deucravacitinib (Rx)

>10%

Infections (29%)

Upper respiratory tract infections (19.2%)

1-10%

Blood creatine phosphokinase increased (2.7%)

Herpes simplex (2%)

Mouth ulcers (1.9%)

Folliculitis (1.7%)

Acne (1.4%)

<1%

Herpes zoster

Contraindications

Hypersensitivity to deucravacitinib or any of excipients in drug product

Cautions

Hypersensitivity reactions (eg, angioedema) have been reported; if a clinically significant reaction occurs, discontinue therapy

Evaluate for TB before initiating

Malignancies, including lymphomas, were observed; consider the benefits and risk for individual, particularly in patients with a known malignancy (other than a successfully treated non-melanoma skin cancer) and patients who develop a malignancy during treatment

Cases of rhabdomyolysis reported resulting in interrupting or discontinuing therapy; discontinue therapy if markedly elevated CPK levels occur or myopathy is diagnosed or suspected; advise patients to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever

May increase triglyceride levels; monitor and manage according to clinical guidelines for hyperlipidemia

Elevated liver enzymes have been reported; evaluate liver enzymes at baseline and then monitor in patients with known or suspected liver disease; if liver enzymes increase or drug-induced liver injury suspected; interrupt therapy until liver injury is ruled out

Before initiating, consider completion of all age-appropriate immunizations according to current immunization guidelines including prophylactic herpes zoster vaccination

Infections

• May increase infection risk; avoid use with active or serious infections, including localized infections
• Closely monitor for developing signs and symptoms of infection during and after treatment
• If infection develops, promptly evaluate and complete diagnostic testing
• Initiate appropriate antimicrobial therapy and closely monitor
• Interrupt therapy if serious infection develops; do not resume until infection resolves or is adequately treated

• Consider risks and benefits of therapy before initiating in patients

  • With chronic or recurrent infection
  • Who have been exposed to tuberculosis
  • With a history of a serious or an opportunistic infection
  • With underlying conditions that may predispose them to infection

• Viral reactivation

  • Herpes virus reactivation (eg, herpes zoster, herpes simplex), was reported
  • Impact on chronic viral hepatitis reactivation is unknown
  • Patients who tested positive for hepatitis B or C, chronic hepatitis B, or untreated hepatitis C were excluded from clinical trials
  • Consider viral hepatitis screening and monitoring for reactivation in accordance with clinical guidelines before initiating and during therapy
  • If signs of reactivation occur, consult a hepatitis specialist
  • Not recommended for use in patients with active hepatitis B or hepatitis C

Potential risks related to Janus kinase (JAK) inhibitors

• Unknown whether TYK2 inhibition may be associated with the observed or potential adverse reactions of JAK inhibition
• In a safety trial of a JAK inhibitor in rheumatoid arthritis (RA), patients aged ≥50 years with at least 1 cardiovascular risk factor, higher rates of all-cause mortality, including sudden cardiovascular death, major adverse cardiovascular events, overall thrombosis, deep venous thrombosis, pulmonary embolism, and malignancies (excluding non-melanoma skin cancer) were observed in patients treated with the JAK inhibitor
• Not approved for use in RA

Drug interaction overview

• Vaccinations

  • Live vaccines: Avoid use
  • Response to live or non-live vaccines not evaluated

Pregnancy

Insufficient data are available from case reports on use during pregnancy to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcome

Report pregnancies to Bristol-Myers Squibb Company’s Adverse Event reporting line at 1-800-721-5072

Animal data

• No effects on embryofetal development were observed with oral administration to rats and rabbits during organogenesis at doses that were at least 91x the maximum recommended human dose of 6 mg once daily

Lactation

There are no data on drug presence in human milk, effects on breastfed infant, or effects on milk production

Present in rat milk; when a drug is present in animal milk, it is likely that it will be present in human milk

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Tyrosine kinase 2 (TYK2) inhibitor, which is a member of JAK family, binds to regulatory domain of TYK2 resulting in inhibitor of receptor-mediated active of TYK2 and its downstream activation of signal transducers and activators of transcription

TYK2 pairs with JAK1 to mediate multiple cytokine pathways and pairs with JAK2 to transmit signals as shown in cell-based assays

Precise mechanism linking inhibition of TYK2 enzyme to therapeutic effectiveness is unknown

Absorption

Bioavailability: 99%

Peak plasma time: 2-3 hr

Peak plasma concentration

• Deucravacitinib: 45 ng/mL
• BMT-153261 (active metabolite): 5 ng/mL

AUC

• Deucravacitinib: 473 ng·hr/mL
• BMT-153261 (active metabolite): 95 ng·hr//mL

Distribution

Vd (steady-state): 140 L

Protein bound: 82-90%

Blood-to-plasma concentration ratio: 1.26

Metabolism

Metabolized by CYP1A2 to form major metabolite BMT-153261 (accounts for ~20% of systemic exposure of total drug-related components)

Also, metabolized by CYP2B6, CYP2D6, carboxylesterase (CES) 2, and uridine glucuronyl transferase (UGT)1A9

Elimination

Half-life: 10 hr

Renal clearance: 27-54 mL/minute

Excretion

• Deucravacitinib: Urine (13%); feces (26%)
• BMT-153261: Urine (6%); feces (12%)

Oral Administration

Take with or without food

Do not crush, cut, or chew tablets

Storage

Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

Keep out of reach of children