Deucravacitinib - Dosage, Uses, Side Effects, Contraindications, and Warnings and Precautions

Overview

Deucravacitinib is a drug indicated for the treatment of moderate to severe plaque psoriasis (skin disorder with white scales and red patches) in adults who are suitable for phototherapy (light treatment) or systemic treatments. It belongs to a class of medications known as kinase inhibitors. It is mainly recommended for patients for whom topical therapies are ineffective. Deucravacitinib was approved by the United States Food and Drug Administration (US FDA) on September 9, 2022, and by the European Medicines Agency on March 24, 2023. Since its approval, Deucravacitinib has become a valuable addition to treating psoriasis for many skin specialists. Patients must be evaluated for tuberculosis (a bacterial infection) before starting treatment with Deucravacitinib.

How Does Deucravacitinib Work?

The tyrosine kinase 2 enzyme belongs to the Janus kinases (JAK) family of proteins and is responsible for signaling inflammation by triggering the production of cytokines. Deucravacitinib is a tyrosine kinase 2 (TYK2) inhibitor that acts by blocking the action of TYK2, thereby lowering inflammation and other symptoms of plaque psoriasis, thus improving the condition of the patient. It has a good safety profile and is usually well-tolerated by most patients.

Indications of Deucravacitinib

Deucravacitinib is indicated for managing moderate to severe plaque psoriasis in adult patients and is suitable for phototherapy or systemic therapy.

Contraindications of Deucravacitinib

• Deucravacitinib is contraindicated for individuals with hypersensitivity to the drug or its components.

• It is contraindicated in patients with active tuberculosis, hepatitis (inflammation of the liver), and other infections, as well as in patients with severe liver disorders and rheumatoid arthritis (autoimmune disease affecting joints).

• Deucravacitinib is also not recommended for children and adolescents.

Available Doses and Dose Forms

Deucravacitinib is recommended at 6 mg (milligrams) to be taken orally daily with or without food.

Warnings and Precautions

• Deucravacitinib can cause hypersensitivity reactions such as angioedema (swelling under the skin) in some patients. In such cases, treatment must be discontinued, and appropriate management must be considered.

• Patients must be evaluated for active or latent tuberculosis (TB) infection, and if positive, anti-tubercular therapy must be initiated before starting Deucravacitinib. Patients must be frequently monitored for the signs and symptoms of active TB during the treatment with Deucravacitinib.

• Deucravacitinib can potentially increase the risk of infection in patients; therefore, the drug must be avoided during serious infections such as pneumonia (lung infection). Patients must be regularly monitored during the treatment. Suppose any signs or symptoms of infection are observed. In that case, a prompt diagnosis must be made, appropriate antimicrobial treatment must be considered, and until the infection subsides, Deucravacitinib must not be resumed.

• Malignancies such as lymphomas were reported during the clinical trials of Deucravacitinib. Therefore, the benefits and risks of using the drug for the patient must be considered before initiating the treatment, especially in patients with a known risk of malignancy or if the patient develops malignancy during treatment.

• Deucravacitinib can increase the levels of triglyceride and liver enzymes; therefore, periodic monitoring must be done during the treatment, and the drug must be interrupted if treatment-related elevations are observed.

• Deucravacitinib can cause rhabdomyolysis and increased creatinine phosphokinase levels in some patients; hence, it must be discontinued in such cases or if myopathy (muscle disorder) is suspected or diagnosed.

• All age-appropriate immunizations must be completed before starting treatment, as live vaccines or prophylactic immunizations must be avoided during treatment with Deucravacitinib.

Adverse Effects of Deucravacitinib

Some of the adverse effects of Deucravacitinib include:

• Sore throat.

• Runny nose.

• Congestion.

• Soreness of the tongue, gums, lips, and roof of the mouth.

• Red, painful, and swollen hair follicles.

• Skin rash, itchy bumps.

• Abdominal pain.

• Yellowish discoloration of the skin and eyes.

• Swelling of the face, lips, tongue, and throat.

• Chest tightness.

• Tiredness.

• Muscle pain.

• Fever.

• Dark urine.

For Patients

What Is Plaque Psoriasis?

Plaque psoriasis is a chronic (long-lasting) skin disorder characterized by large oval or circular raised red patches (plaques) with white spots over the scalp, trunk, elbows, knees, and other body surfaces. It can also be associated with itching, bleeding, pain, and irritation. The exact cause of this disorder is unknown; however, it is considered an autoimmune disease (the body’s immune system attacks healthy cells). There are different types of plaque psoriasis, but the disease is not contagious. Topical medications, systemic drugs, and light therapy usually manage plaque psoriasis.

What Is Deucravacitinib?

Deucravacitinib is a prescription medicine for treating moderate to severe plaque psoriasis in adult patients. It belongs to a class of medicines called kinase inhibitors and acts by blocking the action of abnormal proteins in the body that signal the cells to multiply. Deucravacitinib can control plaque psoriasis, but it cannot completely cure it. This medicine must be taken exactly as prescribed and not stopped without the doctor’s consent, even if the patient feels better.

How Effective Is Deucravacitinib?

Deucravacitinib is prescribed to patients whose disease is too severe to be treated by topical medications. However, it must not be taken with other medications that suppress the immune system. Clinical studies have demonstrated that Deucravacitinib is superior to many other drugs and is safe and well-tolerated. Most patients have shown a significant reduction of the symptoms within a few weeks of treatment.

How Should Deucravacitinib Be Taken?

Deucravacitinib is available as a tablet and must be taken orally once a day around the same time, with or without food. The tablet must be taken whole and not be chewed, crushed, split, or dissolved in fluids. It must be taken exactly as prescribed, and the dose must not be increased or decreased. Patients must read the label provided with the medicine or consult the doctor to understand the treatment before starting Deucravacitinib.

What Are the Side Effects of Deucravacitinib?

The side effects of Deucravacitinib include the following:

• Skin rash, itching.

• Red, painful, and swollen itchy bumps.

• Acne.

• Runny nose, sore throat.

• Chest congestion.

• Sores on the lips, gums, roof of the mouth, and tongue.

• Yellowish discoloration of the skin and eyes.

• Abdominal pain.

• Difficulty breathing.

• Swelling of the face, lips, and tongue.

• Dark urine.

What Must the Patient Inform the Doctor Before Taking Deucravacitinib?

• Before starting the treatment, patients must tell the doctor if they are allergic to Deucravacitinib, its components, or other medications.

• Patients must inform the doctor if they have any long-term infections or frequent infections before starting treatment with Deucravacitinib.

• Before taking Deucravacitinib, female patients must tell the doctor if they are pregnant, breastfeeding, planning, or suspecting pregnancy.

• Patients must check with their doctor if they are due for any vaccinations or must inform the doctor if they have received any vaccines recently before starting the treatment with Deucravacitinib.

• Patients must tell the doctor if they have or have ever had pneumonia, tuberculosis, liver disease (hepatitis), increased triglyceride levels (cholesterol), cancer, or any other medical conditions before starting Deucravacitinib.

• Before taking Deucravacitinib, patients must inform their healthcare provider if they take vitamins, nutritional supplements, herbal medicines, other medications, or over-the-counter (OTC) drugs.

What Are the Precautionary Measures to Be Followed While Taking Deucravacitinib?

• The doctor will recommend certain blood tests to check liver function and cholesterol levels before and during the treatment with Deucravacitinib.

• Deucravacitinib can decrease the ability of the immune system to fight diseases and thus increase the risk of frequent infections; hence, the patient must inform the doctor immediately if they experience fever, chills, cough, sore throat, muscle ache, or any other symptoms.

• Deucravacitinib can cause severe allergic reactions in some patients; therefore, patients or caregivers must inform the doctor if they experience severe itching, skin rash, difficulty breathing, swelling of the face, or any other symptoms during the treatment.

• Deucravacitinib can increase the risk of developing muscle problems or rhabdomyolysis (muscle breakdown) and cancer; hence, patients must inform the doctor if they experience severe muscle pain or weakness accompanied by fever during the treatment.

Dietary Considerations

No dietary restrictions are required during the treatment with Deucravacitinib unless instructed by the prescribing doctor.

Missed Dose

Deucravacitinib must be taken regularly; however, if a dose is missed, it must be taken as soon as remembered. If it is almost time for the next dose, the missed dose can be skipped, and the normal dosing schedule must be followed. A double dose of Deucravacitinib must not be taken to compensate for the missed dose.

Overdose

The healthcare provider must be contacted immediately in the event of an overdose or if the patient experiences any serious side effects.

Storage

Deucravacitinib must be stored in its original container at a room temperature of about 20 to 25 degrees Celcius (68 to 77 degrees Fahrenheit), away from excess heat and moisture.

For Doctors

Pharmacological Aspects of Deucravacitinib

Mechanism of Action

Deucravacitinib is a tyrosine kinase 2 (TYK2) inhibitor and a member of the Janus kinase family. It selectively binds to the TYK2 receptor (regulatory domain) and stabilizes an inhibitory interaction between the catalytic and regulatory domains of the enzyme. This prevents the receptor-mediated activation of TYK2 and its downstream functions in the tissues. TYK2 is responsible for the mediation of the signaling of interleukins (IL-23 and IL-12) and type 1 interferon (IFN), which are the cytokines involved in producing inflammatory and immune responses. Deucravacitinib acts by inhibiting the release of these proinflammatory cytokines and chemokines.

Pharmacodynamics

Deucravacitinib reduces psoriasis-associated gene expression and also the genes regulating the IL-23 and IFN type 1 pathways. After approximately 16 weeks of once-daily treatment with Deucravacitinib, the levels of interleukins (IL-17A and IL-19) and beta-defensin were reduced by 47 to 50 percent, 72 percent, and 81 to 84 percent, respectively.

Pharmacokinetics

• Absorption: After an oral administration of Deucravacitinib, the maximum plasma concentration and area under the curve (AUC) increased proportionally depending on the dose. After a 6 mg once-daily dose, the steady state was 45 ng/ml (nanogram per milliliter), and the AUC was 473 ng hr/mL (nanogram per hour per milliliter). The steady state of the metabolite of Deucravacitinib BMT-153261 after a 6 mg once-daily dose was 5 ng/ml, and the AUC was 95 ng. Hr/mL. The absolute oral bioavailability of the drug was 99 percent, with a time taken to reach the maximum concentration (Tmax) of about two to three hours.

• Distribution: Approximately 82 to 90 percent of Deucravacitinib is bound to plasma proteins, and the blood-to-plasma concentration was about 1.26. The volume of distribution of the drug in a steady state was 140 L (liters).

• Metabolism: Deucravacitinib gets metabolized into its major active metabolite, BMT-153261, by cytochrome P-450 1A2, CYP2B6, CYP2D6, and other enzymes. The metabolite accounts for about 20 percent of the total drug-related components.

• Excretion: Following a single dose of Deucravacitinib (radiolabeled), around 13 was recovered in urine and about 26 percent in the feces; approximately 6 percent and 12 percent of the metabolite were detected in urine and feces, respectively.

Drug Interactions

The following drugs are known to interact with Deucravacitinib:

• Abatacept.

• Alefacept.

• Anakinra.

• Betamethasone.

• Budesonide.

• Chloramphenicol.

• Cyclosporine.

• Dexamethasone.

• Idelalisib.

• Influenza virus vaccine.

• Ketoconazole.

• Measles vaccine.

• Methylprednisolone.

• Polio vaccine.

• Prednisolone.

• Rubella vaccine.

• Rituximab.

• Ublituximab.

• Zanubrutinib.

Clinical Studies

Two randomized, double-blind, multicenter, placebo, and active-controlled studies (PSO-1 and PSO-2) were conducted to determine the safety and efficacy of Deucravacitinib in adult patients. 1684 subjects with a mean age of 47 years and a mean weight of 91 kg (200 pounds) were included and randomized to receive either Deucravacitinib or a placebo, or 30 mg of Apremilast orally, twice daily.

Around 18 percent of the patients had a history of psoriatic arthritis, 40 percent had received phototherapy, 41 percent had received non-biologic systemic treatment, 35 percent had prior biologic therapy, and 42 percent were new to any systemic therapy. The results were assessed after 16 weeks of treatment, and Deucravacitinib was found to be safe and effective compared to placebo and superior to Apremilast. No significant differences were observed in drug responses in terms of race, age, gender, weight, disease severity, or prior systemic therapy.

Nonclinical Toxicology

Animal studies have reported that Deucravacitinib did not exhibit carcinogenicity or mutagenicity properties, and the drug did not significantly affect fertility or reproductive parameters in male and female rats.

Specific Considerations

• Pregnancy: Sufficient data is not available to determine the drug-associated risks of Deucravacitinib, such as birth defects, miscarriage, and adverse effects on the mother or fetus. Therefore, the drug is not recommended for pregnant women.

• Lactation: No data is available to determine the presence of Deucravacitinib in breast milk, its effects on milk production, or the breastfed infant. Hence, it is not recommended for lactating women.

• Pediatric Use: The safety and effectiveness of Deucravacitinib have not been determined in pediatric patients.

• Geriatric Use: No significant differences were observed during the treatment with Deucravacitinib between younger adults and patients above 65 years of age.

• Renal and Hepatic Impairment: Dosage adjustment is not required in patients with mild, moderate, or severe kidney disorders or with mild or moderate liver diseases. However, Deucravacitinib is not recommended for patients with severe liver impairment.