Sotyktu (Deucravacitinib)
deucravacitinib
Deucravacitinib Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Moderate-to-severe plaque psoriasis | Adults who are candidates for systemic therapy or phototherapy | Monotherapy (not recommended with other potent immunosuppressants) | FDA Approved |
| Active psoriatic arthritis | Adults | Monotherapy (not recommended with other potent immunosuppressants) | FDA Approved |
Deucravacitinib is the first FDA-approved selective, allosteric TYK2 inhibitor, initially approved in September 2022 for plaque psoriasis and subsequently for active psoriatic arthritis in March 2026. It represents a mechanistically distinct approach within the broader JAK family by targeting the pseudokinase (JH2) regulatory domain of TYK2 rather than the catalytic (JH1) domain targeted by traditional JAK inhibitors. This selectivity for TYK2 over JAK1, JAK2, and JAK3 is the rationale for its differentiated safety profile, which notably does not carry the boxed warning applied to other JAK inhibitors. For plaque psoriasis, the POETYK PSO-1 and PSO-2 phase 3 trials demonstrated superiority over placebo and apremilast at weeks 16 and 24, with durable responses maintained through 52 weeks. For psoriatic arthritis, the POETYK PsA-1 and PsA-2 trials showed significant ACR20 improvements over placebo. It is not recommended for use in combination with other potent immunosuppressants.
Systemic lupus erythematosus: Phase 2 trial (PAISLEY) showed encouraging results; phase 3 trials underway. Evidence quality: moderate.
Ulcerative colitis, Crohn disease: Phase 2 trials ongoing. Evidence quality: low (preliminary data).
Sjögren disease: Phase 3 trial in progress. Evidence quality: low (early stage).
Alopecia areata, discoid lupus: Case reports of benefit. Evidence quality: very low.
Deucravacitinib Dosing
Adult Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Moderate-to-severe plaque psoriasis — standard | 6 mg QD | 6 mg QD | 6 mg/day | Single fixed dose; no titration needed Take with or without food; do not crush, cut, or chew tablets |
| Active psoriatic arthritis | 6 mg QD | 6 mg QD | 6 mg/day | Same dose as plaque psoriasis; approved March 2026 Not recommended with other potent immunosuppressants; ACR20 at wk 16: 54.2% vs 34.1% placebo (PsA-1) |
| Renal impairment (any severity, including dialysis) | 6 mg QD | 6 mg QD | 6 mg/day | No dose adjustment required Deucravacitinib is not removed by haemodialysis (FDA PI) |
| Mild-to-moderate hepatic impairment | 6 mg QD | 6 mg QD | 6 mg/day | No dose adjustment required |
| Severe hepatic impairment | Not recommended | Insufficient data; avoid use (FDA PI) | ||
| Elderly (≥65 years) | 6 mg QD | 6 mg QD | 6 mg/day | No dose adjustment; higher incidence of serious AEs and infections in ≥65 age group Limited data in ≥75 years (1.4% of trial participants) |
| Inadequate response assessment | Re-evaluate at 24 weeks | Consider discontinuation if no improvement at 24 weeks | ||
Deucravacitinib offers a uniquely simplified regimen: a single fixed 6 mg tablet once daily with no titration, no renal adjustment, and no routine laboratory monitoring mandate (unlike traditional JAK inhibitors). Critically, because it selectively targets TYK2 via the pseudokinase domain rather than inhibiting JAK1/JAK2/JAK3 catalytic domains, it does not carry the boxed warning for serious infections, mortality, malignancy, MACE, and thrombosis that applies to tofacitinib, baricitinib, upadacitinib, and abrocitinib. This may simplify shared decision-making with patients concerned about the JAK class warnings.
Pharmacology
Mechanism of Action
Deucravacitinib is a first-in-class, oral, selective, allosteric inhibitor of tyrosine kinase 2 (TYK2). Unlike conventional JAK inhibitors that bind to the catalytic (JH1) domain shared across JAK family members, deucravacitinib binds to the pseudokinase (JH2) regulatory domain unique to TYK2. This allosteric mechanism locks TYK2 in an inactive conformation, selectively blocking the signalling of cytokines that drive psoriasis pathogenesis: interleukin-23 (IL-23), interleukin-12 (IL-12), and type I interferons (IFN-alpha/beta). By inhibiting IL-23/IL-12 signalling, deucravacitinib disrupts the Th17 and Th1 inflammatory cascades that sustain psoriatic plaque formation. The selectivity of TYK2 inhibition over JAK1, JAK2, and JAK3 is the basis for the differentiated safety profile: deucravacitinib does not interfere with the haematopoietic (JAK2-dependent), immune-regulatory (JAK1/JAK3-dependent), or lipid-metabolic pathways implicated in the safety concerns associated with broader JAK inhibition.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Bioavailability ~99%; Tmax 2–3 h; linear PK from 3–36 mg; high-fat meal decreases Cmax 24% and AUC 11% (not clinically significant) | Near-complete absorption allows administration with or without food; rapid onset of systemic exposure |
| Distribution | Vd ~140 L; protein binding 82–90%; blood:plasma ratio 1.26 | Extensive tissue distribution beyond total body water; moderate protein binding; distributes into blood cells |
| Metabolism | Primary: CYP1A2 (N-demethylation to active metabolite BMT-153261, comparable potency); also CYP2B6, CYP2D6, CES2, UGT1A9 | Active metabolite contributes ~18% of total pharmacological activity; not a CYP inhibitor or inducer; minimal DDI potential |
| Elimination | t½ ~10 h; feces ~26% (unchanged), urine ~13% (unchanged); renal clearance 27–54 mL/min; total clearance 254 mL/min | Steady state by day 5; modest accumulation (1.4–1.9-fold); no adjustment needed for any degree of renal impairment |
Side Effects
Side effect data are from the POETYK PSO-1 and PSO-2 phase 3 trials (1,519 patients treated with deucravacitinib; 840 randomised to deucravacitinib 6 mg, 419 to placebo, 422 to apremilast). Adverse reaction rates below are from the 16-week placebo-controlled period unless otherwise stated. Long-term data through 3–5 years from the POETYK LTE trial confirm that exposure-adjusted incidence rates (EAIRs) did not increase over time.
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Upper respiratory infections (including nasopharyngitis) | 19.2% | Most common adverse event overall; includes nasopharyngitis, upper respiratory tract infection, and pharyngitis; mostly mild; similar to apremilast rates |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Blood CPK increase | 2.7% | Usually asymptomatic; monitor for symptoms of myopathy; cases of rhabdomyolysis have been reported |
| Herpes simplex | 2.0% (6.8 per 100 PY) | Oral and cutaneous herpes reactivation; most cases were non-serious; 0.8 per 100 PY in placebo |
| Mouth ulcers | 1.9% | Aphthous-type; usually self-limiting; may respond to topical treatments |
| Folliculitis | 1.7% | 3-year EAIR 1.1/100 PY; generally mild |
| Acne | 1.4% | 3-year EAIR 1.3/100 PY; manageable with standard acne therapies; more commonly reported in women |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Serious infections (pneumonia, COVID-19) | 2.5 per 100 PY (0.9 excluding COVID) | Any time during treatment | Interrupt deucravacitinib; initiate appropriate antimicrobial therapy; do not resume until infection resolves |
| Herpes zoster | 0.6 per 100 PY | Any time; multidermatomal reported in 1 immunocompetent patient | Consider herpes zoster vaccination before starting; majority of affected patients were <50 years |
| Rhabdomyolysis / markedly elevated CPK | Rare | Variable | Discontinue if markedly elevated CPK or myopathy diagnosed/suspected; advise patients to report unexplained muscle pain |
| Malignancy (excluding NMSC) | 0.5 per 100 PY | Weeks 24–98 in trial patients | Weigh risk-benefit in patients with known malignancy; 3 lymphomas reported (0.1/100 PY) across trials and LTE |
| MACE (cardiovascular death, MI, stroke) | 0.3 per 100 PY | Variable | Assess cardiovascular risk factors; consistent with background psoriasis population rates |
| VTE (DVT/PE) | 0.1 per 100 PY | Variable | Low rate; no signal above background; evaluate thrombotic risk factors |
| Hypersensitivity (angioedema) | Rare | Any time | Discontinue immediately; initiate appropriate therapy; do not rechallenge |
Three-year cumulative data from the POETYK programme show that serious infection rates (excluding COVID-19) were 0.9/100 PY, MACE rates were 0.3/100 PY, and VTE rates were 0.1/100 PY — all consistent with or lower than background rates in the psoriasis population. These rates remained stable or decreased over time, supporting the hypothesis that selective TYK2 inhibition via the pseudokinase domain avoids the safety signals associated with broader JAK inhibition. Notably, there was no signal for increased all-cause mortality, no clinically meaningful changes in haemoglobin, neutrophils, or platelets, and no lipid metabolism disturbances attributable to deucravacitinib.
Drug Interactions
Deucravacitinib has a notably clean drug interaction profile. It is metabolised primarily by CYP1A2 but is not an inhibitor or inducer of any major CYP enzymes. Formal PK interaction studies with multiple probe substrates and commonly co-prescribed medications showed no clinically significant interactions (FDA PI). Deucravacitinib is a substrate of P-gp, BCRP, and OCT1, and an inhibitor of BCRP and OATP1B3.
Monitoring
- TB ScreeningBaseline
RoutineEvaluate for latent and active TB before starting. Do not administer to patients with active TB. Initiate latent TB treatment prior to deucravacitinib. One case of active TB developed after 54 weeks of treatment in a patient without baseline latent TB. - Hepatitis ScreeningBaseline and during therapy
RoutineScreen for viral hepatitis per clinical guidelines. Not recommended in active hepatitis B or C. Monitor for reactivation during therapy; consult hepatitis specialist if signs of reactivation occur. - CPK LevelsPeriodically
Trigger-basedElevated CPK (2.7% incidence) and rare cases of rhabdomyolysis reported. Discontinue if markedly elevated CPK occurs or myopathy is suspected. Advise patients to report unexplained muscle pain or weakness. - TriglyceridesPeriodically
RoutineDeucravacitinib may increase triglycerides. Evaluate periodically during therapy and manage per cardiovascular risk guidelines. - Liver EnzymesBaseline; periodically in at-risk patients
Trigger-basedAssess at baseline and during therapy in patients with known or suspected liver disease. Interrupt if drug-induced elevation suspected (ALT >3× ULN in 1.1–1.3% of patients). Most elevations were transient and attributable to myositis or fatty liver. - Infection SignsEvery visit
RoutineMonitor for signs and symptoms of infection, especially herpes simplex and zoster reactivation. Interrupt deucravacitinib for serious infections and do not resume until resolved. - Treatment Response16 weeks; then 24 weeks
RoutineAssess response at 16 weeks (pivotal trial primary endpoint). Consider discontinuation if no improvement by 24 weeks. PASI 75 achieved by 58.4% (PSO-1) and 53.0% (PSO-2) at week 16.
Contraindications & Cautions
Absolute Contraindications
- Hypersensitivity to deucravacitinib or any excipient (angioedema reported)
Relative Contraindications (Specialist Input Recommended)
- Active serious infection (including localised infections)—do not initiate until infection controlled
- Active tuberculosis—treat latent TB before starting; do not use in active TB
- Active hepatitis B or C—not recommended; risk of viral reactivation
- Severe hepatic impairment—not recommended; insufficient data
- Known malignancy (other than successfully treated NMSC)—weigh risk-benefit individually
Use with Caution
- Chronic or recurrent infections—increased infection risk with immunomodulatory therapy
- History of herpes simplex or zoster—viral reactivation reported; consider vaccination before initiation
- Elderly (≥65 years)—higher incidence of serious AEs and infections; 10% of trial patients were ≥65, only 1.4% were ≥75
- Paediatric patients—safety and efficacy not established
- Pregnancy and breastfeeding—insufficient human data; report pregnancies to BMS at 1-800-721-5072
Unlike tofacitinib, baricitinib, upadacitinib, and abrocitinib, deucravacitinib does not carry the FDA boxed warning for serious infections, mortality, malignancy, MACE, and thrombosis. This distinction reflects the allosteric, pseudokinase-domain mechanism of TYK2 inhibition, which avoids the broader JAK1/JAK2/JAK3 signalling disruption implicated in those class-wide safety signals. However, deucravacitinib does carry standard warnings for infections, malignancy (including lymphoma), rhabdomyolysis, and hypersensitivity in the non-boxed Warnings and Precautions section.
Patient Counselling
Purpose of Therapy
Deucravacitinib is prescribed for moderate-to-severe plaque psoriasis when other systemic treatments or phototherapy may be appropriate. It works by blocking a specific enzyme called TYK2 that drives the inflammation behind psoriasis. It is taken as one small tablet once a day and does not require dose adjustments for most patients.
How to Take
Take one 6 mg tablet once daily at approximately the same time each day. It may be taken with or without food. Swallow the tablet whole—do not crush, cut, or chew. If a dose is missed, take it as soon as you remember, then resume the regular schedule. Improvement may be noticeable within a few weeks, but the full effect should be assessed after 16–24 weeks.
Sources
- Bristol-Myers Squibb Company. SOTYKTU (deucravacitinib) tablets. Full prescribing information. Princeton, NJ; revised March 2026. packageinserts.bms.comPrimary source for dosing (6 mg QD for both plaque psoriasis and PsA), PK data, adverse reaction rates, contraindications, and monitoring. Updated to include active psoriatic arthritis indication.
- DailyMed. SOTYKTU (deucravacitinib) tablet. National Library of Medicine. dailymed.nlm.nih.govStructured FDA label providing pharmacokinetic parameters, drug interaction data, and detailed safety information.
- 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. 2023;88(1):29–39. doi:10.1016/j.jaad.2022.07.002Pivotal trial (n=666) demonstrating PASI 75 of 58.4% vs 12.7% placebo at week 16, with durability through week 52.
- Strober B, Thaci 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. 2023;88(1):40–51. doi:10.1016/j.jaad.2022.08.061Confirmatory trial (n=1,020) with PASI 75 of 53.0% vs 9.4% placebo; included randomised withdrawal demonstrating relapse with treatment cessation.
- Papp K, Gordon K, Thaçi D, et al. Phase 2 trial of selective TYK2 inhibition in psoriasis. N Engl J Med. 2018;379(14):1313–1321. doi:10.1056/NEJMoa1806382Phase 2 dose-ranging study (n=267) establishing the 6 mg QD regimen and demonstrating proof of concept for TYK2 inhibition in psoriasis.
- Lebwohl M, Warren RB, Sofen H, et al. Deucravacitinib in plaque psoriasis: 2-year safety and efficacy results from the phase III POETYK trials. Br J Dermatol. 2024;190(5):668–679. doi:10.1093/bjd/ljae014Two-year integrated safety analysis confirming stable EAIRs for infections, MACE, VTE, and malignancy with longer exposure.
- Menter A, Strober BE, Kaplan DH, 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.2018.11.057AAD-NPF guideline providing the framework for systemic therapy in moderate-to-severe psoriasis within which deucravacitinib is positioned.
- Burke JR, Cheng L, Gillooly KM, et al. Autoimmune pathways in mice and humans are blocked by pharmacological stabilization of the TYK2 pseudokinase domain. Sci Transl Med. 2019;11(502):eaaw1736. doi:10.1126/scitranslmed.aaw1736Landmark paper establishing the allosteric pseudokinase-domain mechanism of TYK2 inhibition and preclinical efficacy across autoimmune models.
- 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(5):1763–1776. doi:10.1007/s13555-021-00596-8Demonstrates the selectivity of deucravacitinib for TYK2 over JAK1/JAK2/JAK3, providing the pharmacological basis for its differentiated safety profile.
- Chimalakonda A, Li W, Marchisin D, et al. Absolute and relative bioavailability of oral solid dosage formulations of deucravacitinib in humans. Clin Pharmacol Drug Dev. 2023;12(10):956–965. doi:10.1002/cpdd.1308Definitive human PK study establishing ~99% bioavailability, Vd ~140 L, clearance 254 mL/min, and t½ 7.9–15 h.
- 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. 2024;58(4):416–427. doi:10.1177/10600280231153863Comprehensive pharmacological review covering mechanism, PK, clinical trial results, and positioning relative to existing psoriasis therapies.
- Deucravacitinib: adverse events of interest across phase 3 plaque psoriasis trials. 3-year cumulative EAIR data. J Am Acad Dermatol. 2025 (in press). PubMed: 39918727Three-year safety analysis confirming stable or decreasing EAIRs for serious infections (0.9/100 PY excl. COVID), MACE (0.3/100 PY), and malignancy (0.5/100 PY excl. NMSC).