Guselkumab-Treated Patients with Plaque Psoriasis Who Achieved Complete Skin Clearance for ≥ 156 Consecutive Weeks: A Post-Hoc Analysis From the VOYAGE 1 Clinical Trial.

BACKGROUND: Treatment of moderate-to-severe plaque psoriasis with biologics, such as guselkumab, has demonstrated greater efficacy over traditional non-biologic treatments. However, given patient diversity, greater understanding of the relationship between patient characteristics, positive clinical outcomes, and long-term response to biologics is crucial for optimizing treatment choices. MATERIALS AND METHODS: This post-hoc analysis of the 5-year VOYAGE 1 clinical trial compares baseline characteristics of patients maintaining a Psoriasis Area and Severity Index (PASI) score of 0 at all visits for ≥ 156 consecutive weeks (PASI = 0 group) with those that never achieve PASI = 0 (comparator group), using descriptive statistics and a multiple logistic regression model. Guselkumab plasma trough concentrations in both response groups were assessed from Weeks 4-156. RESULTS: Of patients who started guselkumab treatment at Week 0 or at Week 16 after switching from placebo, 22.7% (112/494) maintained PASI = 0 for ≥ 156 consecutive weeks. Numerical differences in baseline characteristics, including age, obesity, diabetes, PASI score, disease duration, smoking status, and psoriatic arthritis comorbidity, were identified between the PASI = 0 group and comparator group. Plasma guselkumab levels were consistently higher in the PASI = 0 group. Multiple logistic regression analysis revealed absence of diabetes, lower Dermatology Life Quality Index score at baseline, and higher Week 4 guselkumab plasma concentration as significantly (p < 0.05) associated with the PASI = 0 group. CONCLUSION: A substantial (22.7%) number of guselkumab-treated patients in the VOYAGE 1 clinical trial maintained complete skin clearance for a consecutive period of ≥ 156 weeks. Factors associated with this outcome may suggest clinical benefits of holistic treatment approaches. TRIAL REGISTRATION: NCT02207231.

The biological basis of disease recurrence in psoriasis: a historical perspective and current models.

A key challenge in psoriasis therapy is the tendency for lesions to recur in previously affected anatomical locations after treatment discontinuation following lesion resolution. Available evidence supports the concept of a localized immunological 'memory' that persists in resolved skin after complete disappearance of visible inflammation, as well as the role of a specific subpopulation of T cells characterized by the dermotropic CCR4+ phenotype and forming a local memory. Increasing knowledge of the interleukin (IL)-23/T helper 17 (Th17) cell pathway in psoriasis immunopathology is pointing away from the historical classification of psoriasis as primarily a Th1-type disease. Research undertaken from the 1990s to the mid-2000s provided evidence for the existence of a large population of CD8+ and CD4+ tissue-resident memory T cells in resolved skin, which can initiate and perpetuate immune responses of psoriasis in the absence of T-cell recruitment from the blood. Dendritic cells (DCs) are antigen-presenting cells that contribute to psoriasis pathology via the secretion of IL-23, the upstream regulator of Th17 cells, while plasmacytoid DCs are involved via IL-36 signalling and type I interferon activation. Overall, the evidence discussed in this review indicates that IL-23-driven/IL-17-producing T cells play a critical role in psoriasis pathology and recurrence, making these cytokines logical therapeutic targets. The review also explains the clinical efficacy of IL-17 and IL-23 receptor blockers in the treatment of psoriasis.