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.

Secukinumab demonstrates superiority over narrow-band ultraviolet B phototherapy in new-onset moderate to severe plaque psoriasis patients: Week 52 results from the STEPIn study.

BACKGROUND: Biologic treatments have been studied mainly in patients with a long-term history of psoriasis and previous treatment failures. OBJECTIVES: The purpose of this primary analysis of the STEPIn study is to determine whether early intervention with secukinumab in patients with new-onset moderate to severe plaque psoriasis is superior to standard of care treatment with narrow band ultraviolet B (nb-UVB) phototherapy. METHODS: The STEPIn study is a randomized, open-label, multicentre study to investigate early intervention with 52 weeks of secukinumab 300 mg administered subcutaneously versus standard treatment with nb-UVB phototherapy in patients with new-onset (≤12 months) moderate to severe plaque psoriasis (NCT03020199). The primary and additional secondary endpoints were ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) at Week 52 and Investigator's Global Assessment (IGA mod 2011) 0/1 response at Week 52, respectively. RESULTS: In the secukinumab and nb-UVB study arms, 77/80 and 76/80 randomized patients received at least one dose of study treatment, respectively. The primary endpoint was achieved: 91.1% (70/77) of patients achieved a PASI 90 response at Week 52 in the secukinumab arm versus 42.3% (32/76) in the nb-UVB arm (p < 0.0001, odds ratio [OR] estimate [95% confidence intervals, CI] = 16.3 [5.6, 46.9]). The additional secondary endpoint was also achieved: 85.7% of patients achieved an IGA 0/1 response at Week 52 in the secukinumab arm versus 36.8% in the nb-UVB arm (p < 0.0001). The safety data were consistent with the safety profiles of secukinumab and nb-UVB with no new or unexpected safety signals. CONCLUSIONS: Secukinumab was superior to nb-UVB in treating patients with new-onset moderate to severe plaque psoriasis. The high and sustained skin clearance observed indicates that biologic treatment for psoriasis may be more effective if used early in the disease course.

[Anti-IL17 induced eczema and the yin-yang of Th2 and Th17]. / Eczéma induit par les anti-IL-17 et le yin-yang Th2/Th17.

Biologics targeting specific cytokines and pathways have revolutionized the management of patients with chronic inflammatory diseases. However, these treatments have their limitations and, surprisingly, can induce novel inflammatory diseases. Here, we present a case of a psoriasis patient developing anti-IL17 induced eczema, an intriguing side effect of IL-17 blockade. The coexistence of psoriasis and eczema in a single patient is uncommon given their distinct and opposing immune mechanisms. Psoriasis is mainly driven by Th17 cells, whereas atopic dermatitis is Th2-dominated. In this article, we propose the yin yang of Th2 and Th17 with IL-4 and IL17 as principal antipodal vectors that control each other. Thus, blocking one of these cytokines can tip the balance between Th2 and Th17 and lead to the induction of the opposing inflammatory pathway via lifting the controlling mediator.

Les biologiques ciblant des cytokines spécifiques ont révolutionné la prise en charge des maladies inflammatoires chroniques. Cependant, ces thérapies possèdent leurs propres limites et peuvent ­ de manière surprenante ­ induire de nouvelles pathologies inflammatoires. Nous présentons le cas d'un patient psoriasique avec un eczéma induit par anti-IL-17. La coexistence du psoriasis et de l'eczéma atopique chez un même patient est rare, du fait de leurs mécanismes inflammatoires distincts. Le psoriasis est médié par la voie Th17, tandis que l'eczéma atopique est dominé par la voie Th2. Nous proposons un modèle yin-yang entre la voie Th17 et Th2, avec respectivement l'IL-17 et l'IL-4 comme vecteurs opposés. Le blocage de l'une de ces deux cytokines peut perturber cet équilibre dynamique et induire l'expression de la voie inflammatoire opposée par levée du médiateur de contrôle.

Real-World Experience of Patient-Relevant Benefits and Treatment Satisfaction with Apremilast in Patients with Psoriasis: An Analysis of the APPRECIATE Study.

INTRODUCTION: In the real-world APPRECIATE study (NCT02740218), most patients with psoriasis demonstrated notable improvements on disease severity measures and reported clinically meaningful treatment benefits with apremilast. OBJECTIVE: We aim to further describe patient-relevant needs and benefits and patient satisfaction with apremilast, including subgroup analyses based on patient characteristics. METHODS: APPRECIATE, a multinational, retrospective, cross-sectional study, enrolled patients with chronic plaque psoriasis who started apremilast according to the European label. Patient Benefit Index (PBI; range 0 (no patient-relevant benefit) to 4 (maximum patient-relevant benefit), global PBI score ≥ 1 indicating minimum patient-relevant benefit and ≥ 3 indicating high benefit) and nine-item Treatment Satisfaction Questionnaire for Medication (TSQM-9; range 0-100) were assessed 6 (± 1) months after apremilast initiation and summarized descriptively. Relationships between global PBI and TSQM-9 assessments were analyzed by Pearson correlations. RESULTS: Of 480 enrolled patients, 347 (72.3%) had remained on apremilast at 6 (± 1) months; 90.9% (300/330) achieved global PBI score ≥ 1. Mean (standard deviation) global PBI score was 2.8 (1.2). Higher achievement of global PBI score ≥ 3 was observed in patients with no prior treatments (61.1% (22/36)) or prior phototherapy (64.6% (42/65)) versus prior conventional systemic (54.4% (100/184)) or biologic (38.6% (17/44)) treatment. Strong correlations were observed between the global PBI score and the TSQM-9 global satisfaction and effectiveness subscale scores. CONCLUSION: Patients continuing apremilast for 6 (± 1) months in APPRECIATE reported patient-relevant treatment benefits. Findings suggest that receiving apremilast earlier versus later in treatment management is consistent with greater improvements in patient-relevant treatment outcomes.

Psoriasis: Classical vs. Paradoxical. The Yin-Yang of TNF and Type I Interferon.

Chronic plaque psoriasis is a common debilitating skin disease. The identification of the pathogenic role of the TNF/IL-23/TH17 pathway has enabled the development of targeted therapies used in the clinic today. Particularly, TNF inhibitors have become a benchmark for the treatment of numerous chronic inflammatory diseases such as psoriasis. Although being highly effective in psoriasis treatment, anti-TNFs can themselves induce psoriasis-like skin lesions, a side effect called paradoxical psoriasis. In this review, we provide a comprehensive look at the different cellular and molecular players involved in classical plaque psoriasis and contrast its pathogenesis to paradoxical psoriasis, which is clinically similar but immunologically distinct. Classical psoriasis is a T-cell mediated autoimmune disease driven by TNF, characterised by T-cells memory, and a relapsing disease course. In contrast, paradoxical psoriasis is caused by the absence of TNF and represents an ongoing type-I interferon-driven innate inflammation that fails to elicit T-cell autoimmunity and lacks memory T cell-mediated relapses.