Real-World 52-Week Effectiveness Study of Deucravacitinib in Psoriasis

Background Introduction

Psoriasis is a chronic inflammatory skin disease with a global prevalence of approximately 1% to 3%. This condition not only affects patients’ quality of life (QoL) but is also often accompanied by comorbidities such as cardiovascular diseases, diabetes, and depression. Recent studies have found that the IL-17 and IL-23 pathways play key roles in the pathogenesis of psoriasis, while tyrosine kinase 2 (TYK2), a member of the Janus kinase (JAK) family, participates in the pathological process of psoriasis by transmitting intracellular signals of IL-12, IL-23, and type I interferons (IFNs). Therefore, therapeutic agents targeting TYK2 may become effective treatments for psoriasis.

Deucravacitinib is an oral TYK2 inhibitor that inhibits TYK2 allosterically by binding to the regulatory domain (pseudokinase domain) rather than directly to its catalytic domain. Compared to JAK1, JAK2, and JAK3, Deucravacitinib exhibits high selectivity for TYK2 and can block intracellular signals mediated by IL-23 and type I IFNs. However, although clinical trials have demonstrated the short-term efficacy of Deucravacitinib, its long-term effectiveness in real-world settings, particularly in detailed analyses stratified by age and body mass index (BMI), has not been sufficiently studied.

Source of the Study

This research was conducted by a team including Teppei Hagino, Marina Onda, and Hidehisa Saeki from the Department of Dermatology at Nippon Medical School Chiba Hokusoh Hospital, Japan. The findings were published in the Journal of Dermatology in 2025. The study aimed to evaluate the 52-week real-world effectiveness of Deucravacitinib in psoriasis patients, with a particular focus on stratified analyses by age (≥65 years vs <65 years) and BMI (≥25 vs <25).

Study Process and Design

Study Design

This prospective study spanned from December 2022 to August 2024 and included 107 Japanese patients aged ≥15 years with moderate to severe psoriasis. Patients received 6 mg of oral Deucravacitinib daily for 52 weeks. The primary evaluation indicators included the achievement rates of PASI 75, PASI 90, and PASI 100, as well as other key clinical metrics such as the Static Physician’s Global Assessment (sPGA) and Dermatology Life Quality Index (DLQI). Data analysis was performed stratified by age and BMI.

Data Collection

Baseline characteristics were recorded before initiating Deucravacitinib treatment, including age, sex, BMI, disease duration, prior treatments (e.g., phosphodiesterase 4 inhibitor apremilast or biologics), presence of arthritis, scalp, nail, or genital lesions, as well as diabetes, cardiovascular diseases, smoking status, baseline PASI scores, sPGA, and DLQI scores.

Inclusion and Exclusion Criteria

The study included patients with psoriasis vulgaris, psoriatic arthritis, and erythrodermic psoriasis. All patients received Deucravacitinib treatment for at least 4 weeks. When switching from prior systemic therapies (e.g., apremilast or biologics) to Deucravacitinib, no washout period was implemented, and data at the time of switching were used as baseline data. Exclusion criteria included patients who resumed Deucravacitinib, those with severe cardiovascular diseases, malignancies, active infections, hypersensitivity to Deucravacitinib or its components, and pregnant or breastfeeding women.

Efficacy Assessment

Changes in PASI and DLQI were recorded over the 52-week period, and achievement rates of PASI 75, PASI 90, PASI 100, as well as PASI ≤2 or PASI ≤1, were calculated. Additionally, achievement rates of sPGA 0/1 and DLQI 0/1 (a reduction of ≥2 points from baseline) were evaluated.

Key Findings

Age-Stratified Analysis

In both patients aged ≥65 years and <65 years, mean PASI scores consistently decreased from baseline to week 52, from 12.41 to 1.03 and from 15.48 to 1.11, respectively. The achievement rates of PASI 75, PASI 90, and sPGA 0/1 were similar at week 52 in both groups; however, the achievement rates of PASI 100 and PASI ≤1 were slightly lower in patients aged ≥65 years compared to those <65 years. Furthermore, the achievement rate of DLQI 0/1 was higher at week 52 in patients aged ≥65 years, indicating a more significant improvement in quality of life among elderly patients.

BMI-Stratified Analysis

In patients with BMI ≥25 and <25, mean PASI scores consistently decreased from baseline to week 52, from 13.53 to 1.28 and from 14.16 to 1.01, respectively. The achievement rates of PASI 75, PASI 90, and sPGA 0/1 at week 52 were slightly lower in patients with BMI ≥25 compared to those with BMI <25, with significant differences observed at weeks 4, 16, 24, and 40. Additionally, the achievement rate of DLQI 0/1 at week 52 was lower in patients with BMI ≥25, suggesting slightly reduced efficacy in patients with higher BMI.

Correlation Between Baseline BMI and Clinical Indices

Spearman correlation analysis revealed significant positive correlations between baseline BMI and PASI, sPGA, and DLQI scores at week 52, indicating that higher BMI was associated with less clinical improvement. In contrast, no significant correlations were observed between baseline age and any clinical indices, suggesting minimal impact of age on efficacy.

Conclusions and Significance

The study demonstrated that Deucravacitinib significantly improved disease severity and quality of life in all psoriasis patients stratified by age or BMI. However, the achievement rates of PASI 75, PASI 90, and PASI 100 were slightly lower in patients with BMI ≥25 compared to those with BMI <25, indicating potentially reduced efficacy in patients with higher BMI. The study also showed that Deucravacitinib is effective in elderly patients, although the rate of complete skin clearance may be lower.

This research provides important guidance for personalized treatment of psoriasis patients, particularly offering valuable references for treatment selection in elderly patients and those with higher BMI. Additionally, the findings suggest that patients with higher BMI may require dose adjustments of Deucravacitinib for optimal efficacy.

Study Highlights

1. Long-Term Real-World Data: This study is the first to evaluate the 52-week effectiveness of Deucravacitinib in real-world settings, filling the gap in long-term efficacy data.
2. Age and BMI Stratified Analysis: The study specifically examined the impact of age and BMI on efficacy, providing crucial insights for personalized treatment.
3. Significant Improvement in Quality of Life: The study demonstrated that Deucravacitinib not only improves skin lesions but also significantly enhances patients’ quality of life, particularly in elderly patients.
4. Clinical Implications: The findings suggest that patients with higher BMI may require dose adjustments or alternative treatment strategies, such as biologics.

Additional Valuable Information

The study also discussed the differences in efficacy between Deucravacitinib and biologics (e.g., Bimekizumab), suggesting that patients with higher BMI may be more suitable for biologics. Furthermore, the results support the potential of TYK2 inhibitors in psoriasis treatment, offering direction for future drug development.