Drug survival, effectiveness, and safety of brodalumab for moderate-to-severe psoriasis up to 3 years.

BACKGROUND: Brodalumab is a monoclonal antibody and IL-17 RA inhibitor that is approved for the treatment of moderate-to-severe psoriasis. The present study aims to estimate the drug survival (DS), effectiveness, and safety of brodalumab over a period of 156 weeks. METHODS: The primary objectives were: (i) to determine the treatment response rate at Weeks 16, 28, 52, 78, 104, and 156 as defined by PASI100, PASI90, and an absolute PASI ≤ 3 and (ii) long-term DS. Secondary objectives included the evaluation of possible predictive factors associated with the achievement of response outcomes, and possible predictive factors associated with lower DS. RESULTS: The treatment response was rapid, with 80.3% of patients achieving PASI ≤ 3, 66% PASI90, and 54.3% the complete clearance of disease at Week 16. The response improved at Week 28, when a plateau was achieved with mild loss of response at later time points, in particular for PASI100 and PASI90 in 55.2 and 65.5% of patients, respectively, at Week 156. After 156 weeks of treatment, 66.22% of patients were still on therapy, and the previous use of IL-17 inhibitors appeared to be associated with an increased risk of treatment discontinuation (HR: 2.51, CI: 1.06-5.98, P = 0.037), and achievement of PASI ≤ 3 until Week 16 with less risk (HR: 0.27 CI: 0.14-0.51, P < 0.001). Bio-naïve status was favorably associated with treatment response, while high BMI negatively affected the achievement of outcomes. CONCLUSION: Our study confirms the good effectiveness and favorable safety profile of brodalumab in a real-world setting for up to 3 years of treatment.

Aging Impact in Response to Different Classes of Biological Treatment in Psoriatic Patients: A Real-Life Observational Study.

Over the last decade, the treatment landscape for moderate to severe psoriasis has undergone transformative changes with the advent of biotechnological drugs. Monoclonal antibodies targeting the IL-17 and IL-23 pathways have displayed remarkable clinical efficacy and safety, even among patients with complex comorbidities. These innovations have extended across various age groups within the psoriatic population. However, a scarcity of age-specific data remains regarding the efficacy and safety of these medications. Our study tries to bridge this gap by systematically presenting data obtained from the analysis of 1055 patients treated for psoriasis with anti-IL17 and anti-IL23 drugs during a 1-year period. The effectiveness and safety of anti-IL-17 and anti-IL23 drugs for moderate to severe psoriasis were assessed across four different age groups ranging from patients less than 26 years old to patients older than 65 years, divided in four year ranges. In the studied population, baseline PASI score was significantly higher in the age group of individuals over 65 years compared to those under 26 years old. Patients over 65 years also exhibited a slower rate of improvement in PASI-90 and PASI < 3 at the 16-week mark compared to other age groups. However, no clinically significant differences in treatment response were found when comparing overall responses among different age groups. In age groups older than 26 years, anti-IL17 drugs seems faster in the achievement of PASI-100 when compared to anti-IL23 drugs. This trend became more pronounced with increasing age. The investigation provides insights into treatment responses and patient characteristics, highlighting the influence of age as a significant variable in patient management.

The Skin Microbiome and Its Role in Psoriasis: A Review.

The skin microbiome is made of various microorganisms, most of which have the function of protecting individuals from harmful pathogens, and they are involved in innate and adaptive immune responses. The skin acts as a physical and immunological barrier against external stimuli, including pathogens and physical damage. Changes in the composition of the skin microbiome can trigger inflammatory processes leading to inflammatory skin diseases in susceptible individuals. Psoriasis (PsO) is a chronic inflammatory disease with a multifactorial etiology, where breakdown of immune tolerance to cutaneous microorganisms is implicated in its pathogenesis. Dysregulation of the microbiome due to genetic and environmental factors plays a significant role in the development of psoriatic disease. Dermatologic conditions such as atopic dermatitis, acne, psoriasis, and rosacea have been associated with intestinal dysbiosis. The skin microbiota composition is crucial for the development of appropriate immune responses, and alterations in the skin microbiome can contribute to changes in physiology and susceptibility to skin diseases or inflammatory conditions. Understanding the microbial settlement of the skin and the network of interactions that occur throughout life is essential for comprehending the pathogenesis of skin diseases and developing innovative treatments. With this article we tried to explore the relationship between the human microbiome and psoriatic disease, shedding light on the functions of the microbiome and the inflammatory disease processes to identify additional therapeutic targets. This review aims to highlight the relationship between skin and gut microbiome functions and inflammatory processes in skin psoriasis and psoriatic arthritis (PsA). The goal is to facilitate future studies on the skin microbiome to identify potential novel therapies for patients with psoriatic disease.

Clinical effectiveness of IL-17 and IL-23 inhibitors on difficult-to-treat psoriasis areas (scalp, genital, and palmoplantar sites): a retrospective, observational, single-center, real-life study.

INTRODUCTION: Psoriasis affecting the genital, palmoplantar, and scalp regions is recognized as difficult-to-treat, and data on the efficacy of biologics in these areas remains limited. RESEARCH DESIGN AND METHODS: This single-center study evaluated the effectiveness of anti-IL-17 and anti-IL-23 agents on scalp, genital, and palmoplantar psoriasis. We retrospectively analyzed data from all patients with psoriasis being treated with IL inhibitors at our clinic. Effectiveness was evaluated at 16, 28, and 52 weeks, according to the achievement of relative and mean PSSI, PGA-G, and ppPASI. RESULTS: In all, 308 patients showed involvement of the scalp, 136 in the genital area, and 94 in the palmoplantar regions. On scalp psoriasis, anti-IL-17 agents demonstrated superiority in disease control compared to anti-IL-23 agents. PSSI100 at week 16 was reached by 59% of patients on an anti-IL17 vs 39.8% on an anti-IL-23 (p < 0.003). At genital sites, no significant differences between anti-IL-17 and anti-IL-23 agents were observed, and all classes achieved PGA-G 0/1. No significant differences between anti-IL-17 and anti-IL-23 agents were observed in palmoplantar areas. CONCLUSIONS: The present data support the utility of both anti-IL-17 and anti-IL-23 agents for the treatment of difficult-to-treat areas in patients with psoriasis. Anti-IL-17 agents achieved better control of scalp psoriasis.

Chronic Pruritus in Atopic Patients Treated with Dupilumab: Real Life Response and Related Parameters in 354 Patients.

Chronic pruritus is a major symptom of atopic dermatitis (AD). Its etiopathogenesis is complex, and an understanding of the driving factors of its pathogenesis allows for the development of new molecule-targeted therapies. Dupilumab, targeting and blocking interleukin-4 (IL-4) and interleukin-13 (IL-13) molecules, has shown great efficacy in treating AD symptoms such chronic itching. We performed a retrospective observational study to evaluate possible chronic-itch-related characteristics and parameters in 356 AD patients who received dupilumab. The objective of the study was to evaluate the factors associated with the level of pruritus reported by patients at each of the 1575 detections in the form of the peak pruritus numerical rating scale (NRSpp) and sleep disturbance numerical rating scale (NRSsd). We focused on: the eczema area and severity index (EASI), dermatology life quality index (DLQI), patient-oriented eczema measure (POEMS), eosinophilia, L-lactate dehydrogenase (LDH), immunoglobulin E (IgE) and the time from the start of dupilumab therapy. NRSpp fell from 8.6 (sd 1.7) at baseline to 1.7 (sd 2.3) at 36 months and NRSsd from 7 (sd 3) to 0. Regarding the parameters that correlate with NRSpp, all the parameters analysed were significantly correlated except for eosinophils (p = 0.136). In the multivariate analysis, both considering and not considering treatment duration, the parameters were correlated (p < 0.001); EASI, DLQI, POEM, and LDH significantly correlated with NRSpp (p < 0.001 for each, except for LDH p = 0.003); while IgE tot lost significance (p = 0.337). Similar results were obtained for the parameters correlating with NRSsd. Our results confirm the efficacy of dupilumab on pruritus. The use of questionnaires such as DLQI and POEM is advisable in clinical practice and is adequate for assessing the impact of itching on AD. The low correlation of IgE and eosinophils, the ambiguity of LDH levels with the level of pruritus, and a poor clinical validity and unclear correlation with disease severity suggest a progressive abandonment of monitoring of these values.