Sotyktu From Bristol Myers Squibb

The FDA has approved deucravacitinib oral tablets (Sotyktu; Bristol Myers Squibb) for the treatment of moderate to severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy. The approval carries the limitation that deucravacitinib is not recommended for use in combination with other potent immunosuppressants.¹ Psoriasis is a chronic, systemic immune-mediated disease that affects an estimated 100 million individuals worldwide, including 7.5 million in the United States. Plaque psoriasis is the most common form of the condition and is characterized by oval or round plaques on the skin that are covered with silvery white scales. Approximately 25% of psoriasis cases are considered moderate to severe.²

Pharmacology and Pharmacokinetics

Deucravacitinib is a tyrosine kinase 2 (TYK2) inhibitor. Its median time to maximum plasma concentration is 2 to 3 hours, and it displays a terminal elimination half-life of 10 hours.¹

Dosage and Administration

The recommended dose of deucravacitinib is 6 mg orally once daily. The medication may be taken with or without food.¹

Clinical Trials

Deucravacitinib was evaluated for efficacy and safety in 2 active- and placebo-controlled, double-blind, multicenter, randomized trials: POETYK-PSO-1 (NCT03624127) and POETYK-PSO-2 (NCT03611751).^3,4 In the trial, 1684 adults with moderate to severe plaque psoriasis who were eligible for phototherapy or systemic therapy were randomly assigned to receive apremilast (Otezla) 30 mg orally twice daily, deucravacitinib 6 mg orally once daily, or a placebo. The trials met their 2 coprimary end points, which were the proportion of participants who achieved a static Physician’s Global Assessment (sPGA) score of 0 (clear) or 1 (almost clear), with at least a 2-grade improvement from baseline at week 16, and the proportion of participants who achieved at least a 75% improvement in the Psoriasis Area and Severity Index (PASI) score from baseline at week 16. Secondary end points met by both trials were the percentage of patients who achieved PASI 75, PASI 90, and sPGA 0/1 compared with apremilast at weeks 16 and 24.

Additionally, 82% of the participants who achieved PASI 75 with deucravacitinib at week 24 in POETYK-PSO-1 maintained their response at week 52.

In POETYK-PSO-2, participants who were originally randomly assigned to deucravacitinib and achieved PASI 75 at week 24 were randomly assigned again to either continue deucravacitinib or receive the placebo. The trial results showed that 80% of participants who continued deucravacitinib maintained their PASI 75 response at week 52 compared with 31% of participants in whom deucravacitinib was discontinued and replaced with the placebo.^1,2

Contraindications, Warnings, and Precautions

The use of deucravacitinib is contraindicated in patients with a known hypersensitivity to the medication or any of its components. Hypersensitivity reactions, such as angioedema, have occurred in patients using deucravacitinib.

Because deucravacitinib may increase the risk of infections, it should not be used in patients with active or serious infections. Evaluate patients for tuberculosis before beginning treatment with deucravacitinib. Malignancies, including lymphoma, were observed during clinical trials with deucravacitinib.

Elevations in creatine phosphokinase, liver enzymes, and triglycerides have occurred and may require periodic evaluation. Rhabdomyolysis has been reported during treat ment with deucravacitinib. Patients using deucravacitinib should not receive live vaccines.

In patients with rheumatoid arthritis (RA), higher rates of all cause mortality, including deep vein thrombosis, major adverse cardiovascular events, malignancies (excluding nonmelanoma skin cancer), overall thrombosis, pulmonary embolism, and sudden cardiovascular death, were observed in patients using a Janus kinase (JAK) inhibitor compared with those using tumor necrosis factor blockers.

It is unknown whether TYK2 inhibitors are associated with these adverse reactions observed with JAK inhibition.

Deucravacitinib should not be used in patients with severe hepatic impairment, and it is not approved for use in patients with RA. The most common adverse reactions are acne, folliculitis, herpes simplex virus, increased blood creatine phosphokinase, mouth ulcers, and upper respiratory infections.¹

References

1. Sotyktu. Prescribing information. Bristol Myers Squibb; 2022. Accessed October 27, 2022.https://packageinserts.bms.com/pi/pi_sotyktu.pdf
2. U.S. Food and Drug Administration approves Sotyktu (deucravacitinib), oral treatment for adults with moderate-to-severe plaque psoriasis. News release. Bristol Myers Squibb. September 9, 2022. Accessed October 27, 2022. https://news.bms.com/news/details/2022/U.S.-Food-and-Drug-Administration-Approves-Sotyktu-deucravacitinib-Oral-Treatment-for-Adults-with-Moderate-to-Severe-Plaque-Psoriasis/default.aspx
3. Effectiveness and safety of BMS-986165 compared to placebo and active comparator in participants with psoriasis (POETYK-PSO-1). Updated September 21, 2021. Accessed January 16, 2023. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03624127
4. An investigational study to evaluate experimental medication BMS-986165 compared to placebo and a currently available treatment in participants with moderate-to-severe plaque psoriasis (POETYK-PSO-2). Updated December 20, 2022. Accessed January 16, 2023.https://clinicaltrials.gov/ct2/show/NCT03611751

About the Author

Monica Holmberg, PharmD, BCPS, is a pharmacist in Phoenix, Arizona, and a Pharmacy Times®