Deucravacitinib Tablets (Sotyktu)
November 30, 2022 4 minutes read
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
The FDA has approved a first-in-class oral tyrosine kinase 2 inhibitor (TYK2) for the treatment of plaque psoriasis. Deucravacitinib targets the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. The JAK family consists of four tyrosine kinases (JAK1, JAK2, JAK3, and TYK2).1 Deucravacitinib is unique in that it binds to the regulatory domain (allosteric) of TYK2, inhibiting downstream activation of STATs.1 This is the latest approval for a drug that targets this signaling pathway for immune-mediated inflammatory diseases. Others include baricitinib for alopecia areata, as well as abrocitinib, upadacitinib, and topical ruxolitinib for atopic dermatitis. Deucravacitinib is distributed as Sotyktu.
INDICATIONS
Deucravacitinib can be prescribed to adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.1
DOSAGE
The recommended dose is 6 mg orally once daily, with or without food.1 Physicians should evaluate patients for active and latent tuberculosis infection before initiating treatment.1 Immunizations should be updated before starting this treatment. Deucravacitinib can be prescribed as a 6 mg tablet.
POTENTIAL ADVANTAGES
Deucravacitinib is the first-in-class oral agent and demonstrated superior efficacy to another oral agent, apremilast.1-3 While deucravacitinib acts on the JAK-STAT pathway, it has high selectivity for the allosteric site of TYK2 and not the active sites of JAK 1-3 without interfering with JAK-dependent functions.4,5 Thus, deucravacitinib is not associated with adverse hematologic parameters and is less likely to lead to dyslipidemia caused by JAK inhibition.5
POTENTIAL DISADVANTAGES
As with other immunomodulating agents, deucravacitinib may increase the risk of infections, viral reactivation, and malignancy (including lymphomas).1 Deucravacitinib has been associated with more episodes of asymptomatic creatine phosphokinase elevation and rhabdomyolysis. Laboratory abnormalities include triglyceride and liver enzyme elevations.
COMMENTS
For patients with psoriasis, deucravacitinib reduces psoriasis-associated gene expression in psoriatic skin, including a reduction in IL-23 pathway and type I interferon pathway-regulated genes.1 Researchers evaluated the efficacy of deucravacitinib in two randomized, double-blind, placebo-and active-controlled trials.1-3 Subjects were adults with moderate-to-severe plaque psoriasis, with body surface involvement of ≥ 10%, Psoriasis Area and Severity Index (PASI) ≥ 12, and static Physician’s Global Assessment (sPGA) ≥ 3. Subjects were randomized to deucravacitinib (Study 1, n = 330; Study 2, n = 511), placebo (Study 1, n = 166; Study 2, n = 255), or apremilast (30 mg twice daily; Study 1, n = 168; Study 2, n = 254). The coprimary endpoints were the proportion of subjects who achieved a sPGA score of 0 (clear) or 1 (almost clear) with at least a two-grade improvement from baseline and the proportion who achieved at least 75% improvement in PASI score (PASI 75).
Researchers assessed deucravacitinib vs. placebo at week 16 and vs. apremilast at week 24. Investigators assessed maintenance and durability of response of deucravacitinib week 52. Treatment responses for sPGA (Study 1) at week 16 were 54%, 7%, and 32% for deucravacitinib, placebo, and apremilast, respectively. Responses for PASI 75 were 58%, 13%, and 35%. For Study 2, responses were 50%, 9%, and 34% for sPGA, and 53%, 9%, and 40% for PASI 75. At week 24, deucravacitinib was 20% to 27% better for sPGA and 20% to 31% better for PASI 75 compared to apremilast. For responders at week 24, 78% to 82% maintained response at week 52. For those re-randomized to treatment withdrawal, 24% to 31% maintained their response at week 52.
CLINICAL IMPLICATIONS
Psoriasis is a common, chronic, inflammatory, immune-mediated disease. The interleukin (IL)-23/17 signaling pathway is considered the main pathogenic pathway. The most effective biologics (brodalumab, guselkumab, risankizumab-rzaa, and ixekizumab) target this pathway.6 Deucravacitinib is the first oral agent that also targets this pathway for this indication and is superior to apremilast, a phosphodiesterase-4 inhibitor.
There are no published comparative studies to other biologic agents. However, reported sPGA responses for risankizumab and ixekizumab at week 12 were 84% to 88% and 81% to 83%, respectively.7,8 This, compared to 50% to 54% for deucravacitinib. The positioning of deucravacitinib in therapy for plaque psoriasis remains to be determined. The cost is $6,164 for a 30-day supply, or nearly $75,000 per year.
REFERENCES
1. Bristol Myers Squibb. Sotyktu prescribing information. September 2022.
2. Armstrong AW, Gooderham M, Warren RB, 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; 2022 Jul 9: S0190-9622(22)02256-3. doi: 10.1016/j.jaad.2022.07.002. [Online ahead of print].
3. Strober B, Thaçi D, Sofen H, 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 POETYK PSO-2 trial. J Am Acad Dermatol; 2022 Sep 14: S0190-9622(22)02643-3. doi: 10.1016/j.jaad.2022.08.061. [Online ahead of print].
4. Chimalakonda A, Burke J, Cheng L, 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.
5. Krueger JG, McInnes IB, Blauvelt A. Tyrosine kinase 2 and Janus kinase-signal transducer and activator of transcription signaling and inhibition in plaque psoriasis. J Am Acad Dermatol 2022;86:148-157.
6. Armstrong AW, Puig L, Joshi A, et al. Comparison of biologics and oral treatments for plaque psoriasis: A meta-analysis. JAMA Dermatol 2020;156:258-269.
7. Eli Lilly and Company. Taltz prescribing information. September 2022.
8. AbbVie. Skyrizi prescribing information. September 2022.
Deucravacitinib can be prescribed to adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
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