Deucravacitinib for plaque psoriasis

Approved indication: treatment of adult patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy
Sotyktu (Bristol-Myers Squibb)
6 mg film-coated tablets

Psoriasis is a chronic inflammatory skin condition. Moderate to severe plaque psoriasis may require systemic drug therapy and/or phototherapy.¹ Deucravacitinib is a recently approved oral psoriasis treatment that selectively inhibits tyrosine kinase 2 enzyme, thereby reducing the production of inflammatory cytokines.²

The efficacy and safety of deucravacitinib were assessed in 2 multicentre, randomised, double-blind, placebo- and active-controlled 52-week clinical trials (POETYK PSO-1 and POETYK PSO-2).^3,4 Together these trials included 1686 participants aged 18 years and older (mean 46 years) with moderate to severe plaque psoriasis.⁵ Participants were randomised to receive either deucravacitinib 6 mg once daily (n=843), apremilast (an oral phosphodiesterase 4 inhibitor used to treat plaque psoriasis) 30 mg twice daily (n=422) or placebo (n=421).^3,4 The primary objective was to compare deucravacitinib and placebo response rates at 16 weeks; comparison with apremilast (active control) was a secondary objective. Response rates were measured as the proportion of patients who achieved at least a 75% reduction in the Psoriasis Area and Severity Index (PASI) score from baseline (PASI 75) and a static Physician’s Global Assessment (sPGA) disease severity score of 0 (clear) or 1 (almost clear).^3,4

In both trials, at week 16 participants randomised to placebo were switched to deucravacitinib. To evaluate maintenance and durability of response to deucravacitinib, in the POETYK PSO-2 trial, patients who initially received deucravacitinib and achieved PASI 75 were re-randomised to continue the treatment or switch to placebo at week 24.⁴

Efficacy compared with placebo: Deucravacitinib was more efficacious than placebo in both POETYK trials: 58.4% (PSO-1) and 53.0% (PSO-2) of patients who received deucravacitinib achieved PASI 75 at week 16, compared with 12.7% (PSO-1) and 9.4% (PSO-2) of patients treated with placebo. An sPGA score of 0 or 1 at week 16 was achieved in 53.6% (PSO-1) and 49.5% (PSO-2) of deucravacitinib-treated patients, compared with 7.2% (PSO-1) and 8.6% (PSO-2) in the placebo group.^3,4

Efficacy compared with apremilast: Deucravacitinib was also more efficacious than apremilast in both POETYK trials: 35.1% (PSO-1) and 39.8% (PSO-2) of apremilast-treated patients achieved PASI 75, and 32.1% (PSO-1) and 33.9% (PSO-2) had achieved an sPGA score of 0 or 1, at 16 weeks.^3,4

Patient-reported outcomes: Patients who received deucravacitinib reported greater improvements in psoriasis symptoms and quality of life–related outcomes compared with those who received placebo or apremilast.^4,6

Maintenance and durability of response: In POETYK PSO‑2, 80.4% of deucravacitinib responders who continued deucravacitinib from weeks 24 to 52 maintained PASI 75, compared with 31.3% of those who switched to placebo; the median time to loss of PASI 75 was approximately 12 weeks.⁴ Results from an open‑label extension study indicated maintained efficacy with deucravacitinib up to 2 years.⁷

Pooled safety analysis from the 2 trials reported that nasopharyngitis and upper respiratory tract infections were the most common adverse effects with deucravacitinib (16.8% and 9.1% of patients, respectively, over 52 weeks), but exposure-adjusted incidence rates were similar to the placebo and apremilast groups.⁵ Acne and folliculitis were more common in deucravacitinib recipients (2.1% and 2.0%, respectively) than placebo or apremilast recipients. Gastrointestinal events such as diarrhoea and nausea were less common with deucravacitinib than apremilast.⁵ Serious infections including COVID-19 were reported for deucravacitinib (1.7 per 100 person-years); this was comparable with apremilast. Non-serious herpes zoster infections were reported for deucravacitinib (0.9 per 100 person-years) but did not require treatment withdrawal. Malignancies (mainly nonmelanoma skin cancer) were also reported (1.0 per 100 person-years).^5,8

Deucravacitinib should not be started in patients with active infection. Tuberculosis screening is recommended prior to starting treatment; viral hepatitis screening may also be considered in those with higher risk. Live vaccines should be avoided during treatment. Patients should be checked for, and advised to report signs and symptoms of, tuberculosis and skin cancer. Monitoring of creatine phosphokinase, serum triglycerides and liver enzymes is advised.^5,9

Deucravacitinib is eliminated via multiple pathways, therefore the risk of significant drug–drug interactions is thought to be low,⁸ and dose adjustments are not needed in renal or hepatic impairment. Deucravacitinib is not recommended for patients with severe hepatic impairment. Safety and efficacy in patients under 18 years of age have not been established.⁹ Limited human data are available on its safety in pregnancy.⁹

Deucravacitinib provides a new oral treatment option for adults with moderate to severe plaque psoriasis. Consideration should be given to its adverse effect profile, and additional screening and monitoring is required.

This new drug comment was finalised on 28 October 2024.

🅃 🅃 manufacturer provided additional useful information. The Transparency Score is explained in New drugs: transparency, Vol 37 No 1, Aust Prescr 2014;37:27.

At the time the comment was prepared, information about this drug was available on the websites of the Food and Drug Administration in the USA, the European Medicines Agency and the Therapeutic Goods Administration.

 

References

1. Psoriasis. In: Therapeutic Guidelines. Melbourne: Therapeutic Guidelines Limited; 2022. [cited 2024 Aug 23]
2. Kingston P, Blauvelt A, Strober B, Armstrong AW. Deucravacitinib: a novel TYK2 inhibitor for the treatment of moderate-to-severe psoriasis. J Psoriasis Psoriatic Arthritis 2023;8:156-65.
3. Armstrong AW, Gooderham M, Warren RB, Papp KA, Strober B, Thaçi D, 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;88:29-39.
4. Strober B, Thaçi D, Sofen H, Kircik L, Gordon KB, Foley P, 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 Program fOr Evaluation of TYK2 inhibitor psoriasis second trial. J Am Acad Dermatol 2023;88:40-51.
5. Strober B, Blauvelt A, Warren RB, Papp KA, Armstrong AW, Gordon KB, et al. Deucravacitinib in moderate-to-severe plaque psoriasis: Pooled safety and tolerability over 52 weeks from two phase 3 trials (POETYK PSO-1 and PSO-2). J Eur Acad Dermatol Venereol 2024;38:1543-54.
6. Armstrong AW, Augustin M, Beaumont JL, Pham TP, Hudgens S, Gordon KB, et al. Deucravacitinib Improves Patient-Reported Outcomes in Patients with Moderate to Severe Psoriasis: Results from the Phase 3 Randomized POETYK PSO-1 and PSO-2 Trials. Dermatol Ther (Heidelb) 2024;14:2235-48.
7. Lebwohl M, Warren RB, Sofen H, Imafuku S, Paul C, Szepietowski JC, et al. Deucravacitinib in plaque psoriasis: 2-year safety and efficacy results from the phase III POETYK trials. Br J Dermatol 2024;190:668-79.
8. Therapeutic Goods Administration. Australian Public Assessment Report for Sotyktu. Canberra; 2023. [cited 2024 Aug 28]
9. Therapeutic Goods Administration. Australian Product Information – Sotyktu (deucravacitinib) film-coated tablets. Canberra: Department of Health and Aged Care; 2024. [cited 2024 Aug 28]

 The new drug commentaries in Australian Prescriber are prepared by the editors and reviewed by the Editorial Advisory Committee. Some of the views expressed on newly approved products should be regarded as preliminary, as there may be limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Advisory Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.