Deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor, has demonstrated sustained efficacy and a consistent safety profile over three years in patients with moderate to severe plaque psoriasis. The findings come from an integrated analysis of the phase 3 POETYK PSO-1, PSO-2, and a nonrandomized long-term extension (LTE) trial, providing crucial insights into the long-term management of this chronic inflammatory skin disease. The study, published in JAMA Dermatology, offers clinicians and patients alike confidence in the durable benefits of deucravacitinib.
The study enrolled 1519 patients with moderate to severe plaque psoriasis. After completing 52 weeks of treatment in the PSO-1 or PSO-2 trials, patients could enroll in the LTE trial and receive open-label deucravacitinib (6 mg once daily). The primary outcome was safety, assessed through adverse events (AEs), serious AEs (SAEs), and AEs of interest (AEIs). Efficacy outcomes included PASI 75/90 and static Physician Global Assessment scores (sPGA 0/1).
Sustained Clinical Response
Results from the analysis showed that 513 patients received continuous deucravacitinib treatment from day 1 of the parent trials and entered the LTE trial. These patients maintained clinical response rates through 3 years. Specifically, PASI 75 was achieved by 72.6% of patients at the start of the LTE and 73.2% at 3 years. PASI 90 was achieved by 45.6% and 48.1%, respectively, and sPGA 0/1 by 58.1% and 54.1%, respectively. These results underscore the long-term effectiveness of deucravacitinib in controlling psoriasis symptoms.
Consistent Safety Profile
The safety profile of deucravacitinib remained consistent over the 3-year period. Exposure-adjusted incidence rates (EAIRs) per 100 person-years were decreased or similar in the 1-year vs 3-year cumulative periods for AEs (229.2 vs 144.8), SAEs (5.7 vs 5.5), discontinuations due to AEs (4.4 vs 2.4), and deaths (0.2 vs 0.3). The most common AEs, such as nasopharyngitis and upper respiratory tract infection, also showed reduced incidence over time. An increase in COVID-19 cases (0.5 vs 8.0) was noted, coinciding with the global pandemic.
Impact on Quality of Life
Beyond clinical efficacy, deucravacitinib has demonstrated a significant positive impact on patients' quality of life. Data from the ARTISTYK trial, a randomized, double-blind, placebo-controlled, phase 4 study, revealed that deucravacitinib can alleviate quality of life impairments in those with moderate to severe plaque psoriasis. After 16 weeks of treatment, 33.3% of patients in the deucravacitinib arm reported experiencing zero effects of psoriasis on their quality of life, compared to 0% at baseline. This improvement highlights the holistic benefits of deucravacitinib, addressing not only the physical symptoms but also the psychological and social burdens of psoriasis.
Deucravacitinib's Effectiveness Across Treatment Histories
Real-world data from a prospective, single-center analysis in Japan further supports the versatility of deucravacitinib. The study, conducted between December 2022 and September 2024, assessed the 52-week effectiveness of deucravacitinib (6 mg/day) in patients with psoriasis, stratified by a history of apremilast or biologic usage. The results indicated that deucravacitinib reduced PASI and DLQI scores throughout the 52-week treatment period, regardless of prior apremilast or biologic use. This suggests that deucravacitinib can be an effective treatment option for patients with varying treatment histories.
Expert Commentary
“This study highlights the negative impact of psoriasis on our patients’ quality of life, but more importantly, we learned that even patients with low body surface area (BSA) involvement are affected by their disease negatively,” said Leon H. Kircik, MD, a steering committee member and investigator in the ARTISTYK trials, clinical professor of dermatology at the Icahn School of Medicine at Mount Sinai. “Deucravacitinib demonstrated consistent clinical efficacy and improvement of quality of life in these patients measures as well as safety.”
Conclusion
The 3-year data from the POETYK PSO trials, combined with real-world evidence, solidify deucravacitinib as a safe and effective long-term treatment option for moderate to severe plaque psoriasis. Its ability to sustain clinical responses, maintain a consistent safety profile, improve quality of life, and remain effective across different treatment histories positions deucravacitinib as a valuable tool in the management of this chronic condition.
