A review of clinical trials finds deucravacitinib to be an effective and safe treatment for moderate-to-severe psoriasis.
Psoriasis is a chronic inflammatory skin disease with an estimated prevalence of 2–3% globally. Systemic therapies are often required for moderate-to-severe disease; however, conventional systemic therapies have numerous disadvantages or limitations.
A literature review published in the Journal of Dermatological Treatment reviewed the current knowledge on deucravacitinib, a new drug that selectively inhibits tyrosine kinase 2 (TYK2), for the treatment of psoriasis.
Highly Selective TYK2 Inhibitor
Deucravacitinib is an oral TYK2 inhibitor recently FDA-approved for treating moderate-to-severe plaque psoriasis. Unlike other JAK inhibitors, deucravacitinib binds allosterically to the regulatory pseudokinase domain of TYK2 and, therefore, inhibits TYK2 with high selectivity with minimal or no inhibition of JAK 1/2/3, lowering the risk of off-target effects.
Remarkable Efficacy and Sustained Improvement in Moderate-to-Severe Psoriasis
In a phase 2 trial comprising 267 patients with moderate-to-severe psoriasis, a remarkably higher percentage of patients on deucravacitinib achieved a Psoriasis Area and Severity Index (PASI) score of 75 at week 12 versus placebo. A similar pattern was observed regarding improvements in quality of life.
Two large recent phase 3 trials (POETYK PSO-1 and POETYK PSO-2) compared deucravacitinib to placebo and apremilast in 1686 moderate-to-severe psoriasis patients. In both trials, deucravacitinib treatment was notably more effective than apremilast and placebo. At week 16, 58.7% and 53.6% (PSO-1 and PSO-2, respectively) of patients on deucravacitinib attained PASI 75, versus 35.1% and 40.2% on apremilast and 12.7% and 9.4% on placebo.
Similarly, at week 16, 53.6% and 50.3% of patients on deucravacitinib attained a static Physician’s Global Assessment (sPGA) 0/1 response versus 32.1% and 34.3% on apremilast and 7.2% and 8.6% on placebo. Deucravacitinib maintained its superiority over apremilast at week 24, with PASI 75: 69% and 59.3% vs. 38.1% and 37.8% in PSO-1 and PSO-2, respectively, and sPGA 0/1 response achieved in 58.4% and 50.4% of deucravacitinib vs. 31% and 29.5% of apremilast patients.
In POETYK PSO-1, participants on continuous deucravacitinib treatment maintained PASI 75 and sPGA 0/1 responses from week 16 to week 52. Additionally, participants who were switched from placebo to deucravacitinib at week 16 demonstrated PASI 75 and sPGA 0/1 responses at week 52 comparable to those on continuous deucravacitinib treatment. In PSO-2, most participants on continuous deucravacitinib therapy maintained PASI 75 and sPGA 0/1 responses from week 24 to week 52.
Long-Term Effectiveness Demonstrated in the POETYK PSO Extension Trial
At the end of the 52-week POETYK PSO-1 and POETYK PSO-2, a total of 1221 participants were switched to a 240-week open-label deucravacitinib extension trial. From week 0 to 60, patients already on deucravacitinib at week 0 continued improving. Those patients who switched from apremilast to deucravacitinib at week 0 also showed improvement.
Well-Tolerated and Safe
In a phase 1 trial that included 108 healthy participants, deucravacitinib was found to be well-tolerated with no serious adverse events (AEs). In a phase 2 trial, AEs were reported in 55–80% of patients on deucravacitinib compared to 51% of those on placebo. There were no cases of opportunistic infections, herpes zoster infection, tuberculosis, or cardiovascular events, and no significant changes in blood counts, serum lipids, creatinine, hepatic enzymes, or immunoglobulins. In phase 3 trials POETYK PSO-1 and PSO-2, a lower percentage of patients on deucravacitinib had AEs leading to treatment discontinuation than apremilast at week 16.
The most frequent AEs with deucravacitinib were nasopharyngitis and upper respiratory tract infection. Headache, nausea, and diarrhea had a similar frequency in the deucravacitinib and placebo groups. No significant changes were observed in creatine phosphokinase, total cholesterol, platelets, or neutrophils with deucravacitinib. There were no opportunistic infections or tuberculosis, and no serious cases of herpes zoster.
Source:
Estevinho, T., Lé, A. M., & Torres, T. (2022). Deucravacitinib in the treatment of psoriasis. Journal of Dermatological Treatment, 34(1). https://doi.org/10.1080/09546634.2022.2154122
