinib long-term efficacy and safety in plaque psoriasis: 2-year results from the phase 3 POETYK PSO program. Poster presented at: European Academy of Dermatology and Venereology Spring Symposium; May 12-14, 2022; Ljubljana, Slovenia. Poster P465.
36.
LebwohlMWarrenRBSofenH, et al.Deucravacitinib long-term efficacy with continuous treatment in plaque psoriasis: 2-year results from the phase 3 POETYK PSO study program. Oral presentation at EADV; September 2022; Milan, ItalyPresentation D3T01.1F.
37.
Data on file. BMS-REF-DEU-0075. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
38.
BlauveltARichPSofenH, et al.Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, versus placebo in scalp, nail, and palmoplantar psoriasis: Subset analyses of the phase 3 POETYK PSO-1 and PSO-2 trials. SKIN J Cutan Med. 2022;6(4):s41. Oral presentation at SDDS 2022.
39.
BlauveltARichPSofenH, et al.Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in scalp, nail, and palmoplantar psoriasis: Subgroup analyses of the phase 3 POETYK PSO-1 and PSO-2 trials. SKIN J Cutan Med. 2022;6(6):s49. Oral presentation at FCDC 2022.
40.
ArmstrongAGooderhamMWarrenRB, et al.Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, compared with placebo and apremilast in moderate to severe plaque psoriasis: Results from the POETYK PSO-1 study. Presented at: the Annual Meeting of the American Academy of Dermatology; March 19, 2021; San Francisco, CA. Oral presentation at AAD 2021. Session S033.
41.
ThaçiDGordonKGooderhamM, et al.Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, compared with placebo and apremilast in moderate to severe psoriasis: Integrated laboratory parameter results from the phase 3 POETYK PSO-1 and POETYK PSO-2 trials. SKIN J Cutan Med. 2021;5(6):s37. Poster presentation at EADV 2021; Poster P1407.
42.
MeasePJDeodharAAvan der HeijdeD, et al.Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis. Ann Rheum Dis. 2022;81(6):815-822. doi:10.1136/annrheumdis-2021-221664
43.
LarousserieFPflanzSCoulomb-L’HerminéA, et al.Expression of IL-27 in human Th1-associated granulomatous diseases. J Pathol. 2004;202(2):164-171. doi:10.1002/path.1508
