Effectiveness of risankizumab for the treatment of psoriatic arthritis: a multicenter, real-world study.

BACKGROUND: IL-23 inhibitors were recently approved for the treatment of skin psoriasis and psoriatic arthritis (PsA). Risankizumab, a humanized monoclonal antibody that specifically binds the p19 subunit of IL-23, has proven effective on PsA in two randomized controlled trials. To date, only a few real-world data are available on this topic. METHODS: Our study aimed to prospectively evaluate the effectiveness of risankizumab in patients with PsA in a real-world setting. For this purpose, both rheumatologic and dermatologic assessments were performed at baseline and after 28-40 weeks of continuous risankizumab administration. Moreover, joint and entheses ultrasound assessment was performed at the mentioned time points. The rheumatologic assessment was carried out by means of the following scores: (i) clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA); (ii) Leeds Enthesitis Index (LEI); (iii) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and (iii) Bath Ankylosing Spondylitis Functional Index (BASFI). The degree of skin involvement was measured by both the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Quality of life was assessed by the Health Assessment Questionnaire (HAQ) and Dermatology Life Quality Index (DLQI). Ultrasound assessment of joints and entheses was performed on the basis of the EULAR-OMERACT score. RESULTS: After treatment, cDAPSA decreased from a mean value of 12.9 ± 7.6 to 7.0 ± 6.1 (P < 0.001), and the median PD score significantly decreased from baseline (3; range 1-8) to TP1 (1; range 0-7) (P < 0.001). PASI score also decreased from 8.4 ± 4.9 to 0.3 ± 0.5 (P < 0.001), and PGA from 3.1 ± 1.0 to 0.4 ± 0.5 (P < 0.001). CONCLUSION: We can conclude that risankizumab led to substantial improvement in both skin and joint involvement.

Effectiveness of risankizumab in the treatment of palmoplantar psoriasis: a 52-week Italian real-life experience.

Background: Data on the treatment of palmoplantar psoriasis (PP) are scarce, representing a therapeutic challenge. This study aims to assess the efficacy and safety of risankizumab in a population of patients with psoriasis with a palmoplantar involvement, over a 52-week treatment period. Methods: We performed a retrospective analysis in a cohort of patients with PP, with or without involvement of other skin sites. Palmoplantar Psoriasis Area and Severity Index (ppPASI) was assessed at baseline and after 4, 16, 28 and 52 weeks, to evaluate the PP severity. Results: Sixteen patients were enrolled. The rates of ppPASI90 responses constantly increased during the period of observation and were 18.7%, 62.2%, 75.0% and 81.2% at weeks 4, 16, 28 and 52, respectively. Only two patients suspended treatment because of ineffectiveness at week 16. Conclusion: Our data from a series of 16 patients reveal that risankizumab could represent an effective and safe therapeutic choice in patients with PP.

Risankizumab for the treatment of moderate-to-severe psoriasis: A multicenter, retrospective, 1 year real-life study.

Several new biologic agents targeting IL23/Th17 axis, such as risankizumab, have been developed for the treatment of psoriasis. The aim of the present study was to analyze the efficacy and safety of risankizumab in patients with moderate-to-severe psoriasis over a 52-week period. A multicentric retrospective study was conducted in patients who initiated risankizumab between July 2019 and December 2020. Psoriasis Area and Severity Index-PASI was measured at baseline and after 4, 16, 28 and 52 weeks. Clinical responses were evaluated by PASI75, PASI90 and PASI100 at the same timepoints. Potential safety issues and adverse events (AEs) were collected. Univariable and multivariable logistic regressions were performed for variables predicting clinical response. One hundred and twelve patients with psoriasis were included. PASI90 response was achieved by 17.86% of patients at week 4, 72.22% at week 16, 91.0% at week 28 and 95.24% at week 52 (as observed analysis). No associations between the considered variables and the efficacy endpoints were retrieved, influence of variables such as Body Mass Index (BMI), baseline PASI or previous biologics were not shown. No serious safety issues or discontinuations related to adverse events were reported. Risankizumab showed high efficacy and a favorable safety profile, regardless of patient- and disease-related factors.

Psoriasis in difficult to treat areas: treatment role in improving health-related quality of life and perception of the disease stigma.

BACKGROUND: When psoriasis affects scalp, nails, palms and soles, it is considered difficult to treat and causes severe impairment of life quality. OBJECTIVE: We evaluated which difficult site most impacts on the patient's quality of life and how quality of life changes during treatment. METHODS: We conducted a prospective observational study in patients receiving adalimumab over a 24 weeks period, through assessment at weeks 0, 4 and 24 using PASI, PAIN VAS, ITCH VAS, DLQI, NAPSI, PSSI. Pearson correlation was used to evaluate the relationship between the various measurements on the basis of three different deltas (between T0 and T24, between T0 and T4, between T0 and average between T4 and T24). RESULTS: The correlation matrix between T0 and T24 shows a significant correlation between delta PASI and delta ITCH and delta ITCH and delta DLQI and a significant correlation between ITCH delta and DLQI delta and a correlation close to significance between DLQI and NAPSI. CONCLUSION: We identified itching as a mediator between the cutaneous extension of psoriasis and the impact on quality of life. We also documented the predominant role of nail psoriasis in defining the impact on the quality of life of the psoriatic patient.

Skin advanced glycation end products as a diagnostic and monitoring tool among psoriatic patients: how the therapy helps reduce cardiovascular disease risk.

BACKGROUND AND AIMS: Psoriasis is a disturbing and burdensome inflammatory skin disorder, with a global prevalence of 2-3%. An increased risk of cardiometabolic disease between psoriatic patients has been recently demonstrated. This is probably due to the psoriasis systemic inflammation and the increased levels of inflammatory cytokines, such as IL-17, IL-23, and TNF-α. Advanced glycation end products (AGEs) are the products of nonenzymatic glycation and oxidation of proteins and lipids which modify their structure and function. They have a significant role in the pathogenesis of diabetic nephropathy, atherosclerosis, and cardiovascular diseases of diabetic adults and children. The accumulation of AGEs can be measured by skin autofluorescence (SAF). Adalimumab (Humira ®) is a fully human monoclonal antibody, administered via subcutaneous injection, which binds the tumor necrosis factor (TNF) and is used to treat moderate-to-severe chronic plaque psoriasis. We performed an observational prospective study of 24 weeks to assess the reduction of AGEs through SAF measurement during treatment with adalimumab. METHODS: SAF measurements in patients were performed at T0 and after 24 weeks of therapy. Adalimumab efficacy was assessed using Psoriasis Area and Severity Index (PASI), Visual Analogue Scale (VAS) for pain, and erythrocyte sedimentation rate (ESR). RESULTS: ESR, AGEs, PASI, and VAS for pain decreased throughout the study period. CONCLUSION: Adalimumab reduced AGEs in psoriatic patients. Biologic therapies may also prevent cardiovascular disease, suggesting a new approach of combined therapy for psoriasis and cardiovascular diseases.

Predictive factors of lack of response to adalimumab among bio-naive patients suffering from moderate-to severe psoriasis: analysis of a multicenter data collection in Italy.

INTRODUCTION: Efficacy of anti-TNF-a agents seems inferior to IL-17 and IL-23 inhibitors. Nevertheless, after biosimilars approval, anti TNF-a agents are recommended as first-line for psoriatic patients, for economic reasons. METHODS: Predictive factors of response or non-response to adalimumab in bionaive patients who started adalimumab (originator or biosimilar) over 12 years in 9 dermatologic centers in Italy. Effectiveness was assessed with Psoriasis Area and Severity Index (PASI75 and PASI90) at weeks 12, 24 and 48. Multiple logistic regressions were used for variables predicting clinical response; Kaplan-Meier survival curves and Cox regression for drug survival. RESULTS: The drug survival analysis showed reduced hazard ratio of overall discontinuation with male gender and scalp localization. In contrast, baseline PASI and genital psoriasis were significantly associated with increased risk of overall discontinuation. Predictive factors of non-response seemed elevated in patients with baseline PASI, older age groups, previously treated patients with phototherapy, females or patients with palmo-plantar while scalp psoriasis, previous cyclosporine and acitretin appeared as a positive predictive factor. CONCLUSIONS: This real-life analysis might be useful for clinicians in case of bio-naive patients with moderate-to-severe psoriasis and various comorbidities.

The Effects of Association of Topical Polydatin Improves the Preemptive Systemic Treatment on EGFR Inhibitors Cutaneous Adverse Reactions.

Epidermal Growth Factor Receptor inhibitors (EGFRi) are approved as therapeutic options in several solid tumors. Cutaneous papulopustular eruption is the most frequent cutaneous adverse-event (AE), usually treated with emollient or corticosteroids according to toxicity grade. Our study evaluated the efficacy and safety of a topical product containing polydatin, a glycosylated polyphenol, natural precursor of resveratrol showing anti-inflammatory and anti-oxidative activities, for the prevention and treatment of skin papulopustular rash in EGFRi-treated patients. Forty oncologic patients treated with EGFRi were enrolled in two groups: group-A, 20 patients with papulopustular AE, and group-B, 20 patients without cutaneous manifestations. The study consisted of twice-daily application of polydatin cream 1.5% (group-A) and 0.8% (group-B) for 6 months. In group-A patients, we observed at week 4 a remarkable improvement of skin manifestation and quality of life evaluated with National-Cancer-Institute-Common-Terminology-Criteria for Adverse-Events (NCI-CTCAE), Dermatology-Life-Quality-Index (DLQI) score and Visual-Analogue-Scale (VAS) pruritus, with a statistical significance of p < 0.05. None of the patients of group-B developed skin AEs to EGFRi. No cutaneous AEs related to the polydatin product were reported in both groups. Polydatin can be a good topical aid for the prevention and management of papulopustular rash in cancer patients receiving EGFRi, also capable of improving cancer patients' quality of life.

A linear forehead lesion caused by intralesional injection of triamcinolone acetonide and treated with hyaluronic acid filler: Case report.

Intralesional steroid injection is a treatment method frequently used to resolve a large number of orthopedic, rheumatological, dermatological, and neurological disorders. Although this treatment is very effective, it is not without possible side effects, both systemic and local, among which we can mention pain, bleeding, ulceration, atrophy, pigmentary changes, calcification, secondary infections, formation of granulomas, allergic reactions and, in very rare cases, the development of linear atrophy, and hypopigmentation. Here, we present a case of frontal linear skin atrophy after intralesional steroid injection for the treatment of alopecia areata (AA) in a 29 year-old patient, successfully treated with a hyaluronic acid filler.

Efficacy and safety of adalimumab in difficult-to-treat psoriasis.

Psoriasis is a chronic immune-mediated inflammatory skin disorder, with a prevalence of 2% to 3% worldwide. Psoriatic lesions affecting scalp, nails, palms, and soles are considered difficult-to-treat and require specific management. When psoriasis involves these areas, it may be considered more severe even if the lesions are not extensive. Adalimumab (Humira) is a fully human monoclonal antibody against tumor necrosis factor (TNF), administered via subcutaneous injection. It has already been used in the treatment of adults and children with moderate-to-severe chronic plaque psoriasis. In literature, few studies investigated its efficacy in difficult-to-treat areas, hence we conducted an observational prospective study of 24 weeks to assess its role in patients with difficult to treat psoriasis. We found out a significant improvement in nail and scalp psoriasis, while palmoplantar and genital psoriasis showed an improvement though not statistically significant. Therefore, adalimumab can be used in difficult-to-treat areas with great results, also allowing an improvement in the quality of life of affected patients, both adults and children.

Omalizumab for chronic spontaneous urticaria in "complex" patients: data from real-life clinical practice.

INTRODUCTION: Omalizumab is a recombinant humanized anti-IgE monoclonal antibody, approved for patients affected by chronic spontaneous urticaria resistant to antihistamines. Although the clinical benefit of omalizumab has been established in several clinical trials, there are very little data about long-term treatment with this drug and real-life reports regarding its use in patients affected by comorbidities other than urticaria are lacking. OBJECTIVES: To assess omalizumab efficacy and safety in a heterogeneous population of patients affected by chronic spontaneous urticaria and several comorbidities in a real-world setting. MATERIALS AND METHODS: Patients affected by chronic spontaneous urticaria with weekly urticaria activity score >16 resistant to antihistamines were treated with omalizumab 300 mg injection as add-on to H1-antihistamines administered every 4 weeks for 6 months. Clinical assessment of weekly urticaria activity score, dermatology life quality index and blood tests were performed at baseline, 12, 24 and 52 weeks of treatment. Response was assessed based on reduction weekly urticaria activity score. RESULTS: Thirty-two patients (22F; 10M) with a mean age of 52.4 years (range 27-72) affected by chronic spontaneous urticaria were enrolled. Comorbidities affecting our study population were divided into 6 categories: cardio-metabolic (77%), oncologic (19%), infectious (16%), allergic (45%) immunologic (41%) and others (18%). Omalizumab determined a satisfactory reduction of symptoms of chronic spontaneous urticaria and an amelioration of quality of life within our population. No relevant alterations regarding patients' underlying conditions were encountered. This is the first study regarding the use of omalizumab for chronic spontaneous urticaria in a population of adult patients affected by several comorbidities, eg, cardio-metabolic, oncologic, infectious, allergic, immunologic and psychiatric diseases. Real-life data represent a valuable source of information about a drug's safety and efficacy profile, especially in patients affected by different comorbidities that are widely diffused in Western countries.

Efficacy and safety of adalimumab after failure of other anti-TNFα agents for plaque-type psoriasis: clinician behavior in real life clinical practice.

Introduction: During treatment with biologic agents for psoriasis (Pso) in a number of patients a failure may occur and discontinuation with transitioning to another drug or an optimization strategy, consisting in a dose-adjustment or a co-medication with a traditional systemic agent, represent two possible alternatives. Objective: The SAFARI study objective was a retrospective observation of adalimumab efficacy and safety profile after switching from other anti-TNFα agents related to clinician behavior after the failure of the first-line agent. Results: The retrospective multicenter observation demonstrated that after a first-line anti-TNFα failure adalimumab efficacy was consistent at week-12 and 24 with a further significant improvement at week-48 with a proportion of patients achieving PASI75/PASI90/PASI100 of 83.3, 71.6, and 56.9.%, respectively. Clinician strategies to extend drug-survival after first-line anti-TNFα failure, such as co-medication or dose-adjustment, were irrelevant to future drug effectiveness. Conclusions: Adalimumab profile was excellent in this 5-year retrospective observation, showing the clinical validity of interclass transitioning among anti-TNFα options.

Long-term treatment of psoriatic patients with adalimumab reduces disease severity and maintains a favorable lipid pattern and a low Atherogenic Index.

BACKGROUND: This retrospective study aimed to evaluate the long-term efficacy and effects on lipid profile and Atherogenic Index of antitumor necrosis factor (TNF)α therapy with adalimumab in patients with moderate-to-severe psoriasis or psoriatic arthritis. METHODS: Sixty-nine psoriatic patients treated with adalimumab 40 mg every other week were included. Patients were treated continuously for four years; study visits took place every 24 weeks. Disease severity (Psoriasis Area Severity Index [PASI], Nail Psoriasis Severity Index [NAPSI], articular pain intensity), disease burden (PSOdisk), serum lipid concentrations, Atherogenic Index, and inflammatory markers were assessed at each visit. RESULTS: Disease severity improved significantly during treatment. After 24 weeks, 89.9% of patients achieved a PAS I75 response; 79.7% and 46.4% had PASI 90 and PASI 100 responses, respectively. Response was sustained over four years. NAPSI Score, articular pain and disease burden improved significantly. Lipid serum concentrations and inflammatory markers were overall stable and within the range of normality. High-density lipoprotein cholesterol concentrations increased significantly and Atherogenic Index improved. The four years of uninterrupted treatment with adalimumab was well tolerated. CONCLUSIONS: Long-term treatment of moderate-to-severe psoriatic disease with adalimumab is effective, well tolerated, and potentially beneficial also in terms of lipid pattern and atherogenic risk.

Expression and potential role of cellular retinol binding protein I in psoriasis.

Psoriasis is a diffuse chronic skin disorder characterized from accelerated epidermal turnover and inflammatory cell infiltrate. Retinoids influence keratinocyte proliferation and differentiation as well as inflammatory response. Cellular retinol binding protein (CRBPI) regulates intracellular vitamin A bioavailability and contributes to maintain skin homeostasis. The aim of present study was to investigate the expression of CRBPI and its role in the pathogenesis of skin psoriasis. Immunohistochemistry revealed more diffuse and increased CRBPI expression in all epidermal layers of human psoriatic lesions except in the stratum corneum. An imiquimod-induced psoriatic-like model documented the increase of skin lesional area and severity index score as well as of the severity of microscopic features as parakeratosis, papillomatosis and spongiosis in CRBPI-knockout compared to wild-type mice, associated to the increased keratinocyte CK17 and Ki-67 expression and the reduction of CK1, CRABPII and RXRα. Gene array of imiquimod-induced psoriatic skin documented the greater up-regulation of EGF/PDGF-related genes and down-regulation of EGR1 and pro-inflammatory IL-related genes in CRBPI-knockout compared to wild-type mice. Finally, CRBPI transfection in HaCaT cells increased AKT and NF-κB-related genes and proteins and down-regulated IL-2, IL-6 and IL-8 pro-inflammatory signalling. Although not recognized as a psoriatic susceptibility gene in our cohort of patients, the present data strongly supported the potential role of CRBPI to sustain keratinocyte proliferation and differentiation and to counteract pro-inflammatory genes expression in psoriatic lesions.

HLA-C*06:02 Does Not Predispose to Clinical Response Following Long-Term Adalimumab Treatment in Psoriatic Patients: A Retrospective Cohort Study.

BACKGROUND: The genetic basis of predisposition to psoriasis is recognised; however, the response to psoriasis treatment in patients with different genetic predisposition is poorly understood. OBJECTIVE: To analyse the presence of the HLA-C*06:02 polymorphism in psoriatic patients treated with adalimumab. METHODS: Genomic DNA was extracted from whole blood of 122 patients with moderate-to-severe psoriasis treated with adalimumab for 3 years. Genotyping was performed using PCR. Disease severity was assessed by the Psoriasis Area and Severity Index (PASI) at day 0 and after 1, 3, 6, 12, 24 and 36 months. Logistic regression was used to evaluate the association between dependent variables (including HLA-C*06:02 status) and achievement of PASI 50, 75 and 90. RESULTS: No difference was observed after adalimumab treatment between C*06:02 positive (HLA-C*06:02-POS) patients (n = 46) and C*06:02 negative (HLA-C*06:02-NEG) patients (n = 76) over the 3-year follow-up period in terms of PASI response or time-course when PASI response was achieved. However, a small, but non-statistically significant difference was noted between genotypes for PASI 50 at 1 month (HLA-C*06:02-NEG: 44.7% vs. HLA-C*06:02-POS: 56.5%) and at 3 months (HLA-C*06:02-NEG: 71.1% vs. HLA-C*06:02-POS: 80.4%). Simple logistic regression analysis did not reveal an association between independent variables (including C*06:02 status) and PASI response; however, multivariate regression revealed that gender (females better than males) was associated with achievement of PASI 50 at month 1 (OR 0.34, 95% CI 0.16-0.72, p = 0.005) and of PASI 75 at 3 months (OR 0.36, 95% CI 0.16-0.8, p = 0.012). CONCLUSION: Adalimumab reduced long-term severity in patients with moderate-severe psoriasis, independent of their HLA-C*06:02 status.

Dermoscopic monitoring of efficacy of ingenol mebutate in the treatment of pigmented and non-pigmented basal cell carcinomas.

Basal cell carcinoma is the most common non-melanoma skin cancer, and its incidence continues to raise. Although surgery can be considered the mainstay of therapy, new current pharmacological options are available and focus on tumor eradication, maximizing cosmetic results, and functional capacity. Several studies have recently reported on safety and efficacy of topical ingenol mebutate gel, a derivative of the plant Euphorbia Peplus, used to treat actinic keratosis and superficial basal cell carcinoma. In our knowledge, we report for the first time the dermoscopic evaluation of outcome and monitoring of superficial pigmented and non-pigmented basal cell carcinomas in four patients treated by this novel non-ablative agent. Ingenol mebutate gel therapy has showed to be effective and without important side-effects for pigmented and non-pigmented superficial basal cell carcinomas. We emphasize the usefulness of dermoscopy in supporting the clinical diagnosis and excluding the presence of tumor residue or recurrence. In a future scenario, we hope it will be soon possible to follow-up the lesions, after treatment, avoiding post-control biopsy punch.