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BACKGROUND: Hidradenitis suppurativa (HS) is a chronic debilitating disease with a significant burden of both organic and psychological comorbidities. It has been shown that certain telomere-related genes (TRGs) affect a wide range of diseases, including HS and its associated comorbidities, but their exact role in HS pathogenesis is still unknown. OBJECTIVES: To determine whether TRG methylomes can be used as biomarkers in HS. METHODS: Using the Illumina HumanMethylation450 BeadChip array, we examined methylation variations associated with TRGs in HS cases and age-, sex- and ethnicity-matched healthy controls. The study utilized integrated bioinformatics statistical methods, such as a false discovery rate (FDR), the area under the receiver operating characteristic curve (AUC) and principal component analysis. RESULTS: There were a total of 585 different differentially methylated CpG sites identified in 585 TRGs associated with HS (474 hypomethylated and 111 hypermethylated) (FDR p-value < 0.05). A number of these CpGs have been identified as being involved in increased pain sensitivity including EPAS1, AHR, CSNK1D, DNMT1, IKBKAP, NOS3, PLCB1 and PRDM16 genes; GABRB3 as a potential alcohol addiction marker; DDB1, NSMCE2 and HNRNPA2B1 associated with cancers. Pathway analysis identified 67 statistically significant pathways, including DNA repair, telomere maintenance, mismatch repair and cell cycle control (p < 0.001). CONCLUSION: The disruption of TRGs leads to the shortening of telomeres, which is associated with HS progression, ageing, cellular senescence and an increased risk of various diseases, including cancer and associated comorbidities, such as metabolic syndrome, cardiovascular disease and inflammatory disorders. Further research is necessary to better understand the underlying mechanisms and establish causal links between TRGs and HS. The present study is the first effort to comprehend potential pathomechanisms of sporadic HS cases concentrating on PBMC methylome since ours.
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Hidradenite Supurativa , Neoplasias , Humanos , Hidradenite Supurativa/genética , Hidradenite Supurativa/epidemiologia , Epigenoma , Leucócitos Mononucleares , Comorbidade , Telômero/genética , LigasesRESUMO
BACKGROUND: There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required. OBJECTIVE: To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes. METHODS: We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18-49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022. RESULTS: We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3-118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2-24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors. CONCLUSIONS: This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research.
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Laser treatments have become popular in Dermatology. In parallel to technologic development enabling the availability of different laser wavelengths, non-invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to explore morphologic and qualitative skin characteristics. Specifically, RCM can be applied to cosmetically sensitive skin areas such as the face, without the need for skin biopsies. For these reasons, apart from its current use in skin cancer diagnosis, our systematic review reveals how RCM can be employed in the field of laser treatment monitoring, being particularly suitable for the evaluation of variations in epidermis and dermis, and pigmentary and vascular characteristics of the skin. This systematic review article aims to provide an overview on current applications of RCM laser treatment monitoring, while describing RCM features identified for different applications. Studies on human subjects treated with laser treatments, monitored with RCM, were included in the current systematic review. Five groups of treatments were identified and described: skin rejuvenation, scar tissue, pigmentary disorders, vascular disorders and other. Interestingly, RCM can assist treatments with lasers targeting all chromophores in the skin and exploiting laser induced optical breakdown. Treatment monitoring encompasses assessment at baseline and examination of changes after treatment, therefore revealing details in morphologic alterations underlying different skin conditions and mechanisms of actions of laser therapy, as well as objectify results after treatment.
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Transtornos da Pigmentação , Dermatopatias , Neoplasias Cutâneas , Humanos , Pele/diagnóstico por imagem , Pele/patologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/radioterapia , Neoplasias Cutâneas/cirurgia , Dermatopatias/patologia , Transtornos da Pigmentação/diagnóstico , Microscopia Confocal/métodosRESUMO
Introduction: Patients with mild-to-moderate acne are frequently colonized by Staphylococcus aureus on their skin, which alters microenvironmental skin conditions and exacerbates disease symptoms. Bacteriocins produced by Bacillus subtilis may act as antimicrobial peptides against Gram-positive bacteria. Aim: To investigate whether topical application of bacteriocins from B. subtilis could serve as a potential strategy for promoting S. aureus decolonization from acneic skin. Material and methods: The research product was a cream formulation containing 1% bacteriocins from B. subtilis. First, we conducted a 60-day pilot study on the effect of topically applied bacteriocins from B. subtilis on the absolute abundance of S. aureus in 12 patients with mild-to-moderate acne. Second, we designed an 8-week, uncontrolled, open-label, multicentre clinical study to investigate whether the topical application of bacteriocins from B. subtilis reduces the number of inflammatory and non-inflammatory lesions, as well as Global Acne Grading Scale (GAGS) scores, in 373 patients with mild-to-moderate acne. Results: At the microbiological level, quantitative PCR showed a decrease in the absolute abundance of S. aureus in acne areas after topical application of the research product for 60 days (-38%, p < 0.001). In the clinical study, the number of inflammatory and non-inflammatory lesions was found to decrease at 8 weeks by 59% (p < 0.001) and 58% (p < 0.001), respectively, compared with baseline. A 56% decrease was observed for GAGS scores. Conclusions: Topical bacteriocins from B. subtilis can promote S. aureus decolonization in acneic skin, ultimately improving the clinical appearance of mild-to-moderate acne.
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Daylight-photodynamic therapy (D-PDT) and ingenol mebutate (IM) are novel therapies directed to actinic keratoses (AK). The purpose of our study was to compare effectiveness, tolerability, cosmetic outcome and patient preference of D-PDT versus IM in the treatment of grade I and II AK. Twenty-seven patients with AK on the face or scalp were enrolled. Each patient received, in a 25 cm(2) target area, D-PDT on right side and IM on left side. Overall 323 AK were treated. Both target areas achieved complete response in 40.47% of the cases and average AK clearance rate was similar for D-PDT and IM (p=0.74). In D-PDT areas mean grade II AK clearance rate was lower compared with that of grade I AK (p=0.015). In IM areas grade I and II AK average clearance rates were similar (p=0.28). At week 1 and month 1, mean local skin responses (LSR) score were higher in areas treated with IM. IM areas showed more severe pain and cosmetic sequelae. D-PDT had similar effectiveness to IM, even if IM demonstrated higher grade II AK clearance rate. Tolerability profile was superior for D-PDT in terms of LSR and pain. D-PDT was more cosmetically acceptable. Patients preferred D-PDT to IM in most cases.
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Ácido Aminolevulínico/análogos & derivados , Fármacos Dermatológicos/uso terapêutico , Diterpenos/uso terapêutico , Dermatoses Faciais/tratamento farmacológico , Ceratose Actínica/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Dermatoses do Couro Cabeludo/tratamento farmacológico , Luz Solar , Idoso , Idoso de 80 Anos ou mais , Ácido Aminolevulínico/efeitos adversos , Ácido Aminolevulínico/uso terapêutico , Fármacos Dermatológicos/efeitos adversos , Diterpenos/efeitos adversos , Dermatoses Faciais/diagnóstico , Feminino , Humanos , Ceratose Actínica/diagnóstico , Masculino , Pessoa de Meia-Idade , Preferência do Paciente , Fotoquimioterapia/efeitos adversos , Fármacos Fotossensibilizantes/efeitos adversos , Indução de Remissão , Dermatoses do Couro Cabeludo/diagnóstico , Luz Solar/efeitos adversos , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoAssuntos
Carcinoma Basocelular , Queilite , Ceratose Actínica , Neoplasias Cutâneas , Adjuvantes Imunológicos , Aminoquinolinas , Carcinoma Basocelular/tratamento farmacológico , Queilite/diagnóstico , Queilite/tratamento farmacológico , Humanos , Imiquimode , Ceratose Actínica/diagnóstico , Ceratose Actínica/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
INTRODUCTION: Since during the COVID-19 pandemic nail psoriasis was evaluated exclusively with teledermatology, dermatologists started to face the difficulty in rating it concurrent with other onycopathies (i.e., onychotillomania and onychophagy). Thus, we aimed to improve the existing severity scores and verify the value in different clinical settings (i.e., in person vs. teledermatology (video or picture)). METHODS: This multicenter prospective observational study evaluated patients with nail psoriasis and screened them for onychophagy or onychotillomania in telemedicine from May 2020 to January 2021. For therapeutic purposes patients with nail psoriasis were followed and rated with the Nijmegen-Nail psoriasis Activity Index tooL (N-NAIL) for 9 months; at the same time, N-NAIL and a new dedicated index that monitor also the changes in nail dimension (Galeazzi-(G) N-NAIL) were tested for accuracy. We assessed inter- and intraobserver agreement for the three different settings (in person, video, and pictures). RESULTS: In our cohort of 382 patients with nail psoriasis after a clinical and dermatoscopic assessment we found 20 (5.24%) patients with onychophagy and 17 (4.45%) patients with onychotillomania. Analysis of the impact of nail psoriasis on patients revealed that onycholysis and crumbing, followed by subungual hyperkeratosis, were the clinical signs that prevalently bothered patients. N-NAIL score displayed moderate intra- and interobserver agreement. Over the 9 months follow-up, N-NAIL vs. GN-NAIL displayed a solid correlation at all the examined time points, i.e., baseline and after 3, 6, and 9 months. CONCLUSION: We created a new tool, the GN-NAIL capable of efficiently scoring nail psoriasis severity in complex cases, such as patients with onychotillomania and onychophagy, and monitor response to treatment during the COVID-19 pandemic.
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Melasma is a frequent condition worldwide, and it represents one of the most challenging disorders to treat in cosmetic dermatology. One of the critical factors for treatment prognosis is the assessment of the depth and distribution of pigment within the hyperpigmented area. Nowadays, non-invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to estimate pigment distribution and depth within different skin layers. This article aims to provide a systematic review of RCM applications in melasma, providing terminology and investigating characteristics of melasma at baseline and after medical and laser treatment. Our results support the recognition of two main types of melasma, epidermal and mixed type, thanks to the role of RCM in highlighting the precise pigment depth location in the skin non-invasively. RCM treatment monitoring enables the objectification of pigment variations after treatment and the identification of prognostic factors for different treatment modalities. After the era of the application of RCM as a technique applied strictly to skin cancers, additional cosmetic applications are emerging, such as the application of melasma treatment monitoring.
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Melanose , Microscopia Confocal , Humanos , Epiderme/patologia , Epiderme/diagnóstico por imagem , Terapia a Laser/métodos , Melanose/diagnóstico por imagem , Melanose/terapia , Melanose/patologia , Microscopia Confocal/métodosRESUMO
BACKGROUND: Genital involvement in atopic dermatitis(AD) can have a significant impact on the patient's quality of life. However, inspection of genital areas is not usually conducted during routine examination and patients may be reluctant to inform the clinician or show this area. OBJECTIVE: to evaluate the efficacy of tralokinumab in AD patients with genital involvement. METHODS: Adult patients with moderate/severe AD and genital involvement receiving tralokinumab have been analyzed. Primary endpoints were EASI, DLQI, PP-NRS, genital-IGA (g-IGA) and genital itching (GI) at week 16. RESULTS: out of 48 patients with moderate/severe AD under treatment with tralokinumab, 12 patients (25%) showed a genital involvement. Seven patients reported itching in the genital area (58%), while none reported a positive history of genital infections. Median scores at T0 were EASI 17.5, PP-NRS 8 and DLQI 14. After 16 weeks of treatment, we observed a median EASI of 3, a median PP-NRS of 1 and a median DLQI of 1. Finally, concerning the genital response, after 16 weeks of treatment, we observed a statistically significant decrease in mean GI and g-IGA scores. CONCLUSION: despite the small size of our sample, tralokinumab can be considered as a valid treatment option for AD with genital involvement.
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Anticorpos Monoclonais , Dermatite Atópica , Índice de Gravidade de Doença , Humanos , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Masculino , Feminino , Adulto , Anticorpos Monoclonais/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento , Prurido/tratamento farmacológico , Prurido/etiologia , Qualidade de Vida , Adulto Jovem , Doenças dos Genitais Femininos/tratamento farmacológico , Doenças dos Genitais Masculinos/tratamento farmacológicoRESUMO
BACKGROUND: Tirbanibulin 1% ointment is approved for the field treatment of Olsen grade I actinic keratoses (AKs) of the face and scalp. METHODS: We performed a multicenter retrospective study involving 15 dermatologic units in Italy to investigate the efficacy and tolerability of tirbanibulin in a real-life setting. 250 patients were enrolled. Tirbanibulin, 1% ointment, was applied daily for five consecutive days. The efficacy of treatment was measured with modifications of the Actinic Keratosis Area and Severity Index (AKASI). A satisfactory response was defined by complete (100% reduction in the number of lesions) or partial clearance (75-99%) of treated AKs. RESULTS: Overall, the AKASI score was significantly reduced in the studied population (mean, from 4.1 ± 2.7 to 1.4 ± 1.5; P < 0.001). A satisfactory response was observed in 222 (88.8%) cases. The proportion of satisfactory responses was higher when follow-up was performed after 8 weeks (34/35, 97.1%). The reduction in AKASI was significant in patients with Olsen grade II or III lesions (from 5.3 ± 2.8 to 1.6 ± 1.6; P < 0.001). A satisfactory response was observed in 91/104 (87.5%) cases. AKASI reduction was also significant in patients with trunk or limb AKs (from 7.0 ± 1.3 to 2.0 ± 1.6; P = 0.018) since a satisfactory response was observed in 7/8 (87.5%) cases. Tirbanibulin was well tolerated; all adverse events (AEs) included transient local reactions at the site of treatment. Overall, 231 patients had at least one AE. Only 7 (2.8%) grade 4 AEs were recorded. CONCLUSION: Our retrospective study confirmed that tirbanibulin 1% ointment is effective and well tolerated in a real-life setting and is also promising for Olsen grade II and grade III AKs and AKs localized on difficult-to-treat areas.
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INTRODUCTION: Genital involvement is observed in approximately 60% of patients with psoriasis, presenting clinicians with formidable challenges in treatment. While new biologic drugs have emerged as safe and effective options for managing psoriasis, their efficacy in challenging-to-treat areas remains inadequately explored. Intriguingly, studies have shown that interleukin (IL)-17 inhibitors exhibit effectiveness in addressing genital psoriasis. OBJECTIVES: We aimed to determine the effectiveness profile of bimekizumab in patients affected by moderate-to-severe plaque psoriasis with involvement of genitalia. METHODS: Bimekizumab, a dual inhibitor of both IL-17A and IL-17F, was the focus of our 16-week study, demonstrating highly favorable outcomes for patients with genital psoriasis. The effectiveness of bimekizumab was evaluated in terms of improvement in Static Physician Global Assessment of Genitalia (sPGA-G) and Psoriasis Area and Severity Index. RESULTS: Sixty-five adult patients were enrolled. Remarkably, 98.4% of our participants achieved a clear sPGA-G score (s-PGA-g = 0) within 16 weeks. Moreover, consistent improvements were observed in Psoriasis Area and Severity Index scores, accompanied by a significant reduction in the mean Dermatology Life Quality Index, signifying enhanced quality of life. Notably, none of the patients reported a severe impairment in their quality of life after 16 weeks of treatment. In our cohort of 65 patients, subgroup analyses unveiled that the effectiveness of bimekizumab remained unaffected by prior exposure to other biologics or by obesity. CONCLUSIONS: Our initial findings suggest that bimekizumab may serve as a valuable treatment option for genital psoriasis. Nevertheless, further research with larger sample sizes and longer-term follow-up is imperative to conclusively validate these results.
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PURPOSE: Tildrakizumab is a selective inhibitor of IL-23 approved for the treatment of moderate-to-severe plaque psoriasis in two dosages. We conducted a 16-week multicenter retrospective study to compare the effectiveness and safety of tildrakizumab 200 mg versus tildrakizumab 100 mg in patients with a high disease burden or high body weight. MATERIALS AND METHODS: Our retrospective study included 134 patients treated with tildrakizumab 200 mg and 364 patients treated with tildrakizumab 100 mg from 28 Italian Dermatology Units affected by moderate-to-severe plaque psoriasis. The patients had a body weight above 90 kg or a high disease burden (Psoriasis Area and Severity Index [PASI] ≥ 16 or the involvement of difficult-to-treat areas). We evaluated the effectiveness of tildrakizumab at the week-16 visit in terms of PASI90, PASI100 and absolute PASI ≤ 2. RESULTS: After 16 weeks of treatment with tildrakizumab 200 mg, PASI90 was reached by 57.5% of patients and PASI100 by 39.6% of patients. At the same time point, 34.3% and 24.2% of patients treated with tildrakizumab 100 mg achieved PASI90 and PASI100, respectively. CONCLUSIONS: Our data suggest that tildrakizumab 200 mg has better effectiveness than tildrakizumab 100 mg in patients with a body weight ≥ 90 kg and a high disease burden.
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Anticorpos Monoclonais Humanizados , Peso Corporal , Psoríase , Índice de Gravidade de Doença , Humanos , Psoríase/tratamento farmacológico , Psoríase/patologia , Estudos Retrospectivos , Masculino , Feminino , Anticorpos Monoclonais Humanizados/administração & dosagem , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Peso Corporal/efeitos dos fármacos , Itália , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , Relação Dose-Resposta a Droga , IdosoRESUMO
INTRODUCTION: Interleukin-17 plays a pivotal role in both hidradenitis suppurativa (HS) and in maintaining oral homeostasis, but their potential link remains unknown. Thus, we aimed to evaluate and quantify the oral burden of patients with HS. METHODS: In this real-life, multicenter, cross-sectional study, patients with HS were clinically evaluated by two board-certified dermatologists and two board-certified dentists. Oral comorbidities were carefully collected with medical history and therapeutic information. RESULTS: A total of 102 patients (44.0 ± 0.9 years, body mass index 27.0 ± 2.2 kg/m2) were enrolled. Remarkably, 48% and 43% did not undergo at least an oral hygiene or a dental visit each year, respectively. Oral disorders were found in 55.9% of patients with HS, in particular 39.2% had caries and 46.7% reported at least one missing tooth. The main oral manifestations in patients with HS were recurrent aphthous stomatitis (N = 19, 19.2%), amalgam tattoo (N = 14, 14.1%), leukoplakia (N = 11, 11.1%), nicotinic stomatitis (N = 9, 9.1%), papilloma (N = 8, 8.1%), and geographic tongue (N = 8, 8.1%). Whilst the main predictor of oral pathological conditions was Hurley staging (P = 0.0276), multivariate regression analysis indicated that gender and International Hidradenitis Suppurativa Severity Score System (IHS4) were the main predictors for the presence of caries and number of missing teeth. CONCLUSION: As a result of the relevant oral burden in patients with HS, dentists should be part of the multidisciplinary team and oral education should be promoted among patients with HS.
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INTRODUCTION: Minimal erythema dose (MED) remains a parameter of paramount importance to orient narrow-band (NB)-UVB phototherapy in psoriatic (PsO) patients. Recently, circadian rhythm and diet were recognized as potential MED modulators, but their mutual interaction remains understudied. Thus, we aimed to evaluate the potential diet modulation of MED circadian oscillations. METHODS: In the first phase, a cohort study was performed comparing potential MED oscillations (morning, afternoon, and evening) among omnivorous psoriatic patients before and after a phototherapy cycle and omnivorous healthy controls. The two groups were age-, gender-, skin-type-, MED-, and diet-matched. Then, in the second phase, another cohort study was carried out comparing MED oscillations 24 h after the last phototherapeutic session only in psoriatic patients cleared with NB-UVB and undergoing different diets (vegan, vegetarian, paleo , ketogenic, intermittent circadian fasting, and omnivore). Patients with different diets were age-, gender-, and skin-type matched. RESULTS: In the first phase, we enrolled only omnivores, specifically 54 PsO patients and 54 healthy individuals. Their MED before and after NB-UVB therapy changed significantly among the three different time-points (morning, afternoon, and evening) (p < 0.001). The time effect was statistically significant in both groups before and after phototherapy. In the second phase, we enrolled 144 PsO patients (vegan, vegetarian, paleo, ketogenic, intermittent circadian fasting, and omnivore). MED circadian oscillations preserved a significant difference also after clearance and were influenced by diet type and time of day (p < 0.001). In particular, vegans displayed the lowest MED values, whilst Ramadan fasting showed the highest values in morning, afternoon, and evening. CONCLUSIONS: Diet, like other ongoing therapies, should be reported in the medical records of patients with psoriasis undergoing NB-UVB and patients with lower MEDs should be preferentially treated in the morning when the MED is higher.
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Introduction: The development of several effective biological drugs for moderate-to-severe plaque psoriasis has dramatically changed the lives of patients. Despite the wide use of interleukin (IL) inhibitors, limited data are available to date regarding long-term treatment persistence. Method: This multicenter retrospective real-world study evaluated 5932 treatment courses across 5300 patients, all treated with interleukin inhibitors. Drug survival was expressed by using the Kaplan-Meier estimator for each biological drug at 6, 12, 24, 36 and 48 months. We also stratified by discontinuation associated with primary or secondary ineffectiveness. Results: In our study, the most prescribed drugs were secukinumab (1412), ixekizumab (1183), and risankizumab (977). After four years of follow-up, risankizumab emerged as the treatment with the highest drug survival overall, as 91.6% of patients were still on treatment. The overall probability of drug survival at four years was comparable for tildrakizumab (83.5%), ixekizumab (82.6%), guselkumab (82.4%) and brodalumab (81.8%). When evaluating only patients who discontinued the treatment because of ineffectiveness, once again risankizumab was the molecule with the highest drug survival at 4 years (93.4%), this time followed by ixekizumab (87%). Our study, in which all IL inhibitors were adequately represented, confirmed a slightly better treatment persistence for IL-23 inhibitors, consistent with other real-world studies. Conclusion: Our experience showed that IL-23 inhibitors, and risankizumab in particular, had a higher probability of drug survival overall during a 4-year follow-up. Risankizumab and ixekizumab were less likely to be discontinued because of ineffectiveness after four years.
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Produtos Biológicos , Psoríase , Humanos , Interleucina-23 , Inibidores de Interleucina , Estudos Retrospectivos , Interleucina-17 , Produtos Biológicos/uso terapêutico , Interleucina-12 , Psoríase/tratamento farmacológico , ItáliaRESUMO
Introduction: Bimekizumab is a monoclonal antibody that targets Interleukin-17 A and F, approved for the treatment of moderate-to-severe plaque psoriasis. While bimekizumab has been evaluated in several phase-III clinical trials, real-world evidence is still very limited. Method: This multicenter retrospective study included patients affected by plaque psoriasis treated with bimekizumab from May 1, 2022 to April 30, 2023, at 19 Italian referral hospitals. Patients affected by moderate-to-severe plaque psoriasis eligible for systemic treatments were included. The effectiveness of bimekizumab was evaluated in terms of reduction in psoriasis area and severity index (PASI) compared with baseline at weeks 4 and 16. The main outcomes were the percentages of patients achieving an improvement of at least 75% (PASI75), 90% (PASI90) and 100% (PASI100) in PASI score. Results: The study included 237 patients who received at least one injection of bimekizumab. One hundred and seventy-one patients and 114 reached four and 16 weeks of follow-up, respectively. Complete skin clearance was achieved by 43.3% and 75.4% of patients at weeks 4 and 16, respectively. At week 16, 86.8% of patients reported no impact on their quality of life. At week 16, there were no significant differences between bio-naïve and bio-experienced patients in terms of PASI75, PASI90 and PASI100. The most commonly reported adverse events (AEs) were oral candidiasis (10.1%). No severe AEs or AEs leading to discontinuation were observed throughout the study. Conclusion: Our experience supports the effectiveness and tolerability of bimekizumab in a real-world setting with similar results compared with phase-III clinical trials.
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Psoriasis is a chronic immune-mediated inflammatory skin disorder affecting children and adults. To date no approved biomarkers for diagnosis of this disease and follow up of patients have been translated into clinical practice. Recently, extracellular vesicles (EVs) secreted by all cells and present in almost all biological fluids are playing a crucial role in diagnosis and follow up of several diseases, including psoriasis. Since many psoriatic patients show altered plasma lipid profiles and since EVs have been involved in psoriasis pathogenesis, we studied the phospholipid profile of EVs, both microvesicles (MV) or exosomes (Exo), derived from plasma of psoriatic patients undergoing systemic biological treatment (secukinumab, ustekinumab, adalimumab), in comparison with EVs of untreated patients and healthy donors (HD). EVs were evaluated by immune electronmicroscopy for their morphology and by NanoSight for their amount and dimensions. EV phospholipid profiling was performed by High Resolution Liquid Chromatography-Mass Spectrometry and statistical Partial Least Squares Discriminant Analysis. Our results demonstrated that psoriatic patients showed a higher concentration of both MV and Exo in comparison to EVs from HD. The phospholipid profile of Exo from psoriatic patients showed increased levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol and lysoPC compared to Exo from HD. Sphingomyelin (SM) and phosphatidylinositol (PI) are the only phospholipid classes whose levels changed in MV. Moreover, the therapy with ustekinumab seemed to revert the PE and PC lipid composition of circulating Exo towards that of HD and it is the only one of the three biological drugs that did not alter SM expression in MV. Therefore, the determination of lipid alterations of circulating EVs could harbor useful information for the diagnosis and drug response in psoriatic patients.
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INTRODUCTION: Treat-to-target strategies are used in several chronic diseases to improve outcomes. Treatment goals have also been suggested for psoriasis, but there is currently no consensus on targets, and guidance is needed to implement this strategy in clinical practice. The project 'Treat to Target Italia' was launched by a scientific board (SB) of 10 psoriasis experts to generate expert consensus recommendations. METHODS: On the basis of the published literature, their clinical experience, and the results of a survey among Italian dermatologists, the SB identified four relevant topics: (1) clinical remission; (2) quality of life; (3) abrogation of systemic inflammation; (4) safety. They drafted 20 statements addressing these four topics and submitted them to a panel of 28 dermatologists, in a Delphi process, to achieve consensus (greater than 80% agreement). RESULTS: Consensus was reached on all statements. Treatment goals defining clinical remission should include a 90% improvement from baseline in the Psoriasis Area and Severity Index (PASI90 response) or an absolute PASI score of less than or equal to 3. Patient's quality of life and satisfaction are important targets. If PASI targets are achieved, there should be no or very low impact of psoriasis on quality of life [Dermatology Life Quality Index (DLQI) score less than or equal to 3]. If PASI or DLQI goals are not achieved within 3-4 months, treatment should be changed. Abrogation of systemic inflammation may be crucial for preventing or delaying inflammatory comorbidities. Safety is an equally important target as efficacy. CONCLUSION: These 20 consensus statements define the parameters of a treat-to-target strategy for psoriasis in Italy. It is hoped that use of these in the management of patients with psoriasis will improve treatment outcomes and patient health-related quality of life.